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Sample records for parp activity-independent ber

  1. Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS

    Energy Technology Data Exchange (ETDEWEB)

    Pachkowski, Brian F. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Tano, Keizo [Research Reactor Institute, Kyoto University, Kumatori (Japan); Afonin, Valeriy [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Elder, Rhoderick H. [School of Environment and Life Sciences, University of Salford, Greater Manchester (United Kingdom); Takeda, Shunichi [Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Watanabe, Masami [Research Reactor Institute, Kyoto University, Kumatori (Japan); Swenberg, James A. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Nakamura, Jun, E-mail: ynakamur@email.unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States)

    2009-12-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is a base excision repair (BER) protein that binds to DNA single strand breaks (SSBs) and subsequently synthesizes and transfers poly(ADP-ribose) polymers to various nuclear proteins. Numerous biochemical studies have implicated PARP-1 as a modulator of BER; however, the role of PARP-1 in BER in living cells remains unclear partly due to lack of accurate quantitation of BER intermediates existing in cells. Since DT40 cells, chicken B lymphocytes, naturally lack PARP-2, DT40 cells allow for the investigation of the PARP-1 null phenotype without confounding by PARP-2. To test the hypothesis that PARP-1 is necessary for efficient BER during methylmethane sulfonate (MMS) exposure in vertebrate cells, intact DT40 cells and their isogenic PARP-1 null counterparts were challenged with different exposure scenarios for phenotypic characterization. With chronic exposure, PARP-1 null cells exhibited sensitivity to MMS but with an acute exposure did not accumulate base lesions or AP sites to a greater extent than wild-type cells. However, an increase in SSB content in PARP-1 null cell DNA, as indicated by glyoxal gel electrophoresis under neutral conditions, suggested the presence of BER intermediates. These data suggest that during exposure, PARP-1 impacts the stage of BER after excision of the deoxyribosephosphate moiety from the 5' end of DNA strand breaks by polymerase {beta}.

  2. Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS.

    Science.gov (United States)

    Pachkowski, Brian F; Tano, Keizo; Afonin, Valeriy; Elder, Rhoderick H; Takeda, Shunichi; Watanabe, Masami; Swenberg, James A; Nakamura, Jun

    2009-12-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is a base excision repair (BER) protein that binds to DNA single strand breaks (SSBs) and subsequently synthesizes and transfers poly(ADP-ribose) polymers to various nuclear proteins. Numerous biochemical studies have implicated PARP-1 as a modulator of BER; however, the role of PARP-1 in BER in living cells remains unclear partly due to lack of accurate quantitation of BER intermediates existing in cells. Since DT40 cells, chicken B lymphocytes, naturally lack PARP-2, DT40 cells allow for the investigation of the PARP-1 null phenotype without confounding by PARP-2. To test the hypothesis that PARP-1 is necessary for efficient BER during methylmethane sulfonate (MMS) exposure in vertebrate cells, intact DT40 cells and their isogenic PARP-1 null counterparts were challenged with different exposure scenarios for phenotypic characterization. With chronic exposure, PARP-1 null cells exhibited sensitivity to MMS but with an acute exposure did not accumulate base lesions or AP sites to a greater extent than wild-type cells. However, an increase in SSB content in PARP-1 null cell DNA, as indicated by glyoxal gel electrophoresis under neutral conditions, suggested the presence of BER intermediates. These data suggest that during exposure, PARP-1 impacts the stage of BER after excision of the deoxyribosephosphate moiety from the 5' end of DNA strand breaks by polymerase beta.

  3. PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility

    International Nuclear Information System (INIS)

    Godon, C.; Cordelieres, F.P.; Giocanti, N.; Megnin-Chanet, F.; Hall, J.; Favaudon, V.; Godon, C.; Giocanti, N.; Megnin-Chanet, F.; Hall, J.; Favaudon, V.; Cordelieres, F.P.; Cordelieres, F.P.; Biard, D.

    2008-01-01

    The consequences of PARP-1 disruption or inhibition on DNA single-strand break repair (SSBR) and radio-induced lethality were determined in synchronized, iso-genic HeLa cells stably silenced or not for poly(ADP-ribose) polymerase-1 (PARP-1) (PARP-1(KD)) or XRCC1 (XRCC1(KD)). PARP-1 inhibition prevented XRCC1-YFP recruitment at sites of 405 nm laser micro irradiation, slowed SSBR 10-fold and triggered the accumulation of large persistent foci of GFP-PARP-1 and GFP-PCNA at photo damaged sites. These aggregates are presumed to hinder the recruitment of other effectors of the base excision repair (BER) pathway.PARP-1 silencing also prevented XRCC1-YFP recruitment but did not lengthen the lifetime of GFP-PCNA foci. Moreover, PARP-1(KD) and XRCC1(KD) cells in S phase completed SSBR as rapidly as controls, while SSBR was delayed in G1. Taken together, the data demonstrate that a PARP-1- and XRCC1-independent SSBR pathway operates when the short patch repair branch of the BER is deficient. Long patch repair is the likely mechanism, as GFP-PCNA recruitment at photo-damaged sites was normal in PARP-1(KD) cells. PARP-1 silencing elicited hyper-radiosensitivity, while radiosensitization by a PARP inhibitor reportedly occurs only in those cells treated in S phase. PARP-1 inhibition and deletion thus have different outcomes in terms of SSBR and radiosensitivity. (authors)

  4. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

    International Nuclear Information System (INIS)

    Swindall, Amanda F.; Stanley, Jennifer A.; Yang, Eddy S.

    2013-01-01

    Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation

  5. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

    Energy Technology Data Exchange (ETDEWEB)

    Swindall, Amanda F.; Stanley, Jennifer A. [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Yang, Eddy S., E-mail: eyang@uab.edu [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States); Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States)

    2013-07-26

    Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation.

  6. 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.

  7. 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.

  8. Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.

    Science.gov (United States)

    Ding, Xiaofeng; Zhou, Xixi; Cooper, Karen L; Huestis, Juliana; Hudson, Laurie G; Liu, Ke Jian

    2017-09-15

    Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR-induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite-inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite's role in DNA repair inhibition and co-carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. PARP-2 regulates cell cycle-related genes through histone deacetylation and methylation independently of poly(ADP-ribosyl)ation

    International Nuclear Information System (INIS)

    Liang, Ya-Chen; Hsu, Chiao-Yu; Yao, Ya-Li; Yang, Wen-Ming

    2013-01-01

    Highlights: ► PARP-2 acts as a transcription co-repressor independently of PARylation activity. ► PARP-2 recruits HDAC5, 7, and G9a and generates repressive chromatin. ► PARP-2 is recruited to the c-MYC promoter by DNA-binding factor YY1. ► PARP-2 represses cell cycle-related genes and alters cell cycle progression. -- Abstract: Poly(ADP-ribose) polymerase-2 (PARP-2) catalyzes poly(ADP-ribosyl)ation (PARylation) and regulates numerous nuclear processes, including transcription. Depletion of PARP-2 alters the activity of transcription factors and global gene expression. However, the molecular action of how PARP-2 controls the transcription of target promoters remains unclear. Here we report that PARP-2 possesses transcriptional repression activity independently of its enzymatic activity. PARP-2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase G9a to the promoters of cell cycle-related genes, generating repressive chromatin signatures. Our findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein–protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression

  10. 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.

  11. BER Science Network Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Alapaty, Kiran; Allen, Ben; Bell, Greg; Benton, David; Brettin, Tom; Canon, Shane; Dart, Eli; Cotter, Steve; Crivelli, Silvia; Carlson, Rich; Dattoria, Vince; Desai, Narayan; Egan, Richard; Tierney, Brian; Goodwin, Ken; Gregurick, Susan; Hicks, Susan; Johnston, Bill; de Jong, Bert; Kleese van Dam, Kerstin; Livny, Miron; Markowitz, Victor; McGraw, Jim; McCord, Raymond; Oehmen, Chris; Regimbal, Kevin; Shipman, Galen; Strand, Gary; Flick, Jeff; Turnbull, Susan; Williams, Dean; Zurawski, Jason

    2010-11-01

    The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the US Department of Energy Office of Science, the single largest supporter of basic research in the physical sciences in the United States. In support of the Office of Science programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet to be a highly successful enabler of scientific discovery for over 20 years. In April 2010 ESnet and the Office of Biological and Environmental Research, of the DOE Office of Science, organized a workshop to characterize the networking requirements of the science programs funded by BER. The requirements identified at the workshop are summarized and described in more detail in the case studies and the Findings section. A number of common themes emerged from the case studies and workshop discussions. One is that BER science, like many other disciplines, is becoming more and more distributed and collaborative in nature. Another common theme is that data set sizes are exploding. Climate Science in particular is on the verge of needing to manage exabytes of data, and Genomics is on the verge of a huge paradigm shift in the number of sites with sequencers and the amount of sequencer data being generated.

  12. 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.

  13. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

    Science.gov (United States)

    Nitta, Masayuki; Kozono, David; Kennedy, Richard; Stommel, Jayne; Ng, Kimberly; Zinn, Pascal O; Kushwaha, Deepa; Kesari, Santosh; Inda, Maria-del-Mar; Wykosky, Jill; Furnari, Frank; Hoadley, Katherine A; Chin, Lynda; DePinho, Ronald A; Cavenee, Webster K; D'Andrea, Alan; Chen, Clark C

    2010-05-24

    Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

  14. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

    Directory of Open Access Journals (Sweden)

    Masayuki Nitta

    Full Text Available Despite the critical role of Epidermal Growth Factor Receptor (EGFR in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER genes required for the repair of Reactive Oxygen Species (ROS-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1. Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

  15. Distinct spatio temporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair

    International Nuclear Information System (INIS)

    Campalans, Anna; Kortulewski, Thierry; Amouroux, Rachel; Radicella, J. Pablo; Menoni, Herve; Vermeulen, Wim

    2013-01-01

    Single-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1, responsible for the initial recognition of the break. The recruitment of XRCC1 to BER is still poorly understood. Here we show by using both local and global induction of oxidative DNA base damage that XRCC1 participation in BER complexes can be distinguished from that in SSBR by several criteria. We show first that XRCC1 recruitment to BER is independent of PARP. Second, unlike SSBR complexes that are assembled within minutes after global damage induction, XRCC1 is detected later in BER patches, with kinetics consistent with the repair of oxidized bases. Third, while XRCC1-containing foci associated with SSBR are formed both in eu- and heterochromatin domains, BER complexes are assembled in patches that are essentially excluded from heterochromatin and where the oxidized bases are detected. (authors)

  16. Functional characterisation of an Arabidopsis gene strongly induced by ionising radiation: the gene coding the poly(ADP-ribose)polymerase-1 (AthPARP-1)

    International Nuclear Information System (INIS)

    Doucet-Chabeaud, G.

    2000-01-01

    Arabidopsis thaliana, the model-system in plant genetics, has been used to study the responses to DNA damage, experimentally introduced by γ-irradiation. We have characterised a radiation-induced gene coding a 111 kDa protein, AthPARP-1, homologous to the human poly(ADP-ribose)polymerase-1 (hPARP-1). As hPARP-1 is composed by three functional domain with characteristic motifs, AthPARP-1 binds to DNA bearing single-strand breaks and shows DNA damage-dependent poly(ADP-ribosyl)ation. The preferential expression of AthPARP-1 in mitotically active tissues is in agreement with a potential role in the maintenance of genome integrity during DNA replication, as proposed for its human counterpart. Transcriptional gene activation by ionising radiation of AthPARP-1 and AthPARP-2 genes is to date plant specific activation. Our expression analyses after exposure to various stress indicate that 1) AthPARP-1 and AthPARP-2 play an important role in the response to DNA lesions, particularly they are activated by genotoxic agents implicating the BER DNA repair pathway 2) AthPARP-2 gene seems to play an additional role in the signal transduction induced by oxidative stress 3) the observed expression profile of AthPARP-1 is in favour of the regulation of AthPARP-1 gene expression at the level of transcription and translation. This mode of regulation of AthPARP-1 protein biosynthesis, clearly distinct from that observed in animals, needs the implication of a so far unidentified transcription factor that is activated by the presence of DNA lesions. The major outcome of this work resides in the isolation and characterisation of such new transcription factor, which will provide new insight on the regulation of plant gene expression by genotoxic stress. (author) [fr

  17. Decreased expression level of BER genes in Alzheimer's disease patients is not derivative of their DNA methylation status.

    Science.gov (United States)

    Sliwinska, Agnieszka; Sitarek, Przemysław; Toma, Monika; Czarny, Piotr; Synowiec, Ewelina; Krupa, Renata; Wigner, Paulina; Bialek, Katarzyna; Kwiatkowski, Dominik; Korycinska, Anna; Majsterek, Ireneusz; Szemraj, Janusz; Galecki, Piotr; Sliwinski, Tomasz

    2017-10-03

    Neurodegeneration in Alzheimer's disease can be caused by accumulation of oxidative DNA damage resulting from altered expression of genes involved in the base excision repair system (BER). Promoter methylation can affect the profile of BER genes expression. Decreased expression of BER genes was observed in the brains of AD patients. The aim of our study was to compare the expression and methylation profiles of six genes coding for proteins involved in BER, namely: hOGG1, APE1, MUTYH, NEIL1, PARP1 and XRCC1, in the peripheral blood cells of AD patients and healthy volunteers. The study consisted of 100 persons diagnosed with Alzheimer's disease according to DSM-IV criteria, and 110 healthy volunteers. DNA and total RNA were isolated from venous blood cells. Promoter methylation profiles were obtained by High Resolution Melting (HRM) analysis of bisulfide converted DNA samples. Real-time PCR with TaqMan probes was employed for gene expression analysis. APE1, hOGG1, MUTYH, PARP1 and NEIL1 were significantly (pgenes. The methylation status of promoters is not associated with downregulation of BER genes. Our results show that downregulation of BER genes detected in peripheral blood samples could reflect the changes occurring in the brain of patients with AD, and may be a useful biomarker of this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Structural Implications for Selective Targeting of PARPs.

    Science.gov (United States)

    Steffen, Jamin D; Brody, Jonathan R; Armen, Roger S; Pascal, John M

    2013-12-20

    Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents in combination with traditional chemotherapy to reduce side effects. An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair proteins (e.g., BRCA1/2) through an approach termed "synthetic lethality." In the midst of the tremendous efforts that have brought PARP inhibitors to the forefront of modern chemotherapy, most clinically used PARP inhibitors bind to conserved regions that permits cross-selectivity with other PARPs containing homologous catalytic domains. Thus, the differences between therapeutic effects and adverse effects stemming from pan-PARP inhibition compared to selective inhibition are not well understood. In this review, we discuss current literature that has found ways to gain selectivity for one PARP over another. We furthermore provide insights into targeting other domains that make up PARPs, and how new classes of drugs that target these domains could provide a high degree of selectivity by affecting specific cellular functions. A clear understanding of the inhibition profiles of PARP inhibitors will not only enhance our understanding of the biology of individual PARPs, but may provide improved therapeutic options for patients.

  19. Effect of APE1 T2197G (Asp148Glu Polymorphism on APE1, XRCC1, PARP1 and OGG1 Expression in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Juliana C. Santos

    2014-09-01

    Full Text Available It has been hypothesized that genetic variation in base excision repair (BER might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1. In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.

  20. Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry

    Directory of Open Access Journals (Sweden)

    Isabelle Maxim

    2010-04-01

    Full Text Available Abstract Background Poly(ADP-ribose polymerases (PARPs catalyze the formation of poly(ADP-ribose (pADPr, a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose glycohydrolase (PARG, on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosylation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions. Results PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1. Conclusions This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose metabolism.

  1. 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.

  2. 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.

  3. PARP Inhibitors in Ovarian Cancer.

    Science.gov (United States)

    Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Genta, Sofia; Aglietta, Massimo; Sapino, Anna; Valabrega, Giorgio

    2018-03-05

    Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis. We performed a review on Pubmed using 'ovarian cancer' and the name of each PARPi (PARP inhibitor) discussed in the review as Medical Subject Headings (MeSH) keywords. The same search was performed on "clinicaltrial.gov" to identify ongoing clinical trials and on "google.com/patents" and "uspto.gov" for recent patents exploring PARPIs in ovarian cancer. Olaparib, Niraparib and Rucaparib are already approved for treatment of recurrent EOC and their indications are partially overlapping. Talazoparib and Veliparib are promising PARPis, but currently under investigation in early phase trials. Several studies are evaluating PARPis in monotherapy or in associations, in a wide range of settings (i.e. first line, neoadjuvant, platinum-sensitive and resistant disease). PARPis are valuable options in patients with recurrent ovarian cancer with promising activity in different stages of this disease. Further studies are required to better define optimal clinical settings, predictors of response beyond BRCA mutations and strategies to overcome secondary resistance of PARPis therapy in EOC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Radiosensitivity modulating factors: Role of PARP-1, PARP-2 and Cdk5 proteins and chromatin implication

    International Nuclear Information System (INIS)

    Boudra, M.T.

    2011-12-01

    The post-translational modifications of DNA repair proteins and histone remodeling factors by poly(ADP-ribose)ylation and phosphorylation are essential for the maintenance of DNA integrity and chromatin structure, and in particular in response to DNA damaging produced by ionizing radiation (IR). Amongst the proteins implicated in these two processes are the poly(ADP-ribose) polymerase -1 (PARP-1) and PARP-2, and the cyclin-dependent kinase Cdk5: PARP-1 and 2 are involved in DNA single strand break (SSB) repair (SSBR) and Cdk5 depletion has been linked with increased cell sensitivity to PARP inhibition. We have shown by using HeLa cells stably depleted for either CdK5 or PARP-2, that the recruitment profile of PARP-1 and XRCC-1, two proteins involved in the short-patch (SP) SSBR sub-pathway, to DNA damage sites is sub-maximal and that of PCNA, a protein involved in the long-patch (LP) repair pathway, is increased in the absence of Cdk5 and decreased in the absence of PARP-2 suggesting that both Cdk5 and PARP-2 are involved in both SSBR sub-pathways. PARP-2 and Cdk5 also impact on the poly(ADP-ribose) levels in cells as in the absence of Cdk5 a hyper-activation of PARP-1 was found and in the absence of PARP-2 a reduction in poly(ADP-ribose) glyco-hydrolase (PARG) activity was seen. However, in spite of these changes no impact on the repair of SSBs induced by IR was seen in either the Cdk5 or PARP-2 depleted cells (Cdk5 KD or PARP-2 KD cells) but, interestingly, increased radiation sensitivity in terms of cell killing was noted in the Cdk5 depleted cells. We also found that Cdk5, PARP-2 and PARG were all implicated in the regulation of the recruitment and the dissociation of the chromatin-remodeling factor ALC1 from DNA damage sites suggesting a role for these three proteins in changes in chromatin structure after DNA photo-damage. These results, taken together with the observation that PARP-1 recruitment is sub-optimal in both Cdk5 KD and PARP-2 KD cells, show that

  5. Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

    Science.gov (United States)

    Gill, Sonja J; Travers, Jon; Pshenichnaya, Irina; Kogera, Fiona A; Barthorpe, Syd; Mironenko, Tatiana; Richardson, Laura; Benes, Cyril H; Stratton, Michael R; McDermott, Ultan; Jackson, Stephen P; Garnett, Mathew J

    2015-01-01

    Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.

  6. PARP-1 Interaction with and Activation by Histones and Nucleosomes.

    Science.gov (United States)

    Thomas, Colin; Kotova, Elena; Tulin, Alexei V

    2017-01-01

    Poly(ADP-ribose) Polymerase 1 (PARP-1) is an abundant chromatin associated protein, typical for most eukaryotic nuclei. The localization of PARP-1 in chromatin and its enzymatic activation involves multiple interactions of PARP-1 with nucleosomal histones, other proteins, and DNA. We report a set of methods designed to reconstitute PARP-1 regulation in vitro. These methods involve the expression of PARP-1 and PARP-1-regulating proteins using bacterial and eukaryotic systems, purification of these proteins using chromatography, testing of individual interactions in vitro, assembly of active complexes, and reconstitution of PARP-1 regulating reactions in vitro.

  7. Kultur als Ordnungshypothese über Raum?

    OpenAIRE

    Klüter, Helmut

    2009-01-01

    Inhalt: 1 Einleitung 2 Zur Attraktivität von Kultur 3 Kulturologische Methodik 4 Schnittmengen mit und Bindearme zur Kulturgeographie 5 Kritische Argumente gegen Kultur als Ordnungshypothese über Raum 6 Räumliche Abstraktion als Ordnungsstrategie über „Kultur“? 7 Zusammenfassung

  8. PARP1 Val762Ala polymorphism reduces enzymatic activity

    International Nuclear Information System (INIS)

    Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

    2007-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

  9. PARP-1 como regulador del ciclo celular

    OpenAIRE

    Iglesias Vázquez, Pablo

    2015-01-01

    En el presente estudio hemos querido investigar las implicaciones biológicas de la interacción PARP-1/E2F-1 en escenarios en los que el factor de transcripción E2F-1 resulta de gran importancia como son el desarrollo embrionario y la oncogénesis. En este respecto, hemos demostrado que tanto PJ34, inhibidor de la actividad enzimática de PARP, como gosipol, inhibidor de las interacciones proteína-proteína, son capaces de reducir la actividad transcripcional de E2F-1 y la proli...

  10. Mittheilungen über Scyphomedusen I

    NARCIS (Netherlands)

    Stiasny, G.

    1921-01-01

    Hiemit beabsichtige ich eine Reihe kleinerer Mittheilungen über Semaeostomeen und Rhizostomeen des Rijksmuseums van Natuurlijke Historie in Leiden zu veröffentlichen, welche die Systematik, Biologie, Entwicklungsgeschichte und Anatomie verschiedener Scyphomedusen behandeln. Die vorliegenden beiden

  11. Über dieses Heft

    Directory of Open Access Journals (Sweden)

    Editors / Herausgeber

    2013-06-01

    Full Text Available Bilder, audiovisuelle Medien, elektronische Medien, World Wide Web: Das Erzählen vollzieht sich mittlerweile in vielfältigen Formen. Der intensive Gebrauch von neuen Medien in unterschiedlichen Zusammenhängen begegnet, überlagert und vermischt sich mit der Rezeption traditioneller literarischer Medien, die nach wie vor weit verbreitet sind. Für die Erzählforschung ergibt sich aus der veränderten kulturellen Praxis eine Vielzahl von Folgen. Die vorliegende Ausgabe von DIEGESIS soll einen Eindruck davon vermitteln. So rückt etwa ein Korpus in den Vordergrund, das lange Zeit eine Randexistenz führte: Erzählungen, die nicht oder nicht ausschließlich durch Sprache vermittelt werden, und solche, die nicht mehr nur die Kulturtechnik des Lesens und Schreibens voraussetzen. Andere Techniken, andere Gesten begleiten den Umgang mit diesen Erzählungen, und diese Differenz wird an denjenigen Stellen besonders deutlich, wo unterschiedliche Medien ineinander verschachtelt sind. Die Erzeugung von Komplexität durch intermediale Relationen charakterisiert dieses neue Korpus und öffnet für die Erzählforschung neue Arbeitsfelder. Gerade die markanten Medienwechsel, die mit der Vermarktung erfolgreicher Stoffe – als Roman, als Film, als Computerspiel, als Comic, als YouTube-Parodie – einhergehen, werfen die doppelte Frage auf, was in diesen Varianten das gemeinsame narrative Substrat, und was hingegen medienspezifische Erzählverfahren sind. Der ersten Perspektive folgt in der vorliegenden Ausgabe Matthias Brütsch mit einer kritischen Prüfung transmedialer Narrativitätsvergleiche; die zweite entfalten Sebastian Armbrusts Beitrag über Komplexität in bekannten Fernsehserien wie House und The Wire und Markus Kuhns Analyse der narrativen Funktion der Handkamera als spezifischem Verfahren in Spielfilmen und fiktionalen Internetclips. Selbstverständlich haben sich auch bestehende Kategorien der Erzählforschung unter dem Eindruck gewandelt, dass

  12. Über dieses Heft

    Directory of Open Access Journals (Sweden)

    Editors / Herausgeber

    2013-12-01

    Full Text Available Das journalistische Erzählen ist nicht erst neu zu entdecken – es besitzt eine lange und prominente eigenständige Tradition, die von so unterschiedlichen Autoren wie Émile Zola, Egon Erwin Kisch, Gabriel García Márquez, Tom Wolfe u.v.a.m. geprägt wurde. Narratologische Zugänge haben jedoch in den letzten Jahren zu einer präziseren Beschreibung der besonderen Leistungen journalistischen Erzählens beigetragen. Das verdeutlichen auch die Beiträge dieses Heftes. Ethische Aspekte journalistischer Texte können eng mit den jeweils verwendeten Erzählverfahren zusammenhängen – so die These Friederike Herrmanns. Sie kritisiert den vermeintlich objektiven, quasi erzählerlosen Darstellungsstil von Nachrichten in Printmedien als einen weit verbreiteten, aber vergeblichen Versuch, mit Hilfe einer unsichtbar gemachten Erzählinstanz das Ideal einer reinen Faktenpräsentation zu erreichen. Stattdessen, so ihr Vorschlag, solle der Reporter die Standpunktgebundenheit seines Nachrichtentextes stilistisch und erzählerisch deutlich machen. Im interaktiven Online-Journalismus seien Ansätze zu einer derartigen Nachrichtenvermittlung auf Augenhöhe mit den Lesern erkennbar. Narrativer Journalismus, führt Marie Vanoost aus, sei als hybrides Genre zwischen fiktionaler Erzählliteratur und konventionellen Pressemeldungen angesiedelt. Er zeichne sich durch ebenso komplexe wie spezifische Plotkonstruktionen aus. In drei Fallanalysen untersucht Vanoost mit Hilfe von Begriffen Raphäel Baronis und Paul Ricoeurs das Zusammenspiel von intriguing function (fonction intriguante, in der die Dynamik des Leseprozesses im Vordergrund stehe, und configuring function (fonction configurante, die eher informativ und explikativ orientiert sei. Plotkonstruktionen stehen auch im Vordergrund von Valérie Roberts Beitrag über den journalistischen Umgang mit der „Wulff-Affäre“, die im Jahr 2012 zum Rücktritt des deutschen Bundespräsidenten Christian Wulff f

  13. PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.

    Science.gov (United States)

    Barreiro, Esther; Gea, Joaquim

    2018-01-26

    Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.

  14. Trial watch – inhibiting PARP enzymes for anticancer therapy

    Science.gov (United States)

    Sistigu, Antonella; Manic, Gwenola; Obrist, Florine; Vitale, Ilio

    2016-01-01

    ABSTRACT Poly(ADP-ribose) polymerases (PARPs) are a members of family of enzymes that catalyze poly(ADP-ribosyl)ation (PARylation) and/or mono(ADP-ribosyl)ation (MARylation), two post-translational protein modifications involved in crucial cellular processes including (but not limited to) the DNA damage response (DDR). PARP1, the most abundant family member, is a nuclear protein that is activated upon sensing distinct types of DNA damage and contributes to their resolution by PARylating multiple DDR players. Recent evidence suggests that, along with DDR, activated PARP1 mediates a series of prosurvival and proapoptotic processes aimed at preserving genomic stability. Despite this potential oncosuppressive role, upregulation and/or overactivation of PARP1 or other PARP enzymes has been reported in a variety of human neoplasms. Over the last few decades, several pharmacologic inhibitors of PARP1 and PARP2 have been assessed in preclinical and clinical studies showing potent antineoplastic activity, particularly against homologous recombination (HR)-deficient ovarian and breast cancers. In this Trial Watch, we describe the impact of PARP enzymes and PARylation in cancer, discuss the mechanism of cancer cell killing by PARP1 inactivation, and summarize the results of recent clinical studies aimed at evaluating the safety and therapeutic profile of PARP inhibitors in cancer patients. PMID:27308587

  15. Neue Werkstoffe über additive Fertigung

    OpenAIRE

    Günther, Johannes; Niendorf, Thomas

    2016-01-01

    Über die additive Fertigung, oftmals bezeichnet als 3D-Druck, lassen sich Bauteile nahezu beliebiger geometrischer Komplexität herstellen. Gleichzeitig lassen die Prozessrandbedingungen die direkte Einstellung der Mikrostruktur in den verwendeten metallischen Werkstoffen zu. Hieraus ergeben sich weitreichende Möglichkeiten bezüglich der Eigenschaftsoptimierung aktueller Hochleistungswerkstoffe.

  16. Bemerkungen über Pedipalpi (Fortsetzung)

    NARCIS (Netherlands)

    Speijer, E.A.M.

    1931-01-01

    In meiner vorigen Mitteilung (Bemerkungen über Pedipalpi, Zoologische Mededeelingen 's Rijks Museum van Natuurlijke Historie te Leiden Deel XIV, Afl. 1—2, 1931, p. 79—88) habe ich schon darauf hingewiesen, dass man bei der Bearbeitung der Thelyphonidae auf eigentümliche Schwierigkeiten stösst. Diese

  17. The NAD+/PARP1/SIRT1 Axis in Aging.

    Science.gov (United States)

    Mendelsohn, Andrew R; Larrick, James W

    2017-06-01

    NAD+ levels decline with age in diverse animals from Caenorhabditis elegans to mice. Raising NAD+ levels by dietary supplementation with NAD+ precursors, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), improves mitochondrial function and muscle and neural and melanocyte stem cell function in mice, as well as increases murine life span. Decreased NAD+ levels with age reduce SIRT1 function and reduce the mitochondrial unfolded protein response, which can be overcome by NR supplementation. Decreased NAD+ levels cause NAD+-binding protein DBC1 to form a complex with PARP1, inhibiting poly(adenosine diphosphate-ribose) polymerase (PARP) catalytic activity. Old mice have increased amounts of DBC1-PARP1 complexes, lower PARP activity, increased DNA damage, and reduced nonhomologous end joining and homologous recombination repair. DBC1-PARP1 complexes in old mice can be broken by increasing NAD+ levels through treatment with NMN, reducing DNA damage and restoring PARP activity to youthful levels. The mechanism of declining NAD+ levels and its fundamental importance to aging are yet to be elucidated. There is a correlation of PARP activity with mammalian life span that suggests that NAD+/SIRT1/PARP1 may be more significant than the modest effects on life span observed for NR supplementation in old mice. The NAD+/PARP1/SIRT1 axis may link NAD+ levels and DNA damage with the apparent epigenomic DNA methylation clocks that have been described.

  18. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Directory of Open Access Journals (Sweden)

    Fenqing Shang

    Full Text Available Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose polymerase 1 (PARP1. Biguanides and angiotensin II receptor blockers (ARBs such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs, diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosylation (PARylation, but increased endothelial nitric oxide synthase (eNOS activity and silent mating type information regulation 2 homolog 1 (SIRT1 expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

  19. Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in pancreatic cancer.

    Science.gov (United States)

    Martínez-Bosch, Neus; Iglesias, Mar; Munné-Collado, Jessica; Martínez-Cáceres, Carlos; Moreno, Mireia; Guerra, Carmen; Yélamos, Jose; Navarro, Pilar

    2014-10-01

    Pancreatic cancer has a dismal prognosis and is currently the fourth leading cause of cancer-related death in developed countries. The inhibition of poly(ADP-ribose) polymerase-1 (Parp-1), the major protein responsible for poly(ADP-ribosy)lation in response to DNA damage, has emerged as a promising treatment for several tumour types. Here we aimed to elucidate the involvement of Parp-1 in pancreatic tumour progression. We assessed Parp-1 protein expression in normal, preneoplastic and pancreatic tumour samples from humans and from K-Ras- and c-myc-driven mouse models of pancreatic cancer. Parp-1 was highly expressed in acinar cells in normal and cancer tissues. In contrast, ductal cells expressed very low or undetectable levels of this protein, both in a normal and in a tumour context. The Parp-1 expression pattern was similar in human and mouse samples, thereby validating the use of animal models for further studies. To determine the in vivo effects of Parp-1 depletion on pancreatic cancer progression, Ela-myc-driven pancreatic tumour development was analysed in a Parp-1 knock-out background. Loss of Parp-1 resulted in increased tumour necrosis and decreased proliferation, apoptosis and angiogenesis. Interestingly, Ela-myc:Parp-1(-/-) mice displayed fewer ductal tumours than their Ela-myc:Parp-1(+/+) counterparts, suggesting that Parp-1 participates in promoting acinar-to-ductal metaplasia, a key event in pancreatic cancer initiation. Moreover, impaired macrophage recruitment can be responsible for the ADM blockade found in the Ela-myc:Parp-1(-/-) mice. Finally, molecular analysis revealed that Parp-1 modulates ADM downstream of the Stat3-MMP7 axis and is also involved in transcriptional up-regulation of the MDM2, VEGFR1 and MMP28 cancer-related genes. In conclusion, the expression pattern of Parp-1 in normal and cancer tissue and the in vivo functional effects of Parp-1 depletion point to a novel role for this protein in pancreatic carcinogenesis and shed light

  20. PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals.

    Science.gov (United States)

    Zakaria, Esraa M; El-Bassossy, Hany M; El-Maraghy, Nabila N; Ahmed, Ahmed F; Ali, Abdelmoneim A

    2016-11-15

    Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms. Copyright © 2016. Published by Elsevier B.V.

  1. BER of subcarrier MPSK and MDPSK systems in atmospheric turbulence

    KAUST Repository

    Song, Xuegui

    2015-01-01

    Bit-error rate (BER) performance of subcarrier $M$-ary phase-shift keying (MPSK) and $M$-ary differential PSK (MDPSK) is analyzed for optical wireless communications over Gamma-Gamma and lognormal turbulence channels. We study the relation between the exact BER and the approximate BER, which is obtained by dividing the symbol-error rate by the number of bits per symbol, for subcarrier MPSK and MDPSK modulations. The asymptotic BER performance gap between the exact and the approximate BERs is quantified analytically through our asymptotic analyses. The accuracy of the approximate BER of both MPSK and MDPSK depends on the channel conditions. Under weak turbulence conditions, the approximate BER expression can be used to predict the system performance with high accuracy, while under strong turbulence conditions the approximate BER becomes inaccurate and can only serve as a loose lower bound of the exact BER. The asymptotic BER performance loss of MDPSK with respect to MPSK is also quantified analytically.

  2. Gõtter, Grãber und Gelehrte

    Directory of Open Access Journals (Sweden)

    Pedro Moacyr Campos

    1953-09-01

    Full Text Available CERAM, (C. W.. — Gõtter, Grãber und Gelehrte, Rowohlt Verlag, Hamburg.,  1951, 494 págs. (Primeiro Parágrafo do Artigo Bem merecido foi o sucesso encontrado pelo livro de Ceram, Gotter, Graber und Gelehrte, ("Deuses, túmulos e eruditos", que alcançou a cifra de 106.000 exemplares entre novembro de 1949 e março de 1951, continuando a ser reimpresso após esta data.

  3. Lipman Bers, a life in mathematics

    CERN Document Server

    Keen, Linda; Rodríguez, Rubí E

    2015-01-01

    The book is part biography and part collection of mathematical essays that gives the reader a perspective on the evolution of an interesting mathematical life. It is all about Lipman Bers, a giant in the mathematical world who lived in turbulent and exciting times. It captures the essence of his mathematics, a development and transition from applied mathematics to complex analysis-quasiconformal mappings and moduli of Riemann surfaces-and the essence of his personality, a progression from a young revolutionary refugee to an elder statesman in the world of mathematics and a fighter for global h

  4. Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

    Science.gov (United States)

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

  5. PARP Inhibition Restores Extrinsic Apoptotic Sensitivity in Glioblastoma

    Science.gov (United States)

    Karpel-Massler, Georg; Pareja, Fresia; Aimé, Pascaline; Shu, Chang; Chau, Lily; Westhoff, Mike-Andrew; Halatsch, Marc-Eric; Crary, John F.; Canoll, Peter; Siegelin, Markus D.

    2014-01-01

    Background Resistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo. Methods The sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model. Results The combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation of caspases and inhibition of formation of neurospheres when compared to single-agent treatment. Mechanistically, pharmacological PARP inhibition elicited a nuclear stress response with up-regulation of down-stream DNA-stress response proteins, e.g., CCAAT enhancer binding protein (C/EBP) homology protein (CHOP). Furthermore, Olaparib and PJ34 increased protein levels of DR5 in a concentration and time-dependent manner. In turn, siRNA-mediated suppression of DR5 mitigated the effects of TRAIL/PARP inhibitor-mediated apoptosis. In addition, suppression of PARP-1 levels enhanced TRAIL-mediated apoptosis in malignant glioma cells. Treatment of human astrocytes with the combination of TRAIL/PARP inhibitors did not cause toxicity. Finally, the combination treatment of TRAIL and PJ34 significantly reduced tumor growth in vivo when compared to treatment with each agent alone. Conclusions PARP inhibition represents a promising avenue to overcome apoptotic resistance in GBM. PMID:25531448

  6. Inhibition of matrix metalloproteinase-2 by PARP inhibitors

    International Nuclear Information System (INIS)

    Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D.; Pacher, Pal; Schulz, Richard

    2009-01-01

    Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC 50 values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

  7. Inhibition of matrix metalloproteinase-2 by PARP inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Nicolescu, Adrian C.; Holt, Andrew; Kandasamy, Arulmozhi D. [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada); Pacher, Pal [National Institutes of Health, NIAAA, Laboratory of Physiologic Studies, Bethesda, MD (United States); Schulz, Richard, E-mail: richard.schulz@ualberta.ca [Departments of Pharmacology and Pediatrics, Cardiovascular Research Centre, University of Alberta, Edmonton, Alta., Canada T6G 2S2 (Canada)

    2009-10-02

    Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC{sub 50} values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity.

  8. Optical fiber communication — An overview

    Indian Academy of Sciences (India)

    This paper deals with the historical development of optical communication systems and their failures initially. Then the different generations in optical fiber communication along with their features are discussed. Some aspects of total internal reflection, different types of fibers along with their size and refractive index profile, ...

  9. Multiscale Computation. Needs and Opportunities for BER Science

    Energy Technology Data Exchange (ETDEWEB)

    Scheibe, Timothy D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Smith, Jeremy C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-01-01

    The Environmental Molecular Sciences Laboratory (EMSL), a scientific user facility managed by Pacific Northwest National Laboratory for the U.S. Department of Energy, Office of Biological and Environmental Research (BER), conducted a one-day workshop on August 26, 2014 on the topic of “Multiscale Computation: Needs and Opportunities for BER Science.” Twenty invited participants, from various computational disciplines within the BER program research areas, were charged with the following objectives; Identify BER-relevant models and their potential cross-scale linkages that could be exploited to better connect molecular-scale research to BER research at larger scales and; Identify critical science directions that will motivate EMSL decisions regarding future computational (hardware and software) architectures.

  10. Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP

    Directory of Open Access Journals (Sweden)

    Hsueh Chung-Tsen

    2011-04-01

    Full Text Available Abstract We reviewed preclinical data and clinical development of MDM2 (murine double minute 2, ALK (anaplastic lymphoma kinase and PARP (poly [ADP-ribose] polymerase inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC. Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib, another oral small-molecule PARP inhibitor, demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation.

  11. Analyzing structure–function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells

    Science.gov (United States)

    Rank, Lisa; Veith, Sebastian; Gwosch, Eva C.; Demgenski, Janine; Ganz, Magdalena; Jongmans, Marjolijn C.; Vogel, Christopher; Fischbach, Arthur; Buerger, Stefanie; Fischer, Jan M.F.; Zubel, Tabea; Stier, Anna; Renner, Christina; Schmalz, Michael; Beneke, Sascha; Groettrup, Marcus; Kuiper, Roland P.; Bürkle, Alexander; Ferrando-May, Elisa; Mangerich, Aswin

    2016-01-01

    Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure–function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1–PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\\L713F expression triggered apoptosis, whereas PARP1\\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure–function relationships of natural and artificial PARP1 variants. PMID:27694308

  12. Alfredo Häberli ja Iittala : Senta / Piret Veigel

    Index Scriptorium Estoniae

    Veigel, Piret, 1961-

    2004-01-01

    Jaanuaris Pariisi messil Maison & Objet aasta disaineriks kuulutatud Alfredo Häberli esitles veebruaris Frankfurdi messil Ambiente oma neljandat ühisprojekti Soome Iittalaga: Senta-nimelisi valge, punase ja vahuveini klaase

  13. Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.

    Science.gov (United States)

    Thorsell, Ann-Gerd; Ekblad, Torun; Karlberg, Tobias; Löw, Mirjam; Pinto, Ana Filipa; Trésaugues, Lionel; Moche, Martin; Cohen, Michael S; Schüler, Herwig

    2017-02-23

    Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.

  14. Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-01-15

    Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

  15. Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

    International Nuclear Information System (INIS)

    Sun, Xi; Zhou, Xixi; Du, Libo; Liu, Wenlan; Liu, Yang; Hudson, Laurie G.; Liu, Ke Jian

    2014-01-01

    Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

  16. The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

    International Nuclear Information System (INIS)

    Lakatos, Petra; Hegedűs, Csaba; Salazar Ayestarán, Nerea; Juarranz, Ángeles; Kövér, Katalin E.; Szabó, Éva; Virág, László

    2016-01-01

    Highlights: • PARP-1 is not a key regulator of photochemotherapy. • The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism. • Photosensitization by PJ-34 is associated with increased ROS production and DNA damage. • Cells sensitized by PJ-34 undergo caspase-mediated apoptosis. - Abstract: A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5 J/cm"2) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ–34 + UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and −8. In conclusion, PJ-34 is a photosensitizer and PJ–34 + UVA causes DNA damage and caspase

  17. The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lakatos, Petra; Hegedűs, Csaba [Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Salazar Ayestarán, Nerea; Juarranz, Ángeles [Department of Biology, Faculty of Sciences, Universidad Autónoma of Madrid, 28049-Madrid (Spain); Kövér, Katalin E. [Department of Inorganic and Analytical Chemistry, Faculty of Sciences, University of Debrecen, Debrecen (Hungary); Szabó, Éva [Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Virág, László, E-mail: lvirag@med.unideb.hu [Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); MTA-DE Cell Biology and Signaling Research Group, Debrecen (Hungary)

    2016-08-15

    Highlights: • PARP-1 is not a key regulator of photochemotherapy. • The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism. • Photosensitization by PJ-34 is associated with increased ROS production and DNA damage. • Cells sensitized by PJ-34 undergo caspase-mediated apoptosis. - Abstract: A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5 J/cm{sup 2}) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ–34 + UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and −8. In conclusion, PJ-34 is a photosensitizer and PJ–34 + UVA causes DNA damage and caspase

  18. Risk of the research reactor BER II in Berlin; Risiken des Berliner Experimentierreaktors BER II

    Energy Technology Data Exchange (ETDEWEB)

    Paulitz, Henrik; Hoevener, Barbara; Rosen, Alex

    2015-04-20

    The research reactor BER II is sited at the periphery of Berlin in the neighborhood of residential areas. The operational license is limited until December 31, 2019. The reactor is funded by the Federal Government (90%) and the city of Berlin (10%). The stress test has shown that the reactor is not secured against an aircraft crash (airliner or fast flying military jet), meltdown with remarkable radiological consequences to the public would be the consequence. Further hazards result from the radioactive waste transport, explosions and fires. The emergency measures cannot be considered to be sufficient. The city of Berlin would not be able to fulfill the required measures in case of a radiation accident.

  19. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment

    DEFF Research Database (Denmark)

    Oplustilova, L.; Wolanin, K.; Bartkova, J.

    2012-01-01

    combinations with camptothecin or ionizing radiation. Furthermore, monitoring pARsylation and Rad51 foci formation as surrogate markers for PARP activity and HR, respectively, supported their candidacy for biomarkers of PARP-1i responses. As to resistance mechanisms, we confrmed the role of the multidrug......(ADp-ribose) polymerase-1 (PARP-1), an enzyme critical for repair pathways alternative to HR. While promising, treatment with PARP-1 inhibitors (PARP-1i) faces some hurdles, including (1) acquired resistance, (2) search for other sensitizing, non-BRCA1/2 cancer defects and (3) lack of biomarkers to predict response...

  20. Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dong Hou

    2018-07-01

    Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer

  1. BER of subcarrier MPSK/MDPSK modulated OWC systems in Gamma-Gamma turbulence

    KAUST Repository

    Song, Xuegui

    2013-12-01

    Bit-error rate (BER) performance of subcarrier Mary phase-shift keying (MPSK) and M-ary differential PSK (MDPSK) is analyzed for optical wireless communications in Gamma-Gamma turbulence. We study the relation between the exact BER and the approximate BER, which is obtained by dividing the symbol error rate by the number of bits per symbol, for subcarrier MPSK and MDPSK modulations. The asymptotic performance gap between the exact and the approximate BERs is quantified analytically through our asymptotic analyses. The accuracy of the approximate BER of both MPSK and MDPSK depends on the channel conditions. Under weak turbulence conditions, the approximate BER expression can be used to predict the system performance with high accuracy, while under strong turbulence conditions the approximate BER becomes inaccurate and can only serve as a loose lower bound of the exact BER. The asymptotic BER performance loss of MDPSK with respect to MPSK is also quantified analytically. © 2013 IEEE.

  2. PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration

    Directory of Open Access Journals (Sweden)

    Alexander Jonathan S

    2010-12-01

    Full Text Available Abstract The normal function of poly (ADP-ribose polymerase-1 (PARP-1 is the routine repair of DNA damage by adding poly (ADP ribose polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.

  3. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Directory of Open Access Journals (Sweden)

    Raimundo M. G. del Moral

    2013-01-01

    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  4. The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism.

    Science.gov (United States)

    Lakatos, Petra; Hegedűs, Csaba; Salazar Ayestarán, Nerea; Juarranz, Ángeles; Kövér, Katalin E; Szabó, Éva; Virág, László

    2016-08-01

    A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5J/cm(2)) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ-34+UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and -8. In conclusion, PJ-34 is a photosensitizer and PJ-34+UVA causes DNA damage and caspase-mediated cell death independently of PARP-1 inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Storage temperature affects fruit quality attributes of Ber ( Ziziphus ...

    African Journals Online (AJOL)

    Fruit utilization is affected by quality attributes and shelf life. The quality of Jujube or Ber (Ziziphus mauritiana Lamk.) fruits after harvest depends on storage conditions used. In this study, different storage temperatures and durations were evaluated to determine the appropriate storage conditions of fresh fruits of Z.

  6. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

    Directory of Open Access Journals (Sweden)

    Andrea Buchfellner

    Full Text Available Poly(ADP-ribose polymerase 1 (PARP1 is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa, termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

  7. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

    Science.gov (United States)

    Buchfellner, Andrea; Yurlova, Larisa; Nüske, Stefan; Scholz, Armin M; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E; Drexler, Guido A; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A; Rothbauer, Ulrich

    2016-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

  8. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells

    Science.gov (United States)

    Nüske, Stefan; Scholz, Armin M.; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E.; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A.; Rothbauer, Ulrich

    2016-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair. PMID:26950694

  9. Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    M. Sambucci

    2013-01-01

    Full Text Available T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosylation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose polymerases (PARPs. Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.

  10. Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison with standard PARP inhibitors.

    Science.gov (United States)

    Eltze, Tobias; Boer, Rainer; Wagner, Thomas; Weinbrenner, Steffen; McDonald, Michelle C; Thiemermann, Christoph; Bürkle, Alexander; Klein, Thomas

    2008-12-01

    We have identified three novel structures for inhibitors of the poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA and implicated in DNA repair, apoptosis, organ dysfunction or necrosis. 2-[4-(5-Methyl-1H-imidazol-4-yl)-piperidin-1-yl]-4,5-dihydro-imidazo[4,5,1-i,j]quinolin-6-one (BYK49187), 2-(4-pyridin-2-yl-phenyl)-4,5-dihydro-imidazo[4,5,1-i,j]quinolin-6-one (BYK236864), 6-chloro-8-hydroxy-2,3-dimethyl-imidazo-[1,2-alpha]-pyridine (BYK20370), and 4-(1-methyl-1H-pyrrol-2-ylmethylene)-4H-isoquinolin-1,3-dione (BYK204165) inhibited cell-free recombinant human PARP-1 with pIC(50) values of 8.36, 7.81, 6.40, and 7.35 (pK(i) 7.97, 7.43, 5.90, and 7.05), and murine PARP-2 with pIC(50) values of 7.50, 7.55, 5.71, and 5.38, respectively. BYK49187, BYK236864, and BYK20370 displayed no selectivity for PARP-1/2, whereas BYK204165 displayed 100-fold selectivity for PARP-1. The IC(50) values for inhibition of poly(ADP-ribose) synthesis in human lung epithelial A549 and cervical carcinoma C4I cells as well in rat cardiac myoblast H9c2 cells after PARP activation by H(2)O(2) were highly significantly correlated with those at cell-free PARP-1 (r(2) = 0.89-0.96, P < 0.001) but less with those at PARP-2 (r(2) = 0.78-0.84, P < 0.01). The infarct size caused by coronary artery occlusion and reperfusion in the anesthetized rat was reduced by 22% (P < 0.05) by treatment with BYK49187 (3 mg/kg i.v. bolus and 3 mg/kg/h i.v. during 2-h reperfusion), whereas the weaker PARP inhibitors, BYK236864 and BYK20370, were not cardioprotective. In conclusion, the imidazoquinolinone BYK49187 is a potent inhibitor of human PARP-1 activity in cell-free and cellular assays in vitro and reduces myocardial infarct size in vivo. The isoquinolindione BYK204165 was found to be 100-fold more selective for PARP-1. Thus, both compounds might be novel and valuable tools for investigating PARP-1-mediated effects.

  11. PARP2 Is the Predominant Poly(ADP-Ribose Polymerase in Arabidopsis DNA Damage and Immune Responses.

    Directory of Open Access Journals (Sweden)

    Junqi Song

    2015-05-01

    Full Text Available Poly (ADP-ribose polymerases (PARPs catalyze the transfer of multiple poly(ADP-ribose units onto target proteins. Poly(ADP-ribosylation plays a crucial role in a variety of cellular processes including, most prominently, auto-activation of PARP at sites of DNA breaks to activate DNA repair processes. In humans, PARP1 (the founding and most characterized member of the PARP family accounts for more than 90% of overall cellular PARP activity in response to DNA damage. We have found that, in contrast with animals, in Arabidopsis thaliana PARP2 (At4g02390, rather than PARP1 (At2g31320, makes the greatest contribution to PARP activity and organismal viability in response to genotoxic stresses caused by bleomycin, mitomycin C or gamma-radiation. Plant PARP2 proteins carry SAP DNA binding motifs rather than the zinc finger domains common in plant and animal PARP1 proteins. PARP2 also makes stronger contributions than PARP1 to plant immune responses including restriction of pathogenic Pseudomonas syringae pv. tomato growth and reduction of infection-associated DNA double-strand break abundance. For poly(ADP-ribose glycohydrolase (PARG enzymes, we find that Arabidopsis PARG1 and not PARG2 is the major contributor to poly(ADP-ribose removal from acceptor proteins. The activity or abundance of PARP2 is influenced by PARP1 and PARG1. PARP2 and PARP1 physically interact with each other, and with PARG1 and PARG2, suggesting relatively direct regulatory interactions among these mediators of the balance of poly(ADP-ribosylation. As with plant PARP2, plant PARG proteins are also structurally distinct from their animal counterparts. Hence core aspects of plant poly(ADP-ribosylation are mediated by substantially different enzymes than in animals, suggesting the likelihood of substantial differences in regulation.

  12. Untersuchungen über Veronica triloba (Opiz) Kerner in Rheinhessen

    OpenAIRE

    Oesau, Albert

    1981-01-01

    Untersuchungen in den Jahren 1977-1979 ergaben, daß Veronica triloba (Opiz) Kerner, eine Sippe aus dem Veronica hederifolia-Aggregat, in Rheinhessen überraschenderweise weit verbreitet ist und bisher übersehen wurde. Sie siedelt vor allem in Ackerunkraut- und Felsgrus-Gesellschaften sowie lückigen Trockenrasen, ohne eine gesellschaftsspezifische Bindung zu zeigen. Gut ausgeprägte morphologische Merkmale gestatten eine sichere Differenzierung gegenüber den übrigen Sippenvertretern V. hederifol...

  13. Research progress of PARP-1 inhibitors in antitumor drugs and radionuclide markers

    International Nuclear Information System (INIS)

    Zhao Lingzhou; Zhang Huabei

    2011-01-01

    Poly(ADP-ribose)polymerase (PARP) is a new target in the cancer treatment nowadays. PARP not only can repair DNA damage, regulate and control transcription, maintain the stability of intracellular environment and genome, regulate the process of cell survival and death, but also is the main transcription factor in the development of inflammation and the process of cancer. To inhibit PARP activity can reduce the DNA repair function in tumor cells, and increase the sensibility to DNA damage agents, so as to improve the efficacy of radiation therapy and chemotherapy for tumor. A number of studies have suggested that, whether used alone or combination with other chemotherapy drugs, PARP inhibitors show the potential in the anti-tumor therapeutic areas. In this paper, PARP-1 inhibitors were reviewed in antitumor research progress. According to the stage of development , PARP-1 inhibitors are classified. Several representative PARP-1 inhibitors, in clinical trials, with potential clinical value were introduced. Positron emission tomography (PET), uses the main short half-life elementary in human body as tracer, and at the molecular level, achieve the no wound, quantitative and dynamic observation about the different changes of metabolites or drugs in the body. PET is the most advanced contemporary video diagnostic technology, and this paper simply introduce the research progress of PARP-1 inhibitors labeled with radioactive nuclides. (authors)

  14. Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy

    Directory of Open Access Journals (Sweden)

    Daniel Sultanov

    2017-01-01

    Full Text Available DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose polymerase 1 increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer microscopy. PARP-1 binding to a double-strand break in the vicinity of a nucleosome results in a significant increase of the distance between the adjacent gyres of nucleosomal DNA. This partial uncoiling of the entire nucleosomal DNA occurs without apparent loss of histones and is reversed after poly(ADP-ribosylation of PARP-1. Thus PARP-1-nucleosome interactions result in reversible, partial uncoiling of the entire nucleosomal DNA.

  15. Characterization of Novel Cytoplasmic PARP in the Brain of Octopus vulgaris

    Science.gov (United States)

    DE LISA, EMILIA; DE MAIO, ANNA; MOROZ, LEONID L.; MOCCIA, FRANCESCO; MENNELLA, MARIA ROSARIA FARAONE; DI COSMO, ANNA

    2014-01-01

    Recent investigation has focused on the participation of the poly (ADP-ribose) polymerase (PARP) reaction in the invertebrate central nervous system (CNS) during the process of long-term memory (LTM). In this paper, we characterize, localize, and assign a possible role to a cytoplasmic PARP in the brain of Octopus vulgaris. PARP activity was assayed in optic lobes, supraesophageal mass, and optic nerves. The highest levels of enzyme were found in the cytoplasmic fraction. Hyper-activation of the enzyme was detected in Octopus brain after visual discrimination training. Finally, cytoplasmic PARP was found to inhibit Octopus vulgaris actin polymerization. We propose that the cytoplasmic PARP plays a role in vivo to induce the cytoskeletonal reorganization that occurs during learning-induced neuronal plasticity. PMID:22815366

  16. SNR and BER Models and the Simulation for BER Performance of Selected Spectral Amplitude Codes for OCDMA

    Directory of Open Access Journals (Sweden)

    Abdul Latif Memon

    2014-01-01

    Full Text Available Many encoding schemes are used in OCDMA (Optical Code Division Multiple Access Network but SAC (Spectral Amplitude Codes is widely used. It is considered an effective arrangement to eliminate dominant noise called MAI (Multi Access Interference. Various codes are studied for evaluation with respect to their performance against three noises namely shot noise, thermal noise and PIIN (Phase Induced Intensity Noise. Various Mathematical models for SNR (Signal to Noise Ratios and BER (Bit Error Rates are discussed where the SNRs are calculated and BERs are computed using Gaussian distribution assumption. After analyzing the results mathematically, it is concluded that ZCC (Zero Cross Correlation Code performs better than the other selected SAC codes and can serve larger number of active users than the other codes do. At various receiver power levels, analysis points out that RDC (Random Diagonal Code also performs better than the other codes. For the power interval between -10 and -20 dBm performance of RDC is better ZCC. Their lowest BER values suggest that these codes should be part of an efficient and cost effective OCDM access network in the future.

  17. Poly(ADP-ribose polymerase (PARP-1 is not involved in DNA double-strand break recovery

    Directory of Open Access Journals (Sweden)

    Fernet Marie

    2003-07-01

    Full Text Available Abstract Background The cytotoxicity and the rejoining of DNA double-strand breaks induced by γ-rays, H2O2 and neocarzinostatin, were investigated in normal and PARP-1 knockout mouse 3T3 fibroblasts to determine the role of poly(ADP-ribose polymerase (PARP-1 in DNA double-strand break repair. Results PARP-1-/- were considerably more sensitive than PARP-1+/+ 3T3s to induced cell kill by γ-rays and H2O2. However, the two cell lines did not show any significant difference in the susceptibility to neocarzinostatin below 1.5 nM drug. Restoration of PARP-1 expression in PARP-1-/- 3T3s by retroviral transfection of the full PARP-1 cDNA did not induce any change in neocarzinostatin response. Moreover the incidence and the rejoining kinetics of neocarzinostatin-induced DNA double-strand breaks were identical in PARP-1+/+ and PARP-1-/- 3T3s. Poly(ADP-ribose synthesis following γ-rays and H2O2 was observed in PARP-1-proficient cells only. In contrast neocarzinostatin, even at supra-lethal concentration, was unable to initiate PARP-1 activation yet it induced H2AX histone phosphorylation in both PARP1+/+ and PARP-1-/- 3T3s as efficiently as γ-rays and H2O2. Conclusions The results show that PARP-1 is not a major determinant of DNA double-strand break recovery with either strand break rejoining or cell survival as an endpoint. Even though both PARP-1 and ATM activation are major determinants of the cell response to γ-rays and H2O2, data suggest that PARP-1-dependent poly(ADP-ribose synthesis and ATM-dependent H2AX phosphorylation, are not inter-related in the repair pathway of neocarzinostatin-induced DNA double-strand breaks.

  18. PARP activity and inhibition in fetal and adult oligodendrocyte precursor cells: Effect on cell survival and differentiation.

    Science.gov (United States)

    Baldassarro, Vito A; Marchesini, Alessandra; Giardino, Luciana; Calzà, Laura

    2017-07-01

    Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy

    DEFF Research Database (Denmark)

    Rodríguez-Vargas, José Manuel; Ruiz-Magaña, María José; Ruiz-Ruiz, Carmen

    2012-01-01

    , leading to ATP depletion (an early event after nutrient deprivation). The absence of PARP-1 blunted AMPK activation and prevented the complete loss of mTOR activity, leading to a delay in autophagy. PARP-1 depletion favors apoptosis in starved cells, suggesting a pro-survival role of autophagy and PARP-1...

  20. Irradiation devices at the upgraded research reactor BER II

    International Nuclear Information System (INIS)

    Gawlik, D.; Robertson, T.

    1992-06-01

    An overview is given of those properties of the BER II research reactor which are important for carrying out irradiation experiments. The subsequent section describes the irradiation devices currently installed in the reactor, or which are under construction, and some of the experiments which can be conducted using them. The field of application of these experiments extends from the study of the metabolism of trace elements in man, employing a highly sensitive element analysis, via radiation damage of high-tech materials, to the identification of paintings of the old masters. The report concludes with a review of the technical details of the irradiation devices, giving information of interest for potential users. (orig.)

  1. Richard Wollheim über die Metapher in der Malerei

    OpenAIRE

    Heinrich, Richard

    1993-01-01

    Es handelt sich um den Text eines Vortrages, den ich Jänner 1993 im Rahmen einer Vortragsreihe am Institut für Kunstgeschichte der Universität Wien gehalten habe. Er ist bisher unpubliziert und nicht redigiert. Das worüber ich spreche ist ein Artikel von Richard Wollheim mit dem Titel "Die Metapher in der Malerei". Diesen Artikel habe ich herausgegeben, gemeinsam mit meinem Kollegen Helmuth Vetter, 1991 in dem Band "Bilder der Philosophie". Ursprünglich handelt es sich um einen Vortrag, d...

  2. Regulation of FOXO1-mediated transcription and cell proliferation by PARP-1

    Energy Technology Data Exchange (ETDEWEB)

    Sakamaki, Jun-ichi; Daitoku, Hiroaki; Yoshimochi, Kenji [Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Miwa, Masanao [Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829 (Japan); Fukamizu, Akiyoshi, E-mail: akif@tara.tsukuba.ac.jp [Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan)

    2009-05-08

    Forkhead box O (FOXO) transcription factors play an important role in a wide range of biological processes, including cell cycle control, apoptosis, detoxification of reactive oxygen species, and gluconeogenesis through regulation of gene expression. In this study, we demonstrated that PARP-1 functions as a negative regulator of FOXO1. We showed that PARP-1 directly binds to and poly(ADP-ribosyl)ates FOXO1 protein. PARP-1 represses FOXO1-mediated expression of cell cycle inhibitor p27{sup Kip1} gene. Notably, poly(ADP-ribosyl)ation activity was not required for the repressive effect of PARP-1 on FOXO1 function. Furthermore, knockdown of PARP-1 led to a decrease in cell proliferation in a manner dependent on FOXO1 function. Chromatin immunoprecipitation experiments confirmed that PARP-1 is recruited to the p27{sup Kip1} gene promoter through a binding to FOXO1. These results suggest that PARP-1 acts as a corepressor for FOXO1, which could play an important role in proper cell proliferation by regulating p27{sup Kip1} gene expression.

  3. Autoimmune response to PARP and BRCA1/BRCA2 in cancer

    Science.gov (United States)

    Zhu, Qing; Han, Su-Xia; Zhou, Cong-Ya; Cai, Meng-Jiao; Dai, Li-Ping; Zhang, Jian-Ying

    2015-01-01

    Purpose To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which were involved in the synthetic lethal interaction in cancer. Methods Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer, 41 from pancreatic cancer and 135 from normal individuals. The positive sera with ELISA were confirmed by Western blot. Immunohistochemistry was used to examine the expression of PARP1 and BRCA1/BRCA2 in breast cancer. Results Autoantibody frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the sera from cancer patients were tested for the presence of autoantibodies to PARP1 and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive autoantibody reactions varied from 0% to 50.0%. This was significantly higher autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1) in ovarian cancer and breast cancer compared to normal control sera (P cancer was different (P cancers have different profiles of autoantibodies. The autoantibodies to proteins involving the synthetic lethal interactions would be novel serological biomarker in some selective cancers. PMID:25865228

  4. PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.

    Directory of Open Access Journals (Sweden)

    Tomasz Dziaman

    Full Text Available The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo level in leukocyte DNA of healthy controls (138 individuals, patients with benign adenomas (AD, 137 individuals and with malignant carcinomas (CRC, 169 individuals revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.

  5. PARP-1 modulation of mTOR signaling in response to a DNA alkylating agent.

    Directory of Open Access Journals (Sweden)

    Chantal Ethier

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP-1 is widely involved in cell death responses. Depending on the degree of injury and on cell type, PARP activation may lead to autophagy, apoptosis or necrosis. In HEK293 cells exposed to the alkylating agent N-methyl-N'-nitro-N'-nitrosoguanine (MNNG, we show that PARP-1 activation triggers a necrotic cell death response. The massive poly(ADP-ribose (PAR synthesis following PARP-1 activation leads to the modulation of mTORC1 pathway. Shortly after MNNG exposure, NAD⁺ and ATP levels decrease, while AMP levels drastically increase. We characterized at the molecular level the consequences of these altered nucleotide levels. First, AMP-activated protein kinase (AMPK is activated and the mTORC1 pathway is inhibited by the phosphorylation of Raptor, in an attempt to preserve cellular energy. Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate. These results provide new evidence that cell death by necrosis is orchestrated by the balance between several signaling pathways, and that PARP-1 and PAR take part in these events.

  6. PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

    Science.gov (United States)

    Li, Jiatong; Dou, Dongwei; Li, Ping; Luo, Wenqi; Lv, Wenxin; Zhang, Chengdong; Song, Xiaowei; Yang, Yuan; Zhang, Yuening; Xu, Yanzhen; Xiao, Feifan; Wei, Yan; Qin, Jian; Li, Hongtao; Yang, Xiaoli

    2017-07-01

    PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p  0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

  7. Differential expression of PARP1 mRNA in leucocytes of patients ...

    Indian Academy of Sciences (India)

    P. 2011 Differential expression of PARP1 mRNA in leucocytes of patients with Down's syndrome. J. Genet. ... of Alzheimer disease at an earlier age than subjects with- ... family and personal informed consent. .... In effect, they report that.

  8. Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells

    International Nuclear Information System (INIS)

    Moonen, Harald J.J.; Geraets, Liesbeth; Vaarhorst, Anika; Bast, Aalt; Wouters, Emiel F.M.; Hageman, Geja J.

    2005-01-01

    Oxidative DNA damage, as occurs during exacerbations in chronic obstructive pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its substrate NAD + , resulting in an energy crisis and ultimately in cell death. Inhibition of PARP-1 results in preservation of the intracellular NAD + pool, and of NAD + -dependent cellular processes. In this study, PARP-1 activation by hydrogen peroxide decreased intracellular NAD + levels in human pulmonary epithelial cells, which was found to be prevented in a dose-dependent manner by theophylline, a widely used compound in the treatment of COPD. This enzyme inhibition by theophylline was confirmed in an ELISA using purified human PARP-1 and was found to be competitive by nature. These findings provide new mechanistic insights into the therapeutic effect of theophylline in oxidative stress-induced lung pathologies

  9. Targeted Radiosensitization of ETS Fusion-Positive Prostate Cancer through PARP1 Inhibition

    Directory of Open Access Journals (Sweden)

    Sumin Han

    2013-10-01

    Full Text Available ETS gene fusions, which result in overexpression of an ETS transcription factor, are considered driving mutations in approximately half of all prostate cancers. Dysregulation of ETS transcription factors is also known to exist in Ewing's sarcoma, breast cancer, and acute lymphoblastic leukemia. We previously discovered that ERG, the predominant ETS family member in prostate cancer, interacts with the DNA damage response protein poly (ADP-ribose polymerase 1 (PARP1 in human prostate cancer specimens. Therefore, we hypothesized that the ERG-PARP1 interaction may confer radiation resistance by increasing DNA repair efficiency and that this radio-resistance could be reversed through PARP1 inhibition. Using lentiviral approaches, we established isogenic models of ERG overexpression in PC3 and DU145 prostate cancer cell lines. In both cell lines, ERG overexpression increased clonogenic survival following radiation by 1.25 (±0.07 fold (mean ± SEM and also resulted in increased PARP1 activity. PARP1 inhibition with olaparib preferentially radiosensitized ERG-positive cells by a factor of 1.52 (±0.03 relative to ERG-negative cells (P < .05. Neutral and alkaline COMET assays and immunofluorescence microscopy assessing γ-H2AX foci showed increased short- and long-term efficiencies of DNA repair, respectively, following radiation that was preferentially reversed by PARP1 inhibition. These findings were verified in an in vivo xenograft model. Our findings demonstrate that ERG overexpression confers radiation resistance through increased efficiency of DNA repair following radiation that can be reversed through inhibition of PARP1. These results motivate the use of PARP1 inhibitors as radiosensitizers in patients with localized ETS fusion-positive cancers.

  10. Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts.

    Directory of Open Access Journals (Sweden)

    Natalie R Gassman

    Full Text Available Regulation of poly(ADP-ribose (PAR synthesis and turnover is critical to determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by poly(ADP-ribose polymerase-1 (PARP-1 occurs when cells deficient in DNA repair are exposed to genotoxic agents; however, the function of this hyperactivation has not been adequately explained. Here, we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β (pol β. The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS, or to low energy laser-induced DNA damage. There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells, but not in wild-type cells. In the case of MMS treatment, PAR synthesis did not lead to cell death in the pol β null cells, but instead resulted in increased PARylation of the nonhomologous end-joining (NHEJ protein Ku70 and increased association of Ku70 with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS-induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised.

  11. PARP-1 Inhibition Is Neuroprotective in the R6/2 Mouse Model of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Antonella Cardinale

    Full Text Available Poly (ADP-ribose polymerase 1 (PARP-1 is a nuclear enzyme that is involved in physiological processes as DNA repair, genomic stability, and apoptosis. Moreover, published studies demonstrated that PARP-1 mediates necrotic cell death in response to excessive DNA damage under certain pathological conditions. In Huntington's disease brains, PARP immunoreactivity was described in neurons and in glial cells, thereby suggesting the involvement of apoptosis in HD. In this study, we sought to determine if the PARP-1 inhibitor exerts a neuroprotective effect in R6/2 mutant mice, which recapitulates, in many aspects, human HD. Transgenic mice were treated with the PARP-1 inhibitor INO-1001 mg/Kg daily starting from 4 weeks of age. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that INO 1001-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as striatal atrophy, morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. INO-1001 was effective in significantly increasing activated CREB and BDNF in the striatal spiny neurons, which might account for the beneficial effects observed in this model. Our findings show that PARP-1 inhibition could be considered as a valid therapeutic approach for HD.

  12. PARP1 inhibitors: contemporary attempts at their use in anticancer therapy and future perspective

    Directory of Open Access Journals (Sweden)

    Ewelina Wiśnik

    2016-04-01

    Full Text Available Current cancer therapies are based mainly on the use of compounds that cause DNA damage. Unfortunately, even the combination therapies do not give rewarding effects, due to the high efficiency of DNA damage repair mechanisms in tumor cells. Therefore, the present studies should be focused on proteins that are involved in DNA repair systems. Poly(ADP-ribose polymerase-1 is an example of a protein commonly known as an enzyme that plays a role in the detection of DNA damage and repair. Activation of PARP1 in response to DNA damage leads to poly-ADP-ribosylation of proteins contributing to DNA repair systems, therefore facilitating the maintenance of genome stability. On the other hand, inhibition of PARP1 enzyme results in the accumulation of DNA damage, which in turn contributes to cell death. Studies on inhibitors of PARP1 are still ongoing, and some of them are currently in the third phase of clinical trials. To date, only one representative of the PARP1 inhibitors, called olaparib, has been approved for anti-cancer therapy in the EU and the USA. Moreover, a growing body of evidence indicates a role of this protein in various intracellular processes such as bioenergetics, proliferation, regulation of gene expression, cell death as well as immunoregulation. A number of different intracellular processes regulated by PARP1 give rise to potential wider use of PARP1 inhibitors in treatment of other diseases, including immune or autoimmune disorders.

  13. Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

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    Daniëlle M. P. H. J. Boesten

    2013-01-01

    Full Text Available Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose polymerase-1 (PARP-1 and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline in human fibroblasts (HF cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP. Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

  14. Deficiency in Poly(ADP-ribose Polymerase-1 (PARP-1 Accelerates Aging and Spontaneous Carcinogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Tatiana S. Piskunova

    2008-01-01

    Full Text Available Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosylation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosylation and PARP-1 may also play an important role in aging. Here we show that PARP-1−/− mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1−/− mice. The incidence of spontaneous tumors in both PARP-1−/− and PARP-1+/+ groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP-1−/− mice than PARP-1+/+ mice (72% and 49%, resp.; < .05. In addition, spontaneous tumors appear earlier in PARP-1−/− mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.

  15. BER Science Network Requirements Workshop -- July 26-27,2007

    Energy Technology Data Exchange (ETDEWEB)

    Tierney, Brian L.; Dart, Eli

    2008-02-01

    The Energy Sciences Network (ESnet) is the primary provider of network connectivity for the US Department of Energy Office of Science, the single largest supporter of basic research in the physical sciences in the United States of America. In support of the Office of Science programs, ESnet regularly updates and refreshes its understanding of the networking requirements of the instruments, facilities, scientists, and science programs that it serves. This focus has helped ESnet to be a highly successful enabler of scientific discovery for over 20 years. In July 2007, ESnet and the Biological and Environmental Research (BER) Program Office of the DOE Office of Science organized a workshop to characterize the networking requirements of the science programs funded by the BER Program Office. These included several large programs and facilities, including Atmospheric Radiation Measurement (ARM) Program and the ARM Climate Research Facility (ACRF), Bioinformatics and Life Sciences Programs, Climate Sciences Programs, the Environmental Molecular Sciences Laboratory at PNNL, the Joint Genome Institute (JGI). National Center for Atmospheric Research (NCAR) also participated in the workshop and contributed a section to this report due to the fact that a large distributed data repository for climate data will be established at NERSC, ORNL and NCAR, and this will have an effect on ESnet. Workshop participants were asked to codify their requirements in a 'case study' format, which summarizes the instruments and facilities necessary for the science and the process by which the science is done, with emphasis on the network services needed and the way in which the network is used. Participants were asked to consider three time scales in their case studies--the near term (immediately and up to 12 months in the future), the medium term (3-5 years in the future), and the long term (greater than 5 years in the future). In addition to achieving its goal of collecting and

  16. Risk of the research reactor BER II in Berlin

    International Nuclear Information System (INIS)

    Paulitz, Henrik; Hoevener, Barbara; Rosen, Alex

    2015-01-01

    The research reactor BER II is sited at the periphery of Berlin in the neighborhood of residential areas. The operational license is limited until December 31, 2019. The reactor is funded by the Federal Government (90%) and the city of Berlin (10%). The stress test has shown that the reactor is not secured against an aircraft crash (airliner or fast flying military jet), meltdown with remarkable radiological consequences to the public would be the consequence. Further hazards result from the radioactive waste transport, explosions and fires. The emergency measures cannot be considered to be sufficient. The city of Berlin would not be able to fulfill the required measures in case of a radiation accident.

  17. Workshop on instrumentation of the disassembled BER II

    International Nuclear Information System (INIS)

    Jauch, W.; Steiner, M.

    1982-01-01

    A workshop on the instrumentation of a disassembled BER II-reactor took place in the Hahn-Meitner-Institute in Berlin on April 19 and 20, 1982. Invited were all groups that are promoted by the associations 'Neutron Scattering for Investigation of Condensed Substance' and 'Neutron Scattering and Complementary Methods in Chemistry and Biology', along with experts for neutron spectrometers. 40 foreign scientists from 22 different institutes had accepted the invitation. The actual questions were treated in 13 presentations and a certain number of posters, with the latter also comprising activation analysis. The present report contains the presentations submitted, the final discussion minutes and a summary from HMI-view. (orig./RW) [de

  18. Neutron scattering-instrumentation at the upgraded research reactor BER II

    International Nuclear Information System (INIS)

    1991-01-01

    The Berlin Neutron Scattering Centre (BENSC) is a newly created special department of the Hahn-Meitner-Institut, in the framework of which the BER II neutron beam reactor is made available to external users. BENSC is devoted to development, continuous modernisation and maintenance of the scientific instrumets at the BER II and to the support of their users. (orig./HSI)

  19. Vasoactivity of rucaparib, a PARP-1 inhibitor, is a complex process that involves myosin light chain kinase, P2 receptors, and PARP itself.

    Directory of Open Access Journals (Sweden)

    Cian M McCrudden

    Full Text Available Therapeutic inhibition of poly(ADP-ribose polymerase (PARP, as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699, induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.

  20. Effect of MRE11 loss on PARP-inhibitor sensitivity in endometrial cancer in vitro.

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    Romana Koppensteiner

    Full Text Available To evaluate the frequency of MRE11/RAD50/NBS1 (MRN-complex loss of protein expression in endometrial cancers (EC and to determine whether loss of MRE11 renders the cancer cells sensitive to Poly(ADP-ribose polymerase (PARP-inhibitory treatment.MRN expression was examined in 521 samples of endometrial carcinomas and in 10 cancer cell lines. A putative mutation hotspot in the form of an intronic poly(T allele in MRE11 was sequenced in selected cases (n = 26. Sensitivity to the PARP-inhibitor, BMN673 was tested in colony formation assays before and after MRE11 silencing using siRNA. Homologous recombination (HR DNA repair was evaluated by RAD51-foci formation assay upon irradiation and drug treatment.Loss of MRE11 protein was found in 30.7% of EC tumours and significantly associated with loss of RAD50, NBS1 and mismatch repair protein expression. One endometrial cell line showed a markedly reduced MRE11 expression due to a homozygous poly(T mutation of MRE11, thereby exhibiting an increased sensitivity to BMN673. MRE11 depletion sensitizes MRE11 expressing EC cell lines to the treatment with BMN673. The increased sensitivity to PARP-inhibition correlates with reduced RAD51 foci formation upon ionizing radiation in MRE11-depleted cells.Loss of the MRE11 protein predicts sensitivity to PARP-inhibitor sensitivity in vitro, defining it as an additional synthetic lethal gene with PARP. The high incidence of MRE11 loss in ECs can be potentially exploited for PARP-inhibitor therapy. Furthermore, MRE11 protein expression using immunohistochemistry could be investigated as a predictive biomarker for PARP-inhibitor treatment.

  1. MicroRNAs Modulate Oxidative Stress in Hypertension through PARP-1 Regulation

    Directory of Open Access Journals (Sweden)

    Douglas F. Dluzen

    2017-01-01

    Full Text Available Oxidative stress is thought to contribute to aging and age-related diseases, such as cardiovascular and neurodegenerative diseases, and is a risk factor for systemic arterial hypertension. Previously, we reported differential mRNA and microRNA (miRNA expression between African American (AA and white women with hypertension. Here, we found that the poly-(ADP-ribose polymerase 1 (PARP-1, a DNA damage sensor protein involved in DNA repair and other cellular processes, is upregulated in AA women with hypertension. To explore this mechanism, we identified two miRNAs, miR-103a-2-5p and miR-585-5p, that are differentially expressed with hypertension and were predicted to target PARP1. Through overexpression of each miRNA-downregulated PARP-1 mRNA and protein levels and using heterologous luciferase reporter assays, we demonstrate that miR-103a-2-5p and miR-585-5p regulate PARP1 through binding within the coding region. Given the important role of PARP-1 in DNA repair, we assessed whether overexpression of miR-103a-2-5p or miR-585-5p affected DNA damage and cell survival. Overexpression of these miRNAs enhanced DNA damage and decreased both cell survival and colony formation. These findings highlight the role for PARP-1 in regulating oxidative DNA damage in hypertension and identify important new miRNA regulators of PARP-1 expression. These insights may provide additional avenues to understand hypertension health disparities.

  2. Hyperthermia and PARP1-inhibition for sensitization of radiation and cisplatin treatment of cervical carcinoma cells

    International Nuclear Information System (INIS)

    Franken, Nicolaas; Oei, Arlene; Leeuwen, Caspar van; Stalpers, Lukas; Rodermond, Hans; Bel, Arjan; Kok, Petra; Crezee, Hans

    2014-01-01

    Ionizing radiation causes single and double strand breaks (SSBs and DSBs). DSBs are among the most critical DNA lesions and can be repaired via either non-homologous end joining (NHEJ) in which PARP1, Ku70 and DNA-PKcs are important, or homologous recombination (HR), where BRCA2 and Rad51 are essential. Hyperthermia disturbs HR by temporary inactivation of BRCA2. Cisplatin disrupts NHEJ and PARP1-inhibitor blocks Poly-(ADP-ribose)polymerase- 1, which is important in SSB repair, NHEJ and backup-NHEJ. Our goal was to investigate the additional effectiveness of hyperthermia and PARP1-inhibition on radiation and/or cisplatin treatment. Cervical carcinoma cells (SiHa) were treated at different temperature levels levels (41.0-43.0℃, PARP1-inhibitor (100 μM; NU1025), gamma-irradiation doses (0-8 Gy) or cisplatin (1'R for 1 h). Clonogenic assays were carried out to measure survival and γH2AX staining was used to visualize DSBs. To elucidate mechanisms of action expression levels of DNA repair proteins BRCA2 and DNA-PKcs were investigated after 42.0℃ (1 h) using western blot. Combined hyperthermia and radiation resulted in an increased number of γH2AX foci as compared to radiation alone. Hyperthermia treatment in combination with cisplatin and PARP1 inhibitor and with radiation and PARP1 inhibitor significantly decreased cell survival. Western blot demonstrated a decreased expression of BRCA2 protein at 30 min after hyperthermia treatment. Adding PARP1-inhibitor significantly improves the effectiveness of combined hyperthermia radiotherapy and combined hyperthermia-cisplatin treatment on cervical carcinoma cells. Hyperthermia affects DNA-DSB repair as is indicated by increased γH2AX foci numbers and decreased BRCA2 expression. (author)

  3. PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

    Science.gov (United States)

    Tajuddin, Nuzhath; Kim, Hee-Yong

    2018-01-01

    Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

  4. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

    2017-12-01

    Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

  5. BET Bromodomain Inhibition Synergizes with PARP Inhibitor in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sergey Karakashev

    2017-12-01

    Full Text Available PARP inhibition is known to be an effective clinical strategy in BRCA mutant cancers, but PARP inhibition has not been applied to BRCA-proficient tumors. Here, we show the synergy of BET bromodomain inhibition with PARP inhibition in BRCA-proficient ovarian cancers due to mitotic catastrophe. Treatment of BRCA-proficient ovarian cancer cells with the BET inhibitor JQ1 downregulated the G2-M cell-cycle checkpoint regulator WEE1 and the DNA-damage response factor TOPBP1. Combining PARP inhibitor Olaparib with the BET inhibitor, we observed a synergistic increase in DNA damage and checkpoint defects, which allowed cells to enter mitosis despite the accumulation of DNA damage, ultimately causing mitotic catastrophe. Moreover, JQ1 and Olaparib showed synergistic suppression of growth of BRCA-proficient cancer in vivo in a xenograft ovarian cancer mouse model. Our findings indicate that a combination of BET inhibitor and PARP inhibitor represents a potential therapeutic strategy for BRCA-proficient cancers.

  6. HEU/LEU-conversion of BER II successfully finished

    International Nuclear Information System (INIS)

    Haas, K.; Fischer, C.-O.; Krohn, H.

    2000-01-01

    The BER II (Berliner Experimental Reactor) research reactor is a swimming pool type reactor located in Berlin, Germany. The reactor operates with a thermal power of 10 MW and is primarily used to produce neutrons for neutron scattering experiments. The conversion from HEU- to LEU-fuel elements began in August, 1997. At the last RERTR Meeting 1999 in Budapest, Hungary, Hahn-Meitner-Institut (HMI) presented a 'Status Report' on the conversion of 10 HEU/LEU mixed cores. In February 2000, HMI finished the HEU/LEU-conversion. Hereby, the first pure LEU-standard-core went into operation. Our second LEU-core just ends its operation at the end of July. The third LEU-core will be built up in the beginning of August. The average burn-up rate was improved from 50 - 55% (HEU) to 60 - 65% (LEU). Therefore, only 14 elements/year are now used instead of 28/year. The following report describes our first steps in building pure LEU-cores from mixed HEU/LEU-cores, as well as our initial experience using the pure LEU-cores. (author)

  7. Analysis Of Impact Of Various Parameters On BER Performance For IEEE 802.11b

    Directory of Open Access Journals (Sweden)

    Nilesh B. Kalani

    2015-08-01

    Full Text Available Abstract This paper discusses about IEEE 802.11b simulation model implemented using LabVIEW software and its analyses for impact on bit error rate BER for different parameters as channel type channel number data transmission rate and packet size. Audio file is being transmitted processed and analyzed using the model for various parameters. This paper gives analysis of BER verses ESN0 for various parameter like data rate packet size and communication channel for the IEEE 802.11b simulation model generated using LabVIEW. It is proved that BER can be optimized by tweaking different parameters of wireless communication system.

  8. A New Closed Form Approximation for BER for Optical Wireless Systems in Weak Atmospheric Turbulence

    Science.gov (United States)

    Kaushik, Rahul; Khandelwal, Vineet; Jain, R. C.

    2018-04-01

    Weak atmospheric turbulence condition in an optical wireless communication (OWC) is captured by log-normal distribution. The analytical evaluation of average bit error rate (BER) of an OWC system under weak turbulence is intractable as it involves the statistical averaging of Gaussian Q-function over log-normal distribution. In this paper, a simple closed form approximation for BER of OWC system under weak turbulence is given. Computation of BER for various modulation schemes is carried out using proposed expression. The results obtained using proposed expression compare favorably with those obtained using Gauss-Hermite quadrature approximation and Monte Carlo Simulations.

  9. BER estimation for all-optical regenerators influenced by pattern effects

    DEFF Research Database (Denmark)

    Bischoff, Svend; Lading, B.; Mørk, Jesper

    2002-01-01

    An efficient method is presented for the estimation of the bit-error rate (BER) of a system employing all-optical regenerators influenced by pattern effects. We theoretically study noise accumulation and noise redistribution in long distance transmission systems employing a delayed interference...... signal wavelength converter for all-optical regeneration. The BER is studied for return-to-zero signals at bit rates of 2.5 Gb/s (no patterning) up to 40 Gb/s (strong patterning). The calculation of the BER is based on pattern dependent transfer functions, which may be obtained numerically or measured....

  10. Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications

    Science.gov (United States)

    Yoon, Sarah; Jo, Yuna; Kwon, So Mee; Kim, Kyoung Min; Kwon, Keun Sang; Kim, Chan Young; Woo, Hyun Goo

    2015-01-01

    Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A− expression had the worst prognosis while the patient group with PARP1−/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10−9, RFS: P = 2.2 × 10−8). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic. PMID:26540566

  11. Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Hassan, Saima; Esch, Amanda; Liby, Tiera; Gray, Joe W; Heiser, Laura M

    2017-12-01

    Effective treatment of patients with triple-negative (ER-negative, PR-negative, HER2-negative) breast cancer remains a challenge. Although PARP inhibitors are being evaluated in clinical trials, biomarkers are needed to identify patients who will most benefit from anti-PARP therapy. We determined the responses of three PARP inhibitors (veliparib, olaparib, and talazoparib) in a panel of eight triple-negative breast cancer cell lines. Therapeutic responses and cellular phenotypes were elucidated using high-content imaging and quantitative immunofluorescence to assess markers of DNA damage (53BP1) and apoptosis (cleaved PARP). We determined the pharmacodynamic changes as percentage of cells positive for 53BP1, mean number of 53BP1 foci per cell, and percentage of cells positive for cleaved PARP. Inspired by traditional dose-response measures of cell viability, an EC 50 value was calculated for each cellular phenotype and each PARP inhibitor. The EC 50 values for both 53BP1 metrics strongly correlated with IC 50 values for each PARP inhibitor. Pathway enrichment analysis identified a set of DNA repair and cell cycle-associated genes that were associated with 53BP1 response following PARP inhibition. The overall accuracy of our 63 gene set in predicting response to olaparib in seven breast cancer patient-derived xenograft tumors was 86%. In triple-negative breast cancer patients who had not received anti-PARP therapy, the predicted response rate of our gene signature was 45%. These results indicate that 53BP1 is a biomarker of response to anti-PARP therapy in the laboratory, and our DNA damage response gene signature may be used to identify patients who are most likely to respond to PARP inhibition. Mol Cancer Ther; 16(12); 2892-901. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Structure/function analysis of PARP-1 in oxidative and nitrosative stress-induced monomeric ADPR formation.

    Directory of Open Access Journals (Sweden)

    Ben Buelow

    2009-07-01

    Full Text Available Poly adenosine diphosphate-ribose polymerase-1 (PARP-1 is a multifunctional enzyme that is involved in two major cellular responses to oxidative and nitrosative (O/N stress: detection and response to DNA damage via formation of protein-bound poly adenosine diphosphate-ribose (PAR, and formation of the soluble 2(nd messenger monomeric adenosine diphosphate-ribose (mADPR. Previous studies have delineated specific roles for several of PARP-1's structural domains in the context of its involvement in a DNA damage response. However, little is known about the relationship between the mechanisms through which PARP-1 participates in DNA damage detection/response and those involved in the generation of monomeric ADPR. To better understand the relationship between these events, we undertook a structure/function analysis of PARP-1 via reconstitution of PARP-1 deficient DT40 cells with PARP-1 variants deficient in catalysis, DNA binding, auto-PARylation, and PARP-1's BRCT protein interaction domain. Analysis of responses of the respective reconstituted cells to a model O/N stressor indicated that PARP-1 catalytic activity, DNA binding, and auto-PARylation are required for PARP-dependent mADPR formation, but that BRCT-mediated interactions are dispensable. As the BRCT domain is required for PARP-dependent recruitment of XRCC1 to sites of DNA damage, these results suggest that DNA repair and monomeric ADPR 2(nd messenger generation are parallel mechanisms through which PARP-1 modulates cellular responses to O/N stress.

  13. PARPi-FL - a Fluorescent PARP1 Inhibitor for Glioblastoma Imaging

    Directory of Open Access Journals (Sweden)

    Christopher P. Irwin

    2014-05-01

    Full Text Available New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic.

  14. Human mass balance study and metabolite profiling of 14C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer

    NARCIS (Netherlands)

    van Andel, Lotte; Zhang, Z; Lu, S.; Kansra, V; Agarwal, S.; Hughes, L.; Tibben, M.; Gebretensae, A.; Lucas, L.; Hillebrand, Michel J X; Rosing, H.; Schellens, J H M|info:eu-repo/dai/nl/073926272; Beijnen, J H|info:eu-repo/dai/nl/071919570

    2017-01-01

    Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive,

  15. Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

    Science.gov (United States)

    2012-01-01

    The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide. PMID:24900418

  16. Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1.

    Science.gov (United States)

    Sriram, Chandra Shaker; Jangra, Ashok; Gurjar, Satendra Singh; Mohan, Pritam; Bezbaruah, Babul Kumar

    2016-02-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10mg/kgi.p.) once daily for 14days. On the 14th day 30min after edaravone treatment mice were challenged with LPS (1mg/kgi.p.). After 3h and 24h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12h of LPS administration. Moreover, after 24h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10mg/kg). Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression. Copyright © 2015. Published by Elsevier Inc.

  17. Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells

    International Nuclear Information System (INIS)

    McDonald, Elizabeth S.; Mankoff, Julia; Makvandi, Mehran; Chu, Wenhua; Chu, Yunxiang; Mach, Robert H.; Zeng, Chenbo

    2017-01-01

    The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation. - Highlights: • PARPi, YUN3-6 and olaparib, and σ2 ligands, SV119 and SW43, were evaluated. • Mouse and human breast cancer cells, EMT6 and MDA-MB-231 respectively, were used. • YUN3-6 and SV119 synergistically triggered cell death in EMT6 cells. • Olaparib and SW43 additively triggered cell death in MDA-MB-231 cells. • Olaparib arrested cells in G2/M in MDA-MB-231 cells.

  18. Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Colombo I

    2018-03-01

    Full Text Available Ilaria Colombo, Stephanie Lheureux, Amit Manulal Oza Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada Abstract: Rucaparib is a potent small-molecule inhibitor of poly (ADP-ribose polymerase (PARP proteins (PARP-1, PARP-2 and PARP-3 that play an important role in repairing DNA damage and maintaining genomic stability. Tumors with mutations in BRCA1/2 or other homologous recombination deficiency (HRD genes are particularly sensitive to PARP inhibitors because of “synthetic lethality”, whereby a therapeutic agent can take advantage of an intrinsic weakness in DNA repair. Rucaparib has been investigated in several preclinical and clinical studies showing promising activity in BRCA-mutant and BRCA–wild-type epithelial ovarian cancers (EOCs. Dose-escalation Phase I studies have established the recommended Phase II dose to be 600 mg twice a day for oral rucaparib. Phase II and III studies have defined its role as treatment for BRCA-mutant recurrent high-grade EOC and as maintenance treatment for platinum-sensitive relapsed EOC following response to platinum-based chemotherapy. Genomic loss of heterozygosity has also been investigated as a potential signature of HRD and as a potential predictive biomarker of response. Treatment-induced adverse events (AEs have been observed in almost all patients treated with rucaparib, but mainly lower grade; with the most common being nausea, vomiting, asthenia/fatigue, anemia and transient transaminitis. The majority of AEs occurred early in treatment, were transient and have been easily managed with supportive treatment, dose interruption or discontinuation. This review will analyze the results of clinical trials investigating efficacy and safety of rucaparib in patients with ovarian cancer. Keywords: rucaparib, ovarian cancer, BRCA mutations, homologous recombination deficiency, maintenance treatment, PARP inhibitor

  19. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction

    DEFF Research Database (Denmark)

    Fang, Evandro Fei; Scheibye-Knudsen, Morten; Brace, Lear E

    2014-01-01

    with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD(+)-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP-1. This phenotype is rescued by PARP-1 inhibition...... or by supplementation with NAD(+) precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration...

  20. The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma

    DEFF Research Database (Denmark)

    Hjortkjær, Mette; Waldstrøm, Marianne; Jakobsen, Anders

    2017-01-01

    BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene...... tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient...

  1. A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors

    Science.gov (United States)

    2017-02-01

    affecting the function of Fanconi Anemia (FA) genes ( FANCA /B/C/D2/E/F/G/I/J/L/M, PALB2) or DNA damage response genes involved in HR 5 (ATM, ATR...Award Number: W81XWH-10-1-0585 TITLE: A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors...To) 15 July 2010 – 2 Nov.2016 4. TITLE AND SUBTITLE A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP

  2. Impact of Mutual Coupling and Polarization of Antennas on BER Performances of Spatial Multiplexing MIMO Systems

    Directory of Open Access Journals (Sweden)

    Jianfeng Zheng

    2012-01-01

    Full Text Available This paper is aimed at studying the impacts of mutual coupling, matching networks, and polarization of antennas on performances of Multiple-Input Multiple-Output (MIMO systems employing Spatial Multiplexing (SM. In particular, the uncoded average Bit Error Rate (BER of MIMO systems is investigated. An accurate signal analysis framework based on circuit network parameters is presented to describe the transmit/receive characteristics of the matched/unmatched antenna array. The studied arrays consist of matched/unmatched compact copolarization and polarization diversity antenna array. Monte-Carlo numerical simulations are used to study the BER performances of the SM MIMO systems using maximum-likelihood and/or zero-forcing detection schemes. The simulation results demonstrate that the use of matching networks can improve the BER performance of SM MIMO systems significantly, and the BER performance deterioration due to antenna orientation randomness can be compensated by use of polarization diversity antenna arrays.

  3. Minimum BER Receiver Filters with Block Memory for Uplink DS-CDMA Systems

    Directory of Open Access Journals (Sweden)

    Mérouane Debbah

    2008-05-01

    Full Text Available The problem of synchronous multiuser receiver design in the case of direct-sequence single-antenna code division multiple access (DS-CDMA uplink networks is studied over frequency selective fading channels. An exact expression for the bit error rate (BER is derived in the case of BPSK signaling. Moreover, an algorithm is proposed for finding the finite impulse response (FIR receiver filters with block memory such that the exact BER of the active users is minimized. Several properties of the minimum BER FIR filters with block memory are identified. The algorithm performance is found for scenarios with different channel qualities, spreading code lengths, receiver block memory size, near-far effects, and channel mismatch. For the BPSK constellation, the proposed FIR receiver structure with block memory has significant better BER with respect to Eb/N0 and near-far resistance than the corresponding minimum mean square error (MMSE filters with block memory.

  4. Minimum BER Receiver Filters with Block Memory for Uplink DS-CDMA Systems

    Directory of Open Access Journals (Sweden)

    Debbah Mérouane

    2008-01-01

    Full Text Available Abstract The problem of synchronous multiuser receiver design in the case of direct-sequence single-antenna code division multiple access (DS-CDMA uplink networks is studied over frequency selective fading channels. An exact expression for the bit error rate (BER is derived in the case of BPSK signaling. Moreover, an algorithm is proposed for finding the finite impulse response (FIR receiver filters with block memory such that the exact BER of the active users is minimized. Several properties of the minimum BER FIR filters with block memory are identified. The algorithm performance is found for scenarios with different channel qualities, spreading code lengths, receiver block memory size, near-far effects, and channel mismatch. For the BPSK constellation, the proposed FIR receiver structure with block memory has significant better BER with respect to and near-far resistance than the corresponding minimum mean square error (MMSE filters with block memory.

  5. Effect of gamma irradiation on antioxidant properties of ber (Zizyphus mauritiana) fruit

    International Nuclear Information System (INIS)

    Kavitha, C.; Kuna, Aparna; Sagar, S.B.; Padmavati, T.V.N.; Supraja, T.; Prabhakar, N.

    2015-01-01

    Effect of gamma irradiation (0.25 to 1.0kGy) on antioxidant properties of ber fruit was studied. Antioxidant properties of ber fruits were determined by scavenging DPPH radical activity, reducing power assay, super oxide anion radical activity, TBARS, total phenolic content and total flavonoid content. Gamma irradiation treatment up to 1.0 kGy elevated the scavenging DPPH radical activity (9 %), super oxide anion radical activity (26 %) and total flavonoid content (208 %) compared to fresh ber fruit. On the other hand it brought down the reducing power activity (65 %) and total phenolic content (18 %) as compared to raw fruit. The TBARS activity statistically increased upon irradiation of ber fruit. It indicated that total antioxidant activity decreased as TBARS value increased. Therefore 0.25 to 0.5kGy is better dose to retain the natural antioxidant in fruit. (author)

  6. Bulgarian Emergency Response System (BERS) in case of nuclear accident with exposure doses’estimation

    Energy Technology Data Exchange (ETDEWEB)

    Syrakov, M.; Prodanova, M.; Slavov, K.; Veleva, B.

    2015-07-01

    A PC-oriented Emergency Response System in case of nuclear accident (BERS) is developed and works operationally in the National Institute of Meteorology and Hydrology (NIMH). The creation and development of BERS was highly stimulated by the ETEX (European Tracer Experiment) project. BERS comprises two main parts - the operational and the accidental ones. The operational part, run automatically every 12 hours, prepares the input meteorological file used by both trajectory and dispersion models, runs the trajectory models, visualizes the results and uploads the maps of trajectories to a dedicated web-site. The accidental part is activated manually when a real radioactive releases occur or during emergency exercises. Its core is the Bulgarian dispersion models EMAP. Outputs are concentration, accumulated deposition and selected doses fields. In the paper, the BERS overall structure is described and examples of its products are presented. (Author)

  7. Bulgarian Emergency Response System (BERS) in case of nuclear accident with exposure doses estimation

    Energy Technology Data Exchange (ETDEWEB)

    Syrakov, D.; Prodanova, M.; Slavov, K.; Veleva, B.

    2015-07-01

    A PC-oriented Emergency Response System in case of nuclear accident (BERS) is developed and works operationally in the National Institute of Meteorology and Hydrology (NIMH). The creation and development of BERS was highly stimulated by the ETEX (European Tracer Experiment) project. BERS comprises two main parts - the operational and the accidental ones. The operational part, run automatically every 12 hours, prepares the input meteorological file used by both trajectory and dispersion models, runs the trajectory models, visualizes the results and uploads the maps of trajectories to a dedicated web-site. The accidental part is activated manually when a real radioactive releases occur or during emergency exercises. Its core is the Bulgarian dispersion models EMAP. Outputs are concentration, accumulated deposition and selected doses fields. In the paper, the BERS overall structure is described and examples of its products are presented. Key words: nuclear accident, emergency response, early warning system, air dispersion models, radioactive exposure dose. (Author)

  8. Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1 alpha axis

    DEFF Research Database (Denmark)

    Fakouri, Nima Borhan; Durhuus, Jon Ambaek; Regnell, Christine Elisabeth

    2017-01-01

    (ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD+, low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via...... the PARP-NAD+-SIRT1-PGC1α axis....

  9. The role of hnRPUL1 involved in DNA damage response is related to PARP1.

    Directory of Open Access Journals (Sweden)

    Zehui Hong

    Full Text Available Heterogeneous nuclear ribonucleoprotein U-like 1 (hnRPUL1 -also known as adenovirus early region 1B-associated proteins 5 (E1B-AP5 - plays a role in RNA metabolism. Recently, hnRPUL1 has also been shown to be involved in DNA damage response, but the function of hnRPUL1 in response to DNA damage remains unclear. Here, we have demonstrated that hnRPUL1 is associated with PARP1 and recruited to DNA double-strand breaks (DSBs sites in a PARP1-mediated poly (ADP-ribosyl ation dependent manner. In turn, hnRPUL1 knockdown enhances the recruitment of PARP1 to DSBs sites. Specifically, we showed that hnRPUL1 is also implicated in the transcriptional regulation of PARP1 gene. Thus, we propose hnRPUL1 as a new component related to PARP1 in DNA damage response and repair.

  10. ROS-mediated PARP activity undermines mitochondrial function after permeability transition pore opening during myocardial ischemia-reperfusion.

    Science.gov (United States)

    Schriewer, Jacqueline M; Peek, Clara Bien; Bass, Joseph; Schumacker, Paul T

    2013-04-18

    Ischemia-reperfusion (I/R) studies have implicated oxidant stress, the mitochondrial permeability transition pore (mPTP), and poly(ADP-ribose) polymerase (PARP) as contributing factors in myocardial cell death. However, the interdependence of these factors in the intact, blood-perfused heart is not known. We therefore wanted to determine whether oxidant stress, mPTP opening, and PARP activity contribute to the same death pathway after myocardial I/R. A murine left anterior descending coronary artery (LAD) occlusion (30 minutes) and release (1 to 4 hours) model was employed. Experimental groups included controls and antioxidant-treated, mPTP-inhibited, or PARP-inhibited hearts. Antioxidant treatment prevented oxidative damage, mPTP opening, ATP depletion, and PARP activity, placing oxidant stress as the proximal death trigger. Genetic deletion of cyclophilin D (CypD(-/-)) prevented loss of total NAD(+) and PARP activity, and mPTP-mediated loss of mitochondrial function. Control hearts showed progressive mitochondrial depolarization and loss of ATP from 1.5 to 4 hours of reperfusion, but not outer mitochondrial membrane rupture. Neither genetic deletion of PARP-1 nor its pharmacological inhibition prevented the initial mPTP-mediated depolarization or loss of ATP, but PARP ablation did allow mitochondrial recovery by 4 hours of reperfusion. These results indicate that oxidant stress, the mPTP, and PARP activity contribute to a single death pathway after I/R in the heart. PARP activation undermines cell survival by preventing mitochondrial recovery after mPTP opening early in reperfusion. This suggests that PARP-mediated prolongation of mitochondrial depolarization contributes significantly to cell death via an energetic crisis rather than by mitochondrial outer membrane rupture.

  11. PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS.

    Science.gov (United States)

    Almeida, Gilberto S; Bawn, Carlo M; Galler, Martin; Wilson, Ian; Thomas, Huw D; Kyle, Suzanne; Curtin, Nicola J; Newell, David R; Maxwell, Ross J

    2017-09-01

    Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ( 1 H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD + ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild-type (WT) and PARP1 knock-out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. 1 H-MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD + levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD + levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD + levels in the temozolomide-treated group. The combination of rucaparib and temozolomide did not prevent the NAD + depletion caused by temozolomide treatment. The 1 H-MRS results show that NAD + levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD + would be valuable. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Germanismen im epilinguistischen Diskurs über die Zagreber Umgangssprache und in der Reflexion über den eigenen Sprachgebrauch

    Directory of Open Access Journals (Sweden)

    Goranka Rocco

    2014-03-01

    Full Text Available Abstract – This paper sheds light on the epilinguistic discourse on germanisms in themetropolitan dialect of Zagreb. The empirical study is based on two methods: 1 the qualitative analysis of the internet forum discussion on what the dialectof Zagreb is, what the germanisms "purger" and "purgerski" mean, to what extent germanisms and elements from other languages should beused and why they are used; 2 the written questionnaire assessing theself-perception of the use of germanisms. The results of both inquiries arecompared and contrasted in order to gain a more complete picture of languageattitudes and language use in a given situation and the way of expressing themin the epilinguistic discourse.Keywords:epilinguisticdiscourse, germanisms, self-perception, language attitudes, language useAbstract –  Die Studie wendet sich dem epilinguistischen Diskursüber die Germanismen in der Stadtsprache von Zagreb zu. Sie setzt sich zumZiel, anhand der qualitätiven Analyse der Internetforum-Beiträge und der schriftlichenBefragung herauszufinden, um welche Themen der epilinguistische Diskurs überdie Germanismen kreist, wie lebendig diese in der Sprache zweier verschiedenenGenerationen der gebürtiger Zagreber sind, inweiweit die Sprecher Veränderungenim eigenen Sprachgebruch wahrnehmen, ob und welche Ausdrücke von den ihnen alstypisch für die Zagreber Umgangssprache (purgerski betrachtet werden und,damit verbunden, wie die Bedeutung der auf die Stadtsprache und -mentalitätbezogenen Germanismen „purger" und "purgerski" definiert wird.Schlüsselwörter:epilinguistischerDiskurs, Germanismus, Selbstwahrnehmung, Spracheinstellungen, Sprachgebrauch.

  13. A atualidade da visão de Ab’Sáber / The current view of Ab’Sáber

    Directory of Open Access Journals (Sweden)

    Claudio Antonio Di Mauro

    2012-04-01

    Full Text Available A produção científica⃰ pela lavra do Professor Aziz Nacib Ab´Sáber é revisitada em, pelo menos, três aspectos considerados fundamentais: 1 a geomorfologia e a evolução paleoclimática no terciário e quaternário, quando o autor reconhece que os estudos de fisiologia de paisagens, ainda que essenciais para os objetivos dos geomorfologistas, somente podem ser esclarecidos à custa de pesquisas marcadamente interdisciplinares; 2 as mudanças climáticas em processos, que são ignoradas nos conhecimentos sobre o presente, e as heranças obtidas ao longo da história do Planeta Terra, para planejar, com cuidados, as ações que as sociedades promoveriam em busca do “desenvolvimento”; 3 o sítio urbano de São Paulo, em meados do século passado, quando, em menos de 15 anos, a cidade que nasceu e cresceu sobre colinas, e que elegeu as colinas como seu tipo ideal de sítio topográfico, desceu para as várzeas, ocupando setores e glebas importantes das planícies recém enxugadas pelas obras da Companhia Light. As contribuições, inicialmente elaboradas sob a perspectiva geomorfológica, tinham, em suas essências, a visão geográfica do cidadão do mundo.

  14. Das Volkslied in Deutschland, Frankreich, Belgien und Holland. Untersuchungen über die Auffassung des Begriffes; Über die traditionellen Zeilen, die Zahlen-, Blumen- und Farbensymbolik

    NARCIS (Netherlands)

    Brouwer, Cornelis

    1930-01-01

    Wenn man die gewaltige Menge Publikationen über das Volkslied, die im Laufe des 19. und 20. Jahrhunderts in Deutschland, Frankreich, Belgien und Holland erschienen sind, vergleicht, springen zwei Punkte sofort ins Auge: 1. der Unterschied zwischen den verschiedenen Auffassungen vom Begriff Volkslied

  15. Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne muscular dystrophy.

    Science.gov (United States)

    Aguennouz, M'Hammed; Vita, Gian Luca; Messina, Sonia; Cama, Annamaria; Lanzano, Natalia; Ciranni, Annamaria; Rodolico, Carmelo; Di Giorgio, Rosa Maria; Vita, Giuseppe

    2011-12-01

    Telomere shortening is thought to contribute to premature senescence of satellite cells in Duchenne muscular dystrophy (DMD) muscle. Telomeric repeat binding factor-1 (TRF1) and poly (ADP-ribose) polymerase-1 (PARP1) are proteins known to modulate telomerase reverse transcriptase (TERT) activity, which controls telomere elongation. Here we show that an age-dependent telomere shortening occurs in DMD muscles and is associated to overexpression of mRNA and protein levels of TRF1 and PARP1. TERT expression and activity are detectable in normal control muscles and they slightly increase in DMD. This is the first demonstration of TRF1 and PARP1 overexpression in DMD muscles. They can be directly involved in replicative senescence of satellite cells and/or in the pathogenetic cascade through a cross-talk with oxidative stress and inflammatory response. Modulation of these events by TRF1 or PARP1 inhibition might represent a novel strategy for treatment of DMD and other muscular dystrophies. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. RECOVERY OF amiRNA3-PARP1 TRANSGENIC MAIZE PLANTS ...

    African Journals Online (AJOL)

    ACSS

    Positive plant selectable marker genes are commonly used in plant transformation because they not only enhance the frequency of generation transgenic tissues but are considered biosafe, unlike antibiotic or herbicide resistance genes. In this study, the binary vector pNOV2819-ubiamiRNA3PARP1, harbouring the ...

  17. Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin.

    Directory of Open Access Journals (Sweden)

    Claudia A Benavente

    Full Text Available Sirtuins (SIRTs and poly(ADP-ribose polymerases (PARPs, NAD(+-dependent enzymes, link cellular energy status with responses to environmental stresses. Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known etiology in skin cancer. Thus, understanding the defense mechanisms in response to UV, including the role of SIRTs and PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT family members in human skin. SIRTs gene expressions are progressively upregulated in A431 epidermoid carcinoma cells (SIRTs1 and 3, actinic keratoses (SIRTs 2, 3, 5, 6, and 7 and squamous cell carcinoma (SIRTs 1-7. Photodamage induces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases NAD(+, the sirtuin substrate, results in an increase in acetylated proteins, upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT responses to photodamage, abrogation of PARP activation following photodamage, and increased sensitivity to photodamage that is completely reversed by repleting niacin. These data support the hypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamage and may be targets for skin cancer prevention.

  18. REV7 counteracts DNA double-strand break resection and affects PARP inhibition

    NARCIS (Netherlands)

    Xu, Guotai; Chapman, J. Ross; Brandsma, Inger; Yuan, Jingsong; Mistrik, Martin; Bouwman, Peter; Bartkova, Jirina; Gogola, Ewa; Warmerdam, Daniël; Barazas, Marco; Jaspers, Janneke E.; Watanabe, Kenji; Pieterse, Mark; Kersbergen, Ariena; Sol, Wendy; Celie, Patrick H. N.; Schouten, Philip C.; van den Broek, Bram; Salman, Ahmed; Nieuwland, Marja; de Rink, Iris; de Ronde, Jorma; Jalink, Kees; Boulton, Simon J.; Chen, Junjie; van Gent, Dik C.; Bartek, Jiri; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

    2015-01-01

    Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway(1). In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with

  19. BZLF1 Expression of EBV is correlated with PARP1 Regulation on Nasopharyngeal Carcinoma Tissues

    Directory of Open Access Journals (Sweden)

    Wahyu nur laili fajri, Ahmad Rofi'i, Fatchiyah Fatchiyah

    2013-04-01

    Full Text Available Nasopharyngeal carcinomas (NPC is a cancer that arises in the epithelial tissue that covers the inside of the nasopharyngeal mucosa and nasopharynx. Infected Epstein Barr Virus (EBV cell in a latent infection associated with the expression of nine latent proteins. Latent Membrane Protein 1 (LMP1 is one of latent proteins, and mayor EBV oncoprotein, with functions including virus growth, and to activate BamHI-Z Leftward Reading Frame 1 (BZLF1-EBV, which can inhibit p53 to induce apoptotic resistance, metastasis, and immune modulation. The body will respond to the expansion of EBV infection with activation of Poly(ADP-ribosePolymerase-1 (PARP1. The objective of study is to observe the expression of BZLF1 and determine PARP1 regulation in nasopharyngeal tissues. NPC-T2, NPC-T3 and polyp tissues slides are from Ulin Hospital, Banjarmasin. To characterize the necrotic cells such as pyknosis, karyorrhexsis, and karyolysis, histological slides were stained by HE that the necrotic cells measured by using a BX-53 microscope (Olympus with CellSens Standard software. Tissues slides were stained by using immunofluorohistochemistry with EBV-BZLF1 antibody-Mouse anti-EBV monoclonal antibody against Goat anti-mouse IgG-FITC and anti-PARP1 antibody (MC-10 against Goat anti-mouse IgG labeled Rhodamin. The expression intensities were measured by Confocal Laser Scanning Microscope (Olympus. The percentage number of necrotic cells and BZLF1 and PARP1 expression intensity were analyzed using SPSS 16.0 by one-way ANOVA test with α = 0.05, beside that we use correlate and regression analyze. The research showed that the amount of karryorhexis higher than pyknosis and karyolysis in both tissues. BZLF1 expression 1.79 INT/sel (in polyp, 2.76 INT/sel (NPC Type 2 and 4.36 INT/sel (NPC Type 3, PARP1 expression 2.25 INT/sel (in polyp, 3.31 INT/sel (NPC Type 2, dan 5.93 INT/sel (NPC Type 3.The high of intensity of expression BZLF1 induced the increasing of PARP1 expression

  20. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    Directory of Open Access Journals (Sweden)

    Ji Yang eKim

    2015-09-01

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP1 plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE in the distinct brain regions. In addition, P2X7 receptor (P2X7R, an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death. Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.

  1. PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Jelena Marković

    Full Text Available Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12 transcription. The roles of poly(ADP-ribose polymerase-1 (PARP-1 and transcription factor Yin Yang 1 (YY1 in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the

  2. Comparative analyses of ber (zizyphus) honey with other types of honey

    International Nuclear Information System (INIS)

    Iftikhar, F.; Mehmood, R.

    2007-01-01

    Eight different honey samples were collected from different ecological areas of Pakistan and analyzed for various physico-chemical parameters. The aim was to evaluate the quality, difference in the composition and comparison of Ber/Sidder (Zizyphus spp.) honey with other types of honey. The two samples of Ber honey and six other floral honey i.e., Citrus, mixed (citrus + Justicia), Acacia modesta, multi-flora and mixed (zizyphus + sesamum) were collected from Apis mellifera colonies. The colonies of Apis mellifera foraged on the above-mentioned flora in different ecological areas i.e. ber honey from Bannu and Karak, Citrus and mixed (citrus + Justicia) honey from Mandi Bahauddin, Acacia honey from Peshawar + Islamabad and multi-flora from Lahore. Nine legal parameters of honey quality control were followed. All honey samples were well within the limits of Codex Alimentarius Commission except ber and citrus. The ber honey showed high pH (6.85) and low reducing sugars (67.66%), sucrose (1.0%), free acidity (6.09 meq/kg) and total acidity (7.68 meq/kg). Mixed honey (zizyphus + sesamum) exhibited highest pH (6.88), lowest free acidity (2.80 meq/kg) and total acidity (5.50 meq/kg). Citrus honey was also found high in Hydroxy-methyl-furfural (HMF, 22.75 meql kg). (author)

  3. Activity-based assay for human mono-ADP-ribosyltransferases ARTD7/PARP15 and ARTD10/PARP10 aimed at screening and profiling inhibitors.

    Science.gov (United States)

    Venkannagari, Harikanth; Fallarero, Adyary; Feijs, Karla L H; Lüscher, Bernhard; Lehtiö, Lari

    2013-05-13

    Poly(ADP-ribose) polymerases (PARPs) or diphtheria toxin like ADP-ribosyl transferases (ARTDs) are enzymes that catalyze the covalent modification of proteins by attachment of ADP-ribose units to the target amino acid residues or to the growing chain of ADP-ribose. A subclass of the ARTD superfamily consists of mono-ADP-ribosyl transferases that are thought to modify themselves and other substrate proteins by covalently adding only a single ADP-ribose moiety to the target. Many of the ARTD enzymes are either established or potential drug targets and a functional activity assay for them will be a valuable tool to identify selective inhibitors for each enzyme. Existing assays are not directly applicable for screening of inhibitors due to the different nature of the reaction and different target molecules. We modified and applied a fluorescence-based assay previously described for PARP1/ARTD1 and tankyrase/ARTD5 for screening of PARP10/ARTD10 and PARP15/ARTD7 inhibitors. The assay measures the amount of NAD(+) present after chemically converting it to a fluorescent analog. We demonstrate that by using an excess of a recombinant acceptor protein the performance of the activity-based assay is excellent for screening of compound libraries. The assay is homogenous and cost effective, making it possible to test relatively large compound libraries. This method can be used to screen inhibitors of mono-ARTDs and profile inhibitors of the enzyme class. The assay was optimized for ARTD10 and ARTD7, but it can be directly applied to other mono-ARTDs of the ARTD superfamily. Profiling of known ARTD inhibitors against ARTD10 and ARTD7 in a validatory screening identified the best inhibitors with submicromolar potencies. Only few of the tested ARTD inhibitors were potent, implicating that there is a need to screen new compound scaffolds. This is needed to create small molecules that could serve as biological probes and potential starting points for drug discovery projects against

  4. Studies of the expression of human poly(ADP-ribose) polymerase-1 in Saccharomyces cerevisiae and identification of PARP-1 substrates by yeast proteome microarray screening.

    Science.gov (United States)

    Tao, Zhihua; Gao, Peng; Liu, Hung-Wen

    2009-12-15

    Poly(ADP-ribosyl)ation of various nuclear proteins catalyzed by a family of NAD(+)-dependent enzymes, poly(ADP-ribose) polymerases (PARPs), is an important posttranslational modification reaction. PARP activity has been demonstrated in all types of eukaryotic cells with the exception of yeast, in which the expression of human PARP-1 was shown to lead to retarded cell growth. We investigated the yeast growth inhibition caused by human PARP-1 expression in Saccharomyces cerevisiae. Flow cytometry analysis reveals that PARP-1-expressing yeast cells accumulate in the G(2)/M stage of the cell cycle. Confocal microscopy analysis shows that human PARP-1 is distributed throughout the nucleus of yeast cells but is enriched in the nucleolus. Utilizing yeast proteome microarray screening, we identified 33 putative PARP-1 substrates, six of which are known to be involved in ribosome biogenesis. The poly(ADP-ribosyl)ation of three of these yeast proteins, together with two human homologues, was confirmed by an in vitro PARP-1 assay. Finally, a polysome profile analysis using sucrose gradient ultracentrifugation demonstrated that the ribosome levels in yeast cells expressing PARP-1 are lower than those in control yeast cells. Overall, our data suggest that human PARP-1 may affect ribosome biogenesis by modifying certain nucleolar proteins in yeast. The artificial PARP-1 pathway in yeast may be used as a simple platform to identify substrates and verify function of this important enzyme.

  5. Purification, crystallization and initial crystallographic characterization of brazil-nut allergen Ber e 2

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Feng; Jin, Tengchuan; Howard, Andrew; Zhang, Yu-Zhu, E-mail: zhangy@iit.edu [Department of Biology, Illinois Institute of Technology, Chicago, IL 60616 (United States)

    2007-11-01

    The crystallization of the brazil nut allergen Ber e 2 is reported. Peanut and tree-nut allergies have attracted considerable attention because of their frequency and their lifelong persistence. Brazil-nut (Bertholletia excelsa) allergies have been well documented and the 11S legumin-like seed storage protein Ber e 2 (excelsin) is one of the two known brazil-nut allergens. In this study, Ber e 2 was extracted from brazil-nut kernels and purified to high purity by crystalline precipitation and gel-filtration chromatography. Well diffracting single crystals were obtained using the hanging-drop vapour-diffusion method. A molecular-replacement structural solution has been obtained. Refinement of the structure is currently under way.

  6. On the BER and capacity analysis of MIMO MRC systems with channel estimation error

    KAUST Repository

    Yang, Liang

    2011-10-01

    In this paper, we investigate the effect of channel estimation error on the capacity and bit-error rate (BER) of a multiple-input multiple-output (MIMO) transmit maximal ratio transmission (MRT) and receive maximal ratio combining (MRC) systems over uncorrelated Rayleigh fading channels. We first derive the ergodic (average) capacity expressions for such systems when power adaptation is applied at the transmitter. The exact capacity expression for the uniform power allocation case is also presented. Furthermore, to investigate the diversity order of MIMO MRT-MRC scheme, we derive the BER performance under a uniform power allocation policy. We also present an asymptotic BER performance analysis for the MIMO MRT-MRC system with multiuser diversity. The numerical results are given to illustrate the sensitivity of the main performance to the channel estimation error and the tightness of the approximate cutoff value. © 2011 IEEE.

  7. BER performance comparison of optical CDMA systems with/without turbo codes

    Science.gov (United States)

    Kulkarni, Muralidhar; Chauhan, Vijender S.; Dutta, Yashpal; Sinha, Ravindra K.

    2002-08-01

    In this paper, we have analyzed and simulated the BER performance of a turbo coded optical code-division multiple-access (TC-OCDMA) system. A performance comparison has been made between uncoded OCDMA and TC-OCDMA systems employing various OCDMA address codes (optical orthogonal codes (OOCs), Generalized Multiwavelength Prime codes (GMWPC's), and Generalized Multiwavelength Reed Solomon code (GMWRSC's)). The BER performance of TC-OCDMA systems has been analyzed and simulated by varying the code weight of address code employed by the system. From the simulation results, it is observed that lower weight address codes can be employed for TC-OCDMA systems that can have the equivalent BER performance of uncoded systems employing higher weight address codes for a fixed number of active users.

  8. Do berço ao berçário: a instituição como morada e lugar de contato

    Directory of Open Access Journals (Sweden)

    Marta Nörnberg

    2013-12-01

    Full Text Available Este ensaio aborda o sentido da instituição infantil a partir de uma perspectiva ético-estético-afetiva do viver humano. A abordagem ampara-se em perspectivas filosóficas sobre a existência humana. Os argumentos apresentam o berçário como morada, lugar do viver juntos, instituição que se faz em coletividade, nela e com ela, decorrente do encontro de bebês e adultos. Ao constituir-se como morada dos bebês, o berçário ritualiza e reatualiza a prática pedagógica como lugar de relação entre bebês e adultos, requerendo uma pedagogia do contato.

  9. Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs

    International Nuclear Information System (INIS)

    Chen Haibing; Jia Weiping; Xu Xun; Fan Ying; Zhu Dongqing; Wu Haixiang; Xie Zhenggao; Zheng Zhi

    2008-01-01

    Poly(ADP-ribose)polymerase (PARP) inhibitors decrease angiogenesis through reducing vascular endothelium growth factor (VEGF) induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In contrast to VEGF, pigment epithelium-derived factor (PEDF) has been demonstrated to act as a strong endogenous inhibitor of angiogenesis. Here, we show that PARP inhibition with a specific inhibitor PJ-34 or specific PARP antisense oligonucleotide upregulates hyperglycemia-induced PEDF expression in HUVECs in a dose-dependent manner. This results in the retard of activation of p38 MAP kinase and the concomitant decrease in cell apoptosis. These results give the first direct demonstration that PEDF might represent a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent

  10. The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

    Science.gov (United States)

    Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

    2017-06-01

    Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

  11. Lebensdauer von Stahlseilen beim kombinierten Lauf über Treib- und Ablenkscheiben unterschiedlicher Rillenform

    OpenAIRE

    Berner, Oliver Roger

    2011-01-01

    Die Lebensdauer von Stahldrahtseilen in Treibscheibenaufzügen wird von unterschiedlichen Faktoren beeinflusst. Bei allen Anwendungen, bei denen Seile über Rollen laufen, erfahren die Seile eine Zug- und Biegebeanspruchung, die zu einer Materialermüdung und zu einem Verschleiß der Drähte an der Seiloberfläche und im Inneren der Seile führt. Darüber hinaus findet man bei Treibscheibenaufzügen systembedingt weitere anwendungsspezifische Beanspruchungen, die zu einer zusätzlichen Lebensdauerminde...

  12. Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirai, Takahisa [Department of Radiation Oncology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo (Japan); Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Saito, Soichiro; Fujimori, Hiroaki [Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Matsushita, Keiichiro; Nishio, Teiji [Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima-shi, Hiroshima (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Science, Chiba-shi, Chiba (Japan); Masutani, Mitsuko, E-mail: mmasutan@nagasaki-u.ac.jp [Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

    2016-09-09

    The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in National Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the radiosensitization effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the radiosensitization effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-2. The effect of the PARPi, AZD2281, on radiosensitization to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H2AX (γ-H2AX) foci and enhanced G2/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response. - Highlights: • Effective radiosensitizers for particle radiation therapy have not been reported. • PARP inhibitor treatment radiosensitized after proton beam irradiation. • The sensitization at Bragg peak was greater than that at entrance region. • DSB induction and G2/M arrest is involved in the sensitization mechanism.

  13. ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib.

    Science.gov (United States)

    Wang, Chen; Jette, Nicholas; Moussienko, Daniel; Bebb, D Gwyn; Lees-Miller, Susan P

    2017-04-01

    The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells

    Science.gov (United States)

    Mortusewicz, Oliver; Amé, Jean-Christophe; Leonhardt, Heinrich

    2007-01-01

    Genome integrity is constantly threatened by DNA lesions arising from numerous exogenous and endogenous sources. Survival depends on immediate recognition of these lesions and rapid recruitment of repair factors. Using laser microirradiation and live cell microscopy we found that the DNA-damage dependent poly(ADP-ribose) polymerases (PARP) PARP-1 and PARP-2 are recruited to DNA damage sites, however, with different kinetics and roles. With specific PARP inhibitors and mutations, we could show that the initial recruitment of PARP-1 is mediated by the DNA-binding domain. PARP-1 activation and localized poly(ADP-ribose) synthesis then generates binding sites for a second wave of PARP-1 recruitment and for the rapid accumulation of the loading platform XRCC1 at repair sites. Further PARP-1 poly(ADP-ribosyl)ation eventually initiates the release of PARP-1. We conclude that feedback regulated recruitment of PARP-1 and concomitant local poly(ADP-ribosyl)ation at DNA lesions amplifies a signal for rapid recruitment of repair factors enabling efficient restoration of genome integrity. PMID:17982172

  15. Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS

    Directory of Open Access Journals (Sweden)

    Valovka Taras

    2008-07-01

    Full Text Available Abstract Background The enzymes responsible for the synthesis of poly-ADP-ribose are named poly-ADP-ribose polymerases (PARP. PARP-2 is a nuclear protein, which regulates a variety of cellular functions that are mainly controlled by protein-protein interactions. A previously described non-conventional bipartite nuclear localization sequence (NLS lies in the amino-terminal DNA binding domain of PARP-2 between amino acids 1–69; however, this targeting sequence has not been experimentally examined or validated. Results Using a site-directed mutagenesis approach, we found that lysines 19 and 20, located within a previously described bipartite NLS, are not required for nuclear localization of PARP-2. In contrast, lysine 36, which is located within a predicted classical monopartite NLS, was required for PARP-2 nuclear localization. While wild type PARP-2 interacted with importin α3 and to a very weak extent with importin α1 and importin α5, the mutant PARP-2 (K36R did not interact with importin α3, providing a molecular explanation why PARP-2 (K36R is not targeted to the nucleus. Conclusion Our results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions.

  16. Effect of Post-Harvest Treatments on Enzyme Activity and Quality of Cold Stored Ber Fruit

    Directory of Open Access Journals (Sweden)

    Sukhjit K. JAWANDHA

    2012-11-01

    Full Text Available Ber (Zizyphus mauritiana Lamk fruits are perishable in nature and have poor shelf- life. To extend the storage life of ber fruits different post-harvest treatments, like CaCl2 (0.5, 1.0 and 2.0%, Ca(NO32 (0.5, 1.0 and 2.0%, gibberellic acid (GA3 (20, 40 and 60 ppm and Bavistin (0.1% were given to fruits and their effect was studied on the storage life and quality of Umran ber (Zizyphus mauritiana Lamk fruits under cold storage conditions. Fruits of uniform size and colour were harvested, from healthy plants, and subjected to post harvest dip of different chemicals, before packing in CFB boxes and placed in cold storage (3-5C and 85-90% RH They have been evaluated after 10, 20 and 30 days of storage for physiological loss in weight (PLW, firmness, pectin methyl esterase (PME activity and palatability rating. The PLW increased and fruit firmness decreased during storage at each treatment. The sensory rating increased up to 10 days at all treatments, except control but subsequently it decreased during storage. The increase rate in PME activity was faster, up to 10 days, in untreated fruits, while treated fruits showed slower rise in PME activity, up to 20 days with a decline afterwards. It can be concluded that ber fruits can be stored up to 20 days by post-harvest treatment using GA3 at 60 ppm, with acceptable quality.

  17. On the BER and capacity analysis of MIMO MRC systems with channel estimation error

    KAUST Repository

    Yang, Liang; Alouini, Mohamed-Slim

    2011-01-01

    In this paper, we investigate the effect of channel estimation error on the capacity and bit-error rate (BER) of a multiple-input multiple-output (MIMO) transmit maximal ratio transmission (MRT) and receive maximal ratio combining (MRC) systems over

  18. Outage and BER analysis for ultrawideband-based WPAN in Nakagami-m fading channels

    KAUST Repository

    Mehbodniya, Abolfazl; Aissa, Sonia

    2011-01-01

    layer. Approximate expressions for the outage probability and average bit error rate (BER) are derived in closed form for the MB-OFDM target receiver, taking into account multi-user interference (MUI), as well as external interference in the form of time

  19. BER analysis of DS-UWB system employing a laplace distribution model

    KAUST Repository

    Mehbodniya, Abolfazl; Aissa, Sonia; Adachi, Fumiyuki

    2011-01-01

    This letter takes a new approach to extract a closed-form expression for the bit error rate (BER) of direct-sequence ultra wideband (DS-UWB) system. In the analysis, the main signal is impaired by multi-user interference (MUI) and an external source

  20. Grossforschung in neuen Dimensionen : Denker unserer Zeit über die aktuelle Elementarteilchenphysik am CERN

    CERN Document Server

    Blanchard, Philippe; Kommer, Christoph; ZiF-Konferenz 2013; CERN : Large-scale Research in New Dimension

    2015-01-01

    Der 4. Juli 2012 stellt ein historisches Datum für das Europäische Kernforschungszentrum CERN in Genf dar: die Verkündung der Entdeckung des letzten, vorhergesagten, noch fehlenden und lange gesuchten Elementarteilchens, des Higgs-Bosons. Ein Jahr später kommen im Rahmen der Konferenz des Zentrums für interdisziplinäre Forschung (ZiF) in Bielefeld eine Vielzahl der mit dem Großprojekt am CERN verbundenen Wissenschaftler zusammen, um nicht nur über die Entdeckung des Teilchens, sondern vor allem über die Realisierung und Bedeutung eines derart ungeheuren Unterfangens für solch ein wissenschaftliches Großprojekt zu berichten. Der Generaldirektor des CERN, Prof. Dr. Rolf-Dieter Heuer, liefert in seinem Eröffnungsvortrag die Grundlage für die Diskussion der vielerlei Aspekte, die dabei ins Spiel kommen. So finden sich im vorliegenden Band zum einen Berichte über die Großforschung selbst: von der Entdeckung des Higgs-Teilchens über die Erforschung des Quark-Gluon-Plasmas und die Bedeutung von Th...

  1. BER Reduction for mQAM High-Speed Tranmission in Optical Fiber ...

    African Journals Online (AJOL)

    The study was conducted in a software cosimulation environment with VPITransmissionMaker and Matlab software. The simulation results showed that error correcting codes and particularly LDPC codes are effective and provide satisfactory solutions to reduce the BER by fighting against optical transmission channel ...

  2. BER and total throughput of asynchronous DS-OCDMA/WDM systems with multiple user interference

    OpenAIRE

    Ghiringhelli, F.; Zervas, M.N.

    2003-01-01

    The BER and throughput of Direct-Sequence OCDMA/WDM systems based on quadripolar codes and superstructured fiber Bragg gratings are statistically derived under asynchronous operation, intensity detection, and Multiple User Interference. Performance improvements with Forward Error Correction are included.

  3. Ein Lehrbuch über Psychiatrie und Psychotherapie – Geschlechtsunterschiede unter der Lupe?

    Directory of Open Access Journals (Sweden)

    Isabella Heuser

    2007-07-01

    Full Text Available Anke Rohde und Andreas Marneros haben sich ein hohes Ziel gesetzt: ein übersichtliches Lehrbuch für Psychiatrie und Psychotherapie, das erstmals eine systematische Zusammenstellung des Wissens über geschlechtsspezifische Aspekte von Symptomatologie, Epidemiologie, Diagnostik, Pharmakotherapie und Psychotherapie psychischer Störungen enthält. Bemerkenswert ist dabei zweierlei: Erstens werden bei der Betrachtung geschlechtsspezifischer Unterschiede im Sinne der Genderforschung Frauen und Männer berücksichtigt, zweitens wird ein vollständiger Überblick sowohl über die häufigen und bekannten psychischen Störungen als auch die äußerst seltenen psychiatrischen Erkrankungen der gesamten Altersspanne gegeben. Wenngleich die Qualität der einzelnen Beiträge deutlich zwischen sehr differenzierter und leider auch für ein Handbuch eindeutig zu oberflächlicher Betrachtung variiert, liegt in dem Band ein weitgehend informatives Nachschlagewerk vor, das einen ersten Überblick über die geschlechtsspezifische Psychiatrie gibt.

  4. Notizen über Thatcheria Angas, Clinura Bellardi und Clinuropsis Vincent

    NARCIS (Netherlands)

    Beets, C.

    1942-01-01

    1. Es sind bisher über die merkwürdige rezente marine Gastropoden-Gruppe Thatcheria Angas, 1877 sehr wenige Gegebenheiten bekannt, vergleichende Untersuchungen mit fossilen Arten fehlen (fast) vollkommen und auch die Frage ihrer systematischen Stellung ist nie in befriedigender Weise gelöst worden.

  5. Receptor activity-independent recruitment of βarrestin2 reveals specific signalling modes

    Science.gov (United States)

    Terrillon, Sonia; Bouvier, Michel

    2004-01-01

    The roles of βarrestins in regulating G protein coupling and receptor endocytosis following agonist stimulation of G protein-coupled receptors are well characterised. However, their ability to act on their own as direct modulators or activators of signalling remains poorly characterised. Here, βarrestin2 intrinsic signalling properties were assessed by forcing the recruitment of this accessory protein to vasopressin V1a or V2 receptors independently of agonist-promoted activation of the receptors. Such induction of a stable interaction with βarrestin2 initiated receptor endocytosis leading to intracellular accumulation of the βarrestin/receptor complexes. Interestingly, βarrestin2 association to a single receptor protomer was sufficient to elicit receptor dimer internalisation. In addition to recapitulating βarrestin2 classical actions on receptor trafficking, the receptor activity-independent recruitment of βarrestin2 activated the extracellular signal-regulated kinases. In the latter case, recruitment to the receptor itself was not required since kinase activation could be mediated by βarrestin2 translocation to the plasma membrane in the absence of any interacting receptor. These data demonstrate that βarrestin2 can act as a ‘bonafide' signalling molecule even in the absence of activated receptor. PMID:15385966

  6. UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

    Science.gov (United States)

    Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

  7. Poly(ADP-ribose polymerase 1 (PARP1 overexpression in human breast cancer stem cells and resistance to olaparib.

    Directory of Open Access Journals (Sweden)

    Marine Gilabert

    Full Text Available BACKGROUND: Breast cancer stem cells (BCSCs have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL, BrCA-MZ-01. METHODS: ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+ and mature cancer (ALDH- cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE. Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS. RESULTS: 2-D DIGE identified poly(ADP-ribose polymerase 1 (PARP1 as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor. CONCLUSION: An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors.

  8. The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines

    International Nuclear Information System (INIS)

    Güster, Julian David; Weissleder, Stephanie Valerie; Busch, Chia-Jung; Kriegs, Malte; Petersen, Cordula; Knecht, Rainald; Dikomey, Ekkehard; Rieckmann, Thorsten

    2014-01-01

    Background and purpose: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay. Results: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1. Conclusions: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity

  9. Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Negi, Geeta; Kumar, Ashutosh [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India); Sharma, Shyam S., E-mail: sssharma@niper.ac.in [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India)

    2010-01-01

    Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress-nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative-nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

  10. Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1.

    Science.gov (United States)

    Ge, Rui; Liu, Lin; Dai, Wei; Zhang, Weigang; Yang, Yuqi; Wang, Huina; Shi, Qiong; Guo, Sen; Yi, Xiuli; Wang, Gang; Gao, Tianwen; Luan, Qi; Li, Chunying

    2016-06-01

    Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. The BER necessities: the repair of DNA damage in human-adapted bacterial pathogens.

    Science.gov (United States)

    van der Veen, Stijn; Tang, Christoph M

    2015-02-01

    During colonization and disease, bacterial pathogens must survive the onslaught of the host immune system. A key component of the innate immune response is the generation of reactive oxygen and nitrogen species by phagocytic cells, which target and disrupt pathogen molecules, particularly DNA, and the base excision repair (BER) pathway is the most important mechanism for the repair of such oxidative DNA damage. In this Review, we discuss how the human-specific pathogens Mycobacterium tuberculosis, Helicobacter pylori and Neisseria meningitidis have evolved specialized mechanisms of DNA repair, particularly their BER pathways, compared with model organisms such as Escherichia coli. This specialization in DNA repair is likely to reflect the distinct niches occupied by these important human pathogens in the host.

  12. Categorization of ber varieties in relation to blooming period, fruit setting and harvesting time

    International Nuclear Information System (INIS)

    Sharif, N.; Abbas, M.M.; Ishfaq, M.; Memon, N.U.N.

    2013-01-01

    Thirty four local Ber varieties were evaluated at Horticultural Research Institute AARI, Faisalabad, Horticultural Research Station Bahawalpur (Punjab) and Jujube Research Station, Tandojam (Sindh). Traits viz. total period of blooming (dates), peak period of blooming (dates), total period of fruit set (dates), peak period of fruit set (dates), total period of fruit harvest (dates), peak period of fruit harvest (dates), total flowering days, peak flowering days, total fruit setting days, peak fruit setting days, total harvesting days and peak harvesting days were studied. The results revealed significant differences in parameters studied except total period of blooming under Tandojam, Sindh conditions. Varieties were classified as early, mid and late season for both provinces. Local varieties had potential for further manipulation in terms of variety improvement to attract growers for extensive ber cultivations under changing global climatic scenario. (author)

  13. The research reactor BER II at the Helmholtz-Center Berlin

    Energy Technology Data Exchange (ETDEWEB)

    Krohn, Herbert [Helmholtz-Zentrum Berlin (HZB), Berlin (Germany)

    2012-10-15

    For basic and application-oriented research assignments the Helmholtz-Center Berlin (Helmholtz Zentrum Berlin - HZB) runs a research reactor that operates as a source of neutron beams for a wide range of scientific investigations. At the end of the 1980{sup th} the BER II was completed renewed and fitted with new experimental facilities. The BER II is a light water cooled and moderated swimming pool type reactor to be operated at 10 MW thermal power. Six neutron guides deliver cold neutrons from the cold moderator cell to a neutron guide hall adjacent to the experiment hall. With its 24 experimental stations, experimenters at HZB have practically all neutron scattering or neutron radiography techniques at their disposal. (orig.)

  14. Natural biostimulants reduce the incidence of BER in sweet yellow pepper plants (Capsicum annuum L.

    Directory of Open Access Journals (Sweden)

    Nada Parađiković

    2013-06-01

    Full Text Available Modern greenhouse pepper production should evolve towards more sustainable systems. The growing technique which combines soilless culture and biostimulants may reduce nutrient and water use with beneficial impact on the environment. Therefore, this work aimed to investigate effects of biostimulants application on hydroponically produced pepper plants (Capsicum annuum L. in conditions of reduced fertilization. Positive influence of biostimulant treatment on yield parameters was observed along with significant decrease in incidence of blossom-end rot (BER in two pepper cultivars. Biostimulants application resulted in overall increase in macro- and microelement content in fruits of treated pepper cultivars. Generally, biostimulants improved the yield of pepper plants grown hydroponically by increasing the nutrient uptake and decreasing the occurrence of BER. Thus, the application of biostimulants could be considered as a good production strategy for obtaining high yields of nutritionally valuable vegetables with lower impact on the environment.

  15. The research reactor BER II at the Helmholtz-Center Berlin

    International Nuclear Information System (INIS)

    Krohn, Herbert

    2012-01-01

    For basic and application-oriented research assignments the Helmholtz-Center Berlin (Helmholtz Zentrum Berlin - HZB) runs a research reactor that operates as a source of neutron beams for a wide range of scientific investigations. At the end of the 1980 th the BER II was completed renewed and fitted with new experimental facilities. The BER II is a light water cooled and moderated swimming pool type reactor to be operated at 10 MW thermal power. Six neutron guides deliver cold neutrons from the cold moderator cell to a neutron guide hall adjacent to the experiment hall. With its 24 experimental stations, experimenters at HZB have practically all neutron scattering or neutron radiography techniques at their disposal. (orig.)

  16. Effect of Post-Harvest Treatments on Enzyme Activity and Quality of Cold Stored Ber Fruit

    Directory of Open Access Journals (Sweden)

    Sukhjit K. JAWANDHA

    2012-11-01

    Full Text Available Ber (Zizyphus mauritiana Lamk fruits are perishable in nature and have poor shelf- life. To extend the storage life of ber fruits different post-harvest treatments, like CaCl2 (0.5, 1.0 and 2.0%, Ca(NO32 (0.5, 1.0 and 2.0%, gibberellic acid (GA3 (20, 40 and 60 ppm and Bavistin (0.1% were given to fruits and their effect was studied on the storage life and quality of �Umran� ber (Zizyphus mauritiana Lamk fruits under cold storage conditions. Fruits of uniform size and colour were harvested, from healthy plants, and subjected to post harvest dip of different chemicals, before packing in CFB boxes and placed in cold storage (3-5�C and 85-90% RH They have been evaluated after 10, 20 and 30 days of storage for physiological loss in weight (PLW, firmness, pectin methyl esterase (PME activity and palatability rating. The PLW increased and fruit firmness decreased during storage at each treatment. The sensory rating increased up to 10 days at all treatments, except control but subsequently it decreased during storage. The increase rate in PME activity was faster, up to 10 days, in untreated fruits, while treated fruits showed slower rise in PME activity, up to 20 days with a decline afterwards. It can be concluded that ber fruits can be stored up to 20 days by post-harvest treatment using GA3 at 60 ppm, with acceptable quality.

  17. Briti teadlane: kübersõda ei tule / Thomas Rid ; intervjueerinud Raimo Poom

    Index Scriptorium Estoniae

    Rid, Thomas

    2013-01-01

    Sõjauuringute õppejõud Thomas Rid leiab, et internetis on palju ohte, kuid kübersõda ei ole üks neist. Ridi arvates on äärmiselt ebatõenäoline, et NATO käivitaks kunagi küberrünnaku tõttu 5. artikli. Interneti kõige suuremaks ohustajaks pole NSA, vaid vabadust piirata soovivad autoritaarsed riigid

  18. Rehabilitierungs-Szenarien, Geschichten über Hexen, Verdingkinder, Flüchtlingshelfer usw.

    OpenAIRE

    Rüegger, Vanessa

    2015-01-01

    In den vergangenen Jahren haben Parlamente, Regierungen und Gerichte unterschiedliche Personen und Personengruppen rehabilitiert. Der vorliegende Beitrag bietet einen Überblick über die jüngst in der Schweiz ausgesprochenen Rehabilitierungen, ordnet diese rechtsdogmatisch ein und zeigt weiter die Funktionen und Grenzen der Rehabilitierung als Form staatlicher ,Vergangenheitsbewältigung‘ auf. Der Beitrag schliesst mit der Erkenntnis, dass Flüchtlingshelfer, Spanienkämpfer, administrativ Versor...

  19. Neural Network based Minimization of BER in Multi-User Detection in SDMA

    OpenAIRE

    VENKATA REDDY METTU; KRISHAN KUMAR,; SRIKANTH PULLABHATLA

    2011-01-01

    In this paper we investigate the use of neural network based minimization of BER in MUD. Neural networks can be used for linear design, Adaptive prediction, Amplitude detection, Character Recognition and many other applications. Adaptive prediction is used in detecting the errors caused in AWGN channel. These errors are rectified by using Widrow-Hoff algorithm by updating their weights andAdaptive prediction methods. Both Widrow-Hoff and Adaptive prediction have been used for rectifying the e...

  20. PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system

    Directory of Open Access Journals (Sweden)

    Picard-Cloutier Aude

    2007-12-01

    Full Text Available Abstract Background In the "post-genome" era, mass spectrometry (MS has become an important method for the analysis of proteins and the rapid advancement of this technique, in combination with other proteomics methods, results in an increasing amount of proteome data. This data must be archived and analysed using specialized bioinformatics tools. Description We herein describe "PARPs database," a data analysis and management pipeline for liquid chromatography tandem mass spectrometry (LC-MS/MS proteomics. PARPs database is a web-based tool whose features include experiment annotation, protein database searching, protein sequence management, as well as data-mining of the peptides and proteins identified. Conclusion Using this pipeline, we have successfully identified several interactions of biological significance between PARP-1 and other proteins, namely RFC-1, 2, 3, 4 and 5.

  1. Clustered DNA lesions containing 5-formyluracil and AP site: repair via the BER system.

    Directory of Open Access Journals (Sweden)

    Ekaterina A Belousova

    Full Text Available Lesions in the DNA arise under ionizing irradiation conditions or various chemical oxidants as a single damage or as part of a multiply damaged site within 1-2 helical turns (clustered lesion. Here, we explored the repair opportunity of the apurinic/apyrimidinic site (AP site composed of the clustered lesion with 5-formyluracil (5-foU by the base excision repair (BER proteins. We found, that if the AP site is shifted relative to the 5-foU of the opposite strand, it could be repaired primarily via the short-patch BER pathway. In this case, the cleavage efficiency of the AP site-containing DNA strand catalyzed by human apurinic/apyrimidinic endonuclease 1 (hAPE1 decreased under AP site excursion to the 3'-side relative to the lesion in the other DNA strand. DNA synthesis catalyzed by DNA polymerase lambda was more accurate in comparison to the one catalyzed by DNA polymerase beta. If the AP site was located exactly opposite 5-foU it was expected to switch the repair to the long-patch BER pathway. In this situation, human processivity factor hPCNA stimulates the process.

  2. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  3. SU-E-T-245: MR Guided Focused Ultrasound Increased PARP Related Apoptosis On Prostate Cancer in Vivo

    International Nuclear Information System (INIS)

    Chen, L; Chen, X; Cvetkovic, D; Gupta, R; Yang, D; Ma, C

    2014-01-01

    Purpose: Our previous study demonstrated that significant tumor growth delay was observed in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. Temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level, which is the intensity of the DAB reaction. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality might be able to synergize with PARP inhibitors to achieve better result

  4. Melatonin regulates PARP1 to control the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cells.

    Science.gov (United States)

    Yu, Songtao; Wang, Xiaojiao; Geng, Peiliang; Tang, Xudong; Xiang, Lisha; Lu, Xin; Li, Jianjun; Ruan, Zhihua; Chen, Jianfang; Xie, Ganfeng; Wang, Zhe; Ou, Juanjuan; Peng, Yuan; Luo, Xi; Zhang, Xuan; Dong, Yan; Pang, Xueli; Miao, Hongming; Chen, Hongshan; Liang, Houjie

    2017-08-01

    Cellular senescence is an important tumor-suppressive mechanism. However, acquisition of a senescence-associated secretory phenotype (SASP) in senescent cells has deleterious effects on the tissue microenvironment and, paradoxically, promotes tumor progression. In a drug screen, we identified melatonin as a novel SASP suppressor in human cells. Strikingly, melatonin blunts global SASP gene expression upon oncogene-induced senescence (OIS). Moreover, poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, was identified as a new melatonin-dependent regulator of SASP gene induction upon OIS. Here, we report two different but potentially coherent epigenetic strategies for melatonin regulation of SASP. The interaction between the telomeric repeat-containing RNA (TERRA) and PARP-1 stimulates the SASP, which was attenuated by 67.9% (illustrated by the case of IL8) by treatment with melatonin. Through binding to macroH2A1.1, PARP-1 recruits CREB-binding protein (CBP) to mediate acetylation of H2BK120, which positively regulates the expression of target SASP genes, and this process is interrupted by melatonin. Consequently, the findings provide novel insight into melatonin's epigenetic role via modulating PARP-1 in suppression of SASP gene expression in OIS-induced senescent cells. Our studies identify melatonin as a novel anti-SASP molecule, define PARP-1 as a new target by which melatonin regulates SASP, and establish a new epigenetic paradigm for a pharmacological mechanism by which melatonin interrupts PARP-1 interaction with the telomeric long noncoding RNA(lncRNA) or chromatin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Nachrichtenberichterstattung über Terrorismus. Eine Analyse der TV-Nachrichten über die Terroranschläge in Kenia 2002

    Directory of Open Access Journals (Sweden)

    Nicole Haußecker

    2007-04-01

    Full Text Available Nach der starken Kritik der Medienberichterstattung über Terrorismus, besonders nach dem 11.09.2001, werden die theoretischen Hintergründe ausgewählter Kritikpunkte betrachtet und ein weiteres terroristisches Ereignis, die Anschläge in Kenia am 28.11.2002, inhaltsanalytisch untersucht. Ziel dabei ist es, Aussagen bezüglich inhaltlicher und formaler Merkmale der Fernseh-berichterstattung über ein terroristisches Ereignis zu treffen. Deshalb liegt der Fokus auf den folgenden drei Forschungsfragen: 1. Welche Nachrichtenfaktoren spielen für die Selektion und Intensität der Berichterstattung über das terroristische Ereignis eine Rolle? 2. Wird mit Emotionalisierung gearbeitet? 3. Liegen negative Stereotype und/oder Feindbilder bezüglich der islamischen und arabischen Welt vor? Die Ergebnisse der Untersuchung zeigen erwartete Tendenzen sowohl die Merkmale der Terrorismusberichterstattung als auch die Senderkonvergenzen und -divergenzen im dualen System betreffend. Der Nachrichtenwert eines terroristischen Ereignisses ist anfänglich sehr hoch, jedoch verliert das Ereignis ab dem dritten Tag aufgrund diverser Nachrichtenfaktoren deutlich an Beachtung in der Berichterstattung. Das Vorkommen emotionalisierender Mittel wird empirisch bestätigt. Nicht nur emotionale Sprache und Sprechweise, sondern vor allem Formen der expliziten Emotionalisierung sind vertreten. Damit wird die Vermutung bekräftigt, dass die Medien die mit den terroristischen Ereignissen verbundene beängstigende Stimmung senderabhängig unterschiedlich stark aufgreifen. Ein direkter islamischer Feindbildaufbau ist in der Berichterstattung nicht zu verzeichnen. Allerdings liegen latente negative Bewertungstendenzen sowie negative Stereotype bezüglich der arabischen und islamischen Welt vor, die das seit dem 11.09.2001 negativ geprägte Bild festigen. Die meist narrativ inszenierte Fixierung auf Bin Laden und al Qaida erfolgt oberflächlich und vernachlässigt m

  6. BER Analysis of Coherent Free-Space Optical Communication Systems with a Focal-Plane-Based Wavefront Sensor

    Science.gov (United States)

    Cao, Jingtai; Zhao, Xiaohui; Liu, Wei; Gu, Haijun

    2018-03-01

    A wavefront sensor is one of most important units for an adaptive optics system. Based on our previous works, in this paper, we discuss the bit-error-rate (BER) performance of coherent free space optical communication systems with a focal-plane-based wavefront sensor. Firstly, the theory of a focal-plane-based wavefront sensor is given. Then the relationship between the BER and the mixing efficiency with a homodyne receiver is discussed on the basis of binary-phase-shift-keying (BPSK) modulation. Finally, the numerical simulation results are shown that the BER will be decreased obviously after aberrations correction with the focal-plane-based wavefront sensor. In addition, the BER will decrease along with increasing number of photons received within a single bit. These analysis results will provide a reference for the design of the coherent Free space optical communication (FSOC) system.

  7. Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex.

    Science.gov (United States)

    Gisslen, Tate; Ennis, Kathleen; Bhandari, Vineet; Rao, Raghavendra

    2015-11-01

    Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood. Rat pups were subjected to recurrent hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day 3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-κB and their downstream effectors were determined in the cerebral cortex. Microgliosis was determined using CD11 immunohistochemistry. Recurrent hyperglycemia increased PARP-1 expression confined to the nucleus and without causing PARP-1 overactivation and cell death. NF-κB mRNA expression was increased, while IκB mRNA expression was decreased. inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the number of microglia. Recurrent hyperglycemia in neonatal rats is associated with upregulation of PARP-1 and NF-κB expression and subsequent microgliosis but not neuronal cell death in the cerebral cortex.

  8. The nuclear protein Poly(ADP-ribose) polymerase 3 (AtPARP3) is required for seed storability in Arabidopsis thaliana.

    Science.gov (United States)

    Rissel, D; Losch, J; Peiter, E

    2014-11-01

    The deterioration of seeds during prolonged storage results in a reduction of viability and germination rate. DNA damage is one of the major cellular defects associated with seed deterioration. It is provoked by the formation of reactive oxygen species (ROS) even in the quiescent state of the desiccated seed. In contrast to other stages of seed life, DNA repair during storage is hindered through the low seed water content; thereby DNA lesions can accumulate. To allow subsequent seedling development, DNA repair has thus to be initiated immediately upon imbibition. Poly(ADP-ribose) polymerases (PARPs) are important components in the DNA damage response in humans. Arabidopsis thaliana contains three homologues to the human HsPARP1 protein. Of these three, only AtPARP3 was very highly expressed in seeds. Histochemical GUS staining of embryos and endosperm layers revealed strong promoter activity of AtPARP3 during all steps of germination. This coincided with high ROS activity and indicated a role of the nuclear-localised AtPARP3 in DNA repair during germination. Accordingly, stored parp3-1 mutant seeds lacking AtPARP3 expression displayed a delay in germination as compared to Col-0 wild-type seeds. A controlled deterioration test showed that the mutant seeds were hypersensitive to unfavourable storage conditions. The results demonstrate that AtPARP3 is an important component of seed storability and viability. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  9. PARP-1 is a key player in controlling apoptosis induced by high LET carbon ion beam and low LET gamma radiation in HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Ghosh, Utpal; Bhattacharyya, Nitai P.; Sarma, Asitikantha

    2014-01-01

    PARP-1 inhibitors have long been used as chemo-sensitizer or radio-sensitizer and specific PARP-1 inhibitors are also in clinical trial for the treatment of various cancers. PARP-1 is not only involved in DNA repair but also plays very complex role in induction of apoptosis in postirradiation condition. Our objective is to investigate role of PARP-1 in apoptosis triggered by high LET carbon ion beam (CIB) and low LET gamma. We have treated HeLa and PARP-1 knock down HeLa (Hsil) cells with various doses of CIB and gamma. We measured DNA damage by comet assay and various apoptotic parameters such as nuclear fragmentation, activation of caspase-3,8,9, AIF translocation etc. We observed higher DNA breaks and also higher apoptosis in HsiI cells compared with HeLa cells. Both CIB and gamma treatment results G2/M arrest but unlike gamma CIB makes S-phase delay, implicating that gamma and CIB triggers different pathway after DNA damage. Cell death by CIB or by gamma increased up on knocking down of PARP-1 but increase is higher for high LET CIB compared with low LET gamma. Furthermore, expression level of PARP-1 controls the intensity of overall apoptosis in cells in post-irradiation condition. So, combination of PARP-1 inhibition with high LET CIB could be a promising tool to combat cancer. (author)

  10. Neuronale Korrelate sozialer Interaktion beim Menschen und deren genetische Modulation unter besonderer Berücksichtigung des Spiegelneuronensystems

    OpenAIRE

    Cordes, Andrea

    2013-01-01

    Die in vielen Lebenssituationen über Erfolg und Misserfolg, Sympathie und Antipathie entscheidende, unterschiedlich ausgeprägte Fähigkeit zur sozialen Interaktion ist Gegenstand neurowissenschaftlicher Untersuchungen. Die Versuche einer kortikalen Lokalisierung führten zur Beschreibung des Spiegelneuronensystems (SNS) in Hirnregionen, die sowohl beim Ausführen einer Aktion Aktivität zeigten als auch beim Beobachten derselben beim Gegenüber. Die stärkste Aktivierung dieser Areale wurde bei sch...

  11. Paradigmenwechsel in der politischen Ökologie? Zur deutschen Diskussion über die Lokale Agenda 21

    OpenAIRE

    Pettenkofer, Andreas

    2001-01-01

    Der Text berichtet über die in Deutschland geführte sozialwissenschaftliche Diskussion über das umweltpolitische Programm Lokale Agenda 21; er versucht eine vorläufige Rekonstruktion der spezifischen Gestalt der Agenda-Prozesse und ihrer Abweichungen von der westdeutschen Tradition der Politischen Ökologie, und diskutiert die theoretischen Fragen, die sich angesichts dieser neuartigen Phänomene stellen. Dabei geht es vor allem um die Angemessenheit der modernisierungstheoretischen Perspektive...

  12. Erstellung eines multimedialen Lernprogramms über die Grundlagen der EKG-Aufzeichnung und Auswertung bei Hund und Katze

    OpenAIRE

    Weigel-Ossiander, Fiona Sarah

    2016-01-01

    Mit EKG Basics wurde ein detailliertes multimediales Lernprogramm über die Grundlagen der Elektrokardiographie bei Hund und Katze erstellt unter besonderer Berücksichtigung von didaktischen und ergonomischen Gesichtspunkten. Da vielen Veterinärmedizinerinnen/Veterinärmedizinern das Erlernen, Verstehen und Interpretieren der Elektrokardiographie schwer fällt, war das Ziel der vorliegenden Arbeit, sowohl Studierenden der Tiermedizin als auch interessierten Tierärztinnen/Tierärzten die Thema...

  13. The dual action of poly(ADP-ribose polymerase -1 (PARP-1 inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

    Directory of Open Access Journals (Sweden)

    Slava eRom

    2015-08-01

    Full Text Available The transcription of HIV-1 (HIV is regulated by complex mechanisms involving various cellular factors and virus-encoded transactivators. Poly(ADP-ribose polymerase 1 (PARP-1 inhibition has emerged recently as a potent anti-inflammatory tool, since PARP-1 is involved in the regulation of some genes through its interaction with various transcription factors. We propose a novel approach to diminish HIV replication via PARP-1 inhibition using human primary monocyte-derived macrophages (MDM as an in vitro model system. PARP-1 inhibitors were able to reduce HIV replication in MDM by 60-80% after 7 days infection. Long Terminal Repeat (LTR acts as a switch in virus replication and can be triggered by several agents such as: Tat, tumor necrosis factor α (TNFα, and phorbol 12-myristate 13-acetate (PMA. Overexpression of Tat in MDM transfected with an LTR reporter plasmid led to a 4.2-fold increase in LTR activation; PARP inhibition resulted in 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFα treatment, was reduced by PARP inhibition (by 85-95%. MDM treated with PARP inhibitors showed 90% reduction in NFκB activity (known to mediate PMA- and TNFα-induced HIV LTR activation. Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These findings suggest that HIV replication in MDM could be suppressed by PARP inhibition via NFκB suppression, diminution of LTR activation and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide a potent approach to treatment of HIV infection.

  14. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Masaaki Yasukawa

    2016-02-01

    Full Text Available Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosylation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose polymerase (PARP inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs. However, the effects on oral cancer have not been fully evaluated. In this study, we examined the effects of PARP inhibitor on the survival of human oral cancer cells in vitro and xenografted tumors derived from human oral cancer cells in vivo. In vitro effects were assessed by microculture tetrazolium and survival assays. The PARP inhibitor AZD2281 (olaparib showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or AZD2281. Histopathological analysis revealed that cisplatin and AZD2281 increased TUNEL-positive cells and decreased Ki67- and CD31-positive cells. These results suggest that PARP inhibitors have the potential to improve therapeutic strategies for oral cancer.

  15. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors.

    Science.gov (United States)

    Izhar, Lior; Adamson, Britt; Ciccia, Alberto; Lewis, Jedd; Pontano-Vaites, Laura; Leng, Yumei; Liang, Anthony C; Westbrook, Thomas F; Harper, J Wade; Elledge, Stephen J

    2015-06-09

    Localization to sites of DNA damage is a hallmark of DNA damage response (DDR) proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS) candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose) polymerase (PARP)-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Lior Izhar

    2015-06-01

    Full Text Available Localization to sites of DNA damage is a hallmark of DNA damage response (DDR proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose polymerase (PARP-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins.

  17. Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis.

    Science.gov (United States)

    Loor, Gabriel; Kondapalli, Jyothisri; Schriewer, Jacqueline M; Chandel, Navdeep S; Vanden Hoek, Terry L; Schumacker, Paul T

    2010-12-15

    Low levels of reactive oxygen species (ROS) can function as redox-active signaling messengers, whereas high levels of ROS induce cellular damage. Menadione generates ROS through redox cycling, and high concentrations trigger cell death. Previous work suggests that menadione triggers cytochrome c release from mitochondria, whereas other studies implicate the activation of the mitochondrial permeability transition pore as the mediator of cell death. We investigated menadione-induced cell death in genetically modified cells lacking specific death-associated proteins. In cardiomyocytes, oxidant stress was assessed using the redox sensor RoGFP, expressed in the cytosol or the mitochondrial matrix. Menadione elicited rapid oxidation in both compartments, whereas it decreased mitochondrial potential and triggered cytochrome c redistribution to the cytosol. Cell death was attenuated by N-acetylcysteine and exogenous glutathione or by overexpression of cytosolic or mitochondria-targeted catalase. By contrast, no protection was observed in cells overexpressing Cu,Zn-SOD or Mn-SOD. Overexpression of antiapoptotic Bcl-X(L) protected against staurosporine-induced cell death, but it failed to confer protection against menadione. Genetic deletion of Bax and Bak, cytochrome c, cyclophilin D, or caspase-9 conferred no protection against menadione-induced cell death. However, cells lacking PARP-1 showed a significant decrease in menadione-induced cell death. Thus, menadione induces cell death through the generation of oxidant stress in multiple subcellular compartments, yet cytochrome c, Bax/Bak, caspase-9, and cyclophilin D are dispensable for cell death in this model. These studies suggest that multiple redundant cell death pathways are activated by menadione, but that PARP plays an essential role in mediating each of them. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Solution structure, copper binding and backbone dynamics of recombinant Ber e 1-the major allergen from Brazil nut.

    Directory of Open Access Journals (Sweden)

    Louise Rundqvist

    Full Text Available BACKGROUND: The 2S albumin Ber e 1 is the major allergen in Brazil nuts. Previous findings indicated that the protein alone does not cause an allergenic response in mice, but the addition of components from a Brazil nut lipid fraction were required. Structural details of Ber e 1 may contribute to the understanding of the allergenic properties of the protein and its potential interaction partners. METHODOLOGY/PRINCIPAL FINDINGS: The solution structure of recombinant Ber e 1 was solved using NMR spectroscopy and measurements of the protein back bone dynamics at a residue-specific level were extracted using (15N-spin relaxation. A hydrophobic cavity was identified in the structure of Ber e 1. Using the paramagnetic relaxation enhancement property of Cu(2+ in conjunction with NMR, it was shown that Ber e 1 is able to specifically interact with the divalent copper ion and the binding site was modeled into the structure. The IgE binding region as well as the copper binding site show increased dynamics on both fast ps-ns timescale as well as slower µs-ms timescale. CONCLUSIONS/SIGNIFICANCE: The overall fold of Ber e 1 is similar to other 2S albumins, but the hydrophobic cavity resembles that of a homologous non-specific lipid transfer protein. Ber e 1 is the first 2S albumin shown to interact with Cu(2+ ions. This Cu(2+ binding has minimal effect on the electrostatic potential on the surface of the protein, but the charge distribution within the hydrophobic cavity is significantly altered. As the hydrophobic cavity is likely to be involved in a putative lipid interaction the Cu(2+ can in turn affect the interaction that is essential to provoke an allergenic response.

  19. Outage and BER analysis for ultrawideband-based WPAN in Nakagami-m fading channels

    KAUST Repository

    Mehbodniya, Abolfazl

    2011-09-01

    This paper presents a performance analysis of multiband orthogonal frequency-division multiplexing (MB-OFDM) in ultra wideband (UWB)-based personal area networks (UPANs). A UPAN consists of devices with different UWB technologies at the physical layer. Approximate expressions for the outage probability and average bit error rate (BER) are derived in closed form for the MB-OFDM target receiver, taking into account multi-user interference (MUI), as well as external interference in the form of time-hopping (TH) and direct-sequence (DS) UWB signals. © 2010 IEEE.

  20. Blinde Mimesis. Über Ordo und Kontingenz in der literaturgeschichtlichen Traditionsbildung (Horaz und Petron

    Directory of Open Access Journals (Sweden)

    Jürgen Paul Schwindt

    2010-11-01

    Full Text Available me truncus illapsus cerebro / sustulerat, nisi Faunus ictum / dextra levasset, Mercurialium / custos virorum.(Hor. carm. 2, 17, 27–30... et ipse Trimalchio capillatus caduceum tenebat Minervaque ducente Romam intrabat.(Petron. 29, 3Es ist zuweilen das Schicksal besonders gut erforschter Texte, daß sie im System der Bezüge, der Quellen und Verweise, das die gelehrte Erklärung über, neben und unter ihnen errichtet hat (Hyper-, Para-, Prae- oder Subtext, zu verschwimmen, konturlos zu werden, ...

  1. EMI and BER/PER Analysis of Wi-Fi and Bluetooth Communication for CRIP Platform

    DEFF Research Database (Denmark)

    Ravelo, Blaise; Cabral, Jorge; Wagner, Stefan Rahr

    This paper is devoted to the characterization of the electromagnetic interference (EMI) effects on wireless communication devices for telemedicine healthcare application. The proposed wireless system operates at the 2.4GHz ISM band with a hardware interface communicating by Wi-Fi and BLE (Bluetooth...... path loss model is investigated for the indoor RF link budget. The quality of the EM coverage and SNR and SINR on QoS with transmitted data BER and PER is analysed. It was examined that the QoS can be degraded according to the distance between the Wi-Fi and BLE device sensitivity and also...

  2. GFDM performance in terms of BER, PAPR and OOB and comparison to OFDM system

    Energy Technology Data Exchange (ETDEWEB)

    Antapurkar, Shwetal K., E-mail: h2014077@pilani.bits-pilani.ac.in; Pandey, Avinash, E-mail: h2014083@pilani.bits-pilani.ac.in [P G student, Dept. of EEE, Birla Institute of Technology and Science, Pilani, Rajasthan, India-333031 (India); Gupta, K. K., E-mail: kgupta@pilani.bits-pilani.ac.in [Asst Prof, Dept. of EEE, Birla Institute of Technology and Science, Pilani, Rajasthan, India-333031 (India)

    2016-03-09

    Generalized frequency division multiplexing is a multicarrier modulation technique which can be foreseen as a potential alternative for upcoming wireless networks. GFDM attractive features include reduced out-of-band radiation(OOB) and low peak-to-average ratio(PAPR), which are the crucial shortcomings of OFDM used in present day wireless communication networks. This paper gives detailed description of GFDM system model and further studies and validates through simulations, the performance of GFDM in terms of OOB, PAPR and Bit Error Rate (BER) and compares the results obtained with OFDM system.

  3. GFDM performance in terms of BER, PAPR and OOB and comparison to OFDM system

    International Nuclear Information System (INIS)

    Antapurkar, Shwetal K.; Pandey, Avinash; Gupta, K. K.

    2016-01-01

    Generalized frequency division multiplexing is a multicarrier modulation technique which can be foreseen as a potential alternative for upcoming wireless networks. GFDM attractive features include reduced out-of-band radiation(OOB) and low peak-to-average ratio(PAPR), which are the crucial shortcomings of OFDM used in present day wireless communication networks. This paper gives detailed description of GFDM system model and further studies and validates through simulations, the performance of GFDM in terms of OOB, PAPR and Bit Error Rate (BER) and compares the results obtained with OFDM system.

  4. A Qualidade Observada em Salas de Berçário

    OpenAIRE

    Tadeu, Bárbara; Aguiar, Cecília

    2017-01-01

    RESUMO Este estudo teve como objetivo investigar a qualidade de estruturas formais de educação para crianças com menos de 12 meses de idade. Participaram 30 salas de berçário de Setúbal e Palmela, no sul de Portugal. A qualidade global das salas foi avaliada com base na Infant/Toddler Environment Rating Scale - Revised Edition e as práticas de socialização, com base na Caregiver Interaction Scale. Os resultados revelam qualidade global média moderada das salas e elevada qualidade nas práticas...

  5. BER analysis of DS-UWB system employing a laplace distribution model

    KAUST Repository

    Mehbodniya, Abolfazl

    2011-01-01

    This letter takes a new approach to extract a closed-form expression for the bit error rate (BER) of direct-sequence ultra wideband (DS-UWB) system. In the analysis, the main signal is impaired by multi-user interference (MUI) and an external source of interference originated by simultanously transmitting multiband orthogonal frequency division multiplexing (MB-OFDM) systems which are located in the vicinity of the DS-UWB receiver. All the transmission channels are affected by Nakagami-m fading. A Laplacian distribution is considered for MUI to comply more with real statistical behaviors of this kind of interference. © IEICE 2011.

  6. Improving 3D-Turbo Code's BER Performance with a BICM System over Rayleigh Fading Channel

    Directory of Open Access Journals (Sweden)

    R. Yao

    2016-12-01

    Full Text Available Classical Turbo code suffers from high error floor due to its small Minimum Hamming Distance (MHD. Newly-proposed 3D-Turbo code can effectively increase the MHD and achieve a lower error floor by adding a rate-1 post encoder. In 3D-Turbo codes, part of the parity bits from the classical Turbo encoder are further encoded through the post encoder. In this paper, a novel Bit-Interleaved Coded Modulation (BICM system is proposed by combining rotated mapping Quadrature Amplitude Modulation (QAM and 3D-Turbo code to improve the Bit Error Rate (BER performance of 3D-Turbo code over Raleigh fading channel. A key-bit protection scheme and a Two-Dimension (2D iterative soft demodulating-decoding algorithm are developed for the proposed BICM system. Simulation results show that the proposed system can obtain about 0.8-1.0 dB gain at BER of 10^{-6}, compared with the existing BICM system with Gray mapping QAM.

  7. Hilfe oder Hindernis? Meinungen finnischer Sprachstudierender über Mehrsprachigkeit als Ressource beim Deutschlernen

    Directory of Open Access Journals (Sweden)

    Sabine Grasz

    2017-10-01

    Full Text Available Der Fremdsprachenunterricht in Finnland befindet sich gerade in einer Umbruchphase, denn mit der Einführung neuer Lehrpläne im Jahr 2016 werden Verfahren der Mehrsprachigkeitsdidaktik in Zukunft eine zentrale Rolle spielen. In diesem Beitrag wird untersucht, ob und wie finnische Universitätsstudierende, die selbst von einer eher monolingual ausgerichteten Lerntradition geprägt sind, ihr mehrsprachiges Repertoire als Ressource beim Lernen weiterer Fremdsprachen sehen. Zu diesem Zweck wurde eine Befragung unter Lehramtsstudierenden der Fächer Anglistik und Skandinavistik, die Germanistik als Nebenfach studieren möchten, durchgeführt. Die Analyse zeigt, dass die Studierenden zwar mehrheitlich positive Einstellungen gegenüber Mehrsprachigkeit aufweisen, dass es aber Entwicklungsbedarf im Hinblick auf Sprachbewusstheit, multilinguale Fähigkeiten und bei den Einstellungen gegenüber Sprachmischungen gibt. Foreign language education in Finland is currently undergoing a period of change, as the introduction of new curricula in 2016 will lead to a central role of multilingualism in teaching. This article examines whether and how Finnish university students, who themselves were influenced by a more monolingual learning tradition, consider their multilingual repertoire as a resource for learning other foreign languages. For this purpose, a survey was conducted among teacher students of English and Swedish, who would like to study German as a minor. The analysis shows that while the majority of students have positive attitudes towards multilingualism, there is a need for development in terms of language awareness, multilingual skills, and attitudes towards language mixes.

  8. The new 'BerSANS-PC' software for reduction and treatment of small angle neutron scattering data

    International Nuclear Information System (INIS)

    Keiderling, U.

    2002-01-01

    Measurements on small angle neutron scattering (SANS) instruments are typically characterized by a large number of samples, short measurement times for the individual samples, and a frequent change of visiting scientist groups. Besides this, recent advances in instrumentation have led to more frequent measurements of kinetic sequences and a growing interest in analyzing two-dimensional scattering data, these requiring special software tools that enable the users to extract physically relevant information from the scattering data with a minimum of effort. The new 'BerSANS-PC' data-processing software has been developed at the Hahn-Meitner-Institut (HMI) in Berlin, Germany, to meet these requirements and to support an efficiently working guest-user service. Comprising some basic functions of the 'BerSANS' program available at the HMI and other institutes in the past, BerSANS-PC is a completely new development for network-independent use on local PCs with a full-feature graphical interface. (orig.)

  9. Berührt sein – Ein Fallbericht zur Rolle von WATSU (WasserShiatsu) in der Rehabilitation nach Polytrauma

    OpenAIRE

    Schitter, Agnes Maria; Fleckenstein, Johannes

    2017-01-01

    Hintergrund: Die herausragende Bedeutung von Körperkontakt für den Menschen ist bekannt und nachgewiesen. Während aber intensiver Körperkontakt in der medizinischen Versorgung von Frühgeborenen etabliert ist, wird Berührung in schulmedizinische Therapiekonzepte für Erwachsene bisher nur marginal integriert. Massnahmen aus der Komplementärmedizin berücksichtigen den individuellen Bedarf an körperlicher Nähe und leisten einen klinischen Mehrwert für den Gesundungsprozess. In besonderer Weise...

  10. BER and FER Prediction of Control and Traffic Channels for a GSM type of interface

    DEFF Research Database (Denmark)

    Wigard, Jeroen; Nielsen, Thomas Toftegaard; Michaelsen, Per Henrik

    1998-01-01

    in a network simulator, but without having to simulate every single link, since this would be to time consuming. In this paper a method is presented to find the BER and FER from the signal to interference (C/I) values for a GSM type of air-interface, which can be used for integration of link aspects...... in a network simulator. The accuracy is within 0.2 dB in case of the BER and 0.5 for the FER. Both traffic and control channels are studied and the method is independent of hopping sequences and speed...

  11. Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor

    Directory of Open Access Journals (Sweden)

    d'Avila Joana C

    2012-02-01

    Full Text Available Abstract Background Traumatic brain injury (TBI induces activation of microglia. Activated microglia can in turn increase secondary injury and impair recovery. This innate immune response requires hours to days to become fully manifest, thus providing a clinically relevant window of opportunity for therapeutic intervention. Microglial activation is regulated in part by poly(ADP-ribose polymerase-1 (PARP-1. Inhibition of PARP-1 activity suppresses NF-kB-dependent gene transcription and thereby blocks several aspects of microglial activation. Here we evaluated the efficacy of a PARP inhibitor, INO-1001, in suppressing microglial activation after cortical impact in the rat. Methods Rats were subjected to controlled cortical impact and subsequently treated with 10 mg/kg of INO-1001 (or vehicle alone beginning 20 - 24 hours after the TBI. Brains were harvested at several time points for histological evaluation of inflammation and neuronal survival, using markers for microglial activation (morphology and CD11b expression, astrocyte activation (GFAP, and neuronal survival (NeuN. Rats were also evaluated at 8 weeks after TBI using measures of forelimb dexterity: the sticky tape test, cylinder test, and vermicelli test. Results Peak microglial and astrocyte activation was observed 5 to 7 days after this injury. INO-1001 significantly reduced microglial activation in the peri-lesion cortex and ipsilateral hippocampus. No rebound inflammation was observed in rats that were treated with INO-1001 or vehicle for 12 days followed by 4 days without drug. The reduced inflammation was associated with increased neuronal survival in the peri-lesion cortex and improved performance on tests of forelimb dexterity conducted 8 weeks after TBI. Conclusions Treatment with a PARP inhibitor for 12 days after TBI, with the first dose given as long as 20 hours after injury, can reduce inflammation and improve histological and functional outcomes.

  12. Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

    International Nuclear Information System (INIS)

    Koh, Seong-Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung-Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

    2005-01-01

    We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p < 0.05). Plasma MMP-9 increased maximally at 4 h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-κB increased maximally at 24 h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke

  13. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

    Directory of Open Access Journals (Sweden)

    Alecu I

    2018-02-01

    Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.

  14. A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells

    Directory of Open Access Journals (Sweden)

    Izraeli Shai

    2011-09-01

    Full Text Available Abstract Background Cells of most human cancers have supernumerary centrosomes. To enable an accurate chromosome segregation and cell division, these cells developed a yet unresolved molecular mechanism, clustering their extra centrosomes at two poles, thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome clustering causes multipolar spindle structures and aberrant chromosomes segregation that prevent normal cell division and lead to 'mitotic catastrophe cell death'. Methods We used cell biology and biochemical methods, including flow cytometry, immunocytochemistry and live confocal imaging. Results We identified a phenanthrene derived PARP inhibitor, known for its activity in neuroprotection under stress conditions, which exclusively eradicated multi-centrosomal human cancer cells (mammary, colon, lung, pancreas, ovarian while acting as extra-centrosomes de-clustering agent in mitosis. Normal human proliferating cells (endothelial, epithelial and mesenchymal cells were not impaired. Despite acting as PARP inhibitor, the cytotoxic activity of this molecule in cancer cells was not attributed to PARP inhibition alone. Conclusion We identified a water soluble phenanthridine that exclusively targets the unique dependence of most human cancer cells on their supernumerary centrosomes bi-polar clustering for their survival. This paves the way for a new selective cancer-targeting therapy, efficient in a wide range of human cancers.

  15. ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD+ Depletion

    Directory of Open Access Journals (Sweden)

    Elise Fouquerel

    2014-09-01

    Full Text Available ARTD1 (PARP1 is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose (PAR in response to strand breaks, and it plays an important role in cell death following excessive DNA damage. ARTD1-induced cell death is associated with NAD+ depletion and ATP loss; however, the molecular mechanism of ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared the effects of ARTD1 activation and direct NAD+ depletion. We found that ARTD1-mediated PAR synthesis, but not direct NAD+ depletion, resulted in a block to glycolysis and ATP loss. We then established a proteomics-based PAR interactome after DNA damage and identified hexokinase 1 (HK1 as a PAR binding protein. HK1 activity is suppressed following nuclear ARTD1 activation and binding by PAR. These findings help explain how prolonged activation of ARTD1 triggers energy collapse and cell death, revealing insight into the importance of nucleus-to-mitochondria communication via ARTD1 activation.

  16. Upper Bounds on the BER Performance of MTCM-STBC Schemes over Shadowed Rician Fading Channels

    Directory of Open Access Journals (Sweden)

    M. Uysal

    2004-08-01

    Full Text Available Space-time block coding (STBC provides substantial diversity advantages with a low decoding complexity. However, these codes are not designed to achieve coding gains. Outer codes should be concatenated with STBC to provide additional coding gain. In this paper, we analyze the performance of concatenated trellis-coded STBC schemes over shadowed Rician frequency-flat fading channels. We derive an exact pairwise error probability (PEP expression that reveals the dominant factors affecting performance. Based on the derived PEP, in conjunction with the transfer function technique, we also present upper bounds on the bit error rate (BER, which are further shown to be tight through a Monte-Carlo simulation study.

  17. Über die Verknüpfung von Hörspiel und Pädagogik

    Directory of Open Access Journals (Sweden)

    Leah Lobensommer

    2013-09-01

    Full Text Available Dieser Artikel legt die Ergebnisse einer Bachelorarbeit zum Thema „Hörspiel als Lernmethode unter besonderer Berücksichtigung sonderpädagogischer Aspekte“ dar. Die Beziehung von Hörspiel und Pädagogik wird durchleuchtet und zeitgemäße Ansätze zur Verwirklichung eines Hörspielprojektes mit Jugendlichen werden dargestellt. Mit Hilfe der Aussagen der qualitativen Forschung wird ein Fazit und ein Ausblick in die Zukunft gewagt.The following article focuses on the results of a Bachelor’s thesis on the subject of "Radio drama as a learning method in supportive educational settings". The link between pedagogics and radio drama and contemporary efforts to create radio dramas in class will be shown. The statements obtained by empiric research have the goal to transport insights of radio drama professionals in order to enlighten the subject. Finally, on the basis of the gained knowledge a conclusion will be made.

  18. Mediennutzung und Informationsbeschaffung über Studium- bzw. Berufswahl - Ingenieurberufe in den Medien

    Directory of Open Access Journals (Sweden)

    Amina Ovcina Cajacob

    2014-06-01

    Full Text Available Diese Publikation basiert auf der Befragung von 4 125 Jugendlichen (SchülerInnen der Altersgruppe 12 bis 21 Jahre. Dafür wurden im Zeitraum vom 22. Oktober bis 12. November 2013 Jugendliche befragt, um Antworten auf folgenden Fragen zu bekommen: Welches Bild haben die Schüler vom Ingenieurberuf? Wie ist ihr allgemeines Mediennutzungsverhalten und wie beeinflussen Medien das Bild des Ingenieurs? Welche Berufe interessieren Jugendliche und wie informieren sie sich über Studien- bzw. Berufswahl? Welche Einflüsse spielen bei den Jugendlichen bezüglich der eigenen Berufs- und Studienwahl eine Rolle? Die Ergebnisse dieser umfassenden Analyse sind Grundlage für die Konzeption einer crossmedialen Sensibilisierungskampage, die zum Ziel hat, Vorurteile über den Ingenieurberuf abzubauen, Wissen und ein zeitgemässes Berufsbild zu vermitteln sowie Neugier auf ein Ingenieurstudium zu wecken. This publication is based on a survey of 4125 young people (pupils and students aged 12 to 21 years. In the period from October 22 to November 12, 2013 young people were interviewed to obtain answers to the following questions: . What an idea do young people have about an engineer and his profession? . What is their general media usage behavior? . How do media influence the image of the engineer? . Which professions are the most attractive for young people and how do they inform themselves about study or career choices? . Which influences are important for the study and career choice of young people? The results of this comprehensive analysis are the basis for the conception of a cross-media awareness campaign, which aims to reduce prejudices about the engineering profession, to impart knowledge as well as a contemporary professional image of engineer and to arouse interest for an engineering degree.

  19. Natura2000 : Information und Kommunikation über die Ausweisung und die Pflege von Natura2000 Schutsgebieten : Zusammenfassung Hauptbericht 1: die Ausweisung in 27 EU Mitgliedsstaten

    NARCIS (Netherlands)

    Apeldoorn, van R.C.; Kruk, R.W.; Bouwma, I.M.; Ferranti, F.; Blust, De G.; Sier, A.R.J.

    2010-01-01

    Die Europäischen Kommission (EK) möchte die Mitgliedsstaaten unterstützen und den Austausch von Wissen, Information und Praxiserfahrung fördern: sowohl über den Prozess der Ausweisung von Vogelschutz- und FFH- Gebieten, als über mögliche Schutzmassnahmen und Instrumente für diese Gebiete in den

  20. Suppression of Homologous Recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors

    International Nuclear Information System (INIS)

    Amin, Oreekha; Beauchamp, Marie-Claude; Nader, Paul Abou; Laskov, Ido; Iqbal, Sanaa; Philip, Charles-André; Yasmeen, Amber; Gotlieb, Walter H.

    2015-01-01

    Impairment of homologous recombination (HR) is found in close to 50 % of ovarian and breast cancer. Tumors with BRCA1 mutations show increased expression of the Insulin-like growth factor type 1 receptor (IGF-1R). We previously have shown that inhibition of IGF-1R results in growth inhibition and apoptosis of ovarian tumor cells. In the current study, we aimed to investigate the correlation between HR and sensitivity to IGF-1R inhibition. Further, we hypothesized that IGF-1R inhibition might sensitize HR proficient cancers to Poly ADP ribose polymerase (PARP) inhibitors. Using ovarian and breast cancer cellular models with known BRCA1 status, we evaluated their HR functionality by RAD51 foci formation assay. The 50 % lethal concentration (LC50) of Insulin-like growth factor type 1 receptor kinase inhibitor (IGF-1Rki) in these cells was assessed, and western immunoblotting was performed to determine the expression of proteins involved in the IGF-1R pathway. Moreover, IGF-1R inhibitors were added on HR proficient cell lines to assess mRNA and protein expression of RAD51 by qPCR and western blot. Also, we explored the interaction between RAD51 and Insulin receptor substance 1 (IRS-1) by immunoprecipitation. Next, combination effect of IGF-1R and PARP inhibitors was evaluated by clonogenic assay. Cells with mutated/methylated BRCA1 showed an impaired HR function, and had an overactivation of the IGF-1R pathway. These cells were more sensitive to IGF-1R inhibition compared to HR proficient cells. In addition, the IGF-IR inhibitor reduced RAD51 expression at mRNA and protein levels in HR proficient cells, and sensitized these cells to PARP inhibitor. Targeting IGF-1R might lead to improved personalized therapeutic approaches in cancer patients with HR deficiency. Targeting both PARP and IGF-1R might increase the clinical efficacy in HR deficient patients and increase the population of patients who may benefit from PARP inhibitors

  1. Vorläufige Mitteilung über die Beschaffenheit der Ovarialtasche von Chrysochloris, Galeopithecus und Tupaja

    NARCIS (Netherlands)

    Lange, de Daniel

    1922-01-01

    Im Jahre 1917 ist in den Anatomischen Heften die bekannte und schöne Arbeit Sobotta’s erschienen über das Vorkommen und die Bedeutung der Ovarialtasche bei den Säugetieren ¹). Das Hauptergebniss dieser Arbeit ist, dass bei alien Säugetieren (vielleicht mit Ausnahne der Primaten und des Menschen) die

  2. Effect of Pointing Error on the BER Performance of an Optical CDMA FSO Link with SIK Receiver

    Science.gov (United States)

    Nazrul Islam, A. K. M.; Majumder, S. P.

    2017-12-01

    An analytical approach is presented for an optical code division multiple access (OCDMA) system over free space optical (FSO) channel considering the effect of pointing error between the transmitter and the receiver. Analysis is carried out with an optical sequence inverse keying (SIK) correlator receiver with intensity modulation and direct detection (IM/DD) to find the bit error rate (BER) with pointing error. The results are evaluated numerically in terms of signal-to-noise plus multi-access interference (MAI) ratio, BER and power penalty due to pointing error. It is noticed that the OCDMA FSO system is highly affected by pointing error with significant power penalty at a BER of 10-6 and 10-9. For example, penalty at BER 10-9 is found to be 9 dB corresponding to normalized pointing error of 1.4 for 16 users with processing gain of 256 and is reduced to 6.9 dB when the processing gain is increased to 1,024.

  3. Die kupferzeitliche Siedlung Pietrele an der Unteren Donau. Bericht über die Ausgrabungen und geomorphologischen Untersuchungen im Sommer 2010

    DEFF Research Database (Denmark)

    Nørgaard, Heide Wrobel

    2012-01-01

    Seit der Kampagne 2008 und dem letzten Zwischenbericht über den nichtmetallenen Schmuck wurden zahlreiche weitere Stücke dieser Kleinfundkategorie auf dem Tell und in der Außensiedlung gefunden. Auch das Formenspektrum hat sich erheblich erweitert. Der in der bisherigen Forschung als elitär anges...

  4. Increased transcript level of poly(ADP-ribose) polymerase (PARP-1) in human tricuspid compared with bicuspid aortic valves correlates with the stenosis severity

    International Nuclear Information System (INIS)

    Nagy, Edit; Caidahl, Kenneth; Franco-Cereceda, Anders; Bäck, Magnus

    2012-01-01

    Highlights: ► Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. ► We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. ► Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. ► The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. ► Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C 4 (LTC 4 ) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = −0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = −0.498; P = 0.0298) only in tricuspid aortic valves. LTC 4 (1 nM) significantly elevated the mRNA levels of PARP-1 by 2.38-fold in VICs. Taken together, these data suggest that

  5. Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.

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    Michal Yalon

    Full Text Available Inhibitors of poly[ADP-ribose] polymerase 1 (PARPis show promise for treatment of cancers which lack capacity for homologous recombination repair (HRR. However, new therapeutic strategies are required in order to overcome innate and acquired resistance to these drugs and thus expand the array of cancers that could benefit from them. We show that human cancer cell lines which respond poorly to ABT-888 (a PARPi, become sensitive to it when co-treated with vorinostat (a histone deacetylase inhibitor (HDACi. Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG-a drug that targets PARPis sensitive cells. The sensitizing effect of vorinostat was associated with increased phosphorylation of eukaryotic initiation factor (eIF 2α which in and of itself increases the sensitivity of cancer cells to ABT-888. Importantly, these drug combinations did not affect survival of normal fibroblasts and breast cells, and significantly increased the inhibition of xenograft tumor growth relative to each drug alone, without affecting the mice weight or their liver and kidney function. Our results show that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. Importantly, drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors.

  6. Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients

    Directory of Open Access Journals (Sweden)

    See-Hyoung Park

    2015-08-01

    Full Text Available BACKGROUND: Poly(ADP-ribose polymerase 1 (PARP1, γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS, and relapse-free survival (RFS by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph was an additional independent prognostic predictor for OS (P < .001 and RFS (P < .001. The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1 subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4 subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

  7. PARP-1 Variant Rs1136410 Confers Protection against Coronary Artery Disease in a Chinese Han Population: A Two-Stage Case-Control Study Involving 5643 Subjects

    Directory of Open Access Journals (Sweden)

    Xue-bin Wang

    2017-11-01

    Full Text Available Inhibition of poly(ADP-ribose polymerase (PARP may protect against coronary artery disease (CAD in animal models, and rs1136410, a non-synonymous single nucleotide polymorphism (SNP in PARP-1, has a potential impact on PARP activities in vitro. This two-stage case-control study, involving 2803 CAD patients and 2840 controls, aimed to investigate the associations of PARP-1 rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2′-dexyguanosine (8-OHdG, and interleukin (IL-6 levels in a Chinese Han population. Assuming a recessive model, the variant genotype GG of SNP rs1136410 showed a significantly inverse association with CAD risk (adjusted odds ratio (OR = 0.73, P < 0.001, left main coronary artery (LMCA lesions (P = 0.003, vessel scores (P = 0.003, and modified Gensini scores (P < 0.001. There were significant correlations of SNP rs1136410 with higher levels of total cholesterol (TC and lower levels of high-density lipoprotein cholesterol (HDL-c. In gene-environment interaction analyses, participants with the variant genotype GG, but without smoking habit, type 2 diabetes mellitus, and hyperlipidemia, conferred an 84% (P < 0.001 decreased risk of CAD. The genotype-phenotype correlation analyses further supported the functional roles of SNP rs1136410 in decreasing PARP activities and 8-OHdG levels. Taken together, our data suggest that SNP rs1136410 may confer protection against CAD through modulation of PARP activities and gene-environment interactions in a Chinese Han population.

  8. New approaches of PARP-1 inhibitors in human lung cancer cells and cancer stem-like cells by some selected anthraquinone-derived small molecules.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Lee

    Full Text Available Poly (ADP-ribose polymerase-1 (PARP-1 and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60 in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.

  9. New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules

    Science.gov (United States)

    Yu, Dah-Shyong; Huang, Kuo-Feng; Chou, Shih-Jie; Chen, Tsung-Chih; Lee, Chia-Chung; Chen, Chun-Liang; Chiou, Shih-Hwa; Huang, Hsu-Shan

    2013-01-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy. PMID:23451039

  10. Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers.

    Science.gov (United States)

    Lombardi, Anne J; Hoskins, Elizabeth E; Foglesong, Grant D; Wikenheiser-Brokamp, Kathryn A; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R; Jacobs, Allison J; Olson, Susan B; Keeble, Winifred W; Hays, Laura E; Wells, Susanne I

    2015-04-15

    Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. ©2015 American Association for Cancer Research.

  11. Combination strategy of PARP inhibitor with antioxidant prevent bioenergetic deficits and inflammatory changes in CCI-induced neuropathy.

    Science.gov (United States)

    Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

    2017-02-01

    Neuropathic pain, a debilitating pain condition and the underlying pathogenic mechanisms are complex and interwoven amongst each other and still there is scant information available regarding therapies which promise to treat the condition. Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic crisis culminating into neurodegenerative changes following nerve injury. Hence, we investigated the therapeutic effect of combining an antioxidant, quercetin and a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits induced by chronic constriction injury (CCI) of sciatic nerve in rats. Quercetin (25 mg/kg, p.o.) and 4-ANI (3 mg/kg, p.o.) were administered either alone or in combination for 14 days to examine sciatic functional index, allodynia and hyperalgesia using walking track analysis, Von Frey, acetone spray and hot plate tests respectively. Malondialdehyde, nitrite and glutathione levels were estimated to detect oxidative/nitrosative stress; mitochondrial membrane potential and cytochrome c oxidase activity to assess mitochondrial function; NAD & ATP levels to examine the bioenergetic status and levels of inflammatory markers were evaluated in ipsilateral sciatic nerve. Quercetin and 4-ANI alone improved the pain behaviour and biochemical alterations but the combination therapy demonstrated an appreciable reversal of CCI-induced changes. Nitrotyrosine and Poly ADP-Ribose (PAR) immunopositivity was decreased and nuclear factor erythroid 2-related factor (Nrf-2) levels were increased significantly in micro-sections of the sciatic nerve and dorsal root ganglion (DRG) of treatment group. These results suggest that simultaneous inhibition of oxidative stress-PARP activation cascade may potentially be useful strategies for management of trauma induced neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Regulation of HFE expression by poly(ADP-ribose) polymerase-1 (PARP1) through an inverted repeat DNA sequence in the distal promoter.

    Science.gov (United States)

    Pelham, Christopher; Jimenez, Tamara; Rodova, Marianna; Rudolph, Angela; Chipps, Elizabeth; Islam, M Rafiq

    2013-12-01

    Hereditary hemochromatosis (HH) is a common autosomal recessive disorder of iron overload among Caucasians of northern European descent. Over 85% of all cases with HH are due to mutations in the hemochromatosis protein (HFE) involved in iron metabolism. Although the importance in iron homeostasis is well recognized, the mechanism of sensing and regulating iron absorption by HFE, especially in the absence of iron response element in its gene, is not fully understood. In this report, we have identified an inverted repeat sequence (ATGGTcttACCTA) within 1700bp (-1675/+35) of the HFE promoter capable to form cruciform structure that binds PARP1 and strongly represses HFE promoter. Knockdown of PARP1 increases HFE mRNA and protein. Similarly, hemin or FeCl3 treatments resulted in increase in HFE expression by reducing nuclear PARP1 pool via its apoptosis induced cleavage, leading to upregulation of the iron regulatory hormone hepcidin mRNA. Thus, PARP1 binding to the inverted repeat sequence on the HFE promoter may serve as a novel iron sensing mechanism as increased iron level can trigger PARP1 cleavage and relief of HFE transcriptional repression. © 2013.

  13. Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

    Science.gov (United States)

    Ieraci, Alessandro; Herrera, Daniel G

    2018-06-01

    Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

  14. BER PERFORMANCE COMPARISON OF MIMO SYSTEMS USING OSTBC WITH ZF AND ML DECODING

    Directory of Open Access Journals (Sweden)

    Zenitha Rehman

    2014-12-01

    Full Text Available Multiple Input Multiple Output (MIMO systems with multiple antenna elements at both transmitter and receiver ends are an efficient solution for wireless communication systems. They provide high data rates by exploiting the spatial domain under the constraints of limited bandwidth and transmit power. Space-Time Block Coding (STBC is a MIMO transmit strategy which exploits transmit diversity and provides high reliability. Implementation of orthogonal space-time block codes (OSTBCs for a two transmitter–two receiver system under AWGN (Additive White Gaussian Noise channel and flat fading channel is performed. Alamouti code is employed for the STBC. The modulation techniques used are BPSK, QPSK and 16-QAM. Decoding is done using the Zero Forcing (ZF algorithm and Maximum Likelihood (ML algorithm. The BER Performance of each modulation scheme is compared with the un-coded version of the same. Performance comparison between the two decoding techniques is also done. It is found that ML detection offers a slightly better performance for BPSK and QPSK system than ZF detection.

  15. Damage by insect pests to the Djingarey Ber Mosque in Timbuktu: detection and control

    Directory of Open Access Journals (Sweden)

    Lara Maistrello

    2011-08-01

    Full Text Available The Djingarey Ber Mosque in Timbuktu (Mali is one of the most significant earthen construction in West Africa. Originally constructed in 1327, it was included in 1988 on the World Heritage UNESCO List for its unique architecture and historical importance. During its restoration, recently undertaken by the Aga Khan Trust for Culture, the wooden parts of the roof and architraves showed clear signs of threatening insect presence. In order to identify the pests responsible of the damage, evaluate its extent and suggest a proper control strategy, a detailed survey was performed inside the Mosque complex and in its immediate surroundings. The entomological inspection, performed in the dry-cold season, allowed to detect signs of insect damage in most of the wooden elements, even in the recently replaced beams, but also in walls, pillars and the precious decorated panels. Damages in the wood elements could be attributed to Amitermes evuncifer Silvestri (Termitidae, Bostrychoplites zycheli Marseuli (Bostrichidae and Lyctus africanus Lesne (Lyctidae, which were collected alive on site. Injures in the walls and decorated panels appeared to be performed by hymenopterans such as “plasterer bees” (Colletidae and Sphecidae. From the evaluation of the type and extent of damage in relation to the architecture and materials used in its construction and decoration, the most serious pest and the worse threat for the mosque is represented by termites. Control and preventive measures, in the view of a sustainable, long-lasting integrated management are suggested.

  16. Echt und modern? Diskurse über Männlichkeit

    Directory of Open Access Journals (Sweden)

    Florian Kahofer

    2014-09-01

    Full Text Available Der vorliegende Artikel befasst sich mit Repräsentationen von Männlichkeit im österreichischen Lifestyle-Magazin für Männer Wiener. Durch eine korpusbasierte Diskursanalyse wird ein umfassendes Korpus aller Ausgaben des Wieners von Anfang 2002 bis Ende 2012 untersucht. Auf theoretischer Ebene wird dabei eine Verbindung von Kritischer Männlichkeitsforschung (KMF und Feministisch Kritischer Diskursanalyse (FCDA unternommen. Es werden aktuelle Veröffentlichungen zu Kritischer Diskursanalyse und Männlichkeit vorgestellt und diskutiert. Durch den Einsatz einer Konkordanzsoftware werden Konkordanzen des Nomens MANN analysiert. Diese werden allerdings insofern eingeschränkt betrachtet, als nur Nominationen in der Form der häufigsten Adjektiv-Konstruktionen untersucht werden. Die Ergebnisse zeigen, dass neben den Diskursen über Krise und Neue Männlichkeit Themen wie Alter, Körper oder Beziehung auftauchen. Männlichkeit wird als ambivalent und vielfältig dargestellt. Deutungskämpfe um Männlichkeit lassen sich ausmachen.

  17. BER Analysis Using Beat Probability Method of 3D Optical CDMA Networks with Double Balanced Detection

    Directory of Open Access Journals (Sweden)

    Chih-Ta Yen

    2015-01-01

    Full Text Available This study proposes novel three-dimensional (3D matrices of wavelength/time/spatial code for code-division multiple-access (OCDMA networks, with a double balanced detection mechanism. We construct 3D carrier-hopping prime/modified prime (CHP/MP codes by extending a two-dimensional (2D CHP code integrated with a one-dimensional (1D MP code. The corresponding coder/decoder pairs were based on fiber Bragg gratings (FBGs and tunable optical delay lines integrated with splitters/combiners. System performance was enhanced by the low cross correlation properties of the 3D code designed to avoid the beat noise phenomenon. The CHP/MP code cardinality increased significantly compared to the CHP code under the same bit error rate (BER. The results indicate that the 3D code method can enhance system performance because both the beating terms and multiple-access interference (MAI were reduced by the double balanced detection mechanism. Additionally, the optical component can also be relaxed for high transmission scenery.

  18. Monitoring artificial radioactivity in the Nordic countries. BER-2 final report

    International Nuclear Information System (INIS)

    Bennerstedt, T.; Rantanen, H.; Mortensen, B.N.

    1994-05-01

    This final report of the Nordic Nuclear Safety Research Project BER-2 gives detailed information on the monitoring of artificial radioactivity in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). A comparison shows that for early warning the Nordic countries use a mix of stations measuring external gamma radiation and stations measuring airborne radioactivity. There is a trade-off between fast alarms and the sensitivity threshold. Total gamma measuring stations cannot detect increases smaller than the variations of normal background. Some stations, notably all Danish stations, are equipped with sodium iodide (NaI) type detectors, and operated in such a way that stray peaks due to an increase in the natural radon background can be subtracted. A Nordic Radiation Data Exchange System has been set up and tested on a trial basis. This system focuses on dose rate data from the automatic gamma monitoring stations. An important goal achieved in the project was to determine which data is essential, and to specify a common format for the data exchange. Various telecommunication methods have been tested, and the actual transfer of monitoring results between the Nordic countries was started. It is recommended as a future approach that every country appoint one organization with the responsibility of operating a national information data base, which can be commonly accessed from all the Nordic countries. A procedure for establishing a system of this type has been outlined

  19. BER IMPROVEMENT OF WIRELESS LAN IEEE 802.11 STANDARD USING WAVELET PACKET TRANSFORMS

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar

    2012-09-01

    Full Text Available High data rates and spectral efficiency is the main requirements for wireless communication systems. Orthogonal Frequency Division Multiplexing (OFDM is a special form of multi carrier transmission used to achieve high data rates of the various WLAN standards. WLAN uses an Inverse Fast Fourier Transform (IFFT at the transmitter to modulate a high bit-rate signal onto a number of carriers and ensure orthogonality between the carriers. The FFT-OFDM has a disadvantage that it is inherently inflexible and requires a complex IFFT core. Recently, Wavelet Packet Transform is proposed as an alternate to FFT. It is a multiplexing method in which data is assigned to wavelet sub bands having different time and frequency resolutions. This paper presents a BER analysis of Fourier-based OFDM (FFT-OFDM and Wavelet Packet based OFDM (WPT-OFDM in WLAN standard (IEEE 802.11a. The performance of FFT and WPT OFDM for various modulation techniques such as PSK, DPSK and QAM for varying values of M was evaluated in AWGN Channel.

  20. Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity

    Czech Academy of Sciences Publication Activity Database

    Frankum, J.; Moudrý, P.; Brough, R.; Hodný, Zdeněk; Ashworth, A.; Bartek, Jiří; Lord, C.J.

    2015-01-01

    Roč. 6, č. 13 (2015), s. 10746-10758 ISSN 1949-2553 R&D Projects: GA ČR GA13-17555S EU Projects: European Commission HEALTH-F2-2010-259893 Grant - others:Lundbeck Foundation(DK) R93-A8990; Danish Council for Independent Research(DK) DFF-1331-00262 Institutional support: RVO:68378050 Keywords : DNA damage response * ubiquitin-proteasome system * RNA interference screens * PARP inhibitors * CBLC Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.008, year: 2015

  1. BER Performance Simulation of Generalized MC DS-CDMA System with Time-Limited Blackman Chip Waveform

    Directory of Open Access Journals (Sweden)

    I. Develi

    2010-09-01

    Full Text Available Multiple access interference encountered in multicarrier direct sequence-code division multiple access (MC DS-CDMA is the most important difficulty that depends mainly on the correlation properties of the spreading sequences as well as the shape of the chip waveforms employed. In this paper, bit error rate (BER performance of the generalized MC DS-CDMA system that employs time-limited Blackman chip waveform is presented for Nakagami-m fading channels. Simulation results show that the use of Blackman chip waveform can improve the BER performance of the generalized MC DS-CDMA system, as compared to the performances achieved by using timelimited chip waveforms in the literature.

  2. The sensitivity of bit error rate (BER) performance in multi-carrier (OFDM) and single-carrier

    Science.gov (United States)

    Albdran, Saleh; Alshammari, Ahmed; Matin, Mohammad

    2012-10-01

    Recently, the single-carrier and multi-carrier transmissions have grabbed the attention of industrial systems. Theoretically, OFDM as a Multicarrier has more advantages over the Single-Carrier especially for high data rate. In this paper we will show which one of the two techniques outperforms the other. We will study and compare the performance of BER for both techniques for a given channel. As a function of signal to noise ratio SNR, the BER will be measure and studied. Also, Peak-to-Average Power Ratio (PAPR) is going to be examined and presented as a drawback of using OFDM. To make a reasonable comparison between the both techniques, we will use additive white Gaussian noise (AWGN) as a communication channel.

  3. ALS Ice Bucket Challenge: Warum die Kampagne über einen „Tsunami Effekt“ beim Spendenverhalten Eisberge versetzen kann

    OpenAIRE

    Decieux, Jean Philippe Pierre

    2015-01-01

    Im Sommer 2014 beherrschte eine Kampagne die sozialen Medien, welche auf originelle Art und Weise auf die Nervenkrankheit Amyotrophe Lateralsklerose (ALS) aufmerksam machen und dadurch Spendengelder für die Erforschung dieser Krankheit generieren wollte. Im Rahmen der sogenannten ALS-Ice-Bucket-Challenge-Kampagne gossen sich die Hauptdarsteller/innen von kleinen Internetclips eiskaltes Wasser über den Kopf und nominierten im Anschluss weitere Personen für die Challenge. Die Herausforderung bz...

  4. Telomerase activity-independent function of telomerase reverse transcriptase is involved in acrylamide-induced neuron damage.

    Science.gov (United States)

    Zhang, P; Pan, H; Wang, J; Liu, X; Hu, X

    2014-07-01

    Polyacrylamide is used widely in industry, and its decomposition product, acrylamide (ACR), readily finds its way into commonly consumed cosmetics and baked and fried foods. ACR exerts potent neurotoxic effects in human and animal models. Telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, traditionally has been considered to play an important role in maintaining telomere length. Emerging evidence has shown, however, that TERT plays an important role in neuroprotection by inhibiting apoptosis and excitotoxicity, and by promoting angiogenesis, neuronal survival and neurogenesis, which are closely related to the telomere-independent functions of TERT. We investigated whether and how the TERT pathway is involved in ACR induced neurotoxicity in rat cortical neurons. We found that ACR 1) significantly reduced the viability of cortical neurons as measured by MTT assay, 2) induced neuron apoptosis as revealed by FITC-conjugated Annexin V/PI double staining and flow cytometry (FACS) analysis, 3) elevated expression of cleaved caspase-3, and 4) decreased bcl-2 expression of cortical neurons. ACR also increased intracellular ROS levels in cortical neurons, increased MDA levels and reduced GSH, SOD and GSH-Px levels in mitochondria in a dose-dependent manner. We found that TERT expression in mitochondria was increased by ACR at concentrations of 2.5 and 5.0 mM, but TERT expression was decreased by 10 mM ACR. Telomerase activity, however, was undetectable in rat cortical neurons. Our results suggest that the TERT pathway is involved in ACR induced apoptosis of cortical neurons. TERT also may exert its neuroprotective role in a telomerase activity-independent way, especially in mitochondria.

  5. BER and optimal power allocation for amplify-and-forward relaying using pilot-aided maximum likelihood estimation

    KAUST Repository

    Wang, Kezhi

    2014-10-01

    Bit error rate (BER) and outage probability for amplify-and-forward (AF) relaying systems with two different channel estimation methods, disintegrated channel estimation and cascaded channel estimation, using pilot-aided maximum likelihood method in slowly fading Rayleigh channels are derived. Based on the BERs, the optimal values of pilot power under the total transmitting power constraints at the source and the optimal values of pilot power under the total transmitting power constraints at the relay are obtained, separately. Moreover, the optimal power allocation between the pilot power at the source, the pilot power at the relay, the data power at the source and the data power at the relay are obtained when their total transmitting power is fixed. Numerical results show that the derived BER expressions match with the simulation results. They also show that the proposed systems with optimal power allocation outperform the conventional systems without power allocation under the same other conditions. In some cases, the gain could be as large as several dB\\'s in effective signal-to-noise ratio.

  6. BER and optimal power allocation for amplify-and-forward relaying using pilot-aided maximum likelihood estimation

    KAUST Repository

    Wang, Kezhi; Chen, Yunfei; Alouini, Mohamed-Slim; Xu, Feng

    2014-01-01

    Bit error rate (BER) and outage probability for amplify-and-forward (AF) relaying systems with two different channel estimation methods, disintegrated channel estimation and cascaded channel estimation, using pilot-aided maximum likelihood method in slowly fading Rayleigh channels are derived. Based on the BERs, the optimal values of pilot power under the total transmitting power constraints at the source and the optimal values of pilot power under the total transmitting power constraints at the relay are obtained, separately. Moreover, the optimal power allocation between the pilot power at the source, the pilot power at the relay, the data power at the source and the data power at the relay are obtained when their total transmitting power is fixed. Numerical results show that the derived BER expressions match with the simulation results. They also show that the proposed systems with optimal power allocation outperform the conventional systems without power allocation under the same other conditions. In some cases, the gain could be as large as several dB's in effective signal-to-noise ratio.

  7. Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1.

    Science.gov (United States)

    Fatima, Sabiha; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2012-08-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) operates in a DNA damage signaling network. Molecular docking and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on human PARP-1 inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into a training set and a test set randomly in four different ways, partial least square analysis was performed to obtain QSAR models using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Derived models showed good statistical reliability that is evident from their r², q²(loo) and r²(pred) values. To obtain a consensus for predictive ability from all the models, average regression coefficient r²(avg) was calculated. CoMFA and CoMSIA models showed a value of 0.930 and 0.936, respectively. Information obtained from the best 3D-QSAR model was applied for optimization of lead molecule and design of novel potential inhibitors.

  8. vPARP Adjusts MVP Expression in Drug-resistant Cell Lines in Conjunction with MDR Proteins.

    Science.gov (United States)

    Wojtowicz, Karolina; Januchowski, Radoslaw; Nowicki, Michal; Zabel, Maciej

    2017-06-01

    The definition of vault (ribonucleoprotein particles) function remains highly complex. Vaults may cooperate with multidrug resistance (MDR) proteins, supporting their role in drug resistance. This topic is the main theme of this publication. The cell viability was determined by an MTT assay. The protein expression was detected by western blot analysis. The proteins were knocked-down using siRNA. No major vault protein (MVP) in the LoVo/Dx and W1PR cell lines after tunicamycin treatment was shown. In W1PR cells with knocked-down MVP, a statistically significant decrease in cell viability was noted. In LoVo/Dx, W1TR and A2780TR cells were vault poly-ADP-ribose polymerase (vPARP) was knockdown, a decrease in cell viability was shown. Also, MVP silencing induced an increase in glycoprotein P (Pgp) expression in LoVo/Dx cells. MVP is important for the drug resistance of cancer cells, but it probably requires the presence of vPARP for full activation. Some correlations between MDR proteins and vaults exist. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer.

    Science.gov (United States)

    Ivy, S Percy; Liu, Joyce F; Lee, Jung-Min; Matulonis, Ursula A; Kohn, Elise C

    2016-01-01

    An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill ~14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC). This combination has the potential to change the treatment of HGSOC. Preclinical and clinical studies of single agent cediranib and olaparib or their combination are reviewed. Data are presented from peer-reviewed published manuscripts, completed and ongoing early phase clinical trials registered in ClinicalTrials.gov, National Cancer Institute-sponsored clinical trials, and related recent abstracts. Advances in the treatment of HGSOC that improve progression-free and overall survival have proven elusive despite examination of molecularly targeted therapy. HGSOC patients with deleterious germline or somatic mutations in BRCA1 or BRCA2 (BRCAm) are most responsive to PARP inhibitors (PARPi). PARPi combined with angiogenesis inhibition improved anti-cancer response and duration in both BRCAm and BRCA wild type HGSOC patients, compared to olaparib single agent treatment, demonstrating therapeutic chemical and contextual synthetic lethality.

  10. IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors.

    Science.gov (United States)

    Molenaar, Remco J; Radivoyevitch, Tomas; Nagata, Yasunobu; Khurshed, Mohammed; Przychodzen, Bartolomiej; Makishima, Hideki; Xu, Mingjiang; Bleeker, Fonnet E; Wilmink, Johanna W; Carraway, Hetty E; Mukherjee, Sudipto; Sekeres, Mikkael A; van Noorden, Cornelis J F; Maciejewski, Jaroslaw P

    2018-04-01

    Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2 MUT enzymes produce D -2-hydroxyglutarate ( D 2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2 MUT AML is not known. Experimental Design: Well-characterized primary IDH1 MUT , IDH2 MUT , and IDH1/2 WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and PARP inhibitors. Results: IDH1/2 MUT caused increased DNA damage and sensitization to daunorubicin, irradiation, and the PARP inhibitors olaparib and talazoparib in AML cells. IDH1/2 MUT inhibitors protected against these treatments. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2 MUT AML cells. We provide evidence that the therapy sensitivity of IDH1/2 MUT cells was caused by D 2HG-mediated downregulation of expression of the DNA damage response gene ATM and not by altered redox responses due to metabolic alterations in IDH1/2 MUT cells. Conclusions: IDH1/2 MUT AML cells are sensitive to PARP inhibitors as monotherapy but especially when combined with a DNA-damaging agent, such as daunorubicin, whereas concomitant administration of IDH1/2 MUT inhibitors during cytotoxic therapy decrease the efficacy of both agents in IDH1/2 MUT AML. These results advocate in favor of clinical trials of PARP inhibitors either or not in combination with daunorubicin in IDH1/2 MUT AML. Clin Cancer Res; 24(7); 1705-15. ©2018 AACR . ©2018 American Association for Cancer Research.

  11. Differential transactivation by orphan nuclear receptor NOR1 and its fusion gene product EWS/NOR1: possible involvement of poly(ADP-ribose) polymerase I, PARP-1.

    Science.gov (United States)

    Ohkura, Naganari; Nagamura, Yuko; Tsukada, Toshihiko

    2008-10-15

    In extraskeletal myxoid chondrosarcoma, a chromosomal translocation creates a gene fusion between EWS and an orphan nuclear receptor, NOR1. The resulting fusion protein EWS/NOR1 has been believed to lead to malignant transformation by functioning as a transactivator for NOR1-target genes. By comparing the gene expression profiles of NOR1- and EWS/NOR1-overexpressing cells, we found that they largely shared up-regulated genes, but no significant correlation was observed with respect to the transactivation levels of each gene. In addition, the proteins associated with NOR1 and EWS/NOR1 were mostly the same in these cells. The results suggest that these proteins differentially transactivate overlapping target genes through a similar transcriptional machinery. To clarify the mechanisms underlying the transcriptional divergence between NOR1 and EWS/NOR1, we searched for alternatively associated proteins, and identified poly(ADP-ribose) polymerase I (PARP-1) as an NOR1-specific binding protein. Consistent with its binding properties, PARP-1 acted as a transcriptional repressor of NOR1, but not EWS/NOR1, in a luciferase reporter assay employing PARP-1(-/-) fibroblasts. Interestingly, suppressive activity of PARP-1 was observed in a DNA response element-specific manner, and in a subtype-specific manner toward the NR4A family (Nur77, Nurr1, and NOR1), suggesting that PARP-1 plays a role in the diversity of transcriptional regulation mediated by the NR4A family in normal cells. Altogether, our findings suggest that NOR1 and EWS/NOR1 regulate overlapping target genes differently by utilizing associated proteins, including PARP-1; and that EWS/NOR1 may acquire oncogenic activities by avoiding (or gaining) transcription factor-specific modulation by the associated proteins. (c) 2008 Wiley-Liss, Inc.

  12. Effects of plasma on polyethylene fiber surface for prosthodontic application

    Directory of Open Access Journals (Sweden)

    Silvana Marques Miranda SPYRIDES

    2015-12-01

    Full Text Available ABSTRACT Plasma technology has the potential to improve the adherence of fibers to polymeric matrices, and there are prospects for its application in dentistry to reinforce the dental particulate composite. Objectives This study aimed to investigate the effect of oxygen or argon plasma treatment on polyethylene fibers. Material and Methods Connect, Construct, InFibra, and InFibra treated with oxygen or argon plasma were topographically evaluated by scanning electron microscopy (SEM, and chemically by X-ray photoelectron spectroscopy (XPS. For bending analysis, one indirect composite (Signum was reinforced with polyethylene fiber (Connect, Construct, or InFibra. The InFibra fiber was subjected to three different treatments: (1 single application of silane, (2 oxygen or argon plasma for 1 or 3 min, (3 oxygen or argon plasma and subsequent application of silane. The samples (25x2x2 mm, 6 unreinforced and 60 reinforced with fibers, were subjected to three-point loading tests to obtain their flexural strength and deflection. The results were statistically analyzed with ANOVA and the Bonferroni correction for multiple comparison tests. Results SEM analysis showed that oxygen and argon plasma treatments promote roughness on the polyethylene fiber surface. X-ray photoelectron spectroscopy (XPS analysis shows that both plasmas were effective in incorporating oxygenated functional groups. Argon or oxygen plasma treatment affected the flexural strength and deflection of a fiber reinforced composite. The application of silane does not promote an increase in the flexural strength of the reinforced composites. Conclusions Oxygen and argon plasma treatments were effective in incorporating oxygenated functional groups and surface roughness. The highest strength values were obtained in the group reinforced with polyethylene fibers treated with oxygen plasma for 3 min.

  13. PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

    2016-01-01

    Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

  14. Kollektivismus, Individualismus und Persönlichkeit als Prädiktoren von Einstellungen gegenüber psychologischer Beratung - Ein Kulturvergleich zwischen deutschen und chinesischen Studierenden

    OpenAIRE

    Schmahl, Anne

    2007-01-01

    Die vorliegende Diplomarbeit beschäftigt sich mit einem Kulturvergleich zwischen deutschen (n=103) und chinesischen Studierenden (n=98) bezüglich ihrer Einstellungen gegenüber psychologischer Beratung. Als Prädiktoren der Einstellungen wurden hierbei zum einen die kulturelle Dimension Individualismus-Kollektivismus nach Hofstede (2005) und zum anderen das Fünf-Faktoren-Modell der Persönlichkeit (FFM) herangezogen. Der Einfluss der Persönlichkeit auf die Einstellungen gegenüber psychologischer...

  15. Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication.

    Science.gov (United States)

    Bj Rås, Karine Ø; Sousa, Mirta M L; Sharma, Animesh; Fonseca, Davi M; S Gaard, Caroline K; Bj Rås, Magnar; Otterlei, Marit

    2017-08-21

    Base lesions in DNA can stall the replication machinery or induce mutations if bypassed. Consequently, lesions must be repaired before replication or in a post-replicative process to maintain genomic stability. Base excision repair (BER) is the main pathway for repair of base lesions and is known to be associated with DNA replication, but how BER is organized during replication is unclear. Here we coupled the iPOND (isolation of proteins on nascent DNA) technique with targeted mass-spectrometry analysis, which enabled us to detect all proteins required for BER on nascent DNA and to monitor their spatiotemporal orchestration at replication forks. We demonstrate that XRCC1 and other BER/single-strand break repair (SSBR) proteins are enriched in replisomes in unstressed cells, supporting a cellular capacity of post-replicative BER/SSBR. Importantly, we identify for the first time the DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA. Our findings suggest that a broad spectrum of DNA base lesions are recognized and repaired by BER in a post-replicative process. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Dong, Xiujuan; Yang, Long; Wang, Hui

    2017-04-01

    The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

  17. The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

    DEFF Research Database (Denmark)

    Wang, Yifan; Bernhardy, Andrea J; Cruz, Cristina

    2016-01-01

    Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and...

  18. 17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha.

    Science.gov (United States)

    Batnasan, Enkhzaya; Wang, Ruoxi; Wen, Jitao; Ke, Yueshuang; Li, Xiaoxue; Bohio, Ameer Ali; Zeng, Xianlu; Huo, Hongliang; Han, Liping; Boldogh, Istvan; Ba, Xueqing

    2015-01-05

    Oxidative stress-induced DNA damage results in over-activation of poly(ADP-ribose) polymerase 1 (PARP1), leading to parthanatos, a newly discovered cell elimination pathway. Inhibition of PARP1-dependent cell death has shown to improve the outcome of diseases, including stroke, heart ischemia, and neurodegenerative diseases. In the present study we aimed to detect whether estrogen plays a protective role in inhibiting parthanatos. We utilized human mammary adenocarcinoma cells (MCF7) that abundantly express the estrogen receptor alpha and beta (ERα and ERβ). Parthanatos was induced by challenging the cells with hydrogen peroxide (H2O2). Microscopic imaging and molecular biological techniques, such as Western blot analysis and RNA interference, were performed. The results showed 17β estradiol (E2) protected MCF7 cells from PARP1-dependent cell death by decreasing protein PARylation, and AIF translocation into nuclei/nucleoli. Down-regulation of ERα expression by siRNA before E2 addition resulted in the failure of the E2-mediated inhibition of H2O2-induced protein PARylation and AIF nucleolar translocation. Together these data suggest that estrogen via its alpha-type receptor inhibits oxidative stress-induced, PARP1-dependent cell death. The present study provided us insight into how to apply hormone therapy in intervention of parthanatos-implicated ischemic and degenerative diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

    NARCIS (Netherlands)

    Verhagen, Caroline V. M.; de Haan, Rosemarie; Hageman, Floor; Oostendorp, Tim P. D.; Carli, Annalisa L. E.; O'Connor, Mark J.; Jonkers, Jos; Verheij, Marcel; van den Brekel, Michiel W.; Vens, Conchita

    2015-01-01

    The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic background dependence

  20. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

    NARCIS (Netherlands)

    Verhagen, C.V.M.; Haan, R. den; Hageman, F.; Oostendorp, T.P.; Carli, A.L.; O'Connor, M.J.; Jonkers, J.; Verheij, M.; Brekel, M.W. van den; Vens, C.

    2015-01-01

    BACKGROUND AND PURPOSE: The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic

  1. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

    NARCIS (Netherlands)

    Verhagen, C.V.M.; de Haan, R.; Hageman, F.; Oostendorp, T.P.D.; Carli, A.L.E.; O'Connor, M.J.; Jonkers, J.; Verheij, M.; van den Brekel, M.W.; Vens, C.

    2015-01-01

    Background and purpose The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic

  2. Effects of 3-AB on PARP expression of Hela cells and apoptosis and cell cycle progression of Hela cells after X-rays irradiation

    International Nuclear Information System (INIS)

    Du Xiang; Zhao Hongguang; Guo Wei; Gong Shouliang; Wang Wen

    2007-01-01

    Objective: To study the changes of apoptosis and cell cycle progression of Hela cells after the poly (ADP- ribose) polymerase (PARP) was inhibited by its inhibitor 3-aminobenzamid (3-AB) and the mechanisms of PARP interaction with Hela cells damaged by irradiation. Methods: Hela cell line was used. Flow cytometry (FCM) was used to examine the PARP expression of control and 3 AB groups at 0, 2, 4, 8, 12 h alter administration with 5 mmol·L -1 3-AB. The percentage of apoptotic cells and cell cycle progression ol control, irradiation, 3-AB plus irradiation groups were measured with FCM at 2, 8, 12, 24 h after exposure to 2 Gy irradiation following administration with 5 mmol·L -1 3-AB. Results: The percentage of Hela cells with positive expression of PARP protein decreased after administration with 3-AB and there was significant difference between 3-AB plus irradiation group and control group (P 2 cells in the 3-AB plus irradiation group were lower than those in the irradiation group (P 2 arrest induced by irradiation. (authors)

  3. Características tecnológicas do processo de trabalho em berçários

    OpenAIRE

    Rocha, Semiramis Melani de Melo; Scochi, Carmen Gracinda Silvan; Souza, Heloisa Garda Borgi Lino de

    1999-01-01

    Este estudo analisa, através de uma descrição dos instrumentos de trabalho utilizados no berçário, na assistência ao recém-nascido, as relações que se estabelecem entre os profissionais de saúde e os bebês, mediadas por conhecimentos científicos. Busca, ainda, demonstrar as possibilidades de compreender os nexos entre tecnologia, relações humanas e um cuidado individualizado cujo significado seja a restauração de vitalidade. Trata-se de um estudo exploratório de caráter qualitativo. Os dados ...

  4. Das Thema “Altern” in Arno Geigers Roman «Alles über Sally»

    Directory of Open Access Journals (Sweden)

    Meike Dackweiler

    2013-11-01

    Full Text Available Alles über Sally (All about Sally is the fifth novel of the successful Austrian author Arno Geiger. While it was both praised and criticized for being a contemporary adaption of the adultery novel, little importance was attached to the theme of ageing, which pervades the whole novel. Moreover, adulterous female characters over fifty are rare in contemporary German literature. Given these premises, this essay examines the composition of the ageing characters in the novel and provides a discussion of the social construction of images of ageing.

  5. Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

    Science.gov (United States)

    Kuenzler, Michael B; Nuss, Katja; Karol, Agnieszka; Schär, Michael O; Hottiger, Michael; Raniga, Sumit; Kenkel, David; von Rechenberg, Brigitte; Zumstein, Matthias A

    2017-05-01

    Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  6. Average BER analysis of SCM-based free-space optical systems by considering the effect of IM3 with OSSB signals under turbulence channels.

    Science.gov (United States)

    Lim, Wansu; Cho, Tae-Sik; Yun, Changho; Kim, Kiseon

    2009-11-09

    In this paper, we derive the average bit error rate (BER) of subcarrier multiplexing (SCM)-based free space optics (FSO) systems using a dual-drive Mach-Zehnder modulator (DD-MZM) for optical single-sideband (OSSB) signals under atmospheric turbulence channels. In particular, we consider the third-order intermodulation (IM3), a significant performance degradation factor, in the case of high input signal power systems. The derived average BER, as a function of the input signal power and the scintillation index, is employed to determine the optimum number of SCM users upon the designing FSO systems. For instance, when the user number doubles, the input signal power decreases by almost 2 dBm under the log-normal and exponential turbulence channels at a given average BER.

  7. Repair of radiation-induced heat-labile sites is independent of DNA-PKcs, XRCC1 or PARP

    Energy Technology Data Exchange (ETDEWEB)

    Stenerl& #246; w, Bo; Karlsson, Karin H.; Radulescu, Irina; Rydberg, Bjorn; Stenerlow, Bo

    2008-04-29

    Ionizing radiation induces a variety of different DNA lesions: in addition to the most critical DNA damage, the DSB, numerous base alterations, SSBs and other modifications of the DNA double-helix are formed. When several non-DSB lesions are clustered within a short distance along DNA, or close to a DSB, they may interfere with the repair of DSBs and affect the measurement of DSB induction and repair. We have previously shown that a substantial fraction of DSBs measured by pulsed-field gel electrophoresis (PFGE) are in fact due to heat-labile sites (HLS) within clustered lesions, thus reflecting an artifact of preparation of genomic DNA at elevated temperature. To further characterize the influence of HLS on DSB induction and repair, four human cell lines (GM5758, GM7166, M059K, U-1810) with apparently normal DSB rejoining were tested for bi-phasic rejoining after gamma irradiation. When heat-released DSBs were excluded from the measurements the fraction of fast rejoining decreased to less than 50% of the total. However, neither the half-times of the fast (t{sub 1/2} = 7-8 min) or slow (t{sub 1/2} = 2.5 h) DSB rejoining were changed significantly. At t=0 the heat-released DSBs accounted for almost 40% of the DSBs, corresponding to 10 extra DSB/cell/Gy in the initial DSB yield. These heat-released DSBs were repaired within 60-90 min in all tested cells, including M059K cells treated with wortmannin or DNA-PKcs defect M059J cells. Furthermore, cells lacking XRCC1 or Poly(ADP-ribose) polymerase-1 (PARP-1) rejoined both total DSBs and heat-released DSBs similar to normal cells. In summary, the presence of heat-labile sites have a substantial impact on DSB induction yields and DSB rejoining rates measured by pulsed-field gel electrophoresis, and HLS repair is independent of DNA-PKcs, XRCC1 and PARP.

  8. Berlin Brandenburg International (BER: planning and implementation of a concrete supply chain for the airport construction site

    Directory of Open Access Journals (Sweden)

    Guido Riedel

    2012-12-01

    Full Text Available Background: With the decision to extend the airport Berlin-Schönefeld to the new airport Berlin Brandenburg International (BER in 2006, a construction of superlatives has emerged. One of the biggest challenges was the supply of around 2.5 million cubic meters of high quality concrete that had to be produced for the construction of the airport. Due to the scale of this enterprise as well as its environment, the logistic solution of raw material supply has to be found.       Method: The planning of the concrete supply chain for the airport construction site BER had to be carried out with two major goals: the stability of the supply chain to assure that the demands of the construction site are met and delays are prevented, as well as assurance of the high quality standards of the concrete production and to avoid an alkali silica reaction and the resulting unavoidable disaggregation of the concrete. External effects, such as the carbon dioxide emission and the effect of the supply chain on adjoining residents were key factors that had to be integrated in a holistic supply chain concept.  The principle underlying method is an analysis of limiting conditions for two approaches: a centralized supply chain with on-site concrete factory and upstream transport of raw materials versus a decentralized supply chain with off-site factories and downstream transport of ready-mixed concrete. Results: The analysis of constraints and the effects on key requirements of the concrete supply chain for the BER airport construction site lead to the installation of the most modern concrete plant in Europe. The benefits of a centralized supply chain are significant. On one hand, the high quality standards can be met with the on-site mixture of the concrete and centralized quality assurance, on the other hand, the majority of the supply traffic for the construction site was moved from the road to train-bound logistics, meeting the emission requirements of the

  9. Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis.

    Science.gov (United States)

    Ghorai, Atanu; Sarma, Asitikantha; Bhattacharyya, Nitai P; Ghosh, Utpal

    2015-04-01

    High linear energy transfer (LET) carbon ion beam (CIB) is becoming very promising tool for various cancer treatments and is more efficient than conventional low LET gamma or X-rays to kill malignant or radio-resistant cells, although detailed mechanism of cell death is still unknown. Poly (ADP-ribose) polymerase-1 (PARP-1) is a key player in DNA repair and its inhibitors are well-known as radio-sensitizer for low LET radiation. The objective of our study was to find mechanism(s) of induction of apoptosis by CIB and role of PARP-1 in CIB-induced apoptosis. We observed overall higher apoptosis in PARP-1 knocked down HeLa cells (HsiI) compared with negative control H-vector cells after irradiation with CIB (0-4 Gy). CIB activated both intrinsic and extrinsic pathways of apoptosis via caspase-9 and caspase-8 activation respectively, followed by caspase-3 activation, apoptotic body, nucleosomal ladder formation and sub-G1 accumulation. Apoptosis inducing factor translocation into nucleus in H-vector but not in HsiI cells after CIB irradiation contributed caspase-independent apoptosis. Higher p53 expression was observed in HsiI cells compared with H-vector after exposure with CIB. Notably, we observed about 37 % fall of mitochondrial membrane potential, activation of caspase-9 and caspase-3 and mild activation of caspase-8 without any detectable apoptotic body formation in un-irradiated HsiI cells. We conclude that reduction of PARP-1 expression activates apoptotic signals via intrinsic and extrinsic pathways in un-irradiated cells. CIB irradiation further intensified both intrinsic and extrinsic pathways of apoptosis synergistically along with up-regulation of p53 in HsiI cells resulting overall higher apoptosis in HsiI than H-vector.

  10. Reducing BER of spectral-amplitude coding optical code-division multiple-access systems by single photodiode detection technique

    Science.gov (United States)

    Al-Khafaji, H. M. R.; Aljunid, S. A.; Amphawan, A.; Fadhil, H. A.; Safar, A. M.

    2013-03-01

    In this paper, we present a single photodiode detection (SPD) technique for spectral-amplitude coding optical code-division multiple-access (SAC-OCDMA) systems. The proposed technique eliminates both phase-induced intensity noise (PIIN) and multiple-access interference (MAI) in the optical domain. Analytical results show that for 35 simultaneous users transmitting at data rate of 622 Mbps, the bit-error rate (BER) = 1.4x10^-28 for SPD technique is much better compared to 9.3x10^-6 and 9.6x10^-3 for the modified-AND as well as the AND detection techniques, respectively. Moreover, we verified the improved performance afforded by the proposed technique using data transmission simulations.

  11. Simultaneous chemical modification and structural transformation of Stöber silica spheres for integration of nanocatalysts

    KAUST Repository

    Yao, Kexin

    2012-01-10

    A synthetic approach has been devised to convert conventional Stöber silica (SiO 2) spheres into a new type of porous structural platform for supporting multicomponent catalysts. With this approach, we have first prepared zinc-doped SiO 2 (Zn-SiO 2) hollow spheres, on which zinc oxide (ZnO) phase and ruthenium (Ru) nanoparticles have been deposited and assembled sequentially in solution phase. A series of complex Ru/ZnO/Zn-SiO 2 nanocatalysts has been thus been integrated onto the zinc-doped SiO 2 supports after additional thermal treatment and reduction. To test their workability under harsh reactive environments, we have further evaluated the above prepared catalysts using arene hydrogenation as model reactions. These integrated nanocatalysts have shown superior activity, high robustness, and easy recovery in the studied heterogeneous catalysis. © 2011 American Chemical Society.

  12. Expression profiles of vault components MVP, TEP1 and vPARP and their correlation to other multidrug resistance proteins in ovarian cancer.

    Science.gov (United States)

    Szaflarski, Witold; Sujka-Kordowska, Patrycja; Pula, Bartosz; Jaszczyńska-Nowinka, Karolina; Andrzejewska, Małgorzata; Zawierucha, Piotr; Dziegiel, Piotr; Nowicki, Michał; Ivanov, Pavel; Zabel, Maciej

    2013-08-01

    Vaults are cytoplasmic ribonucleoprotein particles composed of three proteins (MVP, TEP1, vPARP) and vault‑associated RNAs (vRNAs). Although the cellular functions of vaults remain unclear, vaults are strongly linked to the development of multidrug resistance (MDR), the major obstacle to the efficient treatment of cancers. Available published data suggest that vaults and their components are frequently upregulated in broad variety of multidrug-resistant cancer cell lines and tumors of different histological origin. Here, we provide detailed analysis of vault protein expression in post-surgery ovarian cancer samples from patients that were not exposed to chemotherapy. Our analysis suggests that vault proteins are expressed in the ovaries of healthy individuals but their expression in cancer patients is changed. Specifically, MVP, TEP1 and vPARP mRNA levels are significantly decreased in cancer samples with tendency of lower expression in higher-grade tumors. The pattern of vault protein mRNA expression is strongly correlated with the expression of other MDR-associated proteins such as MDR1, MRP1 and BCRP. Surprisingly, the protein levels of MVP, TEP1 and vPARP are actually increased in the higher‑grade tumors suggesting existence of post-transcriptional regulation of vault component production.

  13. Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

    Directory of Open Access Journals (Sweden)

    Shih-Hung Yang

    2014-01-01

    Full Text Available Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND, a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

  14. Hydrofluoric Acid-Based Derivatization Strategy To Profile PARP-1 ADP-Ribosylation by LC-MS/MS.

    Science.gov (United States)

    Gagné, Jean-Philippe; Langelier, Marie-France; Pascal, John M; Poirier, Guy G

    2018-06-11

    Despite significant advances in the development of mass spectrometry-based methods for the identification of protein ADP-ribosylation, current protocols suffer from several drawbacks that preclude their widespread applicability. Given the intrinsic heterogeneous nature of poly(ADP-ribose), a number of strategies have been developed to generate simple derivatives for effective interrogation of protein databases and site-specific localization of the modified residues. Currently, the generation of spectral signatures indicative of ADP-ribosylation rely on chemical or enzymatic conversion of the modification to a single mass increment. Still, limitations arise from the lability of the poly(ADP-ribose) remnant during tandem mass spectrometry, the varying susceptibilities of different ADP-ribose-protein bonds to chemical hydrolysis, or the context dependence of enzyme-catalyzed reactions. Here, we present a chemical-based derivatization method applicable to the confident identification of site-specific ADP-ribosylation by conventional mass spectrometry on any targeted amino acid residue. Using PARP-1 as a model protein, we report that treatment of ADP-ribosylated peptides with hydrofluoric acid generates a specific +132 Da mass signature that corresponds to the decomposition of mono- and poly(ADP-ribosylated) peptides into ribose adducts as a consequence of the cleavage of the phosphorus-oxygen bonds.

  15. Utopia ou distopia? A ansiedade e o vazio em Schimmernder Dunst über CobyCounty de Leif Randt

    Directory of Open Access Journals (Sweden)

    Valéria Sabrina Pereira

    2014-06-01

    Full Text Available Em Schimmernder Dunst über CobyCounty (2011, Leif Randt apresenta um condado que seria a mais perfeita representação de uma utopia consumista: localizado à beira-mar, CobyCounty é um lugar de festas abundantes, consumo e bem-estar. O livro, contudo, é narrado por um jovem atormentado pela possibilidade de uma catástrofe que se aproxima, desde que seu melhor amigo abandonou a cidade, ouvindo os conselhos da mãe que se afiliou a uma religião esotérica. Se a perfeição do funcionamento dessa sociedade se aproxima muito de uma utopia, o temor de uma catástrofe anunciada aproxima a obra de uma distopia. Deve-se notar, no entanto, que, ao contrário de utopias e distopias, a obra não apresenta uma força centralizadora de poder - mesmo que a menção ao consumismo e às propagandas seja frequente. Neste artigo, Schimmernder Dunst über CobyCounty será apresentado à luz dos estudos da utopia e distopia, enfatizando seus laços com o tempo atual, marcado pela dicotomia entre a sociedade de conforto produzida pelo alto desenvolvimento tecnológico e a necessidade de se evitar os excessos produzidos por essa mesma sociedade em nome de uma possível catástrofe ecológica, anunciada por cientistas e ativistas, mas da qual não se percebe o impacto diretamente.

  16. A CBPR Partnership Increases HIV Testing among Men Who Have Sex with Men (MSM): Outcome Findings from a Pilot Test of the "CyBER/Testing" Internet Intervention

    Science.gov (United States)

    Rhodes, Scott D.; Vissman, Aaron T.; Stowers, Jason; Miller, Cindy; McCoy, Thomas P.; Hergenrather, Kenneth C.; Wilkin, Aimee M.; Reece, Michael; Bachmann, Laura H.; Ore, Addison; Ross, Michael W.; Hendrix, Ellen; Eng, Eugenia

    2011-01-01

    The Internet has emerged as an important tool for the delivery of health promotion and disease prevention interventions. Our community-based participatory research (CBPR) partnership developed and piloted "CyBER/testing", a culturally congruent intervention designed to promote HIV testing among men who have sex with men (MSM) within existing…

  17. Expanded bed adsorption as a fast technique for the large-scale purification of the complete isoform pool of Ber e 1, the major allergen from Brazil nuts.

    NARCIS (Netherlands)

    Boxtel, van E.L.; Koningsveld, van G.A.; Koppelman, S.J.; Broek, van den L.A.M.; Voragen, A.G.J.; Gruppen, H.

    2006-01-01

    A new, fast, large-scale purification method for Ber e 1, the major allergen from Brazil nuts, using expanded bed adsorption (EBA) chromatography, is presented. Using EBA, crude extracts can be applied to a fluidized column, which allows the unhindered passage of particulate impurities, thereby

  18. Blockchain - Von Supply Chain Finance über Smart Payment bis Smart Contracting: BLOG-Beitrag auf https://www.de-hub.de

    OpenAIRE

    Henke, Michael

    2018-01-01

    Alle reden über die Blockchain. Das Thema wird engagiert bis overhyped diskutiert. Gleichzeitig jedoch werden der mächtige Einfluss und die künftigen Auswirkungen von Blockchains auf Supply Chain Management und Handel immer noch unterschätzt.

  19. Intermedialität als Grundsatzdiskussion. Zum Sammelband Sprechen über Bilder. Sprechen in Bildern: Studien zum Wechselverhältnis von Bild und Sprache

    Directory of Open Access Journals (Sweden)

    Angela Oster

    2016-01-01

    Full Text Available Der Sammelband Sprechen über Bilder. Sprechen in Bildern bietet mehr als nur einen weiteren Beitrag zur Intermedialität. Er erforscht anlässlich des interartialen Austauschs zwischen Bild unf Text die Modi der Wissenschaft und versucht, diesbezüglich neue Impulse zu geben. Methodisch wird dabei die Rezeptionsästhetik favorisiert.

  20. Keim, Karl-Dieter, Das Fenster zum Raum : Traktat über die Erforschung sozialräumlicher Transformation / [rezensiert von] Helmut Klüter

    OpenAIRE

    Klüter, Helmut

    2009-01-01

    Rezensiertes Werk: Keim, Karl-Dieter: Das Fenster zum Raum : Traktat über die Erforschung sozialräumlicher Transformation / Karl-Dieter Keim. - Opladen : Leske + Budrich, 2003. - 171 S. : graph. Darst. - (Lehrtexte : Sozialwissenschaften) ISBN 3-8100-4050-9

  1. Inter-symbol interference and beat noise in flexible data-rate coherent OCDMA and the BER improvement by using optical thresholding.

    Science.gov (United States)

    Wang, Xu; Wada, Naoya; Kitayama, Ken-Ichi

    2005-12-26

    Impairments of inter-symbol interference and beat noise in coherent time-spreading optical code-division-multiple-access are investigated theoretically and experimentally by sweeping the data-rate from 622 Mbps up to 10 Gbps with 511-chip superstructured fiber Bragg grating. The BER improvement by using optical thresholding technique has been verified in the experiment.

  2. Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB

    DEFF Research Database (Denmark)

    Fazli, Mustafa; Rybtke, Morten Levin; Steiner, Elisabeth

    2017-01-01

    Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm...... formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm......-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high...

  3. Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population

    International Nuclear Information System (INIS)

    Peña-Chilet, Maria; Ribas, Gloria; Blanquer-Maceiras, Maite; Ibarrola-Villava, Maider; Martinez-Cadenas, Conrado; Martin-Gonzalez, Manuel; Gomez-Fernandez, Cristina; Mayor, Matias; Aviles, Juan Antonio; Lluch, Ana

    2013-01-01

    Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10 -4 ). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10 -4 ). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that

  4. In vivo repair of DNA damage induced by X-rays in the early stages of mouse fertilization, and the influence of maternal PARP1 ablation

    Energy Technology Data Exchange (ETDEWEB)

    Pacchierotti, F., E-mail: francesca.pacchierotti@enea.it [Unit of Radiation Biology and Human Health, ENEA CR Casaccia, Via Anguillarese 301, 00123 Rome (Italy); Ranaldi, R. [Unit of Radiation Biology and Human Health, ENEA CR Casaccia, Via Anguillarese 301, 00123 Rome (Italy); Derijck, A.A.; Heijden, G.W. van der; Boer, P. de [Radboud University Nijmegen Medical Centre, Department of Obstetrics and Gynaecology, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

    2011-09-01

    Highlights: {yields} We measure {gamma}H2AX and chromosome aberrations in mouse zygotes irradiated in vivo. {yields} We compare effects between zygotes obtained from wild type or Parp1 knockout females. {yields} The rate of chromosome aberrations is as high as that previously induced in vitro. {yields} The rate of radiation-induced {gamma}H2AX foci is lower than that measured in other cells. {yields} Without Parp1 there are more {gamma}H2AX foci but chromosome aberration rate is unaffected. - Abstract: The early pronucleus stage of the mouse zygote has been characterised in vitro as radiosensitive, due to a high rate of induction of chromosome-type chromosome abnormalities (CA). We have investigated the repair of irradiation induced double strand DNA breaks in vivo by {gamma}H2AX foci and first cleavage metaphase analysis. Breaks were induced in sperm and in the early zygote stages comprising sperm chromatin remodelling and early pronucleus expansion. Moreover, the role of PARP1 in the formation and repair of spontaneous and radiation-induced double strand breaks in the zygote was evaluated by comparing observations in C57BL/6J and PARP1 genetically ablated females. The results confirmed in vivo that the rate of chromosome aberration induction by X-rays was approximately 3-fold higher in the zygote than in mouse lymphocytes. This finding was related to a diminished efficiency of double strand break signalling, as shown by a lower rate of {gamma}H2AX radiation-induced foci compared to that measured in most other somatic cell types. The spontaneous frequency of CA in PARP1 depleted zygotes was slightly but significantly higher than in wild type zygotes. Also, these zygotes showed some impairment of the radiation-induced DNA Damage Response when exposed closer to the start of S-phase, revealed by a higher number of {gamma}H2AX foci and a longer cell cycle delay. The rate of chromosome aberrations, however, was not elevated over that of wild type zygotes, possibly

  5. Revision of the stiletto fly genera Acupalpa Kröber and Pipinnipons Winterton (Diptera, Therevidae, Agapophytinae using cybertaxonomic methods, with a key to Australasian genera

    Directory of Open Access Journals (Sweden)

    Shaun Winterton

    2011-05-01

    Full Text Available Australian stiletto flies of the sister-genera Acupalpa Kröber, 1912 and Pipinnipons Winterton, 2001 (Diptera: Therevidae: Agapophytinae are revised. Twelve new species of Acupalpa are described, while Acupalpa imitans (White, 1915, comb. n. is transferred from Pipinnipons and Acupalpa albimanis (Kröber, 1914, comb. n. is transferred from Ectinorhynchus Macquart as a senior synonym of Acupalpa pollinosa Mann. The total number of species of Acupalpa is therefore increased to 19: A. albimanis (Kröber, comb. n., A. albitarsa Mann, A. boharti sp. n., A. divisa (Walker, A. dolichorhyncha sp. n., A. glossa sp. n., A. imitans (White, comb. n., A. irwini Winterton, A. melanophaeos sp. n., A. miaboolya sp. n., A. minuta sp. n., A. minutoides sp. n., A. notomelas sp. n., A. novayamarna sp. n., A. rostrata Kröber, A. semirufa Mann, A. westralica sp. n., A. yalgoo sp. n. and A. yanchep sp. n. Three new species of Pipinnipons are described, increasing the total number of species to five: P. chauncyvallis sp. n., P. fascipennis (Kröber, P. kampmeierae sp. n., P. kroeberi Winterton, and P. sphecoda sp. n. Pipinnipons and Acupalpa are rediagnosed in light of the new species presented herein and revised keys to species are included. A dichotomous key to genera of Australasian Therevidae is included. As an empirical example of cybertaxonomy, taxonomic descriptions were composed using a character matrix developed in Lucid Builder (in Structured Descriptive Data (SDD format to generate natural language descriptions supplemented by online specimen and image databases. Web resources are provided throughout the document including: a links to high resolution colour images of all species on Morphbank, b registration of authors, publications, taxon names and other nomenclatural acts in Zoobank, with assignment of Life Science Identifiers (LSIDs for each, c links to Genbank accession records for DNA sequences, and d assignment of LSIDs to specimen records with links

  6. Effect of calcium chloride spraying on BER in two varieties of watermelon (Citrullus lanatus (Thunb Matsum and Nakai

    Directory of Open Access Journals (Sweden)

    mohammad salahifarahi

    2017-10-01

    Full Text Available Introduction: Watermelon, originated from warm regions of Africa, is one of the most important vegetable crops used as human food, forage and for producing alcohol. The area under its cultivation in our province was 1031 ha as irrigated and 3829 ha as rainfed. The average fruit yields under above-mentioned conditions were 23784 and 14888kg ha-1, respectively. Watermelon fruits suffer from a nutritional disorder that is attributed to shortage of calcium in developing fruits. The adsorption and uptake process of calcium by plants is comprised of three main stages; the first stage is passing through root cortex into xylem, the second one is its transport within xylem, and the last one is its distribution into leaves and fruits. Plants obtain calcium preferably from soil solution. Calcium moves upward in apoplastic pathways (with transpiration flow, and reaches different organs of the plants through xylem. Blossom-end rot (BER is a nutritional disorder of watermelon, tomato and pepper that is caused by a shortage of calcium in enlarging fruits. Blossom-end rot of watermelon commonly occurs in our province when fruits are growing rapidly. BER is frequently seen in watermelon genotypes with long fruits, Charleston gray type in particular. Calcium requirement increases at rapidly developing stage of fruit. BER might happen as a result of increased demand of blossom-end rot of fruit (rapidly growing section of the fruits for calcium. It can occur even when there is abundant calcium in the soil, because demand exceeds supply. Since fruits do not transpire as much as leaves, less calcium is deposited when calcium containing water is transpired, resulting in a localized calcium deficiency in the fruit. Materials and methods: In order to investigate the effects of foliar application of calcium on BER of watermelon, an experiment was carried out at the agricultural research station of Gonbad, Gonbad-e Qabus, Iran, in 2008. The soil of the experiment site was

  7. Experiment und Wissensvermittlung. Alexander von Humboldts Darstellungsmethoden in seinen Versuchen über die gereizte Muskel- und Nervenfaser

    Directory of Open Access Journals (Sweden)

    Alexander Stöger

    2016-11-01

    Full Text Available Zusammenfassung Alexander von Humboldt hat sich in jungen Jahren mit galvanischen Experimenten beschäftigt und die Resultate in einem umfassenden, zweibändigen Werk publiziert. Dabei zeigte er nicht nur, dass er als Experimentator und Teil der wissenschaftlichen Gemeinschaft fähig war, sich mit einem so neuen und komplexen Phänomen zu beschäftigen. Es lässt sich auch erkennen, dass er bereits in dieser frühen Schrift versuchte, das umfangreiche Wissen dem Leser zugänglich zu machen. Der Artikel betrachtet Humboldts Galvanismusschrift Versuche über die gereizte Muskel- und Nervenfaser (1797–1798 und untersucht einige Elemente wie Anhänge und Schreibstil, die Humboldt nutzte, um die umfangreichen Informationen zu ordnen und dem Leser so neben den Big Data seiner Erkenntnisse auch passende Suchfunktionen zur Verfügung zu stellen, die eine gezielte Nutzung überhaupt ermöglichen.  Abstract In the early stages of his scientific career, Alexander von Humboldt took an interest in experiments in galvanism. He publicised the results in a two-volume work under the title Versuche über die gereizte Muskel- und Nervenfaser (Experiments on the Stimulated Muscle and Nerve Fibre in 1797 and 1798. In this treatise, he presented himself as competent experimenter and member of the scientific community, but also demonstrated that he was capable of researching new and complex phenomena. These volumes also provide insight into his early attempts to facilitate the readers’ access to the extensive information he had compiled. This article analyses some aspects of Humboldt’s efforts to arrange his vast numbers of observations and theories, for example by means of appendices and narrative style, which he used not only to present the resulting big data collected during his research, but also to make it possible for the reader to organise and utilise this data.   Resumen A temprana edad Alexander von Humboldt se dedicó a galvanismo. En 1797 y 1798

  8. Tutorium Quantenfeldtheorie was Sie schon immer über QFT wissen wollten, aber bisher nicht zu fragen wagten

    CERN Document Server

    Edelhäuser, Lisa

    2016-01-01

    Dieses Buch richtet sich an alle, die sich schon immer gefragt haben, wie die kanonische Quantisierung, die LSZ-Reduktionsformel, Pfadintegrale, Feynman-Graphen und die Renormierung miteinander zusammenhängen. Als locker geschriebene Begleitlektüre zu Vorlesungen über Quantenfeldtheorie oder zum Selbststudium geeignet, gibt sich das Buch gesprächig und liefert Rechentricks und Erklärungen, die für Einsteiger sehr hilfreich sind. Im ersten Teil werden anhand von Skalarfeldern grundlegende Konzepte von der klassischen Feldtheorie bis zur Renormierung eingeführt. Der zweite Teil verallgemeinert diese für Felder mit Spin und legt mit der Einführung des Eichprinzips die Grundlagen für den dritten Teil. Hier werden „Anwendungen auf die reale Welt“ behandelt: Die Quantenelektrodynamik und ihre Renormierung, sowie das Standardmodell der Teilchenphysik und der Higgs-Mechanismus. Durch ausführlich vorgerechnete und in den Text eingebundene Aufgaben eignet sich das Tutorium sowohl zum schnellen Nachschla...

  9. Effects of heat treatment on mechanical properties and microstructure of tungsten fi ber reinforced grey cast iron matrix composites

    Directory of Open Access Journals (Sweden)

    Peng jianHong

    2009-11-01

    Full Text Available In this study, grey cast iron matrix composites reinforced by different volume fractions of tungsten fibers (Vr = 0.95 %, 1.90 %, 2.85 %, 3.80 % were investigated in as-cast and under the heat treatment temperatures of 1,000℃ and 1,100℃. The microstructure and mechanical properties of the composites were analyzed and tested by means of SEM, micro-hardness tester and three-point bend testing. The results show that with increasing of the volume fraction of tungsten fibers, the composites reinforced by the tungsten fiber have higher fl exural strength and modulus than that of cast iron without reinforcement, and the fl exural strength increases with the increasing of heat treatment temperatures. Due to diffusion reaction between matrix and reinforcing phases, the process of heat treatment, the number of graphite fl akes in the matrix seemingly becomes lower; and some hard carbide particles are formed around the residual tungsten fi bers. Not only does the hardness of both matrix and reinforcement change tremendously, but also the region of reinforcement is also extended from the original 0.11 mm to 0.19 mm in radius.

  10. Improved BER based on intensity noise alleviation using developed detection technique for incoherent SAC-OCDMA systems

    Science.gov (United States)

    Al-Khafaji, Hamza M. R.; Aljunid, S. A.; Fadhil, Hilal A.

    2012-06-01

    The major drawback of incoherent spectral-amplitude coding optical code-division multiple-access (SAC-OCDMA) systems is their inherent intensity noise originating due to the incoherency of the broadband light sources. In this paper, we propose a developed detection technique named the modified-AND subtraction detection for incoherent SAC-OCDMA systems. This detection technique is based upon decreasing the received signal strength during the decoding process by dividing the spectrum of the utilized code sequence. The proposed technique is capable of mitigating the intensity noise effect, as well as suppressing the multiple-access interference impact. Based on modified quadratic congruence (MQC) code, the analytical results reveal that the modified-AND detection offer best bit-error rate (BER) performance and enables MQC code to support higher transmission rate up to 1.25 Gb/s compared to conventional AND detection. Furthermore, we ascertained that the proposed technique enhances the system performance using a simulation experiment.

  11. Reduced estradiol-induced vasodilation and poly-(ADP-ribose polymerase (PARP activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Gabriella Masszi

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT. After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE. Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose polymerase (PARP activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  12. Reduced estradiol-induced vasodilation and poly-(ADP-ribose) polymerase (PARP) activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Masszi, Gabriella; Horvath, Eszter Maria; Tarszabo, Robert; Benko, Rita; Novak, Agnes; Buday, Anna; Tokes, Anna-Maria; Nadasy, Gyorgy L; Hamar, Peter; Benyó, Zoltán; Varbiro, Szabolcs

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  13. [Expression of PARP/NF-κB and intervention effect of 5-AIQ/PDTC in SAP rats with adrenal damage].

    Science.gov (United States)

    Yang, Bo; Guo, Wen-Yi; Yu, Jia; Zhao, Kai-liang; Shi, Qiao; Zuo, Teng; Wang, Wei-xing

    2013-10-15

    To explore the expression of poly (ADP-ribose) polymerase/nuclear factor-κB (PARP/NF-κB) and intervention effect of 5-aminoisoquinolinone/pyrrolidine dithiocarbamate (5-AIQ/PDTC) in severe acute pancreatitis (SAP) rats with adrenal damage. The primarily cultured adrenocortical cells were quantitatively divided into control group (SO), pancreatitis group (SAP), PDTC drug control group (SO+PDTC), PDTC intervention group (SAP+PDTC), 5-AIQ drug control group (SO+ 5-AIQ) and 5-AIQ intervention group (SAP+5-AIQ). The SAP and 2 intervention groups were stimulated with the sera of SAP rats. Then corresponding drugs were added and culture continued for 12 hours. The corticosterone levels and PARP/NF-κB expression were observed for each group. Adrenal cells in vitro cultured were round or oval, had secretory granules and could be stained by 3β-hydroxysteroid dehydrogenase antibody. The adherence rate was 60% after 48-hour culturing. The corticosterone level of SAP group was significantly lower than that of SO group [ (216.4 ± 15.7) vs (294.8 ± 16.3) µg/L, P SAP group (P SAP and PDTC intervention groups were higher than SO group while 5-AIQ intervention group was significantly lower than SAP and PDTC intervention groups, but higher than SO and drug control groups. The expression of NF-κB in SAP group was higher than that in SO group. Two intervention groups were lower than SAP group, but higher than SO and drug control groups. The pathway of PARP/NF-κB participates in adrenal damage of SAP rats. To a certain extent, the uses of 5-AIQ and PDTC may alleviate adrenal damage.

  14. Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers.

    Science.gov (United States)

    de Bono, Johann; Ramanathan, Ramesh K; Mina, Lida; Chugh, Rashmi; Glaspy, John; Rafii, Saeed; Kaye, Stan; Sachdev, Jasgit; Heymach, John; Smith, David C; Henshaw, Joshua W; Herriott, Ashleigh; Patterson, Miranda; Curtin, Nicola J; Byers, Lauren Averett; Wainberg, Zev A

    2017-06-01

    Talazoparib inhibits PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2 -mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, MTD, pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%). Grade 3 to 4 adverse events included anemia (17/71 patients; 24%) and thrombocytopenia (13/71 patients; 18%). Sustained PARP inhibition was observed at doses ≥0.60 mg/day. At 1.0 mg/day, confirmed responses were observed in 7 of 14 (50%) and 5 of 12 (42%) patients with BRCA mutation-associated breast and ovarian cancers, respectively, and in patients with pancreatic and small cell lung cancer. Talazoparib demonstrated single-agent antitumor activity and was well tolerated in patients at the recommended dose of 1.0 mg/day. Significance: In this clinical trial, we show that talazoparib has single-agent antitumor activity and a tolerable safety profile. At its recommended phase II dose of 1.0 mg/day, confirmed responses were observed in patients with BRCA mutation-associated breast and ovarian cancers and in patients with pancreatic and small cell lung cancer. Cancer Discov; 7(6); 620-9. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

  15. Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

    Science.gov (United States)

    Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

    2017-07-18

    The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

  16. Machoideal och/eller meningslös underhållning? : Om fem mäns berättelser kring krigsfilmen Saving Private Ryan med fokus på maskulinitet och publiken som meningsskapare.

    OpenAIRE

    Olsson, Eva

    2005-01-01

    Uppsatsen undersöker fem mäns berättelser kring krigsfilmen Saving Private Ryan, med fokus på maskulinitet. Föreställningarna och bilderna kring maskulinitet som kan urskiljas i intervjupersonernas berättelser, knyts till R.W. Connells teoretiska ramverk kring hegemonisk maskulinitet och de hierarkiska relationerna mellan olika maskuliniteter. Vidare resoneras det kring hur berättelserna exemplifierar en syn på mediepublik som aktiva meningsskapare, då intervjupersonerna tar fasta på olika as...

  17. Intervention principles and levels in the event of a nuclear accident. Final report on the Nordic Nuclear Safety Research Project BER-3

    International Nuclear Information System (INIS)

    Walmod-Larsen, O.

    1994-04-01

    The aim of the Nordic BER-3 project has been to harmonize the Nordic intervention levels after a nuclear accident. The paper deals with the findings and recommendations to be presented to the Nordic authorities as background material for common decisions on the most likely protective actions. In the report sheltering, evaluation and relocation are treated in detail. Iodine prophylaxis and foodstuff restrictions are briefly commented on. The basis for this work is the internationally accepted basic principles for interventions

  18. Preparation of chitin–silica composites by in vitro silicification of two-dimensional Ianthella basta demosponge chitinous scaffolds under modified Stöber conditions

    Energy Technology Data Exchange (ETDEWEB)

    Wysokowski, Marcin [Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, M. Skłodowskiej-Curie 2, PL-60965 Poznan (Poland); Behm, Thomas [Institute of Experimental Physics, TU Bergakademie Freiberg, Liepziger 23, 09599 Freiberg (Germany); Born, René [Institute of Materials Science, Dresden University of Technology, Helmholtzstraße 10, 01069 Dresden (Germany); Bazhenov, Vasilii V. [Institute of Experimental Physics, TU Bergakademie Freiberg, Liepziger 23, 09599 Freiberg (Germany); Meißner, Heike; Richter, Gert [Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, 01307 Dresden (Germany); Szwarc-Rzepka, Karolina [Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, M. Skłodowskiej-Curie 2, PL-60965 Poznan (Poland); Makarova, Anna; Vyalikh, Denis [Institute of Solid State Physics, Dresden University of Technology, Helmholtzstraße 10, 01069 Dresden (Germany); Schupp, Peter [Institute for Chemistry and Biology of the Marine Environment, University of Oldenburg, Emsstr. 20, 26382 Wilhelmshaven (Germany); Jesionowski, Teofil, E-mail: teofil.jesionowski@put.poznan.pl [Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, M. Skłodowskiej-Curie 2, PL-60965 Poznan (Poland); Ehrlich, Hermann, E-mail: hermann.ehrlich@physik.tu-freiberg.de [Institute of Experimental Physics, TU Bergakademie Freiberg, Liepziger 23, 09599 Freiberg (Germany)

    2013-10-15

    Chitin is a biopolymer found in cell walls of various fungi and skeletal structures of numerous invertebrates. The occurrence of chitin within calcium- and silica-containing biominerals has inspired development of chitin-based hybrids and composites in vitro with specific physico-chemical and material properties. We show here for the first time that the two-dimensional α-chitin scaffolds isolated from the skeletons of marine demosponge Ianthella basta can be effectively silicified by the two-step method with the use of Stöber silica micro- and nanodispersions under Extreme Biomimetic conditions. The chitin–silica composites obtained at 120 °C were characterized by the presence of spherical SiO{sub 2} particles homogeneously distributed over the chitin fibers, which probably follows from the compatibility of Si–OH groups to the hydroxyl groups of chitin. The biocomposites obtained were characterized by various analytical techniques such as energy dispersive spectrometry, scanning electron microscopy, thermogravimetric/differential thermal analyses as well as X-ray photoelectron spectroscopy, Fourier transform infrared and Raman spectroscopy to determine possible interactions between silica and chitin molecule. The results presented proved that the character and course of the in vitro chitin silicification in Stöber dispersions depended considerably on the degree of hydrolysis of the SiO{sub 2} precursor. - Highlights: • 2D α-chitin scaffolds isolated from marine demosponge can be effectively silicified using Stöber silica. • The chitin–silica composites were obtained under Extreme Biomimetic conditions. • Character and course of the in vitro chitin silicification in Stöber dispersions is discussed.

  19. Ein Lehrbuch über Psychiatrie und Psychotherapie – Geschlechtsunterschiede unter der Lupe? A Textbook for Psychiatry and Psychotherapy—Gender Differences under the Microscope?

    Directory of Open Access Journals (Sweden)

    Isabella Heuser

    2007-07-01

    Full Text Available Anke Rohde und Andreas Marneros haben sich ein hohes Ziel gesetzt: ein übersichtliches Lehrbuch für Psychiatrie und Psychotherapie, das erstmals eine systematische Zusammenstellung des Wissens über geschlechtsspezifische Aspekte von Symptomatologie, Epidemiologie, Diagnostik, Pharmakotherapie und Psychotherapie psychischer Störungen enthält. Bemerkenswert ist dabei zweierlei: Erstens werden bei der Betrachtung geschlechtsspezifischer Unterschiede im Sinne der Genderforschung Frauen und Männer berücksichtigt, zweitens wird ein vollständiger Überblick sowohl über die häufigen und bekannten psychischen Störungen als auch die äußerst seltenen psychiatrischen Erkrankungen der gesamten Altersspanne gegeben. Wenngleich die Qualität der einzelnen Beiträge deutlich zwischen sehr differenzierter und leider auch für ein Handbuch eindeutig zu oberflächlicher Betrachtung variiert, liegt in dem Band ein weitgehend informatives Nachschlagewerk vor, das einen ersten Überblick über die geschlechtsspezifische Psychiatrie gibt.Anke Rohde and Andres Marneros have given themselves a lofty goal: To put together a systematic collection for the first time that contains the entire body of knowledge on the gender-specific aspects of symptomatology, epidemiology, diagnostics, pharmacotherapy, and psychotherapy of psychological disturbances. There are two notable aspects: First, in accordance with contemporary gender analysis, the examination of the gender-specific differences takes both women and men into account; second, the book provides a complete overview of the common and well-known psychological disturbances as well as the extremely rare psychiatric illnesses along the entire age spectrum. Although the quality of the individual articles clearly ranges from the very sophisticated to a superficial treatment inappropriate for a textbook, the volume itself is, for the most part, an informative work of reference that offers an initial overview of

  20. Possible ways and aspects of conversions for the German low power research reactors BER II, FRM, and FMRB

    International Nuclear Information System (INIS)

    Roegler, H.-J.

    1983-01-01

    Based on the overall agreement about methods and principal results on core conversions from HEU to MEU within the work done for the IAEA Guidebook, investigations were started of the three specific cases, that means the conversions of the German Research Reactors within the German AF-Program. The first step of this work was done for the three low power MTR-reactors: the Ber II in Berlin operating at KW, FMRB in Brunswick operating at 1 MW, and FRM near Munich operating at 4 W. The simplest core from the point of view of conversion calculations was the BER II reactor. The core is made up out of 33 fuel elements and 5 control elements, it is built up on a 8 x 8 grid plate. On three sides the core is surrounded by reflector elements partially made of graphite and partially of beryllium. The main purpose of the core is to provide high neutron fluxes for the 12 beam tubes on all reflector sides. A little bit more complicated - from the conversion point of view - was the status of the Munich FRM. This is on one hand due to the two different cores they operate: a so-called normal core and a smaller beryllium core and on the other other hand due to the different uranium-loadings of fuel elements partially 230 g 235-U per element and partially 180 g 235-U per element with control elements of both plate loadings as well. The third reactor investigated was the Brunswick FMRB, which has specific design features that cause specific problems. The core is split into two parts, the so-called north core and the south core interacting via a heavy water reflector in between. Calculations with LEU-fuel - in these three cases no MEU-fuel was used - were done looking at different criteria for the conversion. The first group we call cycle length criteria and they are split into two versions, the same cycle length for LEU-fuel as for the existing HEU-fuel measured in MWd with the same excess reactivity at EOL as it exists at present; the same criterion as the previous except the cycle

  1. The neuroprotective effect of nicotine in Parkinson’s disease models is associated with inhibiting PARP-1 and caspase-3 cleavage

    Directory of Open Access Journals (Sweden)

    Justin Y.D. Lu

    2017-10-01

    Full Text Available Clinical evidence points to neuroprotective effects of smoking in Parkinson’s disease (PD, but the molecular mechanisms remain unclear. We investigated the pharmacological pathways involved in these neuroprotective effects, which could provide novel ideas for developing targeted neuroprotective treatments for PD. We used the ETC complex I inhibitor methylpyridinium ion (MPP+ to induce cell death in SH-SY5Y cells as a cellular model for PD and found that nicotine inhibits cell death. Using choline as a nicotinic acetylcholine receptor (nAChR agonist, we found that nAChR stimulation was sufficient to protect SH-SY5Y cells against cell death from MPP+. Blocking α7 nAChR with methyllycaconitine (MLA prevented the protective effects of nicotine, demonstrating that these receptors are necessary for the neuroprotective effects of nicotine. The neuroprotective effect of nicotine involves other pathways relevant to PD. Cleaved Poly (ADP-ribose polymerase-1 (PARP-1 and cleaved caspase-3 were decreased by nicotine in 6-hydroxydopamine (6-OHDA lesioned mice and in MPP+-treated SH-SY5Y cells. In conclusion, our data indicate that nicotine likely exerts neuroprotective effects in PD through the α7 nAChR and downstream pathways including PARP-1 and caspase-3. This knowledge could be pursued in future research to develop neuroprotective treatments for PD.

  2. BER-3.2 report: Methodology for justification and optimization of protective measures including a case study

    International Nuclear Information System (INIS)

    Hedemann Jensen, P.; Sinkko, K.; Walmod-Larsen, O.; Gjoerup, H.L.; Salo, A.

    1992-07-01

    This report is a part of the Nordic BER-3 project's work to propose and harmonize Nordic intervention levels for countermeasures in case of nuclear accidents. This report focuses on the methodology for justification and optimization of protective measures in case of a reactor accident situation with a large release of fission products to the environment. The down-wind situation is very complicated. The dose to the exposed society is almost unpredictable. The task of the radiation protection experts: To give advice to the decision makers on averted doses by the different actions at hand in the situation - is complicated. That of the decision makers is certainly more: On half of the society they represent, they must decide if they wish to follow the advices from their radiation protection experts or if they wish to add further arguments - economical or political (or personal) - into their considerations before their decisions are taken. Two analysis methods available for handling such situations: cost-benefit analysis and multi-attribute utility analysis are described in principle and are utilized in a case study: The impacts of a Chernobyl-like accident on the Swedish island of Gotland in the Baltic Sea are analyzed with regard to the acute consequences. The use of the intervention principles found in international guidance (IAEA 91, ICRP 91), which can be summarized as the principles of justification, optimization and avoidance of unacceptable doses, are described. How to handle more intangible factors of a psychological or political character is indicated. (au) (6 tabs., 3 ills., 17 refs.)

  3. Lethal and mutagenic properties of MMS-generated DNA lesions in Escherichia coli cells deficient in BER and AlkB-directed DNA repair.

    Science.gov (United States)

    Sikora, Anna; Mielecki, Damian; Chojnacka, Aleksandra; Nieminuszczy, Jadwiga; Wrzesinski, Michal; Grzesiuk, Elzbieta

    2010-03-01

    Methylmethane sulphonate (MMS), an S(N)2-type alkylating agent, generates DNA methylated bases exhibiting cytotoxic and mutagenic properties. Such damaged bases can be removed by a system of base excision repair (BER) and by oxidative DNA demethylation catalysed by AlkB protein. Here, we have shown that the lack of the BER system and functional AlkB dioxygenase results in (i) increased sensitivity to MMS, (ii) elevated level of spontaneous and MMS-induced mutations (measured by argE3 --> Arg(+) reversion) and (iii) induction of the SOS response shown by visualization of filamentous growth of bacteria. In the xth nth nfo strain additionally mutated in alkB gene, all these effects were extreme and led to 'error catastrophe', resulting from the presence of unrepaired apurinic/apyrimidinic (AP) sites and 1-methyladenine (1meA)/3-methylcytosine (3meC) lesions caused by deficiency in, respectively, BER and AlkB dioxygenase. The decreased level of MMS-induced Arg(+) revertants in the strains deficient in polymerase V (PolV) (bearing the deletion of the umuDC operon), and the increased frequency of these revertants in bacteria overproducing PolV (harbouring the pRW134 plasmid) indicate the involvement of PolV in the error-prone repair of 1meA/3meC and AP sites. Comparison of the sensitivity to MMS and the induction of Arg(+) revertants in the double nfo alkB and xth alkB, and the quadruple xth nth nfo alkB mutants showed that the more AP sites there are in DNA, the stronger the effect of the lack of AlkB protein. Since the sum of MMS-induced Arg(+) revertants in xth, nfo and nth xth nfo and alkB mutants is smaller than the frequency of these revertants in the BER(-) alkB(-) strain, we consider two possibilities: (i) the presence of AP sites in DNA results in relaxation of its structure that facilitates methylation and (ii) additional AP sites are formed in the BER(-) alkB(-) mutants.

  4. Stalin Coctail: Schostakowitsch Kammersinfonie Nr. 2 (aus Streichquartett Nr. 3 op. 73). Pärt, Arvo: Collage über das Thema B-A-C-H / Susanne Benda

    Index Scriptorium Estoniae

    Benda, Susanne

    1995-01-01

    Uuest heliplaadist "Stalin Coctail: Schostakowitsch Kammersinfonie Nr. 2 (aus Streichquartett Nr. 3 op. 73). Pärt, Arvo: Collage über das Thema B-A-C-H. Cantus in memoriam B. Britten. Denisov Variationen über Haydns Kanon Tod ist ein langer Schlaf. Schtschedrin Stalin Coctail. Moskauer Virtuosen, Vladimir Spivakov. RCA/BMG-Ariola CD 09026 68061 2 (WD: 67'33")

  5. Mytedræber

    DEFF Research Database (Denmark)

    Albris, Kristoffer

    2016-01-01

    ANALYSE Når katastrofen rammer, er det ikke panik og egoisme, der råder, men derimod næstekærlige værdier.......ANALYSE Når katastrofen rammer, er det ikke panik og egoisme, der råder, men derimod næstekærlige værdier....

  6. Effects of PARP-1 inhibitors AG-014699 and AZD2281 on proliferation and apoptosis of human hepatoma cell line HepG2

    Directory of Open Access Journals (Sweden)

    DU Senrong

    2015-06-01

    Full Text Available ObjectiveTo observe the inhibitory and pro-apoptotic effects of two poly(ADP-ribose polymerase (PARP-1 inhibitors, AG-014699 and AZD2281, on human hepatoma HepG2 cells and preliminarily explore the mechanism by which AG-014699 induces HepG2 cell apoptosis, and to provide a new therapeutic target for hepatoma. MethodsThe effects of different concentrations of AG-014699 and AZD2281 on HepG2 cell proliferation were determined by MTT assay. The cell apoptosis rate was measured by flow cytometry. The expression levels of caspase-3 and caspase-8 were measured by Western Blot. Inter-group comparison was made by t test. ResultsBoth AG-014699 and AZD2281 suppressed HepG2 cell proliferation in a time- and dose-dependent manner. However, the sensitivity of HepG2 cells to the two PARP-1 inhibitors was different. The half-maximal inhibitory concentrations of AG-014699 and AZD2281 at 48 h determined by MTT assay were about 20 μmol/L and 400 μmol/L, respectively. Flow cytometry and Western blot were not used to evaluate the apoptosis of HepG2 cells exposed to AZD2281 to which these cells were not sensitive. HepG2 cell apoptosis could be induced by 10, 30, and 50 μmol/L AG-014699, and the highest apoptosis rate at 48 h was significantly higher than that of the control group (3100%±2.13% vs 09%±0013%, P<0.01. Compared with those in the control group, the protein levels of caspase-3 and caspase-8 in HepG2 cells after 48-h exposure to 30, and 50 μmol/L AG-014699 increased. ConclusionThe two PARP-1 inhibitors AG-014699 and AZD2281 can inhibit the proliferation of HepG2 cells, which showed different sensitivities to the two inhibitors. AG-014699 can induce HepG2 cell apoptosis by up-regulating the protein expression of caspase-3 and caspase-8.

  7. Protective Effects of Chlorella-Derived Peptide Against UVC-Induced Cytotoxicity through Inhibition of Caspase-3 Activity and Reduction of the Expression of Phosphorylated FADD and Cleaved PARP-1 in Skin Fibroblasts

    Directory of Open Access Journals (Sweden)

    Jong Yuh Cherng

    2012-08-01

    Full Text Available UVC irradiation induces oxidative stress and leads to cell death through an apoptotic pathway. This apoptosis is caused by activation of caspase-3 and formation of poly(ADP-ribose polymerase-1 (PARP-1. In this study, the underlying mechanisms of Chlorella derived peptide (CDP activity against UVC-induced cytotoxicity were investigated. Human skin fibroblasts were treated with CDP, vitamin C, or vitamin E after UVC irradiation for a total energy of 15 J/cm2. After the UVC exposure, cell proliferation and caspase-3 activity were measured at 12, 24, 48, and 72 h later. Expression of phosphorylated FADD and cleaved PARP-1 were measured 16 h later. DNA damage (expressed as pyrimidine (6-4 pyrimidone photoproducts DNA concentration and fragmentation assay were performed 24 h after the UVC exposure. Results showed that UVC irradiation induced cytotoxicity in all groups except those treated with CDP. The caspase-3 activity in CDP-treated cells was inhibited from 12 h onward. Expression of phosphorylated FADD and cleaved PARP-1 were also reduced in CDP-treated cells. Moreover, UVC-induced DNA damage and fragmentation were also prevented by the CDP treatment. This study shows that treatment of CDP provides protective effects against UVC-induced cytotoxicity through the inhibition of caspase-3 activity and the reduction of phosphorylated FADD and cleaved PARP-1 expression.

  8. Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1) Restrict Oral Availability and Brain Accumulation of the PARP Inhibitor Rucaparib (AG-014699)

    NARCIS (Netherlands)

    Durmus, Selvi; Sparidans, Rolf W; van Esch, Anita; Wagenaar, Els; Beijnen, Jos H; Schinkel, Alfred H

    BACKGROUND: Rucaparib is a potent, orally available, small-molecule inhibitor of poly ADP-ribose polymerase (PARP) 1 and 2. Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations

  9. Contexto dos berçários e um programa de intervenção no desenvolvimento de bebés

    Directory of Open Access Journals (Sweden)

    Carla Skilhan Almeida

    2013-12-01

    Full Text Available O objetivo deste estudo foi investigar o contexto de berçários que atendesse a famílias de baixa renda e verificar o impacto de uma intervenção cognitivo-motora no desenvolvimento de bebés quanto à motricidade ampla, motricidade fina, linguagem e interação. Participaram do estudo 40 bebés, entre seis e oito meses, provenientes de dez berçários para famílias de baixa renda. As escolas foram agrupadas quanto à qualidade dos cuidados oferecidos; os bebés foram estratificados por gênero e aleatoriamente distribuídos em grupos interventivo (n= 20 e controle (n= 20. Foi utilizada uma ficha de observação para verificar a rotina dos berçários. A motricidade ampla e fina, a linguagem e a interação dos bebés foram avaliadas no pré e no pós intervenção. O programa de intervenção propiciou experiências de perseguição visual, manipulação de brinquedos e controle postural. Observaram-se restrições no espaço físico e nas oportunidades para brincar e interagir. Educadores centravam sua atenção no cuidado com higiene e alimentação dos bebés. Bebés provenientes de escolas com contextos mais apropriadas ao desenvolvimento apresentaram desempenhos superiores; e, a intervenção repercutiu positivamente no desenvolvimento global dos participantes. Em conclusão, ações educativas e estratégias interventivas devem ser implementadas nas creches, priorizando o processo de desenvol­vimento infantil.

  10. Gamma-ray induced DNA breaks and repair studied by immuno-labelling of poly(ADP-ribose) polymerase (PARP) in chinese hamster ovary cells (CHO)

    International Nuclear Information System (INIS)

    Bidon, N.; Noel, G.; Averbeck, D.; Varlet, P.; Salamero, J.; DeMurcia, G.

    1998-01-01

    The poly(ADP-ribose)polymerase is a nuclear ubiquitous enzyme capable of binding to DNA breaks. Chinese hamster ovary cells were (CHO-K1) cultured on slides and γ-irradiated ( 137 Cs) at a high (12.8 Gy/min) or medium dose rate (5 Gy/min), and immuno-labelling against (ADP-ribose) polymers immediately or three hours after irradiation. Quantification and localisation of γ-ray induced breaks was performed by confocal microscopy. The results show a dose effect relationship, a dose-rate effect and the signal disappearance after 3 hours at 37 deg.C. The presence of PARP activity appears to reflect γ-rays induced DNA fragmentation. (authors)

  11. Arbeid som berører : en studie av miljøarbeideres møter med ungdom på ungdomshjem

    OpenAIRE

    Viervang, Irene

    2008-01-01

    Master i sosialt arbeid Det er miljøarbeideres fortellinger om relasjonen og møtet med ungdommer på institusjon som mitt blikk er rettet mot i denne studien. Det settes derfor søkelys på interaksjonen mellom miljøarbeideren og ungdommer, og spesielt hvordan denne berører miljøarbeideren. Dette er en kvalitativ undersøkelse hvor jeg intervjuer syv miljøarbeidere som arbeider på fire forskjellige ungdomshjem. Alle informantene hadde sosialfaglig utdanning og praksiserfaring fr...

  12. Social Bots und Fake News - Was EU- und UNESCO-Referenzrahmen zum Lernen im digitalen Zeitalter darüber (nicht sagen

    Directory of Open Access Journals (Sweden)

    Dietmar Janetzko

    2017-07-01

    Full Text Available In den letzten Jahren haben internationale Organisationen wie die EU und die UNESCO eine Reihe von Vorschlägen und Strategiepapieren zur Bildung und Ausbildung im Zusammenhang mit digitalen Medien entwickelt. Mit den dabei entstandenen Rahmenkonzepten der EU (Digital Competence, DigComp sowie der UNESCO (Media and Information Literacy, MIL werden im Kern zwei zusammenhängende Ziele verfolgt: (i digitale Bildung bzw. digitale Kompetenzen, Fähigkeiten und zugehörige Einstellungen umfassend zu kartographieren sowie (ii über die dabei konzipierten edukativ-politischen Rahmenkonzepte Projektförderungen, Bildungs- bzw. Ausbildungsinitiativen sowie Gesetzesvorlagen anzustossen. Tatsächlich sind DigComp und MIL bereits dabei, auf internationaler Ebene einen prägenden Einfluss zu nahezu allen Fragen der Bildung und Ausbildung im Bereich digitaler Medien auszuüben. Beide Initiativen haben innerhalb der genannten Organisationen Leuchtturmcharakter, werden bislang aber von der allgemeinen Öffentlichkeit und der medienpädagogischen Fachöffentlichkeit kaum wahrgenommen. Dessen ungeachtet verbindet sich mit DigComp und MIL jeweils ein impliziter Anspruch auf einen – im Bedarfsfall zu aktualisierenden – Gesamtentwurf zur Analyse und Gestaltung medienpädagogischer Bildung und Ausbildung. Dies gilt für Gesetzesvorlagen, Regulierungen, Forschungsaktivitäten. Sind diese Rahmenkonzepte anschlussfähig an medienpädagogische Debatten über disruptive Versuche, in via soziale Medien geführte öffentliche Debatten einzugreifen, die sich über social bots, fake news oder andere Formen der Einflussnahme manifestieren? Erschliessen sie dazu Reflexionsräume und Handlungsoptionen? Geleitet von diesen Fragen betrachtet der vorliegende Aufsatz, die Rahmenkonzepte der EU und UNESCO, DigComp and MIL. Dabei zeigt sich, dass beide Rahmenkonzepte von Schieflagen gekennzeichnet sind. DigComp und MIL überbetonen die instrumentelle, auf Verwertung am

  13. A CBPR partnership increases HIV testing among men who have sex with men (MSM): outcome findings from a pilot test of the CyBER/testing internet intervention.

    Science.gov (United States)

    Rhodes, Scott D; Vissman, Aaron T; Stowers, Jason; Miller, Cindy; McCoy, Thomas P; Hergenrather, Kenneth C; Wilkin, Aimee M; Reece, Michael; Bachmann, Laura H; Ore, Addison; Ross, Michael W; Hendrix, Ellen; Eng, Eugenia

    2011-06-01

    The Internet has emerged as an important tool for the delivery of health promotion and disease prevention interventions. Our community-based participatory research (CBPR) partnership developed and piloted CyBER/testing, a culturally congruent intervention designed to promote HIV testing among men who have sex with men (MSM) within existing Internet chat rooms. Using a quasi-experimental, single-group study design, cross-sectional data were collected from chat room participants, known as "chatters," at pretest (n = 346) and posttest (n = 315). Extant profile data also were collected to describe the demographics of the online population. The intervention significantly increased self-reported HIV testing among chatters overall, increasing rates from 44.5% at pretest to nearly 60% at posttest (p testing at posttest. Findings suggest that chat room-based HIV testing intervention may increase testing among MSM who may be difficult to reach in traditional physical spaces.

  14. The wavelength frame multiplication chopper system for the ESS test beamline at the BER II reactor—A concept study of a fundamental ESS instrument principle

    International Nuclear Information System (INIS)

    Strobl, M.; Bulat, M.; Habicht, K.

    2013-01-01

    Contributing to the design update phase of the European Spallation Source ESS–scheduled to start operation in 2019–a test beamline is under construction at the BER II research reactor at Helmholtz Zentrum Berlin (HZB). This beamline offers experimental test capabilities of instrument concepts viable for the ESS. The experiments envisaged at this dedicated beamline comprise testing of components as well as of novel experimental approaches and methods taking advantage of the long pulse characteristic of the ESS source. Therefore the test beamline will be equipped with a sophisticated chopper system that provides the specific time structure of the ESS and enables variable wavelength resolutions via wavelength frame multiplication (WFM), a fundamental instrument concept beneficial for a number of instruments at ESS. We describe the unique chopper system developed for these purposes, which allows constant wavelength resolution for a wide wavelength band. Furthermore we discuss the implications for the conceptual design for related instrumentation at the ESS

  15. Rezension von: Barbara Holland-Cunz: Gefährdete Freiheit. Über Hannah Arendt und Simone de Beauvoir. Opladen u.a.: Verlag Barbara Budrich 2012.

    Directory of Open Access Journals (Sweden)

    Mirjam Dierkes

    2012-11-01

    Full Text Available Von Barbara Holland-Cunz, die sich mit Simone de Beauvoir und Hannah Arendt bereits einzeln beschäftigt hat, liegt nun ein Band vor, in dem sie sich diesen herausragenden Denkerinnen des 20. Jahrhunderts gemeinsam widmet. In einer beinahe synoptisch anmutenden Herangehensweise fokussiert sie dabei auf den Begriff der Freiheit, der bei beiden von eminenter Bedeutung für das jeweilige Theoriegebäude ist. Holland-Cunz zufolge verstehen beide, bei einigen Unterschieden, Freiheit so, dass sie sich vor allem durch eine in sich eingeschriebene Gefährdung auszeichnet: Diese resultiert aus einem heroisch-emphatischen Gestus, der in paradoxer Weise gepaart wird mit einem abgeklärten Realismus. Über weite Strecken liest sich der Weg zu dieser Deutung, v. a. auch wegen einer teilweise sympathisch unkonventionellen und originellen Herangehensweise, sehr anregend und überzeugend.

  16. "Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

    Science.gov (United States)

    Lowsky, Martin

    Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

  17. The NAA system at the reactor BER II clinical analysis of fluorine, calcium, phosphorus and aluminium in bone biopsies, comparison with photon activation analysis and ion sensitive electrode

    International Nuclear Information System (INIS)

    Gawlik, D.; Gatschke, W.; Behne, D.; Braetter, P.

    1981-01-01

    Over the past few years an irradiation and measuring system has been developed for the reactor BER II at the Hahn-Meitner-Institute. It was to be suited in particular to the neutron activation analysis of biological material via short lived radionuclides. The general characteristics of this equipment and some experimental details as the recycling facility and the device used for measuring the irradiation time, the waiting time and the neutron fluency are described. This equipment was used to determine physiological concentrations of the elements sodium, chlorine, aluminium, phosphorus, fluorine, calcium, copper and selenium in biological material. The results have been compared with those obtained by photon activation analysis or ion sensitive electrode. As an example of the application of the apparatus the authors report on the clinical analysis of Ca, F, P and Al in the control of the treatment of patients suffering from osteoporosis. (author)

  18. A Phase 1 trial of the PARP inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer

    Science.gov (United States)

    Liu, Joyce F.; Tolaney, Sara M.; Birrer, Michael; Fleming, Gini F.; Buss, Mary K.; Dahlberg, Suzanne E.; Lee, Hang; Whalen, Christin; Tyburski, Karin; Winer, Eric; Ivy, Percy; Matulonis, Ursula A.

    2014-01-01

    Background PARP-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of VEGFR-1/2/3, and olaparib, a PARP-inhibitor (NCT01116648). Methods Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by RECIST 1.1 or met GCIG CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. Results 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 DLTs (1 grade 4 neutropenia ≥4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30mg daily; olaparib 400mg BID). The RP2D was cediranib 30mg daily and olaparib 200mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus SD >24 weeks) of 61%. None of the 7 evaluable breast cancer patients achieved clinical response; 2 patients had stable disease for >24 weeks. Interpretation The combination of cediranib and olaparib has hematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. PMID:23810467

  19. Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Hui; Shi, Qiong; Song, Xiufang; Fu, Juanli; Hu, Lihua; Xu, Demei; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang, E-mail: songyangwenrong@hotmail.com

    2015-07-01

    Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observed phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.

  20. JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

    Directory of Open Access Journals (Sweden)

    Michael Van Meter

    2016-09-01

    Full Text Available The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6, promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is activated by oxidative stress to promote DNA double-strand break (DSB repair. We show that the stress-activated protein kinase, c-Jun N-terminal kinase (JNK, phosphorylates SIRT6 on serine 10 in response to oxidative stress. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose polymerase 1 (PARP1 to DNA break sites and for efficient repair of DSBs. Our results demonstrate a post-translational mechanism regulating SIRT6, and they provide the link between oxidative stress signaling and DNA repair pathways that may be critical for hormetic response and longevity assurance.

  1. The multikinase inhibitor Sorafenib displays significant antiproliferative effects and induces apoptosis via caspase 3, 7 and PARP in B- and T-lymphoblastic cells

    International Nuclear Information System (INIS)

    Schult, Catrin; Boldt, Sonja; Wolkenhauer, Olaf; Neri, Luca Maria; Freund, Mathias; Junghanss, Christian; Dahlhaus, Meike; Ruck, Sabine; Sawitzky, Mandy; Amoroso, Francesca; Lange, Sandra; Etro, Daniela; Glass, Aenne; Fuellen, Georg

    2010-01-01

    Targeted therapy approaches have been successfully introduced into the treatment of several cancers. The multikinase inhibitor Sorafenib has antitumor activity in solid tumors and its effects on acute lymphoblastic leukemia (ALL) cells are still unclear. ALL cell lines (SEM, RS4;11 and Jurkat) were treated with Sorafenib alone or in combination with cytarabine, doxorubicin or RAD001. Cell count, apoptosis and necrosis rates, cell cycle distribution, protein phosphorylation and metabolic activity were determined. Sorafenib inhibited the proliferation of ALL cells by cell cycle arrest accompanied by down-regulation of CyclinD3 and CDK4. Furthermore, Sorafenib initiated apoptosis by cleavage of caspases 3, 7 and PARP. Apoptosis and necrosis rates increased significantly with most pronounced effects after 96 h. Antiproliferative effects of Sorafenib were associated with a decreased phosphorylation of Akt (Ser473 and Thr308), FoxO3A (Thr32) and 4EBP-1 (Ser65 and Thr70) as early as 0.5 h after treatment. Synergistic effects were seen when Sorafenib was combined with other cytotoxic drugs or a mTOR inhibitor emphasizing the Sorafenib effect. Sorafenib displays significant antileukemic activity in vitro by inducing cell cycle arrest and apoptosis. Furthermore, it influences PI3K/Akt/mTOR signaling in ALL cells

  2. Dohmen, Dieter, Erbes, Annegret, Fuchs, Kathrin & Günzel, Juliane (2008). Was wissen wir über Nachhilfe? Sachstand und Auswertung der Forschungsliteratur zu Angebot, Nachfrage und Wirkungen. Bielefeld: Bertelsmann, 150 S. [Rezension

    OpenAIRE

    Mayr, Thomas

    2014-01-01

    Rezension von Dohmen, Dieter, Erbes, Annegret, Fuchs, Kathrin & Günzel, Juliane (2008). Was wissen wir über Nachhilfe? Sachstand und Auswertung der Forschungsliteratur zu Angebot, Nachfrage und Wirkungen. Bielefeld: Bertelsmann, 150 S. 29,90 EUR, ISBN 978-3763936656

  3. Die Wahrnehmung der Figur „Adolf Hitler“ in Daniel Levys „Mein Führer- die wirklich wahrste Wahrheit über Adolf Hitler“ durch internationales Filmpublikum.

    OpenAIRE

    Herzner, Dominik

    2017-01-01

    Filme beeinflussen die Wahrnehmungen von Figuren. Daniel Levys Film "Mein Führer" (die erste deutschsprachige Komödie über Adolf Hitler) führte zu einer positiven Wahrnehmung der Hauptfigur. In einer empirischen Untersuchung wurde gezeigt, dass sich dieser Effekt bei internationalem Filmpublikum, die einen anderen Zugang zur Thematik Nationalsozialismus haben, verstärkt.

  4. PARP16/ARTD15 is a novel endoplasmic-reticulum-associated mono-ADP-ribosyltransferase that interacts with, and modifies karyopherin-ß1.

    Directory of Open Access Journals (Sweden)

    Simone Di Paola

    Full Text Available BACKGROUND: Protein mono-ADP-ribosylation is a reversible post-translational modification that modulates the function of target proteins. The enzymes that catalyze this reaction in mammalian cells are either bacterial pathogenic toxins or endogenous cellular ADP-ribosyltransferases. The latter include members of three different families of proteins: the well characterized arginine-specific ecto-enzymes ARTCs, two sirtuins and, more recently, novel members of the poly(ADP-ribose polymerase (PARP/ARTD family that have been suggested to act as cellular mono-ADP-ribosyltransferases. Here, we report on the characterisation of human ARTD15, the only known ARTD family member with a putative C-terminal transmembrane domain. METHODOLOGY/PRINCIPAL FINDINGS: Immunofluorescence and electron microscopy were performed to characterise the sub-cellular localisation of ARTD15, which was found to be associated with membranes of the nuclear envelope and endoplasmic reticulum. The orientation of ARTD15 was determined using protease protection assay, and is shown to be a tail-anchored protein with a cytosolic catalytic domain. Importantly, by combining immunoprecipitation with mass spectrometry and using cell lysates from cells over-expressing FLAG-ARTD15, we have identified karyopherin-ß1, a component of the nuclear trafficking machinery, as a molecular partner of ARTD15. Finally, we demonstrate that ARTD15 is a mono-ADP-ribosyltransferase able to induce the ADP-ribosylation of karyopherin-ß1, thus defining the first substrate for this enzyme. CONCLUSIONS/SIGNIFICANCE: Our data reveal that ARTD15 is a novel ADP-ribosyltransferase enzyme with a new intracellular location. Finally, the identification of karyopherin-ß1 as a target of ARTD15-mediated ADP-ribosylation, hints at a novel regulatory mechanism of karyopherin-ß1 functions.

  5. The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.

    Science.gov (United States)

    Booth, Laurence; Roberts, Jane L; Samuel, Peter; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Poklepovic, Andrew; Dent, Paul

    2018-06-03

    The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ovarian cancer cells. Neratinib and niraparib caused the ATM-dependent activation of AMPK which in turn was required to cause mTOR inactivation, ULK-1 activation and ATG13 phosphorylation. The drug combination initially increased autophagosome levels followed later by autolysosome levels. Preventing autophagosome formation by expressing activated mTOR or knocking down of Beclin1, or knock down of the autolysosome protein cathepsin B, reduced drug combination lethality. The drug combination caused an endoplasmic reticulum stress response as judged by enhanced eIF2α phosphorylation that was responsible for reducing MCL-1 and BCL-XL levels and increasing ATG5 and Beclin1 expression. Knock down of BIM, but not of BAX or BAK, reduced cell killing. Expression of activated MEK1 prevented the drug combination increasing BIM expression and reduced cell killing. Downstream of the mitochondrion, drug lethality was partially reduced by knock down of AIF, but expression of dominant negative caspase 9 was not protective. Our data demonstrate that neratinib and niraparib interact to kill ovarian cancer cells through convergent DNA damage and endoplasmic reticulum stress signaling. Cell killing required the induction of autophagy and was cathepsin B and AIF -dependent, and effector caspase independent.

  6. A Sensitive and Robust Ultra HPLC Assay with Tandem Mass Spectrometric Detection for the Quantitation of the PARP Inhibitor Olaparib (AZD2281 in Human Plasma for Pharmacokinetic Application

    Directory of Open Access Journals (Sweden)

    Jeffrey Roth

    2014-06-01

    Full Text Available Olaparib (AZD2281 is an orally active PARP-1 inhibitor, primarily effective against cancers with BRCA1/2 mutations. It is currently in Phase III development and has previously been investigated in numerous clinical trials, both as a single agent and in combination with chemotherapy. Despite this widespread testing, there is only one published method that provides assay details and stability studies for olaparib alone. A more sensitive uHPLC-MS/MS method for the quantification of olaparib in human plasma was developed, increasing the range of quantification at both ends (0.5–50,000 ng/mL compared to previously published methods (10–5,000 ng/mL. The wider range encompasses CMAX levels produced by typical olaparib doses and permits better pharmacokinetic modeling of olaparib elimination. This assay also utilizes a shorter analytical runtime, allowing for more rapid quantification and reduced use of reagents. A liquid-liquid extraction was followed by chromatographic separation on a Waters UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm and mass spectrometric detection. The mass transitions m/z 435.4→281.1 and m/z 443.2→281.1 were used for olaparib and the internal standard [2H8]-olaparib, respectively. The assay proved to be accurate (<9% deviation and precise (CV < 11%. Stability studies showed that olaparib is stable at room temperature for 24 h. in whole blood, at 4 °C for 24 h post-extraction, at −80 °C in plasma for at least 19 months, and through three freeze-thaw cycles. This method proved to be robust for measuring olaparib levels in clinical samples from a Phase I trial.

  7. Männer und Frauen sind nicht gleich. Über Geschlechterstereotype in juristischen Verfahren Men and Women are not Equal. On Gender Stereotypes in Legal Proceedings

    Directory of Open Access Journals (Sweden)

    Claudia Fröhlich

    2004-07-01

    Full Text Available Weibliche und männliche Angeklagte wurden in den NS-Prozessen nach 1945 nicht gleich behandelt. In den Aufsätzen des von Ulrike Weckel und Edgar Wolfrum herausgegebenen Sammelbandes ‚Bestien‘ und ‚Befehlsempfänger‘. Frauen und Männer in NS-Prozessen nach 1945 werden der unmittelbar nach der Kapitulation Deutschlands von den Alliierten initiierte Nürnberger Prozess gegen die Hauptkriegsverbrecher, die Verfahren gegen SS-Aufseherinnen sowie die Hochverratsprozesse in der Weimarer Republik und im Nationalsozialismus analysiert. Daneben ist die Berichterstattung über den Nürnberger Prozess als einem „medialen Großereignis“ ebenso Gegenstand der Untersuchung wie die Fernsehberichterstattung über das in den 1970er Jahren geführte Majdanek-Verfahren gegen SS-Aufseher und -Aufseherinnen. Die Autorinnen fragen, ob und welche Geschlechterstereotype Rechtsprechung und Berichterstattung geprägt haben, welche Funktionen den dabei formulierten Männer- und Frauenbildern im Kontext der Konstituierung der beiden deutschen Gesellschaften nach 1945 zukamen und wie sie kulturgeschichtlich zu verorten sind. Nach der mittlerweile etablierten Täterinnenforschung rückt ein geschlechtergeschichtlicher Ansatz in das Blickfeld der Forschung zu NS-Prozessen und ihrer Wahrnehmung, der frauen- und männergeschichtliche Studien gleichermaßen anregen kann.Accused men and women were not treated equally in the Nazi trials after 1945. In the articles of the volume edited by Ulrike Weckel und Edgar Wolfrum ‘Bestien’ und ‘Befehlsempfänger’. Frauen und Männer in NS-Prozessen nach 1945, the Nuremberg Trials—initiated by the Allies against the main war criminals immediately after the capitulation of Germany, trials against SS concentration camp guards, and trials of high treason during the Weimar Republic and National Socialism are analyzed. A further subject of the study is the reporting of the Nuremberg Trials as a “major media event”, as

  8. Estudo da validade e confiabilidade intra e interobservador da versão modificada do teste de Schöber modificado em indivíduos com lombalgia Study of validity and intra and inter-observer reliability of modified-modified Schöber test in subjects with low-back pain

    Directory of Open Access Journals (Sweden)

    Christiane de Souza Guerino Macedo

    2009-09-01

    Full Text Available Em pacientes com lombalgia, mensura-se a amplitude de movimento (ADM da coluna lombar por meio da versão modificada do teste de Schöber modificado (MTSM, mas suas propriedades psicométricas não são comprovadas para uso clínico. Este estudo verificou a validade e confiabilidade intra e interobservador do MTSM em indivíduos com lombalgia, comparando as medidas da ADM com as obtidas por meio de radiografia, método considerado padrão-ouro. Participaram 20 voluntários com lombalgia, de ambos os sexos, funcionários de um Hospital Universitário. O MTSM foi aplicado duas vezes por dois avaliadores. As medidas obtidas pelo teste e por radiografia foram comparadas usando o coeficiente de correlação de Pearson, obtendo-se r=0,14, ou seja, correlação fraca. O coeficiente de correlação intraclasse (CCI dos MTSM intra-observador foi 0,96 (IC 95% 0,91;0,98 e interobservador 0,93 (IC 95% 0,84;0,97, indicando alta confiabilidade; o teste de Bland & Altman mostrou alta concordância intra e interobservador, com valores de -0,21 e -0,28, respectivamente. Embora tenha sido encontrada alta confiabilidade intra e interobservador na aplicação da versão modificada do teste de Schöber modificado, este apresentou baixa validade para medir a ADM da coluna lombar, quando comparado ao padrão-ouro.In patients with low-back pain the lumbar spine range of motion (ROM is often measured by the modified version of the modified Schöber test (MMST, but its psychometric properties have not been ascertained for clinical use. The purpose here was to verify intra and inter-observer validity and reliability of the MMST in subjects with low-back pain, and to compare obtained ROM measures to those obtained by radiography, taken as gold standard. The study involved 20 subjects with chronic low-back pain, of both sexes, employees at a university hospital. The MMST was applied twice by two examiners each. The Pearson correlation coefficient found when comparing

  9. [Jörg Zägel (in Zusammenarbeit mit Reiner Steinweg). Vergangenheitsdiskurse in der Ostseeregion. Bd. 1. Auseinandersetzungen in den nordischen Staaten über Krieg. Völkermord, Diktatur, Besatzung und Vertreibung; B. 2 : Die Sicht auf Krieg, Diktat

    Index Scriptorium Estoniae

    Hecker-Stampehl, Jan

    2011-01-01

    Arvustus : Jörg Zägel (in Zusammenarbeit mit Reiner Steinweg). Vergangenheitsdiskurse in der Ostseeregion. Bd. 1. Auseinandersetzungen in den nordischen Staaten über Krieg. Völkermord, Diktatur, Besatzung und Vertreibung. Berlin : LIT Verlag, 2007. (Kieler Schriften zur Friedenswissenschaft. 14); Bd. 2 : Die Sicht auf Krieg, Diktatur, Völkermord, Besatsung und Vertreibung in Russland, Polen und den baltischen Staaten. Berlin: Lit Verlag, 2007. (Kieler Schriften zur Friedenswissenschaft. 15)

  10. Alltagsvorstellungen über den Treibhauseffekt und die globale Erwärmung verändern - eine Voraussetzung für Bildung für nachhaltige Entwicklung

    OpenAIRE

    Reinfried, Sibylle; Rottermann, Benno; Aeschbacher, Urs; Huber, Erich

    2010-01-01

    Das korrekte Verstehen des Treibhauseffektes ist eine wichtige Voraussetzung, um politische Maßnahmen zur Reduktion des Treibhausgases CO2 zu unterstützen. Fehlerhafte Alltagsvorstellungen über den Treibhauseffekt und die globale Erwärmung sind jedoch weit verbreitet und schwer zu verändern. Um eine beständige Veränderung der Alltagsvorstellungen zu induzieren, wurde eine instruktionspsychologisch optimierte Lernumgebung zum Treibhauseffekt entwickelt. Ihre Wirksamkeit wurde in einer Interven...

  11. Veränderungen der Serumlipide bei Senioren im Verlauf des Alterns unter Berücksichtigung ausgewählter Einflussfaktoren : eine Untersuchung im Rahmen der Gießener Senioren Langzeitstudie

    OpenAIRE

    Richter, Margrit

    2014-01-01

    In der vorliegenden Arbeit wurde im Rahmen der Giessener Senioren Langzeitstudie (GISELA) untersucht, ob und in wie weit sich die Konzentrationen der Serumlipide (Gesamtcholesterol (TC), HDL-Cholesterol (HDL-C), LDL-Cholesterol (LDL-C), NonHDL-Cholesterol (NonHDL-C) und Triglyceride (TG)) im Verlauf fortgeschrittenen Alterns verändern. Dabei wurden folgende mögliche Einflussfaktoren berücksichtigt: BMI, WHR, PAI, Fettmasse, Kohlenhydrat¬zufuhr, Ballaststoffzufuhr, Zufuhr mehrfach ungesättigte...

  12. Distanzen überwinden: Über das Potenzial audio-visueller e-Tandems für den Deutschunterricht von Erwachsenen in Kolumbien

    Directory of Open Access Journals (Sweden)

    Yasmin El-Hariri

    2015-04-01

    Full Text Available Sprachenlernen im Tandem ist eine Methode, bei der zwei Lernende mit unterschiedlichen Sprachen von- und miteinander lernen. Die wachsende Verfügbarkeit elektronischer Medien ermöglicht solche Kooperationen heutzutage auch über große Distanzen (e-Tandem. Der vorliegende Beitrag präsentiert Ergebnisse einer im August/September 2014 durchgeführten Onlinebefragung unter Deutschlernenden in Kolumbien. Ziel dieser Befragung war es, Sprachlerneinstellungen von Lernenden, deren Beweggründe für die Wahl von DaF sowie Erwartungshaltungen hinsichtlich e-Tandems zu erheben. Die Ergebnisse zeigen prinzipiell ein hohes Potenzial dieser Lernform, geben jedoch auch Hinweise auf in der Planung und Durchführung besonders zu beachtende Aspekte, die für eine gelungene Umsetzung unabdingbar sind.   Tandem language learning is a method which involves two learners with different languages learning from and with each other. The growing availability of electronic media nowadays allows such co-operation across long distances (e-Tandem. The present contribution presents results of an online survey conducted in August/September 2014 among learners of German in Colombia. The aim of this survey was to determine the learners' attitudes towards language learning, their motivation to choose German as a foreign language, as well as their expectations regarding e-Tandem language learning. Results show a high potential of such a learning approach; however, they also indicate crucial aspects which have to be considered specifically during implementation in order to develop the full potential of the method.

  13. Massenmedien und Versöhnung: Die Berichterstattung über den deutsch-französischen Friedensprozeß nach dem 2. Weltkrieg

    Directory of Open Access Journals (Sweden)

    Susanne Jaeger

    2003-10-01

    Full Text Available Der vorliegende Beitrag beinhaltet die ersten Ergebnisse einer Langzeitstudie, bei der flächendeckend die deutsche Nachkriegsberichterstattung über Frankreich von 1946 bis 1970 inhaltsanalytisch ausgewertet wurde. Die Studie stützt sich dabei auf das Modell der Nachrichtenfaktoren von Johan Galtung, welche nach seiner Ansicht die Auswahl der Themen bestimmen, die zu einer Nachricht werden. Genau in diesen Selektionsroutinen liegt jedoch die implizite Gefahr, Konflikte zu vertiefen statt sie einzudämmen bzw. durch ein breites Verständnis der Hintergründe gewaltfrei bearbeitbar zu machen. Für die Zeit nach einem Krieg könnten sie Hindernisse auf dem Weg zur Annäherung und Aussöhnung ehemaliger Gegner darstellen. Wie jedoch sieht die Berichterstattung nach dem Krieg tatsächlich aus? Zeigen Massenmedien Bereitschaft zu einer veränderten Berichterstattung? Der Fall der französisch-deutschen Aussöhnung, welcher als Beispiel für einen gelungenen Aussöhnungsprozess gelten kann, belegt, dass Friedensprozesse von den Medien durchaus adäquat begleitet werden können: Z.B. ist der Anteil "positiver" Themen bzw. Berichterstattung konsistent höher als der "negativer", und der Anteil von Non-Elite-Themen steigt an und kündet von Interesse an französischer Lebensart und Kultur. Die Ergebnisse zeigen, dass Negativismus in den Medien kein Naturgesetz ist, sondern überwunden werden kann, wenn Frieden und Versöhnung auf der Tagesordnung stehen.

  14. Über diese Ausgabe

    Directory of Open Access Journals (Sweden)

    Editors / Herausgeber

    2015-06-01

    Full Text Available Erzählungen können absichtlich die Unwahrheit verbreiten. Ob der Autor bzw. die Autorin selbst der Lüge bezichtigt werden kann oder sollte, hängt allerdings nicht nur davon ab, wie man Lüge definiert, sondern auch davon, welchen Status man der Erzählung zuschreibt: Worin unterscheidet sich der Wahrheitsanspruch fiktionaler Äußerungen in literarischen Texten von dem faktualen Erzählens? Kann Fiktion lügen? Eva-Maria Konrad plädiert nach einer Auseinandersetzung mit Genettes Studie zu Paratexten dafür, vom Autor verantwortete Vorworte in literarischen Texten nicht generell als fiktionale Äußerungen zu betrachten – unter bestimmten Voraussetzungen, so Konrad, könnten daher auch Herausgeberfiktionen als Lügen bezeichnet werden. Jochen Mecke hingegen argumentiert, dass fiktionale Literatur nie lügen kann, da jede Zuschreibung von Aufrichtigkeit an literarische Texte auf jenem Pakt zwischen Leser(in und Autor(in basiert, den Samuel Taylor Coleridge als „willing suspension of disbelief“ bezeichnet hat. Entscheidend ist dabei, so Mecke, nicht die Fiktivität der erzählten Ereignisse, sondern die Fiktionalität der Aussageinstanz. Sabine Schlickers untersucht in ihrem Beitrag zum unzuverlässigen und verstörenden Erzählen im argentinischen Kino, wie Ambiguität entsteht – der zeitgenössische Film macht es dem Publikum häufig schwer, dem impliziten Autor eine eindeutige Intention, sei es Ironie, Spiel oder Lüge, zuzuschreiben. Im vierten Beitrag des Themenhefts widmet sich Tanja Serisier der Problematik der Glaubwürdigkeit in Vergewaltigungsnarrativen und diskutiert die Differenzen zwischen juristischen Wahrheitsbegriffen auf der einen und dem subjektiven Wahrheitsempfinden auf der anderen Seite. Mit Ansgar Nünning konnte diesmal für die Rubrik „My Narratology“ ein Interviewpartner gewonnen werden, dessen Arbeiten zur historischen, kontextorientierten und kulturwissenschaftlichen Narratologie einen maßgeblichen Beitrag zur Weiterentwicklung der postklassischen Erzählforschung leisten. Ein Gastbeitrag der Gdánsk Narratological Group von Marta Aleksandrowicz, Bartosz Lutostański, and Miłosz Wojtyna, ein Tagungsbericht zu dem internationalen Symposium „Relevance and Narrative (Research“ an der Bergischen Universität Wuppertal (30.09.-02.10.2014 sowie vier Rezensionen vervollständigen das Heft.Wir wünschen Ihnen, liebe Leserinnen und Leser, eine anregende Lektüre!

  15. RESONANCE--IOc-to-ber

    Indian Academy of Sciences (India)

    school. Even those who choose professional courses such as engineering or ... go into some detail in a given topic. ... education in India is so rigid that in virtually none of our Universities is it possible for a student in the so-called Arts stream to.

  16. RESONANCE--IOc-to-ber

    Indian Academy of Sciences (India)

    and music. Previous ... frequency, so the minimum power required to sustain oscillations may be rather ... For strictly axial direction, nl = n2 = O. We can write approximately, .... to decrease abruptly and then return to equilibrium with a time.

  17. Nur die ersten Drei zählen! Optimierung der Rankingverfahren über Popularitätsfaktoren bei der Elektronischen Bibliothek Bremen (E-LIB

    Directory of Open Access Journals (Sweden)

    Elmar Haake

    2015-07-01

    Full Text Available Seit Einführung der neuen Discovery-Kataloge stehen unseren Nutzerinnen und Nutzern zusätzlich Millionen von Dokumenten neben dem lokalen Buchbestand zur Verfügung. Diese Zielgruppe muss in die Lage versetzt werden, die für sie relevanten Titel einfach und sicher zu finden. Die Qualität von Empfehlungsfunktionen und besonders der Relevanz-Ranking-Methoden sind daher für den Erfolg eines Discovery-Systems besonders wichtig. Das Ranking bibliothekarischer Suchmaschinentechnik ignoriert bisher das Feedback durch Nutzerinnen und Nutzer. Die Staats- und Universitätsbibliothek Bremen (SuUB setzt mit dem in Bremen entwickelten Discovery-System „E-LIB“ seit Sommer 2011 zusätzlich auf eine Modifikation des Treffer-Rankings über Popularitätsfaktoren der Medien wie Klickstatistik, Auflagen- und Exemplarzahl. Die maßgeschneiderte Entwicklung eines eigenen Bibliothekskataloges, den die SuUB seit 2004 mit dem Discovery-System „E-LIB“ in Bremen betreibt, erlaubt die schnelle und flexible Anpassung von Retrievalfunktionen an die Bedürfnisse der Nutzerinnen und Nutzer vor Ort. Since the introduction of modern discovery catalogues, users have been able to access millions of electronic documents in addition to local print holdings. For a search to be successful, users must be able to find relevant titles easily and reliably. The quality of recommendation functionality and especially the relevance ranking methods are essential for the success of every discovery system. Up to now, ranking methods of library catalogues have largely ignored user feedback. However, since 2011, the State and University Library Bremen (SuUB has developed modified ranking methods for its own discovery system E-LIB. These make use of popularity factors such as click statistics and information about the number of editions as well as the number of copies available for a given title. For the SuUB Bremen, the customized development of the discovery catalogue

  18. Correlação entre os teores de líber e fibras em caules de crotalária e malva Correlation between bast and fiber content in sunn hemp and malva stalks

    Directory of Open Access Journals (Sweden)

    Anísio Azzini

    1986-01-01

    Full Text Available No presente estudo, estimou-se a correlação entre os teores de líber (casca e fibras em caules de crotalária (Crotalaria juncea L. e malva (Urena lobata L., com o objetivo de estabelecer um procedimento simples e rápido de análise de fibra. Os resultados obtidos mostraram que os teores de líber e fibra estão relacionados entre si, com alto nível de significância (p > 0,99 para as correlações entre essas duas características tecnológicas. Os coeficientes de correlação observados, de 0,84 e 0,79, respectivamente, para crotalária e malva, permitem a avaliação indireta do teor de fibra liberiana através do teor de líber, estabelecendo um procedimento simples e rápido de análise de fibra, a ser utilizado especificamente em programas de melhoramento genético.In this paper it was estimated the correlation between the bast and fiber contents in suns hemp (Crotalaria juncea L. and malva (Urena lobata L. stalks. The results showed that fiber contents are related with a high level of signification (p > 0.99 for the correlation between these two technological characteristics. The correlation coefficients observed were of 0.84 and 0.79, respectively to sunn hemp and malva. These high levels of correlation showed that the fiber content may be evaluated indirectly through the bast content, establishing a simple and rapid procedure for fiber determination of both species.

  19. Materiais potencializadores e os bebês-potência : possibilidades de experiências sensoriais e sensíveis no contexto de um berçário

    OpenAIRE

    Elisete Mallmann

    2015-01-01

    A presente Dissertação de Mestrado investiga os modos como um grupo de bebês de sete a vinte e seis meses de idade, de um berçário de uma escola Pública de Educação Infantil no interior do Rio Grande do Sul, se relaciona com diferentes materiais, denominados nesta pesquisa como Materiais Potencializadores. Tais materiais foram organizados à base de produtos naturais e/ou de alimentos, bem como daquilo que é descartado. Em virtude da diversidade de formatos, texturas, cores, cheiros e sabores,...

  20. The Perils of Power-Sharing: Africa and Beyond Die Gefahren der Machtteilung – in Afrika und darüber hinaus

    Directory of Open Access Journals (Sweden)

    Chandra Lekha Sriram

    2009-01-01

    üten, entgegenstehen. Warum ist dies möglicherweise der Fall? Langfristige Friedenssicherung sucht Konflikte durch einen starken und zukunftsfähigen Staat zu verhindern; ein solcher Staat wäre in der Lage, bewaffnete Konflikte dadurch zu verhüten, dass er auf Beschwerden reagiert und gewaltsame Auseinandersetzungen effizient eindämmt. Machtteilungsvereinbarungen können diese Bemühungen jedoch unterminieren, indem sie Personen und Gruppierungen Macht verschaffen, die sich einer Regierungsführung zum Wohl der gesamten Bevölkerung nicht verpflichtet fühlen oder nicht dazu in der Lage sind, denn in solchen Vereinbarungen werden gerade solchen Gruppierungen Machtpositionen zugesichert, die beträchtliche Gewalt zur Erreichung ihrer Ziele angewandt haben. Damit wird es nach Ansicht der Autorinnen weniger wahrscheinlich, dass demokratische Staaten entstehen – auch wenn sie Demokratie nicht als das einzige legitime Ziel von Friedensvereinbarungen ansehen. Sie gehen davon aus, dass Machtteilungsvereinbarungen nicht nur zu undemokratischen Staaten führen können, sondern zu Staaten, die sich den Sicherheitsbedürfnissen der Bevölkerung gegenüber verschließen, sodass sichere Lebensbedingungen und staatliche Legitimität ausgehöhlt werden.

  1. Glucose Elevates NITRATE TRANSPORTER2.1 Protein Levels and Nitrate Transport Activity Independently of Its HEXOKINASE1-Mediated Stimulation of NITRATE TRANSPORTER2.1 Expression1[W][OPEN

    Science.gov (United States)

    de Jong, Femke; Thodey, Kate; Lejay, Laurence V.; Bevan, Michael W.

    2014-01-01

    Mineral nutrient uptake and assimilation is closely coordinated with the production of photosynthate to supply nutrients for growth. In Arabidopsis (Arabidopsis thaliana), nitrate uptake from the soil is mediated by genes encoding high- and low-affinity transporters that are transcriptionally regulated by both nitrate and photosynthate availability. In this study, we have studied the interactions of nitrate and glucose (Glc) on gene expression, nitrate transport, and growth using glucose-insensitive2-1 (gin2-1), which is defective in sugar responses. We confirm and extend previous work by showing that HEXOKINASE1-mediated oxidative pentose phosphate pathway (OPPP) metabolism is required for Glc-mediated NITRATE TRANSPORTER2.1 (NRT2.1) expression. Treatment with pyruvate and shikimate, two products derived from intermediates of the OPPP that are destined for amino acid production, restores wild-type levels of NRT2.1 expression, suggesting that metabolites derived from OPPP metabolism can, together with Glc, directly stimulate high levels of NRT2.1 expression. Nitrate-mediated NRT2.1 expression is not influenced by gin2-1, showing that Glc does not influence NRT2.1 expression through nitrate-mediated mechanisms. We also show that Glc stimulates NRT2.1 protein levels and transport activity independently of its HEXOKINASE1-mediated stimulation of NRT2.1 expression, demonstrating another possible posttranscriptional mechanism influencing nitrate uptake. In gin2-1 plants, nitrate-responsive biomass growth was strongly reduced, showing that the supply of OPPP metabolites is essential for assimilating nitrate for growth. PMID:24272701

  2. Der Lucius-Burckhardt-Platz in Kassel. Eine Geschichte über den Kampf um Legitimität und Deutungshoheit bei der Neugestaltung des Campus der Universität Kassel.

    Directory of Open Access Journals (Sweden)

    Sieben Textfresser*innen von der Initiative „Lucius-Burckhardt-Platz bleibt!“

    2016-11-01

    Full Text Available Als Mitglieder der Initiative „Lucius-Burckhardt-Platz bleibt!“ erzählen wir euch hier von unserem Versuch, die Zerstörung und autoritäre Überplanung eines Quartiersplatzes zu verhindern. Es ist die Geschichte unseres Wiederstandes gegen eine Planung, die Teilhabe als Feigenblatt auf der Ebene von institutionellen Gremien und Ausschüssen proklamiert. Gegen eine Planung, die gewachsene soziale und räumliche Strukturen negiert und die Wünsche der Nutzer*innen mit Absicht überhört. Wir werden Hintergründe und Mechanismen dieser politischen Planungspraxis an der Universität Kassel aufzeigen und über unsere Erfolge, unsere Kompromisse und unser Scheitern berichten.

  3. UBER DEN BEITRITT DER PLURIMODALITÄT DES VERSTEHENS DER NICHTEUROPÄISCHEN TRADITION. DISCOURS ÜBER DISCOURS. (PROBLEMATISIERUNG INITIERT MIT DEM WERK "CARSTVO ZNAKOVA" VON ROLAND BARTHES, AUGUST CESAREC, ZAGREB 1989

    Directory of Open Access Journals (Sweden)

    Jadran Zalokar

    1990-01-01

    Full Text Available In diesem Text problematisiert der Verfasser manche grundsätzlicke Fragen des Verstehens nichteuropäischen Traditionen im Ganzen. Dabei analysiert er das Werk von Roland Barthes in Zusammenhang des Verstehens der Beziehung textuallen im Gegensatz zum geistlichen Tradition Japans, gleichzeitig auf die methodologisch wichtige Frage hinweisend. Alles enken und "Schreiben" darüber ist in nuce zweifelhaft. Das Denken des planetaren Polilogen als Multiloge verlangt einen strengen wissenschaftlichen Beitritt, aber auch einen metawissenschaftlichen und metaphilosphischen Einblick in das geistliche Wesen nichteuropäischen Tradition, weil es gleichmäßige Beachtung verschiedensten geistlichen Erfahrungen und Eingenartigkeiten des geistlichen Lebens aller Traditionen nötig ist und nurwissenschaftlicher und nurphilosophischer Beitritt ist nicht genügend.

  4. Über die Datenakzessivität in Printwörterbüchern. Einblicke in neuere Entwicklungen einer Theorie der Wörterbuchform Über die Datenakzessivität in Printwörterbüchern. Einblicke in neuere Entwicklungen einer Theorie der Wörterbuchform

    Directory of Open Access Journals (Sweden)

    Herbert Ernst Wiegand

    2011-10-01

    Full Text Available

    ZUSAMMENFASSUNG: In diesem Beitrag werden die Begriffe eingeführt, die man benötigt, um das Datenakzessivitätsprofil von Printwörterbüchern genau beschreiben zu können. Es wird zwischen externer und interner Datenakzessivität unterschieden; erstere ist obligatorisch, letztere ist fakultativ. Die externe Datenakzessivität wird durch äußere, die interne Datenakzessivität durch innere Zugriffsstrukturen innerhalb von akzessiven Wörterbucheinträgen hergestellt. Es werden unterschiedliche Typen von äußeren Zugriffsstrukturen als lineare Ordnungsstrukturen, wie z.B. alphabetische äußere Zugriffsstrukturen, numerische mediostrukturelle Zugriffsstrukturen, Regis-terzugriffsstrukturen u.a., beschrieben und ihr Funktionieren erklärt. Weiterhin werden äußere Zugriffsstrukturen von Zugriffspfaden abgegrenzt, die durch die Ausführung externer Zugriffs-handlungen der Benutzer etabliert werden. Der Beitrag gibt insgesamt fünf Einblicke, aber keine zusammenhängende Übersicht über die vielfachen Ausprägungen der Eigenschaften der Wörter-buchform, die die Datenakzessivität sicherstellen.

    Stichwörter: AKZESSIVER WÖRTERBUCHEINTRAG, ALPHABET, ALPHABETISCHE ÄU-ßERE ZUGRIFFSSTRUKTUR, ÄUßERER ZUGRIFFSPFAD, EXTERNE DATENAKZESSIVITÄT, EXTERNE ZUGRIFFSHANDLUNG, INNERE ZUGRIFFSSTRUKTUR, INTERNE DATENAKZES-SIVITÄT, MEDIOSTRUKTURELLES LEITELEMENT, MEDIOSTRUKTURELLE ZUGRIFFSSTRUK-TUR, MONOAKZESSIVES WÖRTERBUCH, REGISTER, REGISTERZUGRIFFSSTRUKTUR, POLY-AKZESSIVES WÖRTERBUCH, SCHNELLZUGRIFFSSTRUKTUR, ZUGRIFFSTEXTELEMENT

    *****

    ABSTRACT: On the Data Accessibility in Printed Dictionaries. Insights into Recent Developments of a Theory of the Form of Dictionaries. In this contribu-tion, concepts are introduced that are needed for a precise description of the data accessibility pro-file of printed dictionaries. A distinction is made between external and internal data accessibility, with the first being obligatory and the

  5. Prüfungen zur Beurteilung der Brandgefahr; Beispiele für Verfahren zur Beurteilung einer Brandgefahr und für die Auslegung von Ergebnissen; 3.1: Kennwerte der Verbrennung und Übersicht über Prüfverfahren zu ihrer Ermittlung; Identisch mit IEC 60695-3-1, Ausgabe 1982

    CERN Document Server

    Deutsches Institut für Normung. Berlin

    1986-01-01

    Prüfungen zur Beurteilung der Brandgefahr; Beispiele für Verfahren zur Beurteilung einer Brandgefahr und für die Auslegung von Ergebnissen; 3.1: Kennwerte der Verbrennung und Übersicht über Prüfverfahren zu ihrer Ermittlung; Identisch mit IEC 60695-3-1, Ausgabe 1982

  6. Verwendung von Kabeln und isolierten Leitungen für Fernmeldeanlagen und Informationsverarbeitungsanlagen; Besondere Richtlinie für selbsttragende Fernmelde-Luftkabel auf Starkstrom-Freileitungen über 1 kV nach DIN 57818/VDE 0818 [VDE-Richtlinie

    CERN Document Server

    Deutsches Institut für Normung. Berlin

    1983-01-01

    Verwendung von Kabeln und isolierten Leitungen für Fernmeldeanlagen und Informationsverarbeitungsanlagen; Besondere Richtlinie für selbsttragende Fernmelde-Luftkabel auf Starkstrom-Freileitungen über 1 kV nach DIN 57818/VDE 0818 [VDE-Richtlinie

  7. A inclusão da criança com necessidades especiais na visão de berçaristas The inclusion of special needs children in the vision of day care center professionals

    Directory of Open Access Journals (Sweden)

    Fabiana Cristina Frigieri de Vitta

    2010-04-01

    Full Text Available A inserção das crianças de zero a 18 meses em creches poderá estimular o seu desenvolvimento motor e perceptocognitivo, podendo essa fase ser considerada a primeira da educação inclusiva. Objetivou-se verificar as concepções das profissionais do berçário relativas à inserção da criança com necessidades especiais na rotina de atividades desenvolvidas. Foram entrevistadas sete berçaristas da Secretaria Municipal de Educação de Bauru. Os dados, organizados segundo categorias analíticas: conceitos relativos ao processo de inclusão, benefícios para a criança e diferenças entre as crianças nessa faixa etária, foram submetidos à análise qualitativa. Os resultados mostraram que a inclusão de crianças com necessidades especiais é vista com reservas, explicitando ideias preconcebidas sobre a deficiência. Eles se justificam pela falta de conhecimento do desenvolvimento infantil e dos fatores que o envolvem, bem como pelo fato de os profissionais vincularem suas atividades às experiências pessoais.The inclusion of children from birth to 18 months in day care centers, a phase that can be considered as the first one for inclusive education, may stimulate their motor development and perceptual-cognitive abilities. The goal of this study was to identify how people working in such centers conceive the inclusion of children with special needs in their routine activities. For such, seven women involved in a municipal day care center in the city of Bauru (SP, Brazil were interviewed. The data - organized according to three analytical categories: believes related to the inclusion process; benefits that it can bring for the child; and differences between children in this age group - were subjected to a qualitative analysis. The results indicated that the inclusion of children with special needs in day-care centers is viewed with reservations. This negative bias toward disability can be explained by the lack of knowledge related to

  8. Katrin Schütz: Geschlechterentwürfe im literarischen Werk von Lou Andreas-Salomé unter Berücksichtigung ihrer Geschlechtertheorie. Würzburg: Verlag Königshausen & Neumann 2008

    Directory of Open Access Journals (Sweden)

    Romana Weiershausen

    2009-03-01

    Full Text Available Katrin Schütz hat eine Studie zu Geschlechterkonzeptionen in Lou Andreas-Salomés Frühwerk vorgelegt, in der auch die bislang wenig berücksichtigten literarischen Texte der Autorin ausgewertet werden. Die Anlage zielt auf eine Überblicksdarstellung, hinter der die differenzierende Reflexion der einzelnen Thesen zurück steht: Schütz geht es um die Konturierung einer Typologie. Durch die erweiterte Textgrundlage wird dabei Neues erschlossen, woraus sich anregende Impulse für die Jahrhundertwende-Forschung ergeben.Katrin Schütz’s study of gender conceptions in Lou Andreas-Salomé’s early work considers those literary texts often ignored by scholarship. The study is constructed as an overview, in light of which a differentiated reflection on the individual theses falls short: Schütz intends to formulate a typology. The expanded textual basis allows for the creation of something new, which will in turn provide inspirational impulses for turn-of-the-century research.

  9. [Carl Schirren als Gelehrter im Spannungsfeld von Wissenschaft und politischer Publizistik. 13 Beiträge zum 22. Baltischen Seminar 2010 ; Carl Schirren. Vorlesungen über livländische Geschichte. Nachschrift von Johannes Lossius] / Karsten Brügge

    Index Scriptorium Estoniae

    Brüggemann, Karsten, 1965-

    2015-01-01

    Arvustus: Carl Schirren als Gelehrter im Spannungsfeld von Wissenschaft und politischer Publizistik. 13 Beiträge zum 22. Baltischen Seminar 2010 (Baltische Seminare, 20). Hrsg. von Michael Garleff. Verlag Carl-Schirren-Gesellschaft. Lüneburg 2013; Carl Schirren. Vorlesungen über livländische Geschichte. Nachschrift von Johannes Lossius (Baltische Seminare, 20-1). Hrsg. von Carl Schirren und Wilhelm Lenz. Verlag Carl-Schirren-Gesellschaft. Lüneburg 2013

  10. RESONANCE--I--Oc-to-ber

    Indian Academy of Sciences (India)

    BOOK I REVIEW. Analysis. S C Bagchi. Analysis by Elliott H Lieb and Michael Loss ... analysis there are a very large number of books at all ... reach, in the space ofless than three hundred pages ... where more general cases involve forbidding.

  11. Kriser der dræber

    DEFF Research Database (Denmark)

    Stahl, Rune Møller; Ditlevsen, Kia

    2014-01-01

    Vi er vant til at se på kriser som rent økonomiske fænomener. Men de sætter sig også igennem rent fysisk – vi bliver syge og dør af dem.......Vi er vant til at se på kriser som rent økonomiske fænomener. Men de sætter sig også igennem rent fysisk – vi bliver syge og dør af dem....

  12. R-ES-ONANCE--IOc-to-ber

    Indian Academy of Sciences (India)

    Email: gadgil@ isibang.ac.in. Information and Announcements. Story of the Oceans. Story of the Oceans is a book primarily intended for educating school children on different aspects of ocean studies. This is brought out by Geological Society of India at the instance of the Department of Ocean Development, Government of ...

  13. BER-Myriant Succinic Acid Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    Shmorhun, Mark [Myriant Lake Providence, Inc., Lake Providence, LA (United States)

    2015-12-31

    Myriant Corporation (Myriant) has successfully produced the bioproduct succinic acid by the fermentation of glucose at a commercial scale operation in Lake Providence, Louisiana. The MySAB facility (Myriant Succinic Acid Biorefinery) came on stream in May 2013 and has been producing product since then. The MySAB facility is a demonstration-scale plant, capable of utilizing sorghum grits and commercially available dextrose, to ferment glucose into succinic acid. A downstream processing train has demonstrated the ability to produce an industrial, a standard and a polymer grade product. It consists of cell separation, membrane filtration, continuous chromatography, polishing to remove ionic and color bodies impurities, and final evaporation and crystallization. A by-product of the process is ammonium sulfate which is sold as a liquid fertilizer product. Since 2007 when development work began in the Woburn, Massachusetts R&D laboratories, the succinic acid bio-process has evolved through: Process development (microbiology, fermentation, and downstream) – R&D development laboratories; Piloting efforts at Fermic S.A. de C.V., Mexico City, Mexico – upstream and downstream processes; Design, construction, commissioning, and commercial production operations at the MySAB facility Additionally, Myriant became a wholly-owned subsidiary of the PTT Global Chemical Plc., Thailand, in late 2015, their investment into and support of Myriant goes back to 2011. The support of PTT Global Chemical Plc. helped to improve the upstream and downstream processes, and produce significant metric ton quantities of high quality bio-based succinic acid. The product has gone into a number of commercial markets worldwide for customer applications, development and production. The experience base gained via operations at the MySAB facility since May 2013, along with continued R&D development efforts involving Microbiology, Fermentation, and Downstream processes, at both the Woburn, Massachusetts and PTT Global Chemical Plc. Thailand laboratories, positions the company well for future production at the plant and commercialization of new bio-based products. This will be especially important and valuable as the green chemistry business climate continues to take root and flourish.

  14. BER ANALYSIS OF MIMO-OFDM SYSTEM

    OpenAIRE

    Devarsh Patel*

    2016-01-01

    MIMO is a system where a number of antennas are used at the transmitter and receiver side. A MIMO system takes advantage of the spatial diversity that is obtained by spatially separated antennas in a dense multipath scattering environment. The combination of OFDM systems with MIMO technology has provided us with increase in link reliability and an improvement in spectral efficiency. For 4G communication MIMO-OFDM is one of the most competitive technologies. The combination of OFDM and MIMO se...

  15. Das Buch über Deutschland

    DEFF Research Database (Denmark)

    Fleischer, Holm

    Bogen giver et indblik i det tyske samfund i begyndelsen af det 21. århunderede. Der bliver gennemgået følgende emner: statsopbygning, sociale forhold, økonomi, uddannelsessystem, forskelle mellem Øst- og Vesttyskland, Immigration, kultur....

  16. BER and Availability Measured on FSO Link

    Czech Academy of Sciences Publication Activity Database

    Kvíčala, R.; Kvičera, V.; Grábner, M.; Fišer, Ondřej

    2007-01-01

    Roč. 16, č. 3 (2007), s. 7-12 ISSN 1210-2512 Grant - others:Ministry of research and technology(DE) 17050531 Institutional research plan: CEZ:AV0Z30420517 Keywords : free space optical links * quality of service * meteorological optical range * link unavailability * bit error rate Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  17. Semantisches Differential über Gott

    Directory of Open Access Journals (Sweden)

    Benesch, Thomas

    2017-11-01

    Full Text Available A qualitative research was performed to explore the semantic differential regarding the image of God from young persons. These pairs of contrast were qualified in the field of environment as well as physical and mental characteristics. 27 contrast pairs from a large number of different options had been selected, to reveal through a written survey with adolescents their relationship with God. The semantic differential was evaluated through a factor analysis.

  18. Luftstaub über den Meeren

    DEFF Research Database (Denmark)

    Kacunko, Slavko; Kacunko, Sabine; Gorbushina, Ana

    2013-01-01

    Staub umgibt uns überall und alles wird auch irgendwann zu Staub - ob wir wollen oder nicht. Staub nicht nur zu bekämpfen, sondern zu untersuchen, bildet den Ausgangspunkt zahlreicher Forschungen in den Natur-, Ingenieur- und Kulturwissenschaften. Der vorliegende Band verbindet solche Beiträge au...

  19. Riscos isolados e agregados de anemia em crianças frequentadoras de berçários de creches Isolated and combined risks for anemia in children attending the nurseries of daycare centers

    Directory of Open Access Journals (Sweden)

    Tulio Konstantyner

    2009-06-01

    Full Text Available OBJETIVO: Identificar e quantificar os fatores de risco isolados e agregados de anemia, proporcionando visão ampliada quanto à probabilidade da sua ocorrência. MÉTODOS: Estudo transversal com 482 crianças, entre 4 e 29 meses de idade, frequentadoras de berçários de creches públicas e filantrópicas do município de São Paulo (SP, que participaram de dois inquéritos (2004 e 2007. Foram realizadas entrevistas com as mães, coleta de sangue por punção digital e antropometria. Considerou-se anemia, hemoglobina inferior a 11 g/dL. Foi ajustado modelo de regressão logística não-condicional para fatores de risco de anemia, considerando-se estatisticamente significantes associações com p OBJECTIVE: To identify and quantify isolated and combined risk factors for anemia, providing a comprehensive view of the likelihood of its occurrence. METHODS: Cross-sectional study with 482 children aged 4 to 29 months attending the nurseries of philanthropic and public daycare centers in the city of São Paulo, Brazil, who participated in two surveys (2004 and 2007. Mothers were interviewed, blood was collected using digital puncture, and anthropometry was performed. Anemia was characterized by hemoglobin levels below 11 g/dL. Unconditional logistic regression was adjusted for anemia risk factors. A value of p < 0.05 indicated statistically significant associations. Post-test odds and likelihood ratios were calculated to define post-test probabilities. Epi-InfoTM 2000 and Stata 10.0 software packages were used for statistical analysis. RESULTS: Prevalence of anemia was 43.6% (95%CI 39.1-48.1. The final logistic model included five categorical variables: mother's age less than 28 years (OR = 1.50; p = 0.041, per capita income below half a minimum wage (OR = 1.56; p = 0.029, exclusive breastfeeding less than 2 months (OR = 1.71; p = 0.009, decrease in weight/age z score from birth to survey (OR = 1.47; p = 0.050, and age less than 17 months (OR = 2

  20. Polyzystisches Ovarsyndrom – ein aktueller Überblick über therapeutische Ansätze bei Kinderwunsch und metabolischen Komorbiditäten // PCOS – A Current Overview of Therapeutic Options for Infertility and Metabolic Co-Morbidities

    Directory of Open Access Journals (Sweden)

    Lunger F

    2017-01-01

    resistance.p bKurzfassung: /bDie Diagnose des polyzystischen Ovarsyndroms (PCOS wird anhand der Rotterdam-Kriterien von 2003 gestellt und beinhaltet Oligo- oder Anovulation, Hyperandrogenämie und/oder klinische Zeichen einer Androgenisierung sowie polyzystische Ovarien im Ultraschall. Die Diagnose ist allerdings nicht immer klar. Bei unklarem Ovulationsstatus kann eine Progesteron-Bestimmung in der Mittlutealphase herangezogen werden. Klinische Zeichen einer Hyperandrogenämie werden durch Ethnizität maßgeblich beeinflusst und sollten in der Diagnosestellung berücksichtigt werden. Eine Kombinationsbestimmung von AMH und LH kann herangezogen werden, um Frauen mit sonographischer PCO-Morphologie von Frauen mit PCOS zu unterscheiden. Bei bestehendem Kinderwunsch ist ein erster wichtiger therapeutischer Schritt eine Gewichtsreduktion und Lifestyle- Management. Medikamentöse Therapieansätze beinhalten Clomifen, niedrig dosierte Gonadotropine sowie Metformin. Clomifen stellt aufgrund der hohen Schwangerschaftsraten immer noch die Erstlinientherapie dar. Anstatt mehrfacher Zyklen mit Clomifen sollten Gonadotropine eingesetzt werden, insbesondere bei Clomifen-resistenten Frauen, da eine höhere Ovulation- und Schwangerschaftsrate nachgewiesen wurde. Metabolische Komorbiditäten bei PCOS kommen gehäuft vor und sollten dementsprechend großzügig diagnostiziert und behandelt werden, um Spätfolgen zu reduzieren und/ oder zu vermeiden. Konsensbeschlüsse internatio naler Fachgesellschaften empfehlen ein metabolisches Screening mittels Nüchternblutzucker-Bestimmung sowie oGTT bei allen Frauen mit PCOS oder zumindest bei PCOS-Patientinnen mit zusätzlicher Adipositas, Anovulation oder positiver Familienanamnese. Nüchtern- Insulin und HOMA-Index können eine IR dia gnostizieren. Gezielte Therapien für die metabolische Komorbiditäten beinhalten Diät und adäquate körperliche Betätigung sowie die Einstellung von Hypertonie und Stoffwechselstörungen mit cholesterinsenkenden

  1. Utilização da artêmia nacional como dieta para pós-larvas do Litopenaeus vannamei (Boone, 1931 na fase berçário = Brazilian artemia as feed for Litopenaeus vannamei post-larvae through the nursery phase

    Directory of Open Access Journals (Sweden)

    Adriano Prysthon da Silva

    2006-07-01

    Full Text Available Experimentos foram realizados em uma fazenda comercial de criação decamarões marinhos, objetivando avaliar a taxa de crescimento e sobrevivência das pós-larvas do Litopenaeus vannamei, quando cultivadas em tanques-berçário e submetidas a diferentes dietas. As pós-larvas utilizadas encontravam-se com 19 dias (PL19 e foram estocadas a 16 PL/L, em tanques-berçário de 60 m3. As pós-larvas foram submetidas ao Método de Alimentação Convencional (MAC e o Método de Alimentação com Artêmia (MAA. Verificou-se que ao se correlacionar o peso em função do comprimento e do tempo de cultivo,o MAA apresentou uma relação estatisticamente superior (pExperiments were carried out in a commercial marine shrimp farm toevaluate growth and survival rate of the Litopenaeus vannamei post-larvae during nursery phase using different diets. The nursery tanks (60 m3 will be provided with post-larvae of 19 days (PL19 with a density of 16 PL/liter. The post-larvae were submitted to a Commercial Feeding Method (MAC and an Artemia Feeding Method (MAA. Considering the correlations between weight and length, and between weight and culture duration, a better efficiency (p<0.05 of the MAA was verified. The survival rate of the post-larvae fed with MAA was 86.25%, while MAC yielded survivorship of 62.12%. Thus, artemia nauplii were proved to be more efficient, providing higher growth and survival rates of Litopenaeus vannamei post-larvae.

  2. Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer

    Science.gov (United States)

    2017-10-01

    Cancer Center Philadelphia, PA 19111 REPORT DATE: TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick...in Ovarian Cancer October 2017 The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed...ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER The Research Institute of Fox Chase Cancer Center 333 Cottman Avenue Philadelphia

  3. Influência de diferentes dietas no desenvolvimento do camarão Litopenaeus vannamei (Boone, 1931 em berçários intensivos - DOI: 10.4025/actascibiolsci.v31i1.454 Development of Pacific white shrimp, Litopenaeus vannamei (Boone, 1931 fed on differents diets in intensives nurseries - DOI: 10.4025/actascibiolsci.v31i1.454

    Directory of Open Access Journals (Sweden)

    Maria Letícia Arena

    2009-04-01

    Full Text Available Objetivou-se avaliar diferentes dietas no desenvolvimento de pós-larvas do L. vannamei em berçários intensivos. Utilizaram-se 264.000 PL10 com peso e comprimento inicial de 11,0 mg e 9,78 mm, respectivamente, distribuídas em 12 berçários de 1.000 L, cultivadas durante dez dias. Foram testados quatro tratamentos (controle – RC40-ART, RC42:48-ART, RC42:48:52 e ART, compostos por quatro dietas artificiais e uma natural, com três repetições, distribuídos em delineamento inteiramente casualizado. As pós-larvas foram alimentadas na proporção de 15% da biomassa total. As melhores taxas de sobrevivência foram verificadas nos tratamentos RC42:48:52, RC42:48-ART, ART e RC40-ART, com 91,3; 90,5; 81,8 e 70,9% (p > 0,05, respectivamente. O melhor desenvolvimento ocorreu nos camarões do tratamento RC42:48:52, confirmado pelo teste de Tukey (p The objective of this work was to evaluate differents diets in development of L. vannamei post-larvae in intensive nurseries. In this experiment were used 264,000 PL10 with initial weight and length of 11.0 mg and 9.78 mm, respectively, distributed in 12 nurseries of 1,000 L, cultured during 10 days. Four treatments were tested (control – CR40-ART, CR42:48¬-ART, CR42:48:52 and ART which were composed of 4 artificial and 1 natural diets, with 3 repetitions, distributed in an entirely casualized experimental delineation. Post-larvae were fed in the proportion of 15 % of total biomass. The best survival rates were verified in the treatments CR42:48:52, CR42:48-ART, ART and CR40-ART, with 91.3; 90.5; 81.8 e 70.9% (P>0.05, respectively. The best development occurred in the shrimp of CR42:48:52 treatments, confirmed by Tukey Test (P<0.05, to final length and weight, weight and length gain, food conversion and increments, in comparison to individuals of ART treatments. That refers to biomass gain and final biomass the CR42:48:52 treatment differed of CR40-ART e ART (P<0.05 treatments. We concluded that

  4. Utilização da artêmia nacional como dieta para pós-larvas do Litopenaeus vannamei (Boone, 1931 na fase berçário - DOI: 10.4025/actascianimsci.v28i3.52 Brazilian artemia as feed for Litopenaeus vannamei post-larvae through the nursery phase - DOI: 10.4025/actascianimsci.v28i3.52

    Directory of Open Access Journals (Sweden)

    Paulo de Paula Mendes

    2006-01-01

    Full Text Available Experimentos foram realizados em uma fazenda comercial de criação de camarões marinhos, objetivando avaliar a taxa de crescimento e sobrevivência das pós-larvas do Litopenaeus vannamei, quando cultivadas em tanques-berçário e submetidas a diferentes dietas. As pós-larvas utilizadas encontravam-se com 19 dias (PL19 e foram estocadas a 16 PL/L, em tanques-berçário de 60 m3. As pós-larvas foram submetidas ao Método de Alimentação Convencional (MAC e o Método de Alimentação com Artêmia (MAA. Verificou-se que ao se correlacionar o peso em função do comprimento e do tempo de cultivo, o MAA apresentou uma relação estatisticamente superior (pExperiments were carried out in a commercial marine shrimp farm to evaluate growth and survival rate of the Litopenaeus vannamei post-larvae during nursery phase using different diets. The nursery tanks (60 m3 will be provided with post-larvae of 19 days (PL19 with a density of 16 PL/liter. The post-larvae were submitted to a Commercial Feeding Method (MAC and an Artemia Feeding Method (MAA. Considering the correlations between weight and length, and between weight and culture duration, a better efficiency (p<0.05 of the MAA was verified. The survival rate of the post-larvae fed with MAA was 86.25%, while MAC yielded survivorship of 62.12%. Thus, artemia nauplii were proved to be more efficient, providing higher growth and survival rates of Litopenaeus vannamei post-larvae

  5. Eight joint BER II and BESSY II users meeting. Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-07-01

    The following topics were dealt with: Accelerator operation and projecs, photon science and instrumentation at BESSY II, status of energy materials in-situ Lab at BESSY II, high resolution spectrometer PEAXIS at BESSY II, sample environment at BESSY II, molecular control mechanisms in the Brr2 RNA helicase for efficient and regulated splicing, the Li conversion reaction of 4CoFe{sub 2}O{sub 4} nanoparticles, buried interfaces in lithium ion batteries probed with HAXPES, ARPES studies of the STO(001) 2DEG, all-in/all-out magnetic order in rare earth iridates, oxygen reduction reaction on graphene in Li-air batteries, electronic order in high-T{sub c} superconductors, in-siu observation of novel switching phenomena in highly porous metal-organic frameworks, photoinduced demagnetization and insulator-to-metal transition in ferromagnetic insulating BaFeO{sub 3} thin films, ARPES measurement of the ferroelectric bulk Rashba system GeTe, bisphenol A on Cu(111) and Ag(111), reverse water-gas shift or Sabathier methanation on N(110), structural studies of molecular machines, multi-MHz time-of-flight electronic band-structure imaging of graphene on Ir(111), diffusion pathways in ion conductors, ground-state potential energy surfaces around selected atoms from resonant inelastic X-ray scattering, solar energy in an emerging country, in-situ neutron analysis of electrode materials for electrochemical energy storage, structure and transport properties in thermoelectric skutterudites, investigation of the interphase formation on solid lithium-ion conductors by neutron reflectometry, load partitin and damage characterization of cast AlSi{sub 12}CuMgNi alloy with ceramic reinforcement, methane adsorption in highly porous metal-organics, structure and magnetic interactions in dimer system Ba{sub (3-x)}Sr{sub x}Cr{sub 2}O{sub 8}, distribution of S in C-S nanocomposites, current status of HFM-EXED FACITIY; SPIN NEAMTICITY IN s=1/2 frustrated zigzag chaIN β-TeVO{sub 4}, electronic properties of U(Ru{sub 0.92}Rh{sub 0.08}){sub 2}Si{sub 2} in high magnetic fields. field-dependent superconducting anisotropa and Pauli paramagnetism in YBa{sub 2}Cu{sub 3}O{sub 7}. (HSI)

  6. Storage temperature affects fruit quality attributes of Ber (Ziziphus ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-03

    Sep 3, 2008 ... 2Department of Agricultural Research and Extension Services, Agronomy Research Institute, Box CY 550, Causeway, ... Fruit utilization is affected by quality attributes and shelf life. ... preserve fresh and dried fruits can ensure its availability ... Vitamin C was determined using titrimetric method with 2,6-.

  7. Die Freizeittheologie mit besonderer Berücksichtigung der Ruhetheologie

    Directory of Open Access Journals (Sweden)

    Maciej Ostrowski

    2017-11-01

    Full Text Available The author performs an analysis of „theological places” („loci theologici”, as the basis on which leisure theology can be developed. These are: time theology (a linear concept of time, which means that time is a gift to man, if properly used, freedom theology (freedom not as a discharge from obligations but as the possibility to do good, new creation theology (renewal made by the redemptive work of Christ, joy theology (joy of gifts of nature, community with other person, being granted God’s grace, feast theology (time given to a man in order that he could turn to supernatural matters. The author develops ‘rest theology’ extensively as one of the fundamental forms of spending free time. He searches for sources in numerous biblical texts, where this term has been used. Furthermore, he interprets, among others, how to understand God’s rest after he created the world, and how his repose becomes an example to follow for a human being. Moreover, the author explains what the final repose is to be for a person, and how man, living on earth, anticipates an eschatological rest.

  8. Polarization modulational instability in a birefringent optical fiber ...

    Indian Academy of Sciences (India)

    We obtain conditions for the occurrence of polarization modulational instability in the anomalous and normal dispersion regimes for the coupled nonlinear Schrödinger equation modelling fourth order dispersion effects when the linearly polarized pump is oriented at arbitrary angles with respect to the slow and fast axes of ...

  9. Bericht über die Pilotphase Handschriftendigitalisierung der deutschen Handschriftenzentren

    Directory of Open Access Journals (Sweden)

    Carolin Schreiber

    2014-12-01

    Full Text Available Im Juni 2013 genehmigte die DFG die Durchführung einer zweijährigen Pilotphase zur Digitalisierung mittelalterlicher Handschriften an den deutschen Handschriftenzentren. Diese wird im DFG-Programm „Erschließung und Digitalisierung handschriftlicher und gedruckter Überlieferung“ im Bereich der Wissenschaftlichen Literaturversorgungs- und Informationssysteme (LIS gefördert.Das Vorhaben besteht aus sieben Digitalisierungsprojekten, die seit Herbst 2013 an fünf deutschen Bibliotheken durchgeführt werden. Die projektübergreifenden Organisations- und Koordinationsarbeiten sind an der Bayerischen Staatsbibliothek angesiedelt. Auf Basis der praktischen Erfahrungen der sieben einzelnen Projekte soll ein sog. Masterplan erarbeitet werden, der bei positiver Begutachtung zur Grundlage einer zukünftigen DFG-Förderlinie werden soll. Ziel der Initiative ist die Gesamtdigitalisierung des mittelalterlichen Handschriftenerbes in Deutschland. In June 2013, a proposal for a two-year pilot phase for the development of a concerted national programme for the digitization of medieval manuscripts in Germany, proposed by five German cataloguing centres, was accepted by the DFG, the largest research funding organization in Germany, in the context of its Scientific Library Services and Information Systems (LIS programme [1]. The pilot phase consists of seven coordinated digitization projects carried out by five German libraries. Project coordination and organization is taken over by the Bayerische Staatsbibliothek (BSB. Based on the practical experience gained in the different digitization projects, a master plan will be developed, which will be the basis for the establishment of a new DFG funding programme. The initiative aims at the digitization of all surviving medieval manuscripts preserved in German cultural heritage institutions.

  10. Aufforderung zur Intervention. Ein Versuch über Guy Debord.

    Directory of Open Access Journals (Sweden)

    Thomas Ballhausen

    2011-09-01

    Full Text Available Die konstruktive Auseinandersetzung mit Guy Debord und der Situationistischen Internationale (SI dauert erfreulicherweise an. Auch die medienspezifischen Implikationen seines Denkens und Wirkens sind immer wieder Teil aktueller Debatten um Möglichkeiten und Limits partizipativer Strategien.

  11. Ber analysis of the box relaxation for BPSK signal recovery

    KAUST Repository

    Thrampoulidis, Christos; Abbasi, Ehsan; Xu, Weiyu; Hassibi, Babak

    2016-01-01

    We study the problem of recovering an n-dimensional BPSK signal from m linear noise-corrupted measurements using the box relaxation method which relaxes the discrete set {±1}n to the convex set [-1,1]n to obtain a convex optimization algorithm followed by hard thresholding. When the noise and measurement matrix have iid standard normal entries, we obtain an exact expression for the bit-wise probability of error Pe in the limit of n and m growing and m/n fixed. At high SNR our result shows that the Pe of box relaxation is within 3dB of the matched filter bound (MFB) for square systems, and that it approaches the (MFB) as m grows large compared to n. Our results also indicate that as m, n → ∞, for any fixed set of size k, the error events of the corresponding k bits in the box relaxation method are independent.

  12. BER analysis of regularized least squares for BPSK recovery

    KAUST Repository

    Ben Atitallah, Ismail; Thrampoulidis, Christos; Kammoun, Abla; Al-Naffouri, Tareq Y.; Hassibi, Babak; Alouini, Mohamed-Slim

    2017-01-01

    This paper investigates the problem of recovering an n-dimensional BPSK signal x0 ∈ {−1, 1}n from m-dimensional measurement vector y = Ax+z, where A and z are assumed to be Gaussian with iid entries. We consider two variants of decoders based on the regularized least squares followed by hard-thresholding: the case where the convex relaxation is from {−1, 1}n to ℝn and the box constrained case where the relaxation is to [−1, 1]n. For both cases, we derive an exact expression of the bit error probability when n and m grow simultaneously large at a fixed ratio. For the box constrained case, we show that there exists a critical value of the SNR, above which the optimal regularizer is zero. On the other side, the regularization can further improve the performance of the box relaxation at low to moderate SNR regimes. We also prove that the optimal regularizer in the bit error rate sense for the unboxed case is nothing but the MMSE detector.

  13. 96 Über die Morphosyntaktische Struktur von Nominalkomposita im ...

    African Journals Online (AJOL)

    Die Yorùbá-Sprache, die von mehr als 25 Millionen Menschen allein in Nigeria gesprochen wird (vgl. Weisser 2008:1), ist die. Sprache der Yorùbá. Sie wird neben anderen Sprachen hauptsächlich in Südwest-Nigeria und z.T. in Benin, Togo,. Brasilien und Kuba gesprochen. Sie ist eine isolierende. Tonsprache, die zum ...

  14. Latein als Sprache der mittelalterlichen Schriften über Wettervorhersage

    Czech Academy of Sciences Publication Activity Database

    Kocánová, Barbora

    -, č. 71 (2013), s. 237-248 ISSN 1376-7453 R&D Projects: GA MŠk(CZ) LD13043 Institutional support: RVO:67985955 Keywords : medieval weather forecasting * medieval Latin * medieval manuscripts Subject RIV: AI - Linguistics

  15. BER analysis of regularized least squares for BPSK recovery

    KAUST Repository

    Ben Atitallah, Ismail

    2017-06-20

    This paper investigates the problem of recovering an n-dimensional BPSK signal x0 ∈ {−1, 1}n from m-dimensional measurement vector y = Ax+z, where A and z are assumed to be Gaussian with iid entries. We consider two variants of decoders based on the regularized least squares followed by hard-thresholding: the case where the convex relaxation is from {−1, 1}n to ℝn and the box constrained case where the relaxation is to [−1, 1]n. For both cases, we derive an exact expression of the bit error probability when n and m grow simultaneously large at a fixed ratio. For the box constrained case, we show that there exists a critical value of the SNR, above which the optimal regularizer is zero. On the other side, the regularization can further improve the performance of the box relaxation at low to moderate SNR regimes. We also prove that the optimal regularizer in the bit error rate sense for the unboxed case is nothing but the MMSE detector.

  16. Ber analysis of the box relaxation for BPSK signal recovery

    KAUST Repository

    Thrampoulidis, Christos

    2016-06-24

    We study the problem of recovering an n-dimensional BPSK signal from m linear noise-corrupted measurements using the box relaxation method which relaxes the discrete set {±1}n to the convex set [-1,1]n to obtain a convex optimization algorithm followed by hard thresholding. When the noise and measurement matrix have iid standard normal entries, we obtain an exact expression for the bit-wise probability of error Pe in the limit of n and m growing and m/n fixed. At high SNR our result shows that the Pe of box relaxation is within 3dB of the matched filter bound (MFB) for square systems, and that it approaches the (MFB) as m grows large compared to n. Our results also indicate that as m, n → ∞, for any fixed set of size k, the error events of the corresponding k bits in the box relaxation method are independent.

  17. Eight joint BER II and BESSY II users meeting. Abstracts

    International Nuclear Information System (INIS)

    2016-01-01

    The following topics were dealt with: Accelerator operation and projecs, photon science and instrumentation at BESSY II, status of energy materials in-situ Lab at BESSY II, high resolution spectrometer PEAXIS at BESSY II, sample environment at BESSY II, molecular control mechanisms in the Brr2 RNA helicase for efficient and regulated splicing, the Li conversion reaction of 4CoFe_2O_4 nanoparticles, buried interfaces in lithium ion batteries probed with HAXPES, ARPES studies of the STO(001) 2DEG, all-in/all-out magnetic order in rare earth iridates, oxygen reduction reaction on graphene in Li-air batteries, electronic order in high-T_c superconductors, in-siu observation of novel switching phenomena in highly porous metal-organic frameworks, photoinduced demagnetization and insulator-to-metal transition in ferromagnetic insulating BaFeO_3 thin films, ARPES measurement of the ferroelectric bulk Rashba system GeTe, bisphenol A on Cu(111) and Ag(111), reverse water-gas shift or Sabathier methanation on N(110), structural studies of molecular machines, multi-MHz time-of-flight electronic band-structure imaging of graphene on Ir(111), diffusion pathways in ion conductors, ground-state potential energy surfaces around selected atoms from resonant inelastic X-ray scattering, solar energy in an emerging country, in-situ neutron analysis of electrode materials for electrochemical energy storage, structure and transport properties in thermoelectric skutterudites, investigation of the interphase formation on solid lithium-ion conductors by neutron reflectometry, load partitin and damage characterization of cast AlSi_1_2CuMgNi alloy with ceramic reinforcement, methane adsorption in highly porous metal-organics, structure and magnetic interactions in dimer system Ba_(_3_-_x_)Sr_xCr_2O_8, distribution of S in C-S nanocomposites, current status of HFM-EXED FACITIY; SPIN NEAMTICITY IN s=1/2 frustrated zigzag chaIN β-TeVO_4, electronic properties of U(Ru_0_._9_2Rh_0_._0_8)_2Si_2 in high magnetic fields. field-dependent superconducting anisotropa and Pauli paramagnetism in YBa_2Cu_3O_7. (HSI)

  18. Über eine neue Dasyproctus-Art aus Java

    NARCIS (Netherlands)

    Kohl, Franz Friedr.

    1908-01-01

    ♂ — Long. 7—8 mm. Niger, ex magna parte (supra) opacus. Tergita 2., 3. et 4. utrinque maculata, 5. et 6. interrupte fasciata, hoc nonnunquam fascia integra flava. Flava sunt insuper: linea suprabasalis mandibularum, scapi ex parte, fascia interrupta collaris, alarum squamulae et 2—4 maculae

  19. Die erste Dissertation über Jaan Kross / Cornelius Hasselblatt

    Index Scriptorium Estoniae

    Hasselblatt, Cornelius

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt/M : P. Lang, 2001.

  20. Etika: Keamanan Berpolitik dan Ber-New Media

    Directory of Open Access Journals (Sweden)

    Nunung Prajarto

    2011-03-01

    Full Text Available The improvement of security in politics and new media calls for fast action. Recent cases indicate that political position and rights to communication using new media cannot be guaranteed due to the problem of security. The reasons rest on the way the people get into politics and the aims they use new media. The following article explores how ethics may solve the problem of security, starting from ethics in democracy, politics, and new media, the causes of ethics violations, and attitudes for coping with security problems.

  1. Über asiatische Coenochilus (Coleoptera, Cetoniidae), mit einer Bestimmungstabelle

    NARCIS (Netherlands)

    Schein, H.

    1953-01-01

    Eine Bestimmungssendung des Deutschen Entomologischen Institutes veranlasste mich, die Systematik der asiatischen Coenochilus zu studieren. Die Museen Leiden, Berlin und München und die Herren Frey, Haberäcker, Klapperich und van Nidek stellten mir ihr Material zur Verfügung; Herr Reichert des

  2. Traethedsbrud af collum femoris hos rask maratonløber

    DEFF Research Database (Denmark)

    Nielsen, Klaus; Christensen, Ole; Lukina, Guy Feruzi

    2009-01-01

    Fatigue fractures of the hip are rare causes of hip pain. Delayed diagnostics of this type of fracture can cause serious complications. We describe a case concerning a 32-year-old male amateur runner who experienced hip pain with rapid onset during his first marathon. After eight days his general...

  3. Traethedsbrud af collum femoris hos rask maratonløber

    DEFF Research Database (Denmark)

    Nielsen, Klaus; Christensen, Ole; Lukina, Guy Feruzi

    2009-01-01

    Fatigue fractures of the hip are rare causes of hip pain. Delayed diagnostics of this type of fracture can cause serious complications. We describe a case concerning a 32-year-old male amateur runner who experienced hip pain with rapid onset during his first marathon. After eight days his general...... practitioner referred him to the hospital and a dislocated fracture of the femoral neck was detected. Udgivelsesdato: 2009-Oct-5...

  4. Efeito da adição do melaço na relação carbono/nitrogênio no cultivo de camarão Litopenaeus vannamei na fase berçário = Effect of molasses addition on carbon/nitrogen ratio in the nursery phase of Litopenaeus vannamei shrimp culture

    Directory of Open Access Journals (Sweden)

    Ugo Lima Silva

    2009-10-01

    Full Text Available Investigou-se o efeito da adição do melaço nas relações carbono:nitrogênio (C:N sobre o desempenho zootécnico do camarão Litopenaeus vannamei, na fase berçário, quando cultivado sem renovação de água. As relações do C:N foram avaliadas nas proporções de 25:1 (25M, 15:1 (15M e o controle (0M, sem aplicação de carbono, em delineamento experimental inteiramente casualizado, com quatro repetições. Pós-larvas (PL com peso inicial de 2,5 ± 0,5 mg, foram estocadas em 12 tanques (800 L volume útil, em densidades de 6,25 PL L-1, durante 42 dias de cultivo. Ao final do cultivo, os pesos finais dos camarões dos tratamentos 25M (532,0 mg e 15M (540,0 mg foram superiores (p The effect of molasses addiction on carbon:nitrogen ratios (C:N on the performance of Litopenaeus vannamei shrimp during the nursery phase cultured without water exchange was investigated. The C:N ratios were evaluated in 25:1 (25M and 15:1 (15M proportion and a control (0M, with no carbon source addition, in a randomized experimental design with four replicates. Post-larvae (PL with initial weight of 2.5 ± 0.5 mg were stocked in 12 tanks (800 L net volume, at the density of 6.25 PL L-1 during 42 culture days. At the end of culture, the shrimps weights on 25M (532.0 mg and 15M (540.0 mg treatments were higher (p < 0.05 than the 0M (428.6 mg treatment. Shrimp survival was high in all treatments (77.9 to 90.0%, but without significant difference (p ≥ 0.05. Therefore, the 15 and 25:1 C:N ratios showed an increased growth performance of nursery phase L. vannamei post-larvae cultured without water exchange.

  5. Fatores de risco para perda ponderal de crianças frequentadoras de berçários em creches do município de São Paulo Risk factors for ponderal loss of children attending the nurseries of day care centers in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Maysa Helena A. Toloni

    2009-03-01

    Full Text Available OBJETIVO: Identificar e quantificar os fatores de risco relacionados ao agravamento da condição nutricional entre o nascimento e a realização deste estudo. MÉTODOS: Estudo transversal com 270 crianças frequentadoras dos berçários de oito creches públicas e filantrópicas do município de São Paulo. Considerou-se com perda ponderal as crianças que apresentaram diferença negativa do escore Z para a relação peso para idade entre o nascimento e a ocasião da realização desse inquérito. No estudo das associações, utilizou-se o teste do qui-quadrado e consideraram-se as variáveis com nível de significância pOBJECTIVE: To identify and quantify risk factors related to the aggravation of nutritional condition from birth until the date of the study. METHODS: Cross-sectional study with 270 children attending nurseries of eight public and non-for-profit daycare centers in the city of São Paulo, Brazil. Ponderal loss was considered when children presented negative difference of Z score for weight-for-age (W/A from birth until the date of the present inquiry. Chi-square was used to test associations and considered significant if p<0.05. Multivariate logistic regression model adjusted Odds Ratio estimates for confounding variables and/or covariables. RESULTS: Anthropometric analysis showed 7.1% prevalence of malnutrition (W/A<-2 Z score at birth and 4.4% by the time of measurement. Ponderal evolution with unfavorable Z score was present in 50.7% of studied children (n=137. In the bivariate analyses, the variables: birth weight (OR=5.35; p<0.001, anemia (OR=1.81; p=0.019 and age less than 19 months (OR=1.67; p=0.036 were statistically significant. CONCLUSIONS: Ponderal loss in Z score during the first months of life has not been often used in epidemiological studies. However, future researches might identify weight loss as an indicator of risk for sociobiological vulnerability. Development of health programs in order to reduce the

  6. Desempenho de pós-larvas do camarão-rosa Farfantepenaeus paulensis alimentadas com diferentes frequências durante a fase de berçário = Performance of Farfantepenaeus paulensis shrimp postlarvae fed in different feeding frequencies during nursery rearing

    Directory of Open Access Journals (Sweden)

    Ronaldo Olivera Cavalli

    2008-07-01

    Full Text Available Este estudo avaliou os efeitos da frequência de arraçoamento na sobrevivência e crescimento do camarão-rosa Farfantepenaeus paulensis criado durante a fase de berçário primário. Uma dieta comercial foi oferecida até a saciedade aparente em um, dois, quatro ou seis refeições, e cada tratamento recebia diariamente a mesma quantidade. A sobrevivência não foi significativamente afetada, mas o peso final dos camarões foi superior com o aumento da frequência de arraçoamento. Algumas hipóteses podem explicar a vantagem emdividir o arraçoamento em várias refeições diárias: a diminuição das perdas de nutrientes por lixiviação, a menor atratividade da dieta exposta à água, a incapacidade dos camarões ingerirem maior quantidade de alimento ou a menor desintegração das partículasalimentares, o que dificultaria a manipulação e ingestão da dieta pelos camarões.This study assessed the effects of feeding frequency on the survival and growth of the shrimp Farfantepenaeus paulensis reared during the nursery phase. Shrimp from each treatment were fed the same dailyamount of a commercial shrimp diet, which was offered to apparent satiation in 1, 2, 4 or 6 meals. Although survival was not significantly affected, final shrimp weight increased significantly at higher feeding frequencies. The advantage of dividing feeding in more than one daily meal may be explained by one or more of the following factors: lower loss of nutrients by lixiviation; smaller disintegration of food particles (which may hinder manipulation by shrimp and hence ingestion; loss of appeal of the diets after a longexposure to water; and the inability of shrimp to ingest large amounts of feed due to their relatively small digestive system.

  7. Revisión crítico-comparada de las principales teorías científico sociales sobre la delincuencia femenina (Vergleichend kritische Überarbeitung der wichtigsten wissenschaftlichen und sozialen Theorien über die Fraunkriminalität

    Directory of Open Access Journals (Sweden)

    Gudrun Stenglein

    2013-03-01

    Full Text Available Wenn man von Verbrechen spricht, scheint man mit einem reinen männlichen Phänomen konfrontiert zu sein. Die wissenschaftlichen Arbeiten über Kriminalität beschäftigen sich normalerweise mit dem Verhalten männlicher Krimineller. Die Frauen werden nur als passive Subjekte, meist als Opfer dargestellt. Die Frauenkriminalitätsproblematik wird aber immer gewichtiger, die Anzahl der Delikte, die durch Frauen begangen werden, und der Frauen als Strafgefangene wächst. Aber in der akademischen Welt wird diese Problematik nach wie vor als nicht wichtig dargestellt, sie spielt eine wesentlich kleinere Rolle. Das Phänomen der Frauenkriminalität wird bis zum heutigen Tage mit dem biologischen Unterschied, mit der Form des Seins der Frau erklärt. Die Vorstellungswelt der Frau beschäftigt sich nur mit der Suche nach einem adäquaten Parter und mit der Rolle als Mutter und Ehefrau, die sich um ihre Familie kümmert. Jahrhundertelang war dieses Thema auf die Verhaltensweisen in Verbindung mit der sozialen Reputation beschränkt. Mit diesem Artikel wird eine Einleitung in die verschiedenen biologischen und sozialen Erklärungsansätze dieses Phänomens unter dem besonderen funktionalistischen Blickwinkel der Rollentheorie und der Theorie der sozialen Kontrolle gegeben. Ein anderer Ansatzpunkt ist die Etikettierungsthorie, Labeling Approach. Einige Erklärungsansätze, wie die Sozialisierung der Frau, haben nach wie vor Gültigkeit, vor allem, weil es sich bei dem Problem der Frauenkriminalität um ein multidisziplinäres Thema handelt. Die individuellen und sozialen Faktoren müssen miteinander verbunden werden. Die Gesellschaft macht aus den Personen, was sie sind, zumindest potenziert sie die individuellen Bedingungen. Einige Erklärungen wurden mit der Zeit relativiert. Manche können mitlerweile für veraltet gehalten werden, andere sind in ihren Ansichtsweisen teilweise zu beschränkt, so dass sie heutzutage als befremdlich oder

  8. Glycyrrhetinic acid and its derivatives as inhibitors of poly(ADP-ribosepolymerases 1 and 2, apurinic/apyrimidinic endonuclease 1 and DNA polymerase β

    Directory of Open Access Journals (Sweden)

    Salakhutdinov N. F.

    2012-06-01

    Full Text Available Aim. For strengthening the efficiency of monofunctional alkylating antineoplastic drugs it is important to lower the capacity of base excision repair (BER system which corrects the majority of DNA damages caused by these reagents. The objective was to create inhibitors of the key BER enzymes (PARP1, PARP2, DNA polymerase β, and APE1 by the directed modification of glycyrrhetinic acid (GA. Methods. Amides of GA were produced from the GA acetate by formation of the corresponding acyl chloride, amidation with the appropriate amine and subsequent deacylation. Small library of 2-cyano substituted derivatives of GA methyl esters was obtained by the structural modification of GA framework and carboxylic acid group. The inhibitory capacity of the compounds was estimated by comparison of the enzyme activities in specific tests in the presence of compounds versus their absence. Results. None of tested compounds inhibits PARP1 significantly. Unmodified GA and its morpholinic derivative were shown to be weak inhibitors of PARP2. The derivatives of GA containing keto-group in 11 triterpene framework were shown to be moderate inhibitors of pol β. Compound 3, containing 12-oxo-9(11-en moiety in the ring C, was shown to be a single inhibitor of APE1 among all compounds studied. Conclusions. The class of GA derivatives, selective pol β inhibitors, was found out. The selective inhibitor of APE1 and weak selective inhibitor of PARP2 were also revealed.

  9. Efeito da adição do melaço na relação carbono/nitrogênio no cultivo de camarão Litopenaeus vannamei na fase berçário - DOI: 10.4025/actascibiolsci.v31i4.4496 Effect of molasses addition on carbon/nitrogen ratio in the nursery phase of Litopenaeus vannamei shrimp culture - DOI: 10.4025/actascibiolsci.v31i4.4496

    Directory of Open Access Journals (Sweden)

    Diogo Bessa Neves Spanghero

    2009-08-01

    Full Text Available Investigou-se o efeito da adição do melaço nas relações carbono:nitrogênio (C:N sobre o desempenho zootécnico do camarão Litopenaeus vannamei, na fase berçário, quando cultivado sem renovação de água. As relações do C:N foram avaliadas nas proporções de 25:1 (25M, 15:1 (15M e o controle (0M, sem aplicação de carbono, em delineamento experimental inteiramente casualizado, com quatro repetições. Pós-larvas (PL com peso inicial de 2,5 ± 0,5 mg, foram estocadas em 12 tanques (800 L volume útil, em densidades de 6,25 PL L-1, durante 42 dias de cultivo. Ao final do cultivo, os pesos finais dos camarões dos tratamentos 25M (532,0 mg e 15M (540,0 mg foram superiores (p L. vannamei cultivadas na fase berçário sem renovação de águaThe effect of molasses addiction on carbon:nitrogen ratios (C:N on the performance of Litopenaeus vannamei shrimp during the nursery phase cultured without water exchange was investigated. The C:N ratios were evaluated in 25:1 (25M and 15:1 (15M proportion and a control (0M, with no carbon source addition, in a randomized experimental design with four replicates. Post-larvae (PL with initial weight of 2.5 ± 0.5 mg were stocked in 12 tanks (800 L net volume, at the density of 6.25 PL L-1 during 42 culture days. At the end of culture, the shrimps weights on 25M (532.0 mg and 15M (540.0 mg treatments were higher (p L. vannamei post-larvae cultured without water exchange.

  10. BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE

    Science.gov (United States)

    Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmac...

  11. Discoidin domain receptor 1 is activated independently of beta(1) integrin

    DEFF Research Database (Denmark)

    Vogel, W; Brakebusch, C; Fässler, R

    2000-01-01

    independent of the epidermal growth factor (EGF) receptor. In cells that endogenously express both DDR1 and the EGF receptor, stimulation with EGF does not induce DDR activation. Third, we detected full DDR1 activation after collagen stimulation in cells that have been treated with blocking antibodies...... for alpha(2)beta(1) integrin or in cells with a targeted deletion of the beta(1) integrin gene. Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers....

  12. Effects of intensity of facial expressions on amygdalar activation independently of valence

    Directory of Open Access Journals (Sweden)

    Huiyan Lin

    2016-12-01

    Full Text Available For several stimulus categories (e.g., pictures, odors and words, the arousal of both negative and positive stimuli has been shown to modulate amygdalar activation. In contrast, previous studies did not observe similar amygdalar effects in response to negative and positive facial expressions with varying intensity of facial expressions. Reasons for this discrepancy may be related to analytical strategies, experimental design and stimuli. Therefore, the present study aimed at re-investigating whether the intensity of facial expressions modulates amygdalar activation by circumventing limitations of previous research. Event-related functional magnetic resonance imaging (fMRI was used to assess brain activation while participants observed a static neutral expression and positive (happy and negative (angry expressions of either high or low intensity from an ecologically valid, novel stimulus set. The ratings of arousal and intensity were highly correlated. We found that amygdalar activation followed a u-shaped activation pattern with highest activation to high intense facial expressions as compared to low intensity facial expressions and to the neutral expression irrespective of valence, suggesting a critical role of the amygdala in valence-independent arousal processing of facial expressions. Additionally, consistent with previous studies, intensity effects were also found in visual areas and generally increased activation to angry vs. happy faces were found in visual cortex and insula, indicating enhanced visual representations of high arousing facial expressions and increased visual and somatosensory representations of threat.

  13. Propolis reversed cigarette smoke-induced emphysema through macrophage alternative activation independent of Nrf2

    NARCIS (Netherlands)

    Barroso, Marina Valente; Cattani-Cavalieri, Isabella; de Brito-Gitirana, Lycia; Fautrel, Alain; Lagente, Vincent; Schmidt, Martina; Porto, Luís Cristóvão; Romana-Souza, Bruna; Valença, Samuel Santos; Lanzetti, Manuella

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is an incurable and progressive disease. Emphysema is the principal manifestation of COPD, and the main cause of this condition is cigarette smoke (CS). Natural products have shown antioxidant and anti-inflammatory properties that can prevent acute lung

  14. Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.

    Science.gov (United States)

    McCoy, Sara S; Reed, Tamra J; Berthier, Celine C; Tsou, Pei-Suen; Liu, Jianhua; Gudjonsson, Johann E; Khanna, Dinesh; Kahlenberg, J Michelle

    2017-11-01

    SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  15. A BCR-ABL Kinase Activity-Independent Signaling Pathway in Chronic Myelogenous Leukemia

    Science.gov (United States)

    2008-02-01

    Breitenstein W, Bruggen J, Cowan-Jacob SW, Ray A, Huntly B, Fabbro D, Fendrich G, Hall-Meyers E, et al. (2005) Cancer Cell 7:129–141. 10. Druker BJ...2532–9. 15. Weisberg E, Manley PW, Breitenstein W, Bruggen J, Cowan-Jacob SW, Ray A, Huntly B, Fabbro D, Fendrich G, Hall-Meyers E, Kung AL, Mestan J...HG, Mountford JC, Holyoake TL. Punish the parent not the progeny. Blood. 2005; 105: 1862–6. 63. Pfeifer H, Wassmann B, Pavlova A, Wunderle L, Oldenburg

  16. Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production.

    Science.gov (United States)

    Uto, Yoshihiro; Kawai, Tomohito; Sasaki, Toshihide; Hamada, Ken; Yamada, Hisatsugu; Kuchiike, Daisuke; Kubo, Kentaro; Inui, Toshio; Mette, Martin; Tokunaga, Ken; Hayakawa, Akio; Go, Akiteru; Oosaki, Tomohiro

    2015-08-01

    Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

    International Nuclear Information System (INIS)

    Rashid-Kolvear, Fariborz; Taboski, Michael AS; Nguyen, Johnny; Wang, Dong-Yu; Harrington, Lea A; Done, Susan J

    2010-01-01

    Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated. In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference. We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's t test. To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined

  18. The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

    International Nuclear Information System (INIS)

    Bolin, Celeste; Boudra, Mohammed-Tayyib; Fernet, Marie; Vaslin, Laurence; Pennaneach, Vincent; Zaremba, Tomasz; Favaudon, Vincent; Megnin-Chanet, Frederique; Hall, Janet; Biard, Denis; Cordelieres, Fabrice P.

    2012-01-01

    Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro irradiated Cdk5KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5- dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels. (authors)

  19. “Blasse Mädchen im SPIEGEL“: Zur Berichterstattung über Politikerinnen im Wahlkampfjahr 2013 am Beispiel von Medientexten über Katja Kipping

    DEFF Research Database (Denmark)

    Heier, Anke

    2016-01-01

    to the opinion that women are suitable for a political office. Since der Spiegel is one of Germany’s most influential weekly news magazines, it is important to be aware of the contribution it makes to a person’s image in the media and the influence on the election campaign, because if this image...... is undifferentiated, the reader may reduce the image even more. This reinforces the process of stereotyping. The purpose is to analyze to what extent der Spiegel and SPON spread a unilateral or a differentiated picture or concept and what features of the investigated person that are highlighted. Methodologically...

  20. An RNA aptamer specific to Hsp70-ATP conformation inhibits its ATPase activity independent of Hsp40.

    Science.gov (United States)

    Thirunavukarasu, Deepak; Shi, Hua

    2015-04-01

    The highly conserved and ubiquitous molecular chaperone heat shock protein 70 (Hsp70) plays a critical role in protein homeostasis (proteostasis). Controlled by its ATPase activity, Hsp70 cycles between two conformations, Hsp70-ATP and Hsp70-ADP, to bind and release its substrate. Chemical tools with distinct modes of action, especially those capable of modulating the ATPase activity of Hsp70, are being actively sought after in the mechanistic dissection of this system. Here, we report a conformation-specific RNA aptamer that binds only to Hsp70-ATP but not to Hsp70-ADP. We have refined this aptamer and demonstrated its inhibitory effect on Hsp70's ATPase activity. We have also shown that this inhibitory effect on Hsp70 is independent of its interaction with the Hsp40 co-chaperone. As Hsp70 is increasingly being recognized as a drug target in a number of age related diseases such as neurodegenerative, protein misfolding diseases and cancer, this aptamer is potentially useful in therapeutic applications. Moreover, this work also demonstrates the feasibility of using aptamers to target ATPase activity as a general therapeutic strategy.

  1. Antigen-specific T cell activation independently of the MHC: chimeric antigen receptor (CAR-redirected T cells.

    Directory of Open Access Journals (Sweden)

    Hinrich eAbken

    2013-11-01

    Full Text Available Adoptive T cell therapy has recently shown powerful in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR which consists in the extracellular part of an antibody-derived domain for binding with a tumor-associated antigen and in the intracellular part of a TCR-derived signaling moiety for T cell activation. The specificity of CAR mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR and review most significant progress recently made in early stage clinical trials to treat cancer.

  2. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice

    DEFF Research Database (Denmark)

    Lund, Leif R; Green, Kirsty A; Stoop, Allart A

    2006-01-01

    Simultaneous ablation of the two known activators of plasminogen (Plg), urokinase-type (uPA) and the tissue-type (tPA), results in a substantial delay in skin wound healing. However, wound closure and epidermal re-epithelialization are significantly less impaired in uPA;tPA double-deficient mice ...

  3. ATP induces NO production in hippocampal neurons by P2X(7 receptor activation independent of glutamate signaling.

    Directory of Open Access Journals (Sweden)

    Juan Francisco Codocedo

    Full Text Available To assess the putative role of adenosine triphosphate (ATP upon nitric oxide (NO production in the hippocampus, we used as a model both rat hippocampal slices and isolated hippocampal neurons in culture, lacking glial cells. In hippocampal slices, additions of exogenous ATP or 2'(3'-O-(4-Benzoylbenzoyl ATP (Bz-ATP elicited concentration-dependent NO production, which increased linearly within the first 15 min and plateaued thereafter; agonist EC50 values were 50 and 15 µM, respectively. The NO increase evoked by ATP was antagonized in a concentration-dependent manner by Coomassie brilliant blue G (BBG or by N(ω-propyl-L-arginine, suggesting the involvement of P2X7Rs and neuronal NOS, respectively. The ATP induced NO production was independent of N-methyl-D-aspartic acid (NMDA receptor activity as effects were not alleviated by DL-2-Amino-5-phosphonopentanoic acid (APV, but antagonized by BBG. In sum, exogenous ATP elicited NO production in hippocampal neurons independently of NMDA receptor activity.

  4. Infection and colonization by Gram-negative bacilli in neonates hospitalized in High Risk Nursery at Uberlandia Federal University Hospital: etiology, resistant phenotypes and risk factors Infecção e colonização por bacilos Gram-negativos em neonatos internados em Berçário de Alto Risco do Hospital da Universidade Federal de Uberlândia: etiologia, fenótipos de resistência e fatores de risco

    Directory of Open Access Journals (Sweden)

    Renata Cristina Cezário

    2004-09-01

    ção e infecção e a presença dos fenótipos de resistência ESBL e AmpC em neonatos admitidos em Berçário de Alto Risco. Durante um período de 21 meses, foi realizado um estudo prospectivo para avaliar os casos de infecções hospitalares e o uso de cefalosporinas de terceira geração; e um estudo caso-controle para determinar os fatores de risco associados a colonização/infecção. Quatro inquéritos de colonização da orofaringe e intestino dos neonatos (Setembro e Novembro/2001, Fevereiro e Agosto/2002. Amostras com resistência a 2 mig/mL de ceftazidima foram isoladas devido a suspeita de produção de b-lactamases (ESBL/ AmpC. A incidência de pacientes infectados por bacilos Gram-negativos foi de 2,4% (89/3.709 neonatos, sendo sepse (35,9% e conjuntivite (31,4% as síndromes mais frequentes. A maioria das infecções foram endêmicas (73,9% e associadas a Enterobacteriaceae (95,5%, estes também foram relacionados à colonização, correspondendo principalmente as amostras de Enterobacter spp e Klebsiella spp.. Foram identificados dois surtos, durante o estudo, associados a Pseudomonas aeruginosa (N=10 e Acinetobacter baumannii (N=11. Os fatores de risco incluindo: tempo de internação, uso de antimicrobianos, ventilação mecânica, cateter vascular central, cirurgia e nutrição parenteral foram significativos em uma análise univariada e considerados um risco para infecção por bacilos Gram-negativos. A maioria das amostras de Enterobacteriaceae (80,9% com resistência a 2 mig/mL de ceftazidima foram do fenótipo ESBL. O uso de cefalosporinas de terceira geração (ceftriaxona na unidade neonatal favoreceu a emergência de bacilos Gram-negativos multiresistentes.

  5. DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity

    DEFF Research Database (Denmark)

    Gupta, Rajat; Somyajit, Kumar; Narita, Takeo

    2018-01-01

    Repair of damaged DNA is essential for maintaining genome integrity and for preventing genome-instability-associated diseases, such as cancer. By combining proximity labeling with quantitative mass spectrometry, we generated high-resolution interaction neighborhood maps of the endogenously expres...... and the evolution of antibody CSR in higher vertebrates....

  6. Effect of small-molecule modification on single-cell pharmacokinetics of PARP inhibitors.

    Science.gov (United States)

    Thurber, Greg M; Reiner, Thomas; Yang, Katherine S; Kohler, Rainer H; Weissleder, Ralph

    2014-04-01

    The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging, given the complex tumor microenvironment including intra- and intertumor heterogeneity. The difficulty in studying this distribution is even more significant for small-molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution in vivo. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, we followed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including in vivo permeability of small-molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model.

  7. Effect of Small Molecule Modification on Single Cell Pharmacokinetics of PARP Inhibitors

    Science.gov (United States)

    Thurber, Greg M.; Reiner, Thomas; Yang, Katherine S; Kohler, Rainer; Weissleder, Ralph

    2014-01-01

    The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging given the complex tumor microenvironment including intra- and inter-tumor heterogeneity. The difficulty in studying this distribution is even more significant for small molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution in vivo. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, we followed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including in vivo permeability of small molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model. PMID:24552776

  8. TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity

    DEFF Research Database (Denmark)

    Moudry, Pavel; Watanabe, Kenji; Wolanin, Kamila M.

    2016-01-01

    to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51...

  9. Potentiation of peptide receptor radionuclide therapy by the PARP inhibitor olaparib

    NARCIS (Netherlands)

    J. Nonnekens (Julie); M. van Kranenburg (Melissa); C.E.M.T. Beerens (Cecile); M. Suker (Mustafa); M. Doukas (Michael); C.H.J. van Eijck (Casper); M. de Jong (Marcel); D.C. van Gent (Dik)

    2016-01-01

    textabstractMetastases expressing tumor-specific receptors can be targeted and treated by binding of radiolabeled peptides (peptide receptor radionuclide therapy or PRRT). For example, patients with metastasized somatostatin receptor-positive neuroendocrine tumors (NETs) can be treated with

  10. The HRD Decision-Which PARP Inhibitor to Use for Whom and When.

    Science.gov (United States)

    Kohn, Elise C; Lee, Jung-Min; Ivy, S Percy

    2017-12-01

    Rucaparib, a polyADPribose polymerase inhibitor (PARPi), was approved recently for use in women with high-grade serous ovarian cancer (HGSOC). It is now one of three approved PARPi for use in recurrent ovarian cancer, a family of agents that has changed the HGSOC treatment landscape and outcome. Clin Cancer Res; 23(23); 7155-7. ©2017 AACR See related article by Balasubramaniam et al., p. 7165 . ©2017 American Association for Cancer Research.

  11. XRCC1 coordinates disparate responses and multiprotein repair complexes depending on the nature and context of the DNA damage

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Sundheim, Ottar

    2011-01-01

    . We demonstrate that the laser dose used for introducing DNA damage determines the repertoire of DNA repair proteins recruited. Furthermore, we demonstrate that recruitment of POLß and PNK to regions irradiated with low laser dose requires XRCC1 and that inhibition of PARylation by PARP......-inhibitors only slightly reduces the recruitment of XRCC1, PNK, or POLß to sites of DNA damage. Recruitment of PCNA and FEN-1 requires higher doses of irradiation and is enhanced by XRCC1, as well as by accumulation of PARP-1 at the site of DNA damage. These data improve our understanding of recruitment of BER......XRCC1 is a scaffold protein capable of interacting with several DNA repair proteins. Here we provide evidence for the presence of XRCC1 in different complexes of sizes from 200 to 1500 kDa, and we show that immunoprecipitates using XRCC1 as bait are capable of complete repair of AP sites via both...

  12. Zur nachhaltig ausgerichteten Dekonstruktion des wirtschafts-didaktischen Diskurses über ökonomische Kategoriensysteme

    Directory of Open Access Journals (Sweden)

    Frank Skrzipietz

    2009-08-01

    Full Text Available Der Beitrag reflektiert am Beispiel wirtschaftskategorialer Systeme den Status quo bezogen auf die Implementierung des normativen Nachhaltigkeitsgedankens in curriculare Strukturen und fachdidaktische Konzepte ökonomischer Bildung. Dazu wird die These entwickelt, dass eine einseitig auf neoklassische Kategorien ausgerichtete Wirtschaftsdidaktik eine nur unzureichend fundierte Plattform darstellt, um wirtschafts- und nachhaltigkeitsbezogene Probleme angemessen diskutieren, bearbeiteten und lösen zu können. Es wird gezeigt, dass die im Modus von wirtschaftkategorialen Struktureinsichten angebotene Objektseite ökonomischer Bildung zu eng angelehnt ist an die Modelle der neoklassisch geprägten Wissenschaftssystematik. Es bedarf hier nachdrücklich einer Erweiterung der an den Logiken neoklassischer Modellierungen orientierten stoffkategorialen Systeme um soziale und ökologische Faktoren bzw. um Kategorien aus dem Nachhaltigkeitsdiskurs, wie z.B. Vernetzung, Gerechtigkeit, Globalität, Zukunft, Kommunikation und Partizipation. Als Grundlage für die Entwicklung wirtschaftskategorialer Systeme und zur fachwissenschaftlichen Fundierung curricularer Konstruktionen ökonomischer Bildung im Sinne der Nachhaltigkeitsidee wird ein interdisziplinärer Zugang sowie ein Rekurs auf alternative ökonomische Referenztheorien bzw. -modelle empfohlen.The article reflects on the status quo with regard to the implementation of the normative sustainability-idea in curricular structures and didactical concepts of economic education using the example of economic-categorical systems. Accordingly, it is not appropriate to discuss and treat economical and sustainable problems through an economic didactic which is based upon neoclassical categories in biased way but to demonstrate that the economical categories intensively refer upon the models of neoclassical economy. Therefore an extension of neoclassical models towards social and ecological factors and categories of the sustainability-discourse respectively is required, e.g. integration, justice, globality, future, communication and participation. As a basis of the development of economic-categorical systems and the science-based foundation of curricular constructions of economic education in a sustainable sense an interdisciplinary access and a regress of alternative economic theories are recommended.

  13. High SNR BER comparison of coherent and differentially coherent modulation schemes in lognormal fading channels

    KAUST Repository

    Song, Xuegui; Cheng, Julian; Alouini, Mohamed-Slim

    2014-01-01

    Using an auxiliary random variable technique, we prove that binary differential phase-shift keying and binary phase-shift keying have the same asymptotic bit-error rate performance in lognormal fading channels. We also show that differential quaternary phase-shift keying is exactly 2.32 dB worse than quaternary phase-shift keying over the lognormal fading channels in high signal-to-noise ratio regimes.

  14. Die Grundlagen der Arithmetik. Eine logisch mathematische Untersuchung über den Begriff der Zahl

    OpenAIRE

    Frege, Gottlob

    1996-01-01

    Auf die Frage, was die Zahl Eins sei, oder was das Zeichen 1 bedeute, wird man meistens die Antwort erhalten: nun, ein Ding. Und wenn man dann darauf aufmerksam macht, dass der Satz "die Zahl Eins ist ein Ding" keine Definition ist, weil auf der einen Seite der bestimmte Artikel, auf der andern der unbestimmte steht, dass er nur besagt, die Zahl Eins gehöre zu den Dingen, aber nicht, welches Ding sie sei, so wird man vielleicht aufgefordert, sich irgendein Ding zu wählen, das man Eins nenn...

  15. Et brand er en samtale, men hvem råber højest?

    DEFF Research Database (Denmark)

    Hansen, Heidi

    2015-01-01

    I samtalen om brandet kan der være mange stakeholdere på banen. Spørgsmålet er, hvem der formår at sætte dagsordenen? Det skorter ikke på gode råd og how-to-do-it bøger i marketing branchen, og mange af disse råd er kloge og indsigtsfulde, men ligegyldigt hvilken opskrift man følger, kan man aldr...... kontrollere et brands betydning. Man kan blot forsøge at påvirke det i en bestemt retning. Et brand er nemlig ikke en fast størrelse, det er en social konstruktion, og virksomheden styrer ikke selv, hvilken brandværdi de tillægges af forbrugerne....

  16. Über den Nachrichtenwert von Friedensjournalismus - Ergebnisse einer experimentellen Studie

    Directory of Open Access Journals (Sweden)

    Monika Spohrs

    2006-04-01

    Full Text Available Laut Nachrichtenwertforschung hängt die Publikations- und Lesenswürdigkeit von Nachrichtentexten von den Nachrichtenfaktoren der zu publizierenden Ereignisse ab. Als anerkannte Nachrichtenfaktoren gelten beispielsweise Negativität, Vereinfachung und Personifizierung. Friedensjournalistische Arbeiten weichen von diesen Kriterien oft ab, indem sie versuchen, die berichteten Ereignisse in ihrer Komplexität darzustellen, den Fokus nicht auf negative Ereignisse zu legen und auch strukturellen Themen Raum zu geben. Aber sind sie deshalb weniger publikationswürdig? Der folgende Artikel zeigt anhand einer experimentellen Studie, welche Akzeptanz Friedensjournalismus beim Leser finden kann, auch wenn dies teilweise den Theorien der Nachrichtenwertforschung widerspricht. Des weiteren wird gezeigt, wie sich konstruktive Berichterstattung auf die mentalen Modelle der Rezipienten auswirkt und in welchem Zusammenhang diese beiden Ergebnisse miteinander stehen. In der vorliegenden Studie wurden einer für die Leserschaft der deutschen Qualitätspresse hinsichtlich Alter und Bildungsgrad repräsentativen Stichprobe von n = 128 Versuchspersonen Zeitungsartikel zu drei verschiedenen Ereignissen im Konfliktfeld des ehemaligen Jugoslawien dargeboten. Zu jedem Ereignis wurden vier verschiedene Textvarianten verwendet: eine gemäßigt eskalationsorientierte Originalfassung aus einer deutschen Qualitätszeitung (Die Welt, Frankfurter Allgemeine Zeitung, Süddeutsche Zeitung und drei modifizierte Versionen dieser Artikel, (a mit gemäßigt deeskalations-orientiertem Framing, (b mit stark deeskalationsorientiertem Framing und (c mit einer Verschärfung der Eskalationsorientierung der dargestellten Konflikte. Die Aufgabe der Vpn bestand darin, zu jedem der drei Ereignisse eine Textvariante zu lesen und danach in eigenen Worten schriftlich wiederzugeben und anschließend einen Fragebogen zu Akzeptanz, Glaubwürdigkeit, Ausgewogenheit, Neuigkeitsgehalt, Bewertung und Unterhaltungswert der Texte auszufüllen. Die mentalen Modelle der Vpn wurden mittels quantitativer Inhaltsanalyse der Nacherzählungen rekonstruiert. Die Ergebnisse der Studie befürworten die Publikation friedensjournalistischer Arbeiten. Deeskalationsorientierte Texte wurden keineswegs weniger akzeptiert als die Original-Artikel, und das deeskalationsorientierte Framing der Konflikte spiegelte sich in den mentalen Modellen der Teilnehmer wider

  17. Prospektive, monozentrische, einarmige, randomisierte, kontrollierte Studie über fraktionierte CO₂-Lasertherapie von freien Hauttransplantaten

    OpenAIRE

    Schönberger, Carmen

    2017-01-01

    Hintergrund: Nach einer Hauttransplantation ist häufig das ästhetische Ergebnis aufgrund von Pigmentverschiebungen und Narben stark beeinträchtigt und wird von den Patienten als unbefriedigend betrachtet. Bisher gibt es keine prospektive, randomisierte, kontrollierte in vivo Studie, die die Wirksamkeit des fraktionierten CO2-Lasers zur Konturanpassung und Narbenkorrektur von Hauttransplantaten nachgewiesen hat. Da sich allerdings in der Vergangenheit in zahlreichen Studien der fraktionierte C...

  18. Über Wahrheit und Lüge jenseits des deutsch-französischen Sinns

    OpenAIRE

    Keller, Thomas

    2017-01-01

    Der Beitrag will die Kontrastierung einer deutschen Abwertung der Lüge und einer französischen Lügenfreundlichkeit durch eine Rekonstruktion von transkulturellen pseudologischen Debatten ersetzen. Er erinnert an die Kollision des Kant’schen Lügenverbots mit der repressiven historischen Situation um 1800; Pragmatismus vermeidet Blutzeugentum (Constant und de Charrière). Er zeigt die lebensphilosophische Aufladung von Wahrheit und Lüge um 1900 – in Rollands Jean-Christophe ist die Wahrheit nur ...

  19. Wie aus dem Nichts etwas entsteht Gespräche über Antimaterie

    CERN Document Server

    AUTHOR|(CDS)2051122

    2018-01-01

    Antimaterie beschäftigt nicht nur Physiker, sondern auch die Phantasie von Science fiction-Autoren, Star Trek-Fans und Laien. Aber was ist eigentlich Antimaterie, und wie stellt man sie her? Kann man sie speichern? Wird sie bald eine Rolle im Alltag spielen? Und warum verdanken wir unsere Existenz – und die unseres Universums – einem winzigen Unterschied zwischen Materie und Antimaterie? Rolf Landua, einer der weltweit führenden Experten auf diesem Gebiet, beantwortet in seinem neuen Buch anschaulich diese und andere Fragen.

  20. RE-SONA-NC-E--I -No-v-em-ber-19-9-7

    Indian Academy of Sciences (India)

    Vineeta Bal and Satyajit Rath. Know Your Personal Computer You and Your PC. 5 K Ghoshal. GENERAL ARTICLES. , .) The Sun - Maior Energy Resource for the Future. Benny Joseph, K G Gopichandran and V K Vaidyan. - ~ Ohm's Law, Kirchoffs Law and the. Drunkard's Walk. Related Electrical Networks. RahulRoy.

  1. Aufklärungspflichten über Innenprovisionen, Kick-backs und Retrozessionen bei der Kapitalanlage

    OpenAIRE

    Decker, Leo

    2008-01-01

    Gegenstand der Arbeit Das Phänomen der Innenprovisionen - auch Kick-backs, Rückvergütungen oder Retrozessionen genannt - ist im Bereich der Kapitalanlage weit verbreitet. Dabei erhält z.B. der Vermittler eines Anlageproduktes oder ein Vermögensverwalter vom Anlageanbieter bzw. einem sonstigen Dritten eine Provision für die Vermittlung bzw. das Erwerben oder "Halten" eines bestimmten Produktes. Der Anleger, welcher den Vermittler oder Vermögensverwalter beauftragt hat, ist sich herkömmlich...

  2. Fully coupled Lattice Boltzmann simulation of fiber reinforced self compacting concrete flow

    DEFF Research Database (Denmark)

    Svec, Oldrich; Skocek, Jan; Stang, Henrik

    accurately the most important phenomena is introduced. A conventional Lattice Boltzmann method has been chosen as a fluid dynamics solver of the non-Newtonian fluid. A Mass Tracking Algorithm has been implemented to correctly represent a free surface and a modified Immersed Boundary Method (IBM) with direct...

  3. Data transmission optical link for LLRF TESLA project part II: application for BER measurements

    Science.gov (United States)

    Pozniak, Krzysztof T.; Romaniuk, Ryszard S.; Jalmuzna, Wojciech; Olowski, Krzysztof; Perkuszewski, Karol; Zielinski, Jerzy; Kierzkowski, Krzysztof

    2006-02-01

    It may be predicted now, even assuming a very conservative approach, that the next generation of the Low Level RF control systems for future accelerators will use extensively such technologies like: very fast programmable circuits equipped with DSP, embedded PC and optical communication I/O functionalities, as well as multi-gigabit optical transmission of measurement data and control signals.

  4. Über 20 Jahre ARIADNE. Die frauenspezifische Information und Dokumentation der Österreichischen Nationalbibliothek

    Directory of Open Access Journals (Sweden)

    Lydia Jammernegg

    2016-09-01

    Full Text Available 1992 wurde Ariadne als Fraueninformations- und -dokumentationsstelle an der Österreichischen Nationalbibliothek (ÖNB eingerichtet und arbeitet seitdem sowohl an der dokumentarischen Aufarbeitung des aktuellen frauen-, geschlechterrelevanten und feministischen Literaturbestandes als auch an der Sichtbarmachung des historischen Bestandes der ÖNB zu diesem Themenbereich. In diesem Beitrag geht es darum, die Position von Ariadne im Fraueninformations- und -dokumentationswesen, als Teil der ÖNB, an der Schnittstelle zur Frauenszene, Frauenbewegung, feministischen Szene und zur Frauen- und Geschlechterforschung einer Reflexion zu unterziehen. Nach einer mehr als 20-jährigen Tätigkeit soll ein Rückblick in die Geschichte zeigen, was Ariadne geleistet hat und wo Grenzen liegen, welche Ansprüche und Anliegen Ausgangspunkte für die Arbeit waren und wofür es heute noch frauenspezifische Informations- und Dokumentationseinrichtungen wie Ariadne braucht.

  5. Gesamtfahrzeugsimulation betriebsfestigkeitsrelevanter Manöver unter Berücksichtigung von Fahrwerkregelsystemen

    OpenAIRE

    Brandes, Sebastian Jürgen

    2016-01-01

    In der Automobilbranche dient im Bereich der betriebsfesten Bemessung des Fahrwerks die Methode der Mehrkörpersysteme als Analyseverfahren zur Ermittlung von Bewegungen und Schnittgrößen an den Fahrwerksbauteilen. Eine der aktuellen Herausforderungen hierbei ist der zunehmende interdisziplinäre Charakter in Form von mechatronischen Fahrwerkssystemen. In rein virtuellen Entwicklungsphasen kann deren Einfluss auf die Fahrwerksbelastungen einzig anhand von Gesamtfahrzeugsimulationen ermittelt we...

  6. R-ES-ONANCE--IOc-tO-ber-19-9-7

    Indian Academy of Sciences (India)

    A clone refers to a population of cells or organisms which were derived asexually from a single ancestor. ... Hence, the nuclei from early embryos seemed to ... have come from a stem cell, which had ... It remains to be seen if a human adult.

  7. Ein kurzer Überblick über die Geschichte der Fledermausforschung

    NARCIS (Netherlands)

    Eisentraut, M.

    1970-01-01

    Es ist das hohe Verdienst unserer Kollegen aus der CSSR, den Anstoss zu einem Zusammentreffen und einer engeren Zusammenarbeit der Chiropteren-Forscher aus aller Welt gegeben zu haben. Sie ergriffen, wie Sie wissen, die Initiative und luden 1968 zu der ersten internationalen Tagung in ihr Land ein.

  8. Globalisierung… und was wir glauben, darüber zu wissen

    DEFF Research Database (Denmark)

    Nell, Phillip Christopher

    2018-01-01

    Gastbeitrag. Wer die Medien aufmerksam verfolgt, wird feststellen, dass es schon seit längerem einen regelrechten Hype um das Thema der Globalisierung gibt.......Gastbeitrag. Wer die Medien aufmerksam verfolgt, wird feststellen, dass es schon seit längerem einen regelrechten Hype um das Thema der Globalisierung gibt....

  9. "Wir wissen, dass man 2050 über unsere Prognosen lachen wird"

    OpenAIRE

    Gugerli, David

    2011-01-01

    Euro, Atom, Umwelt – es kriselt allenthalben. Historiker David Gugerli ist überzeugt, dass der Glaube an die Technik abgenommen hat. Gleichzeitig wir lernen, mit den vielen Optionen unserer Zeit umzugehen.

  10. Andrej Voznesenskij und Genrich Sapgir. Zur Debatte über di postmodernistische Poetik in ihrem Werk

    Czech Academy of Sciences Publication Activity Database

    Ulbrechtová, Helena

    2011-01-01

    Roč. 31, 1/2 (2011), s. 1-15 ISSN 1432-4857 Institutional research plan: CEZ:AV0Z90920516 Keywords : Russian poetry -- 20th Century * Postmodernism * poetics * literary science Subject RIV: AJ - Letters, Mass-media, Audiovision

  11. Nordic nuclear emergency exercises. Final report of the BER-5 project

    International Nuclear Information System (INIS)

    Bennerstedt, T.; Stranden, E.; Salo, A.

    1994-05-01

    In all Nordic countries, nuclear emergency provisions have been revised following the Chernobyl accident. Local and national exercises are carried out regularly in each of the countries. Several actions have been taken to harmonize the approaches of individual Nordic countries. In order to further promote similar decision making procedures in an emergency situation, two Nordic exercises were conducted in 1993. It was important to see if all five countries (Denmark, Finland, Iceland, Norway and Sweden) responded in a similar way to a given situation, as far as risk assessment and countermeasures were concerned. The exercises were mainly aimed at decision makers and advisers of the five national emergency organizations. Thus, the exercises did not include comparison of underlying calculations on, e.g., atmospheric trajectories or transfer of radioactive material from air to ground. Such functions were tested separately in drills that formed part of the overall Nordic emergency preparedness program. It turned out that considerable effort is required to prepare exercises of this kind and magnitude. In each country, a national exercise leader was appointed. A Nordic evaluation team was set up. Common rules for the simulated inputs during the exercise and for the evaluators were decided on. The scenarios were prepared by an independent group. An essential planning item is the coordination of the Nordic exercises with those performed on a more routine basis in each country. The exercises included an acute-phase situation (NORA), and a late-phase situation (ODIN)

  12. Lehrerkooperation: theoretische reflexion über voraussetzungen zur erweiterung von kooperativität bei lehrern

    Directory of Open Access Journals (Sweden)

    Rainer Lengert

    2012-01-01

    Full Text Available Viele Bildungseinrichtungen verfolgen den Ausbau der Zusammenarbeit zwischen Lehrern, mit der Absicht, das Arbeitsklima zu pflegen und vor allem zur Verbesserung der Qualität ihres Bildungsangebotes. Allerdings bereiten die kooperativen Initiativen oft Unannehmlichkeiten, es sei denn, die Beteiligten kennen die umfangreichen Hintergründe, die höhere oder mindere Ebenen von Kooperation erleichtern oder behindern können. Diese Lücke wird im vorliegenden Artikel abgehandelt, indem neun Prämissen als Voraussetzung zur Erweiterung der Kooperation zwischen Lehrern dargestellt werden. Im Bewusstsein dieser Prämissen, ist es möglich, empirische Erforschungen künftig zu instrumentalisieren, wie auch Wege zu schaffen, Anforderungen an Lehrer und Schulen gewisser zu verwalten.Abstract Muitas instituições escolares têm aderido à busca de ampliar a cooperação entre seus professores, com a intenção de cuidar do ambiente de trabalho, mas, principalmente, de melhorar a qualidade de ensino oferecida. Porém, as iniciativas cooperativas costumam enfrentar dificuldades, sem que os envolvidos tenham conhecimento das causas amplas que impedem ou facilitam maiores ou menores níveis de cooperação. É dessa lacuna que trata o presente artigo, discutindo nove premissas que subjazem à possibilidade de ampliar a cooperação entre professores. Tendo consciência das premissas, é possível instrumentalizar futuras pesquisas empíricas, como também criar meios de gerir os requisitos que são de responsabilidade dos professores e das instituições escolares.

  13. Über die amorphen Stoffe in den Tonen verschiedener Böden

    NARCIS (Netherlands)

    Beutelspacher, H.; Marel, van der H.W.

    1961-01-01

    In der Feinfraktion des Bodens findet man die amorphen organischen Stoffe, die hauptsächlich aus Huminsäuren bestehen. W. Flaig und H. Beutelspacher (1950, 1951, 1954) konnten zeigen, daB sie im Elektronenmikroskop als kugelförmige Teilchen zu sehen sind.

  14. Effect of saline irrigation water on gas exchange and proline metabolism in ber (Ziziphus).

    Science.gov (United States)

    Bagdi, D L; Bagri, G K

    2016-09-01

    An experiment was conducted in pots of 25 kg capacity to study the effect of saline irrigation (EC 0,5,10,15 and 20 dSm-1) prepared by mixing NaCl, NaSO4, CaCl and MgCl2 in 3:1 ratio of chloride and sulphate on gas exchange traits, membrane stability, chlorophyll stability index and osmolytic defense mechanism in Ziziphus rotundifolia and Ziziphus nummularia species of Indian jujube (Z.mauritiana). Result showed that net photosynthetic rate (PN), transpiration (e) and stomatal conductance were comparatively lower in Ziziphus nummularia, which further declined with increasing level of saline irrigation water. Chlorophyll stability and membrane stability also declined significantly in salt stress, with higher magnitude in Ziziphus nummularia. The activity of proline anabolic enzymes; Δ1-Pyrrolline-5-carboxylate reductase, Δ1-Pyrrolline-5-carboxylate synthetase and Ornithine-δ-aminotransferase were recorded higher in Ziziphus rotundifolia with decrease in proline dehydrogenase. The sodium content was observed higher in roots of Ziziphus rotundifolia and leaves of Ziziphus nummularia. Therefore, it is suggested that salt tolerance mechanism was more efficiently operative in Ziziphus rotundifolia owing to better management of physiological attributes, osmolytic defense mechanism and restricted translocation of sodium from root to leaves along with larger accumulation of potassium in its leaves.

  15. A Escola de Governo: do berço à idade adulta

    Directory of Open Access Journals (Sweden)

    FÁBIO KONDER COMPARATO

    Full Text Available resumo A Escola de Governo foi criada em São Paulo em 1990, com o objetivo de explicar o mecanismo de funcionamento de nossas instituições políticas. Seu objetivo não é meramente teórico, mas sim prático; ou seja, colaborar para a progressiva correção dos rumos de nossa vida política, em obediência aos princípios fundamentais da República, da Democracia e do Estado de Direito. Para alcançar esse objetivo, os cursos ministrados na Escola focalizam principalmente os dois fatores estruturantes de toda sociedade política; a saber, a estrutura hierarquizada do poder e a mentalidade coletiva dominante. Procura-se mostrar que, desde sempre, tem havido uma dupla vigência do ordenamento jurídico nesse particular: por trás do direito oficial, em geral copiado do estrangeiro e praticamente inaplicado, existe efetivamente um outro direito, todo submetido aos comandos de uma oligarquia binária, composta dos potentados econômicos privados e dos grandes agentes estatais.

  16. "Ein grosser Vorsprung gegenüber Deutschland" : Architekten auf der Bauhausausstellung von 1923 in Weimar

    NARCIS (Netherlands)

    Van Bergeijk, H.

    2013-01-01

    This article discusses the Dutch contribution to the International Architecture Exhibition that was part of the Bauhaus Manifestation in 1923. The Dutch architect J.J.P. Oud, together with the director of the school in Weimar, Walter Gropius, decided which architects would be asked to his own

  17. Über die Gefügeausbildung technischer Magnesiumlegierungen in industriellen Gießprozessen

    OpenAIRE

    Klaus, Gerald

    2011-01-01

    The demand for lightweight constructions and light weight materials is probably as old as the transportation of people and goods. The aspiration in gaining even better light weight materials with increased mechanical properties is an old, but still actual topic. At this point magnesium alloys can be applied to fullfill this demand. Actually available commercial alloys have to be improved regarding their mechanical properties, especially for increased temperatures. This work aims to gain a bet...

  18. Jewish Survivors. Drei Publikationen über das Überleben

    Directory of Open Access Journals (Sweden)

    Sabine Kittel

    2000-11-01

    Full Text Available Drei Bücher aus den USA werden vorgestellt, die sich mit den Erinnerungen und Erzählungen jüdischer Überlebender und dem Leben nach dem Überleben befassen. Alle drei Autoren haben Interviews mit Überlebenden durchgeführt. Jede der Publikationen trägt der Individualität der Erfahrungen der Überlebenden und der Unbeschreibbarkeit ihrer Erlebnisse heute Rechnung. Die Autoren gehen mit unterschiedlichem Blickwinkel an die erzählten Erinnerungen heran: William Helmreich ist Soziologe, Henry Greenspan ist Psychologe und Theater-Schriftsteller, der in der Soziologie lehrt, Jared Stark kommt von der Literaturwissenschaft.

  19. Generation und Familie – über die Ambivalenz eines multistrukturellen Verhältnisses

    Directory of Open Access Journals (Sweden)

    Vera Bollmann

    2008-07-01

    Full Text Available Der Sammelband Generationen und Familien, welcher dem Soziologen Kurt Lüscher zum 70. Geburtstag gewidmet ist, stellt eine kritische Gegenwartsdiagnose des aktuellen Theorie- und Forschungsstandes zu diesem Thema dar. Schon in ihrem Vorwort machen die beiden Herausgeber auf die Diversität und den Facettenreichtum des Familien- und Generationenkonzeptes in modernen Gesellschaften aufmerksam: familiale Generationenbeziehungen werden in ganz unterschiedlicher Weise gelebt, und je nach theoretischer Lesart ergeben sich vielfältige Deutungsmuster. Die Beiträge nähern sich der Verflechtung von Familie, Generation und Gesellschaft sowohl in theoretischer als auch in empirischer Hinsicht. Inhaltlich reihen sie sich in drei übergeordnete Themenblöcke ein: „Generationen, Generationenverhältnisse und Generationenbeziehungen“, „Familie, Alltag und Identität“ und „Soziologie, Recht und Politik”.

  20. Über die Datenakzessivität in Printwörterbüchern

    African Journals Online (AJOL)

    R.B. Ruthven

    Alphabets des neuhochdeutschen Schriftsystems ein. Jedes Alphabet lässt sich unter zwei Aspekten betrachten, nämlich dem Verschriftungs- und dem Ord- nungsaspekt. Anders ausgedrückt heißt das: Jedes Alphabet ist bifunktional: Es dient der Verschriftung einer gesprochenen Sprache und hat damit einen Bezug.

  1. Santeria – von afrikanischen Orishas über kubanische Heilige zur amerikanischen „Lifestyle-Kultur“

    OpenAIRE

    Küpper, Stefan

    2009-01-01

    Diese Arbeit beschäftigt sich mit dem Entwicklungsprozess der Santeria im Rahmen der Afrikanischen Diaspora. Dabei werden die pluralen Formen der Orisha-Religion der Yoruba in Afrika im Hinblick auf ihre Funktion als religiöses Fundament der Santeria untersucht. Im Folgenden wird die Entstehung der Santeria auf Kuba, bedingt durch die Einfuhr einer Vielzahl von Yoruba Sklaven, analysiert. Dabei spielt die Vermischung des kubanischen Volkskatholizismus mit den Orishas der Yoruba, die in einer ...

  2. Modellierung der Energienachfrage unter Berücksichtigung urbaner Formen und individueller Zeitverwendung

    OpenAIRE

    Braun, Stephan

    2013-01-01

    Die Zeitverwendung von Personen als auch die Ausgestaltung und Form von Siedlungen, in denen die Aktivitäten der Menschen stattfinden, stellen zwei wesentliche Einflussfaktoren auf die Energienachfrage wie auch auf die Möglichkeiten der Energiebereitstellung dar. Die Arbeit betrachtet die Zusammenhänge von urbaner Form und Energiebedarf und beschreibt den Wert der Nutzung von Zeitbudgetdaten im Kontext energiegeographischer Fragestellungen. In der praktischen Analyse werden CORINE Landcover D...

  3. Über einige von Edw. Jacobson auf Java gesammelte Trichopteren

    NARCIS (Netherlands)

    Ulmer, Georg

    1913-01-01

    Seit ich das letzte Verzeichniss der javanischen Triphopteren gab (Notes Leyden Mus. 32. 1910, pp. 64—66) beschrieb Cornelius Betten („Notes on the Trichoptera in the collection of the Indian Museum.” Records of the Indian Museum. Calcutta, Oct. 1909, pp. 231—242 t. 14—18) unter andern indischen

  4. Information rates and post-FEC BER prediction in optical fiber communications

    NARCIS (Netherlands)

    Alvarado, Alex

    2017-01-01

    Information-theoretic metrics to analyze optical fiber communications systems with binary and nonbinary soft-decision FEC are reviewed. The numerical evaluation of these metrics in both simulations and experiments is also discussed. Ready-to-use closed-form approximations are presented.

  5. Study of the mechanical properties of Ziziphus nummularia (ber) fibers for formation of fiber reinforced composites

    Science.gov (United States)

    Joshi, Akshay; Mangal, R.; Bhojak, N.

    2018-05-01

    Ziziphus is the one of the most abundant plant of arid region of Rajasthan and rest part of desert land in world. There are a lots of research work going on and has been done on medical applications of this plant and it is playing very important role in economy of desert areas. In this paper our discussion will bring the attention its physical properties so that we can find the possibility of its applications in the various field of fiber reinforced composites which either can be used in such as interior & exterior part of automotive so it can reduce their overall weight, cost and improve its fuel efficiency without compromising in strength or can be used in flywheel technology for energy saving in automobiles or in building materials and so on. In this paper our approach is to extract the fiber from this plant, analyze the mechanical properties of the fiber and then discuss the various possibility of its application in appropriate field of composites. To find the possibility in FRC for Ziziphus fiber our next step is to compare it with other fibers whose composites have already been formed and studied.

  6. Bius, parbaringen und paniaran : über Demokratie und Religion bei den Tobabatak Nordsumatras

    NARCIS (Netherlands)

    Angerler, Johann

    2009-01-01

    This investigation is an attempt to gain a better understanding of the religious and socio-political organization of pre-colonial Tobabatak society. In literature the traditionally stateless Tobabatak society is usually depicted as being organized principally along kinship lines and there is still a

  7. BER EVALUATION OF LDPC CODES WITH GMSK IN NAKAGAMI FADING CHANNEL

    Directory of Open Access Journals (Sweden)

    Surbhi Sharma

    2010-06-01

    Full Text Available LDPC codes (Low Density Parity Check Codes have already proved its efficacy while showing its performance near to the Shannon limit. Channel coding schemes are spectrally inefficient as using an unfiltered binary data stream to modulate an RF carrier that will produce an RF spectrum of considerable bandwidth. Techniques have been developed to improve this bandwidth inefficiency or spectral efficiency, and ease detection. GMSK or Gaussian-filtered Minimum Shift Keying uses a Gaussian Filter of an appropriate bandwidth so as to make system spectrally efficient. A Nakagami model provides a better explanation to less and more severe conditions than the Rayleigh and Rician model and provide a better fit to the mobile communication channel data. In this paper we have demonstrated the performance of Low Density Parity Check codes with GMSK modulation (BT product=0.25 technique in Nakagami fading channel. In results it is shown that average bit error rate decreases as the ‘m’ parameter increases (Less fading.

  8. Beiträge zur Kenntnis der Pupillacea VII. Über zwei Wenig Bekannte Valloniidae

    NARCIS (Netherlands)

    Gittenberger, E.

    1977-01-01

    Spermodea spermatia (Da Silva e Castro) (Fig. 2) Helix spermatia J. da Silva e Castro, 1887: 249 (Locus typicus: "au bois de Bussaco", Bugaco, 40°22'N 8°21'W, etwa 15 km nnö. von Coimbra, Beira Litoral, Portugal — ? Syntypus: MHNG-Bgt2)). — A. Locard, 1899: 61. Helix (Acanthinula) spermatia — C. A.

  9. The upgraded cold neutron three-axis spectrometer FLEXX at BER II at HZB

    DEFF Research Database (Denmark)

    Duc Le, Manh; Skoulatos, Markos; Quintero-Castro, Diana Lucía

    2014-01-01

    Larmor labeling is seen as one of the key ingredients in the development of novel neutron instrumentation. FLEXX puts special emphasis on exploiting the neutron resonance spin echo (NRSE) technique for high-resolution spectroscopy on dispersive quasi-particle excitations. This enables unique...

  10. Financial Literacy in der Schweiz : Erhebung über den Stand des Finanzwissens

    OpenAIRE

    Stäheli, Thomas; Zobl, Matthias; Hobein, Günter A.

    2008-01-01

    Im Jahr 2005 hat die Organisation für wirtschaftliche Kooperation und Entwicklung (OECD) eine internationale Studie zum Thema "Analphabetismus im Finanzbereich" durchgeführt. Dabei wurde festgestellt, dass der Wissensstand bezüglich finanziellen Belangen bei einem Grossteil der Bevölkerung sehr gering ist und zudem stark überschätzt wird. Zudem wurde deutlich, dass die Menschen Schwierigkeiten haben, Informationen im Finanzbereich zu finden und zu verstehen. Zwei weitere Studien aus Deutschla...

  11. Über die des dialekts von Prekmurje in der volks – und Schriftsprache

    Directory of Open Access Journals (Sweden)

    Vilko Novak

    1985-12-01

    Full Text Available Das ca 1000 km2 umfangreiche Land Prekmurje (Übermurgebiet, zwischen der Mur und Raab (Rába, ist der nördlichste Teil der SR Slowenien. Weil das Land bis zum 12. 8. 1919 zu Ungarn gehörte, war es nationalpolitisch und kulturell vom übrigen Slowenentum in Österreich ganz abgetrennt. Die geringe literarische Tätigkeit - in erster Linie für religiöse, volkserbauliche und unterhaltsame Zwecke - konnte sich von 1715 weiter nur im einheimis.chen Dialekt entwickeln. So entstanden zuerst für die Evangelischen bestimmte Katechismen, Lasebücher und als Gipfel- ' punkt: die Übersetzung des Neuen Testaments von Števan Kuzmič (Nouvi Zákon ali Testamentom ••• Halle, 1771. An diese knüpften sich später die Psalmenübersetzung von Aleksander Terplan (1848, kirchliche Gesangbücher (von Mihál Bakoš 1789, Mihál Barla 1823, Jánoš Kardoš 1848', die auch das alte, zuerst im Grunde im kajkavischen Dialekt verfasste Liedergut in handschriftlichen Gesangbüchern (vom 17. Jh. weiter aufgenommen haben.

  12. Professor håber på åbenhed om CRISPR/Cas9

    DEFF Research Database (Denmark)

    Hokland, Peter

    2016-01-01

    CRISPR/Cas9 er navnet på en ny, revolutionerende genteknologi, der på sigt kan ændre menneskeheden. Forhåbentligt vil processen være være løbende opdateringer om frem- og tilbageskridt om teknikken, skriver professor.......CRISPR/Cas9 er navnet på en ny, revolutionerende genteknologi, der på sigt kan ændre menneskeheden. Forhåbentligt vil processen være være løbende opdateringer om frem- og tilbageskridt om teknikken, skriver professor....

  13. Notizen über Ciliaten aus konzentrierten Salzgewässern

    NARCIS (Netherlands)

    Ruinen, J.

    1938-01-01

    Die Kenntnis der Ciliatenfauna der Salzgewässer von höherer Konzentration als Meereswasser ist heute noch als sehr unvollständig zu betrachten. Nur wenige Autoren haben sich eingehender mit der Biologie dieser Wässer beschäftigt. Einerseits ist ein Bestreben wahrzunehmen eine möglichst vollständige

  14. Werte, existentielle Schuld und Hilfsbereitschaft gegenüber Indios und landlosen Bauern in Paraguay

    OpenAIRE

    Schmitt, Manfred; Behner, Robert; Müller, Lothar; Montada, Leo

    1992-01-01

    Die Untersuchung ist eine Replikation vorangegangener Studien zur psychologischen Verarbeitung eigener Bevorteilung in Relation zur Benachteiligung anderer. 80 paraguayischen Studierenden wurden Benachteiligungsepisoden von landlosen Bauern (Campesinos) und Indianern geschildert. Die Probanden sollten anhand vorgegebener Reaktionsmöglichkeiten angeben, wie sie die geschilderten Benachteiligungen beurteilen (z.B. als wie ungerecht), welche Emotionen diese bei ihnen auslösen (z.B. Schuldgefühle...

  15. BER Performance of Stratified ACO-OFDM for Optical Wireless Communications over Multipath Channel

    OpenAIRE

    Gebeyehu, Zelalem Hailu; Langat, Philip Kibet; Maina, Ciira Wa

    2018-01-01

    In intensity modulation/direct detection- (IM/DD-) based optical OFDM systems, the requirement of the input signal to be real and positive unipolar imposes a reduction of system performances. Among previously proposed unipolar optical OFDM schemes for optical wireless communications (OWC), asymmetrically clipped optical OFDM (ACO-OFDM) and direct current biased optical OFDM (DCO-OFDM) are the most accepted ones. But those proposed schemes experience either spectral efficiency loss or energy e...

  16. Die Mathematik und andere Kurzsprachen : Über John von Neumann, The Computer and the Brain

    NARCIS (Netherlands)

    Leydesdorff, L.; Baecker, D.

    2016-01-01

    Das Buch The Computer and the Brain (1958, dt. 1991; im Folgenden wird nach der deutschen Übersetzung zitiert) ist die gedruckte Version der Silliman Lectures, die zu halten John von Neumann 1956 nach Yale eingeladen worden war. Obwohl sie bis zum März 1956 vorbereitet waren, wurden sie nie

  17. Von Fouqué über Oehlenschläger bis Andersen

    DEFF Research Database (Denmark)

    de Mylius, Johan

    2010-01-01

    Centralromantisk myte i dens udformning hos Friedrich de la Motte Fouqué (1811), i Oehlenschlägers forkortede bearbejdelse og oversættelse (Eventyr af forskjellige Digtere, 1816) og HCAs "Den lille Havfrue" (1837)....

  18. BER analysis for MPAM signal constellations in the presence of fading and ADC quantization noise

    NARCIS (Netherlands)

    Rizvi, U.H.; Janssen, G.J.M.; Weber, J.H.

    2009-01-01

    In this letter, closed-form expressions for the bit error rate of M-ary pulse amplitude modulated signal constellations as a function of the analog-to-digital converter word length, the signal-to-noise ratio and the fading distribution, are derived. These results allow for a rapid and accurate

  19. RE-SO-NANCE--Ioc-to-ber-19-9-6

    Indian Academy of Sciences (India)

    of DNA uptake by bacteria laid the ... to study expression of genes. ... by yeasts to produce alcoholic beverages, large scale production of antibiotics and ... in biotechnology are the results of our understanding of biological processes and.

  20. Tres Formas de Libertad: Hayek, Berlín y Rawls

    Directory of Open Access Journals (Sweden)

    Carlos Gil de Gomez Perez-Aradros

    2016-07-01

    Full Text Available Resumen Artículo de reflexión. La libertad –su ejercicio y su titularidad– ha sido un tema recurrente en el pensamiento a lo largo de la Historia. No obstante, cada autor que se ha acercado a ella la ha interpretado de un modo distinto; incluso dentro de la misma escuela de pensamiento. Así las cosas, este estudio pretende contraponer y enfrentar la diferente visión que de la libertad han tenido tres de los intelectuales más influyentes del siglo XX: F. Hayek, Isaiah Berlin y J. Rawls. Esta contraposición doctrinal permitirá concluir que la libertad liberal bascula entre la autoderminación y el reconocimiento. A través de los principales tex- tos originales de los tres autores mencionados y de otros y utilizando una metodología analítica-comparativa, se logran perfilar los distintos contornos de la libertad liberal y sus vínculos con la autodeterminación y el reconocimiento debido. Palabras clave: Libertad, Ética, Coacción, Racionalismo. Abstract Freedom – its exercise and its ownership- has been a recurring theme throughout the history of thought. Nonetheless, each author who has approached it has interpreted it in a different way, even within the same school of thought. Thus, this study aims at comparing and contrasting the different visions of freedom of three of the most influential intellectuals of the twentieth century: F. Hayek, Isaiah Berlin and J. Rawls. This comparison of doctrines will lead to the conclusion that liberal freedom shifts between self-determination and recognition. Through the major texts of the three authors and others, and using an analytical-comparative methodology, the article manages to outline the different shapes of liberal freedom and its links with self-determination and recognition. Keywords: Freedom, Ethics, Coercion, Rationalism. Resumo A Liberdade -seu exercício e posse- tem sido um tema recorrente no pensamento ao longo da história. Entretanto, cada autor se aproximou a ela com uma interpretação a sua maneira diferente, inclusive dentro da mesma escola de pensamento. Assim, este estudo tem o objetivo de opor-se e confrontar as diferentes visões que a liberdade teve a partir de três dos intelectu- ais mais influentes do século XX: F. Hayek, Isaiah Berlin e J. Rawls. Esta oposição doutrinal permite concluir que as liberdades liberais oscilam entre a autoderminação e o reconhecimento. Através dos principais textos originais destes três autores entre outros, e usando uma metodologia de análise comparativa se consegue um esboço dos diferentes contornos da liberdade liberal e de suas ligações com a autodeterminação e o devido reconhecimento. Palavras chave: Liberdade, Ética, Coerção, o Racionalismo. 

  1. På fornavn og sms med verdens mest berømte detektiv

    DEFF Research Database (Denmark)

    Lauridsen, Palle Schantz

    2014-01-01

    Et essay om brugen af nye medier i og omkring BBC's "Sherlock" i anledning af premieren på 3. sæson......Et essay om brugen af nye medier i og omkring BBC's "Sherlock" i anledning af premieren på 3. sæson...

  2. Knochendichte und Laktoseintoleranz - Übersicht über aktuelle Entwicklungen

    Directory of Open Access Journals (Sweden)

    Obermayer-Pietsch B

    2004-01-01

    Full Text Available Osteoporose ist eine multifaktorielle Erkrankung, die zu fast 70 % genetisch bedingt sein dürfte. Unter zahlreichen genetischen Faktoren ist eine primäre (angeborene, im Erwachsenenalter manifeste Laktoseintoleranz (Milchzuckerunverträglichkeit ein wesentlicher Faktor, der etwa 20–25% aller Österreicher betreffen dürfte, wie aus neuesten Studien hervorgeht. Laktase ist ein intestinales Enzym, das Milchzucker (Laktose in Galaktose und Glukose spaltet. Bei Fehlen des Enzyms treten Symptome der Laktosemaldigestion mit Meteorismus bis hin zu Durchfällen auf und führen bei Betroffenen zu einem instinktiven Meiden von Milch und laktosehaltigen Nahrungsmitteln. Der Nachweis einer Mutation der Laktaseregulation ist ein PCRbasierter, direkter Test. Damit ergibt sich für die primäre Laktoseintoleranz im Vergleich zu bisherigen indirekten Tests (H2-Atemtest, Laktosetoleranztest eine präzise Diagnostik. Kontroverse Ergebnisse um die Bedeutung der Laktoseintoleranz für den Knochenstoffwechsel können damit geklärt werden. Personen mit gastrointestinalen Symptomen nach Milchgenuß bzw. Patienten mit erniedrigter Knochendichte sollten einer solchen einfachen Screeningdiagnostik zugeführt werden, um eine adäquate Therapie/Ernährungsumstellung (laktosearme/-freie Ernährung, Laktasezusätze und/oder zusätzliche Kalziumquellen zum Erhalt einer ausgeglichenen Kalziumbilanz einleiten zu können.

  3. Entwicklungen in der Internen und der Externen Revision unter Berücksichtigung mittelgrosser Unternehmen

    OpenAIRE

    Ruud, T F; Friebe, P; Isufi, S

    2009-01-01

    Aufgrund neuer gesetzlicher Bestimmungen sehen sich derzeit in der Schweiz nicht nur Grossunternehmen, sondern auch mittelgrosse Unternehmen mit Herausforderungen hinsichtlich des Risikomanagements und des Internen Kontrollsystems konfrontiert. Der Verwaltungsrat ist sowohl für das Risikomanagement als auch für das Interne Kontrollsystem verantwortlich. Allerdings werden die entsprechenden operativen Aufgaben delegiert, sodass für die Steuerung und Kontrolle der Risiken primär die Geschäftsle...

  4. BER-EUKA KERJA ISLAMI: IBADAH DAN DAKWAH DI TEMPAT KERJA

    Directory of Open Access Journals (Sweden)

    Aris Nurohman

    2016-11-01

    Full Text Available Islamic work ethic is an Islamic ethic that has been pradiced among the staff base on Islamideaching. islamic work ethic is very important applied in the workplace as a guide staff in performing work in accordance with the values of religious teachings, because the Islamic religion is not only seen as the work of worshipthatwill getthe reward forthe perpetrators, butalso can affedtheformation of a good culture work environment. In this case the ethical work has implications for the effort dakwah bil hal to others in the work environment.

  5. Über die Forschung der Siedlung Uugla Veskimäe / Mati Mandel

    Index Scriptorium Estoniae

    Mandel, Mati, 1945-

    2006-01-01

    2005. aastal jätkati Läänemaal muististitekompleksi uurimist Uugla külas Veskimäe asula kaevamistega. Rajatud kolme kaevandi leiumaterjalist. Suurimaks üllatuseks oli neoliitiliste asustusjälgede avastamine Uuglas

  6. A 750 MHz semi-digital clock and data recovery circuit with 10−12 BER

    International Nuclear Information System (INIS)

    Wei Xueming; Wang Yiwen; Li Ping; Luo Heping

    2011-01-01

    A semi-digital clock and data recovery (CDR) is presented. In order to lower CDR trace jitter and decrease loop latency, an average-based phase detection algorithm is adopted and realized with a novel circuit. Implemented in a 0.13 μm standard 1P8M CMOS process, our CDR is integrated into a high speed serial and de-serial (SERDES) chip. Measurement results of the chip show that the CDR can trace the phase of the input data well and the RMS jitter of the recovery clock in the observation pin is 122 ps at 75 MHz clock frequency, while the bit error rate of the recovery data is less than 10 × 10 −12 . (semiconductor integrated circuits)

  7. Excavaciones en el Tíber durante los siglos XVIII y XIX

    Directory of Open Access Journals (Sweden)

    García Sánchez, Jorge

    2004-12-01

    Full Text Available Since the Renaissance, the Tiber River has been the object of the most unusual archaeological quests, driven mainly by fantastic medieval lore. In the 18th and 19th centuries, the excavations on the river intensified and were epitomized by the scientific atmosphere of the Enlightenment, even tough they resulted in little archaeological worth. In 1819, even the Spanish monarch Fernando VII almost became a Shareholder in one of these archaeological companies. After the Italian unification, many finds were discovered in the works done along the Tiber's urban region, of wich many are now in the Museo Nazionale Romano.Desde el Renacimiento el Tiber ha sido objeto de las más peregrinas búsquedas arqueológicas, emprendidas habitualmente sobre la base de fantásticos relatos medievales. En los siglos XVIII y XIX las excavaciones en el río se intensificaron y se dotaron del cientificismo propio de la Ilustración, siendo no obstante el fruto de estos trabajos muy escaso; en 1819, incluso el propio monarca español Fernando VII estuvo a punto de convertirse en accionista de una de estas empresas arqueológicas. Tras la Unificación italiana, las obras de estructuración del curso urbano del Tiber propiciaron finalmente numerosos hallazgos, muchos de los cuales se conservan en el Museo Nazionale Romano.

  8. Die Fußnote über Geognosia in Humboldts Florae Fribergensis specimen

    Directory of Open Access Journals (Sweden)

    Herbert Pieper

    2007-04-01

    Full Text Available Article in German, Abstracts in English and GermanHumboldt distinguished between three disciplines dealing with the inquiring of the earth: geognosia, historia telluris, physiografia. In 1793, he used the notion of “Geognosie” for the first time. He explained the notion in a footnote that was reprinted in 1815, 1817, and again in 1845. The paper analyses the meaning attributed by Humboldt to the notion of “Geognosie” and gives a new German translation of the Latin texts of the footnote.

  9. Resultat och berättelser - En analys av sportnyheterna i finsk och svensk television

    OpenAIRE

    Silfverberg, Kalle

    2004-01-01

    Endast sammandrag. Inbundna avhandlingar kan sökas i Helka-databasen (http://www.helsinki.fi/helka). Elektroniska kopior av avhandlingar finns antingen öppet på nätet eller endast tillgängliga i bibliotekets avhandlingsterminaler. Only abstract. Paper copies of master’s theses are listed in the Helka database (http://www.helsinki.fi/helka). Electronic copies of master’s theses are either available as open access or only on thesis terminals in the Helsinki University Library. Vain tiivi...

  10. Über die normativen Implikationen des Ordoliberalismus für die moderne Wirtschaftsethik

    OpenAIRE

    Klump, Rainer; Wörsdörfer, Manuel

    2014-01-01

    Eucken's writings are rich in content not only from an (constitutional) economic perspective but also from an economic and business ethics perspective – an often neglected perspective of the reception of German Ordoliberalism in general and the Freiburg School of Economics in particular. The paper gives a first insight into the ethical-normative thinking of Eucken, as one of the main representatives of Ordoliberalism, and explains Eucken’s conception of Social Market Economy as a functioning ...

  11. Über die normativen Implikationen des Ordoliberalismus für die moderne Wirtschaftsethik

    OpenAIRE

    Klump, Rainer; Wörsdörfer, Manuel

    2009-01-01

    "Bei der Rezeption der ordoliberalen Freiburger Schule wurde bislang die wirtschaftsethische Perspektive weitgehend vernachlässigt. Der Aufsatz gibt vertiefte Einblicke in das ethisch-normative Denken des Ordoliberalismus am Beispiel des Werkes von Walter Eucken. Dabei wird es neben der Bestimmung der Sozialen Marktwirtschaft als funktionsfähige und menschenwürdige Ordnung um Euckens an Kant angelehntes Freiheitsverständnis gehen sowie um eine Einordnung Euckens in die moderne Wirtschafts- un...

  12. High SNR BER comparison of coherent and differentially coherent modulation schemes in lognormal fading channels

    KAUST Repository

    Song, Xuegui

    2014-09-01

    Using an auxiliary random variable technique, we prove that binary differential phase-shift keying and binary phase-shift keying have the same asymptotic bit-error rate performance in lognormal fading channels. We also show that differential quaternary phase-shift keying is exactly 2.32 dB worse than quaternary phase-shift keying over the lognormal fading channels in high signal-to-noise ratio regimes.

  13. Das alchemistische Traktat des Marcus Eugenius Bonacina von 1616 über Trinkgold

    Czech Academy of Sciences Publication Activity Database

    Purš, Ivo

    -, č. 8 (2008), s. 77-90 ISSN 1213-5372 R&D Projects: GA AV ČR IAA800330702 Institutional research plan: CEZ:AV0Z80330511 Keywords : alchemy * iconography * history Subject RIV: AL - Art, Architecture, Cultural Heritage

  14. Når tælleriet løber af med os

    DEFF Research Database (Denmark)

    Nielsen, Gritt B.; Sarauw, Laura Louise

    2014-01-01

    Studiefremdriftsreformen kan ses som en slags omvendt motorvejslogik, hvor de studerende belønnes for at køre (for) stærkt. Samtidig er den anvendte kilometerenhed, det såkaldte ECTS-system (European Credit Transfer System), en rent kvantitativ logik. Den måler med andre ord ikke det faglige niveau...... eller sværhedsgrad, men den tid, de studerende (teoretisk set) forventes at bruge på et forløb. Kravet om en minimumakkumulation af 60 ECTS-point årligt betyder således, at studerende på tværs af fag vil skulle bevæge sig igennem uddannelsessystemet i samme tempo og takt. Tid bliver hermed en faktor...

  15. Aperture averaging and BER for Gaussian beam in underwater oceanic turbulence

    Science.gov (United States)

    Gökçe, Muhsin Caner; Baykal, Yahya

    2018-03-01

    In an underwater wireless optical communication (UWOC) link, power fluctuations over finite-sized collecting lens are investigated for a horizontally propagating Gaussian beam wave. The power scintillation index, also known as the irradiance flux variance, for the received irradiance is evaluated in weak oceanic turbulence by using the Rytov method. This lets us further quantify the associated performance indicators, namely, the aperture averaging factor and the average bit-error rate (). The effects on the UWOC link performance of the oceanic turbulence parameters, i.e., the rate of dissipation of kinetic energy per unit mass of fluid, the rate of dissipation of mean-squared temperature, Kolmogorov microscale, the ratio of temperature to salinity contributions to the refractive index spectrum as well as system parameters, i.e., the receiver aperture diameter, Gaussian source size, laser wavelength and the link distance are investigated.

  16. Über die Stimmmodalitäten innerhalb der ersten Zenturiatklasse

    OpenAIRE

    Ryan, F.X.

    2003-01-01

    Herausgearbeitet wird eine nicht bezeugte Reform, die auf den ersten Blick die Verfahrensweise innerhalb der ersten Zenturiatklasse regelte, letztlich aber auch zu der Fähigkeit des Systems beitrug, mehrere Gewinner an ein und demselben Tag herbeizuschaffen. An unattested reform of the voting procedures in the first class of the centuriate assembly constitutes at once a new chapter in the history of this assembly and a partial explanation of the success with which the Romans filled several...

  17. Über die Reaktion von [alpha]- und [beta]-Tetralon mit Kaliumsuperoxid

    OpenAIRE

    Lissel, Manfred

    1984-01-01

    The reaction of [alpha]- and [beta]-tetralone with potassium superoxide is described. In addition to 2-hydroxy-1,4-naphthoquinone [alpha]-naphthol is formed from [alpha]-tetralone and [beta]-naphthol and 2-carboxy-benzenepropionic acid from [beta]-tetralone.

  18. Bill Gates køber sig til positive historier om udviklingsbistanden

    DEFF Research Database (Denmark)

    Fejerskov, Adam Moe

    2014-01-01

    Flere store og velansete medier får penge af Bill Gates' fond for at at bringe positive historier om udviklingsbistanden. Men det medfører en risiko for at journalistikken bliver ukritisk og overfladisk......Flere store og velansete medier får penge af Bill Gates' fond for at at bringe positive historier om udviklingsbistanden. Men det medfører en risiko for at journalistikken bliver ukritisk og overfladisk...

  19. Die Tischglocke Rudolfs II: über ihren Urheber und ihre Bedeutung

    Czech Academy of Sciences Publication Activity Database

    Bukovinská, Beket; Purš, Ivo

    -, č. 10 (2010), s. 89-104 ISSN 1213-5372 Institutional research plan: CEZ:AV0Z80330511 Keywords : Rudolphinian art * Rudolf II * magic * hermetic philosophy Subject RIV: AL - Art, Architecture, Cultural Heritage

  20. ULUSLARARASI İLİŞKİLERDE SİBER CAYDIRICILIK

    OpenAIRE

    KORHAN, Sevda

    2017-01-01

    Günümüzde devletler, kendi güvenlik altyapılarını, ekonomilerini ve diğer bütün varlıklarını savunmak amacıyla askeri ve siber alanda caydırıcılığı etkili bir araç olarak kullanmaktadırlar. Siber saldırılar, her ne kadar nükleer alanda oluşabilecek saldırılarla kıyaslanamasa da, uluslararası güvenlik için ciddi bir tehdit oluşturmaktadırlar. Yakın zamanda gerçekleşen siber saldırı örnekleri, gelecekte oluşabilecek uluslararası çatışmalarda siber saldırıların öncü rol oynayacağının sinyallerin...

  1. BER UZAYDA AKTÖR - GÜÇ İLİŞKİSİ

    OpenAIRE

    Korhan, Sevda

    2018-01-01

    Siber alanın hızla büyümesi dünya siyasetinde önemli bir bağlamdır ve siber, gücü kendisine bağlamaktadır. Anonimlik unsuru, güvenlikte asimetrilerin varlığı, siber araçlara erişmenin maliyetinin düşük olması gibi sebepler devletdışı aktörlerin de siber alanda sert ve yumuşak bir güç sunma kapasitesine sahip olmalarını kolaylaştırmaktadır. Siberin doğasında var olan özellikler, aktörler arasındaki güç farklılıklarını önemli oranda azaltmakta ve bu durum 21. yüzyılda küresel siyaseti simgeleye...

  2. Traethedsbrud af collum femoris hos rask maratonløber

    DEFF Research Database (Denmark)

    Nielsen, Klaus; Christensen, Ole; Lukina, Guy Feruzi

    2009-01-01

    Fatigue fractures of the hip are rare causes of hip pain. Delayed diagnostics of this type of fracture can cause serious complications. We describe a case concerning a 32-year-old male amateur runner who experienced hip pain with rapid onset during his first marathon. After eight days his general......-old male amateur runner who experienced hip pain with rapid onset during his first marathon. After eight days his general practitioner referred him to the hospital and a dislocated fracture of the femoral neck was detected. Udgivelsesdato: 2009-Oct-5 Udgivelsesdato: 2009...

  3. RESO-NA-NCEIse-Pt-em-ber-19-9-7

    Indian Academy of Sciences (India)

    I/s Generation, Transmission and Distribution. D P Sen Gupta. FEATURE ARTICLES. 48 What's New in Computers? MMX Technology for Multimedia pes ... A Good Text Book on Group Theory for Post Graduates. K N Rajeswari. REFLECTIONS. The Determinants of the Scientific Revolution. Early Thinking. Virendra Singh.

  4. BER reduction for mQAM high-speed transmission in optical fiber ...

    African Journals Online (AJOL)

    SANOUSerge

    Indeed, OFDM using mQAM modulation seems to be a good candidate in high ... and Matlab software. The simulation results showed that error correcting codes and particularly LDPC codes are .... channel coding as the process consist on.

  5. V4: The Small Angle Scattering Instrument (SANS at BER II

    Directory of Open Access Journals (Sweden)

    Uwe Keiderling

    2016-11-01

    Full Text Available V4 is a small-angle neutron scatting instrument with an accessible range of scattering vector 0.01 nm-1 < Q < 8.5 nm-1. Outstanding features of the instrument are the polarized neutron option and the list mode data acquisition, allowing for time-resolved measurements with µs time resolution.

  6. Effect of buck driver ripple on BER performance in visible light communication using LED

    NARCIS (Netherlands)

    Deng, X.; Linnartz, J.P.M.G.; Arulandu, K.; Zhou, G.; Wu, Y.

    2015-01-01

    This paper analyses the communication performance for visible light communication (VLC) with Manchester encoded amplitude modulation. In particular, it considers the ripple generated by the LED driver as an important noise contribution for VLC. The ripple depends on the oscillation frequency of the

  7. Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat.

    Science.gov (United States)

    Brevik, Asgeir; Joshi, Amit D; Corral, Román; Onland-Moret, N Charlotte; Siegmund, Kimberly D; Le Marchand, Loïc; Baron, John A; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C

    2010-12-01

    A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. ©2010 AACR.

  8. A organização do trabalho na assistência ao recém-nascido em berçários da regional de Ribeirão Preto-SP. Brasil-1992 La organización del trabajo en la asistencia al recién-nacido en guarderías de la región de Ribeirão Preto-SP. Brasil-1992 The organization of newborn care in nurseries in the region of Ribeirão Preto-SP. Brasil-1992

    Directory of Open Access Journals (Sweden)

    Carmen Gracinda Silvan Scochi

    1997-01-01

    Full Text Available O estudo analisa a organização da assistência ao recém-nascido em berçários da regional de Ribeirão Preto e a participação da enfermagem neste trabalho. Através de observação e entrevistas em quatro berçários, constata-se que a organização do trabalho diferencia-se pelo porte e complexidade do hospital. A ação está centrada na criança e nos casos mais complexos prioriza -se a patologia e a assistência clínica. Percebe-se também, algumas ações mais amplas, apreendendo o binômio mãe-filho e a família. O nível de atenção é resultado de uma complexa combinação dos recursos humanos, materiais e área física. A instituição de maior porte e complexidade apresenta diversidade de agentes, trabalho mais burocratizado e hierarquizado, sistema de informação e tecnologias complexas, procedimentos rotinizados mediados por normas escritas e aparelhos sofisticados. O objeto de ação está centrado na criança, mas há práticas cujo objeto é ampliado para o binômio mãe-filho e familiares.Las autoras analizaron la organización de la asistencia al recién-nacido en guarderías de la región de Ribeirão Preto y cómo la enfermería participa de este trabajo. A través de observación y citas en cuatro guarderías, las autoras constataron que la organización del trabajo se diferencia por el porte y complejidad del hospital. La acción está centrada en el niño y en casos más complejos se privilegia la patología y la asistencia clínica. Percibieron también algunas acciones más amplias, aprehendiendo el binomio madre-niño y la familia. El nivel de la atención es el resultado de una compleja combinación de los recursos humanos, materiales e instalaciones. La institución de mayor porte y complejidad presenta diversidad de agentes, trabajo más burocratizado y jerarquizado, sistema de información y tecnología complejas, procedimientos rutinarios mediados por normas escritas y aparatos sofisticados. El objeto de

  9. Human monocytes undergo excessive apoptosis following temozolomide activating the ATM/ATR pathway while dendritic cells and macrophages are resistant.

    Directory of Open Access Journals (Sweden)

    Martina Bauer

    Full Text Available Immunodeficiency is a severe therapy-limiting side effect of anticancer chemotherapy resulting from sensitivity of immunocompetent cells to DNA damaging agents. A central role in the immune system is played by monocytes that differentiate into macrophages and dendritic cells (DCs. In this study we compared human monocytes isolated from peripheral blood and cytokine matured macrophages and DCs derived from them and assessed the mechanism of toxicity of the DNA methylating anticancer drug temozolomide (TMZ in these cell populations. We observed that monocytes, but not DCs and macrophages, were highly sensitive to the killing effect of TMZ. Studies on DNA damage and repair revealed that the initial DNA incision was efficient in monocytes while the re-ligation step of base excision repair (BER can not be accomplished, resulting in an accumulation of DNA single-strand breaks (SSBs. Furthermore, monocytes accumulated DNA double-strand breaks (DSBs following TMZ treatment, while DCs and macrophages were able to repair DSBs. Monocytes lack the DNA repair proteins XRCC1, ligase IIIα and PARP-1 whose expression is restored during differentiation into macrophages and DCs following treatment with GM-CSF and GM-CSF plus IL-4, respectively. These proteins play a key role both in BER and DSB repair by B-NHEJ, which explains the accumulation of DNA breaks in monocytes following TMZ treatment. Although TMZ provoked an upregulation of XRCC1 and ligase IIIα, BER was not enhanced likely because PARP-1 was not upregulated. Accordingly, inhibition of PARP-1 did not sensitize monocytes, but monocyte-derived DCs in which strong PARP activation was observed. TMZ induced in monocytes the DNA damage response pathways ATM-Chk2 and ATR-Chk1 resulting in p53 activation. Finally, upon activation of the Fas-receptor and the mitochondrial pathway apoptosis was executed in a caspase-dependent manner. The downregulation of DNA repair in monocytes, resulting in their selective

  10. Nutritional Quality of Breakfast and Physical Activity Independently Predict the Literacy and Numeracy Scores of Children after Adjusting for Socioeconomic Status

    Science.gov (United States)

    O'Dea, Jennifer A.; Mugridge, Anna C.

    2012-01-01

    Health-related behaviors [physical activity (PA), nutritional quality of breakfast and sleep]; personal variables (self-esteem, attitudes to PA and gender) and socioeconomic status (SES) (school SES and parental education), were examined in relation to literacy and numeracy scores of 824 grade 3-7 children. Participants completed a questionnaire,…

  11. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, Joseph W., E-mail: jwshelt@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waxweiler, Timothy V.; Landry, Jerome; Gao, Huiying; Xu, Yanbo; Wang, Lanfang [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Shu, Hui-Kuo G. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-07-01

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm{sup 3}. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.

  12. Smoking History Predicts Sensitivity to PARP Inhibitor Veliparib in Patients with Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Reck, Martin; Blais, Normand; Juhasz, Erzsebet; Gorbunova, Vera; Jones, C Michael; Urban, Laszlo; Orlov, Sergey; Barlesi, Fabrice; Kio, Ebenezer; Keilholz, Ulrich; Qin, Qin; Qian, Jiang; Nickner, Caroline; Dziubinski, Juliann; Xiong, Hao; Mittapalli, Rajendar K; Dunbar, Martin; Ansell, Peter; He, Lei; McKee, Mark; Giranda, Vincent; Ramalingam, Suresh S

    2017-07-01

    Tobacco-related NSCLC is associated with reduced survival and greater genomic instability. Veliparib, a potent poly(adenosine diphosphate-ribose) polymerase inhibitor, augments platinum-induced DNA damage. A phase 2 trial of untreated advanced NSCLC showed a trend for improved outcomes (hazard ratio [HR] = 0.80, 95% confidence interval: 0.54-1.18, p = 0.27 for overall survival and HR = 0.72, 95% CI: 0.45-1.15, p = 0.17 for progression-free survival) when veliparib was added to carboplatin/paclitaxel. Here we report an exploratory analysis by smoking history. Patients were randomized 2:1 to receive carboplatin/paclitaxel with veliparib, 120 mg (n = 105), or placebo (n = 53). Patients were stratified by histologic subtype and smoking history (recent smokers [n = 95], former smokers [n = 42], and never-smokers [n = 21]). Plasma cotinine level was measured as a chemical index of smoking. Mutation status was assessed by whole exome sequencing (n = 38). Smoking history, histologic subtype, age, Eastern Cooperative Oncology Group performance status, sex, and geographic region predicted veliparib benefit in univariate analyses. In multivariate analysis, history of recent smoking was most predictive for veliparib benefit. Recent smokers treated with veliparib derived significantly greater progression-free survival and overall survival benefits (HR = 0.38 [p Smoking history predicted for efficacy with a veliparib-chemotherapy combination; toxicity was acceptable regardless of smoking history. A prespecified analysis of recent smokers is planned for ongoing phase 3 studies of veliparib in NSCLC. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  13. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); H.B. Beverloo (Berna); A.R.M. von Bergh (Anne); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2005-01-01

    textabstractDrug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7,

  14. Kritische Sicht der Literatur über die (südslawische Entsprechung der Gruppe tl/dl unter spezieller Berücksichtigung des rumänischen mocirlǎ

    Directory of Open Access Journals (Sweden)

    Varja Orešnik Cvetko

    1993-12-01

    Full Text Available Das Problem der Entsprechung der urslawischen Verbindung *tl/dl in den siisla­ wischen Sprachen war teilweise Gegenstand von kontroversen Interpretationen. Noch besonders strittig war die Interpretation des zweifachen Nachweises in den Preisinger Denkmfilem. So stellt z.B. Issatschenko 1943 in seiner deutschen Zusammenfassung folgendes fest (S. 85: "Neben dl in modliti, modlim, vzedli II 59, 36, 62 haben wir bereits assimiliertes l in crilatcem I 4. /.../ Ramovš vertritt nun, ebenso wie Grafenau­ er, die These, Preis. I sei in Kärnten entstanden /.../. Aber gerade die Kärntner slov. Dialekte haben altes dl bewahrt, vgl. gailtalerisch kridųo. Warum  haben  wir dann nicht auch *kridlatcem ? Für uns ist hier wichtig, dass Preis. II eine andere Lautung hat, als die beiden Beichten, die, nach Ramovš, den 'jüngeren' Sprachstand aufwei­ sen."

  15. Untersuchungen zur Involution der Vagina and Zervix beim Rind post partum unter Berücksichtigung der Zervix als Geburtshindernis

    OpenAIRE

    Wehrend, Axel

    2002-01-01

    Ziel der vorliegenden Arbeit war es die physiologische Involution der Zervix im Vergleich zur Vagina beim Rind während der ersten zehn Tage post partum zu charakterisieren. Weiterhin sollte durch klinische Untersuchungen an Kühen nach Dystokie und einer retrospektiven Datenauswertung von Schwergeburten unterschiedlicher Tierarten der Anteil zervikal bedingter Geburtsstockungen im Interspeziesvergleich analysiert und Einflussfaktoren auf das Auftreten dieser Dystokieform sowie Störungen in der...

  16. Das Konzept der "Verkehrssprache" und die frühen geographischen Berichte über Nordeuropa / Dieter Cherubim

    Index Scriptorium Estoniae

    Cherubim, Dieter

    2006-01-01

    Keelest kui keeleteaduse objektist, keelekasutusest ja keelenormist. Esitatakse segakeele ehk lingua franca (Verkehrssprache) kontseptsioon. Samuti tutvustatakse 18. sajandil juurdunud ekspeditsioonide korraldamise tava võõraste keelte uurimiseks ja tundmaõppimiseks ning täpsemalt räägitakse varastest keeleuurimisreisidest Põhja-Euroopasse

  17. Hvorfor køber forbrugerne Coca Cola, når de bedst kan lide Pepsi?

    DEFF Research Database (Denmark)

    Jantzen, Christian

    2011-01-01

    Coca Cola kan i modsætning til Pepsi Cola aktivere den præfrontale cortex – derfor er det selvfølgelig Coca, vi vil have!......Coca Cola kan i modsætning til Pepsi Cola aktivere den præfrontale cortex – derfor er det selvfølgelig Coca, vi vil have!...

  18. Simultaneous chemical modification and structural transformation of Stöber silica spheres for integration of nanocatalysts

    KAUST Repository

    Yao, Kexin; Zeng, Huachun

    2012-01-01

    ) hollow spheres, on which zinc oxide (ZnO) phase and ruthenium (Ru) nanoparticles have been deposited and assembled sequentially in solution phase. A series of complex Ru/ZnO/Zn-SiO 2 nanocatalysts has been thus been integrated onto the zinc-doped SiO 2

  19. Schreiben hat auch eine Stimme. Eine explorative Untersuchung über die Beziehung zwischen lautem Sprechen und Schreiben.

    OpenAIRE

    Lohmeier-Weidner, Yvonne (B. A.)

    2017-01-01

    Die Aufgabe in dieser Arbeit ist die Untersuchung der Beziehung zwischen lautem Sprechen und Schreiben im Schreibprozess. Grundlage ist die Annahme, dass beides zusammengehört und das Verbalisieren von Gedanken zum Schreiben, ob im Dialog oder im Selbstgespräch, selbiges positiv unterstützt. Dazu werden drei Studentinnen der Universität Paderborn, die an einem Abschlussarbeitenworkshop des Kompetenzzentrums Schreiben teilnahmen, durch ein fokussiertes Interview befragt. Diese Interviews werde...

  20. A New Formula for the BER of Binary Modulations with Dual-Branch Selection over Generalized-K

    KAUST Repository

    Ansari, Imran Shafique

    2012-09-08

    Error performance is one of the main performance measures and the derivation of its closed-form expression has proved to be quite involved for certain communication systems operating over composite fading channels. In this letter, a unified closed-form expression, applicable to different binary modulation schemes, for the bit error rate of dual-branch selection diversity based systems undergoing independent but not necessarily identically distributed generalized-K fading is derived in terms of the extended generalized bivariate Meijer G-function.