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Sample records for active demethylation represent

  1. Impacts of Activated Carbon Amendment on Hg Methylation, Demethylation and Microbial Activity in Marsh Soils

    Science.gov (United States)

    Gilmour, C. C.; Ghosh, U.; Santillan, E. F. U.; Soren, A.; Bell, J. T.; Butera, D.; McBurney, A. W.; Brown, S.; Henry, E.; Vlassopoulos, D.

    2015-12-01

    In-situ sorbent amendments are a low-impact approach for remediation of contaminants in sediments, particular in habitats like wetlands that provide important ecosystem services. Laboratory microcosm trials (Gilmour et al. 2013) and early field trials show that activated carbon (AC) can effectively increase partitioning of both inorganic Hg and methylmercury to the solid phase. Sediment-water partitioning can serve as a proxy for Hg and MeHg bioavailability in soils. One consideration in using AC in remediation is its potential impact on organisms. For mercury, a critical consideration is the potential impact on net MeHg accumulation and bioavailability. In this study, we specifically evaluated the impact of AC on rates of methylmercury production and degradation, and on overall microbial activity, in 4 different Hg-contaminated salt marsh soils. The study was done over 28 days in anaerobic, sulfate-reducing slurries. A double label of enriched mercury isotopes (Me199Hg and inorganic 201Hg) was used to separately follow de novo Me201Hg production and Me199Hg degradation. AC amendments decreased both methylation and demethylation rate constants relative to un-amended controls, but the impact on demethylation was stronger. The addition of 5% (dry weight) regenerated AC to soil slurries drove demethylation rate constants to nearly zero; i.e. MeHg sorption to AC almost totally blocked its degradation. The net impact was increased solid phase MeHg concentrations in some of the soil slurries with the highest methylation rate constants. However, the net impact of AC amendments was to increase MeHg (and inorganic Hg) partitioning to the soil phase and decrease concentrations in the aqueous phase. AC significantly decreased aqueous phase inorganic Hg and MeHg concentrations after 28 days. Overall, the efficacy of AC in reducing aqueous MeHg was highest in the soils with the highest MeHg concentrations. The AC addition did not significantly impact microbial activity, as

  2. DNA demethylation activates genes in seed maternal integument development in rice (Oryza sativa L.).

    Science.gov (United States)

    Wang, Yifeng; Lin, Haiyan; Tong, Xiaohong; Hou, Yuxuan; Chang, Yuxiao; Zhang, Jian

    2017-11-01

    DNA methylation is an important epigenetic modification that regulates various plant developmental processes. Rice seed integument determines the seed size. However, the role of DNA methylation in its development remains largely unknown. Here, we report the first dynamic DNA methylomic profiling of rice maternal integument before and after pollination by using a whole-genome bisulfite deep sequencing approach. Analysis of DNA methylation patterns identified 4238 differentially methylated regions underpin 4112 differentially methylated genes, including GW2, DEP1, RGB1 and numerous other regulators participated in maternal integument development. Bisulfite sanger sequencing and qRT-PCR of six differentially methylated genes revealed extensive occurrence of DNA hypomethylation triggered by double fertilization at IAP compared with IBP, suggesting that DNA demethylation might be a key mechanism to activate numerous maternal controlling genes. These results presented here not only greatly expanded the rice methylome dataset, but also shed novel insight into the regulatory roles of DNA methylation in rice seed maternal integument development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan [College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi 712100 (China); Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); Ohms, Stephen J. [ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); Shannon, Frances M. [Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia); The University of Canberra, ACT 2602 (Australia); Sun, Chao, E-mail: sunchao2775@163.com [College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi 712100 (China); Fan, Jun Y., E-mail: jun.fan@anu.edu.au [Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, ACT 2601 (Australia)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer DNA methylation is dynamic and flexible and changes rapidly upon cell activation. Black-Right-Pointing-Pointer DNA methylation controls the inducible gene expression in a given cell type. Black-Right-Pointing-Pointer Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  4. IL-2 and GM-CSF are regulated by DNA demethylation during activation of T cells, B cells and macrophages

    International Nuclear Information System (INIS)

    Li, Yan; Ohms, Stephen J.; Shannon, Frances M.; Sun, Chao; Fan, Jun Y.

    2012-01-01

    Highlights: ► DNA methylation is dynamic and flexible and changes rapidly upon cell activation. ► DNA methylation controls the inducible gene expression in a given cell type. ► Some enzymes are involved in maintaining the methylation profile of immune cells. -- Abstract: DNA demethylation has been found to occur at the promoters of a number of actively expressed cytokines and is believed to play a critical role in transcriptional regulation. While many DNA demethylation studies have focused on T cell activation, proliferation and differentiation, changes in DNA methylation in other types of immune cells are less well studied. We found that the expression of two cytokines (IL-2 and GM-CSF) responded differently to activation in three types of immune cells: EL4, A20 and RAW264.7 cells. Using the McrBC and MeDIP approaches, we observed decreases in DNA methylation at a genome-wide level and at the promoters of the genes of these cytokines. The expression of several potential enzymes/co-enzymes involved in the DNA demethylation pathways seemed to be associated with immune cell activation.

  5. Evidence that active demethylation mechanisms maintain the genome of carcinoma in situ cells hypomethylated in the adult testis

    DEFF Research Database (Denmark)

    Kristensen, D G; Nielsen, J E; Jørgensen, Anne

    2014-01-01

    cells were assessed by quantitative measurements. The expression of TET1, TET2, APOBEC1, MBD4, APEX1, PARP1, DNMT1, DNMT3A, DNMT3B and DNMT3L in adult testis specimens with CIS and in human fetal testis was investigated by immunohistochemistry and immunofluorescence.Results:DNA from micro-dissected CIS...... cells contained very low levels of 5hmC produced by ten eleven translocation (TET) enzymes. CIS cells and fetal germ cells expressed the suggested initiator of active demethylation, APOBEC1, and the base excision repair proteins MBD4, APEX1 and PARP1, whereas TETs - the alternative initiators were...

  6. Stimulation of ribosomal RNA gene promoter by transcription factor Sp1 involves active DNA demethylation by Gadd45-NER pathway.

    Science.gov (United States)

    Rajput, Pallavi; Pandey, Vijaya; Kumar, Vijay

    2016-08-01

    The well-studied Pol II transcription factor Sp1 has not been investigated for its regulatory role in rDNA transcription. Here, we show that Sp1 bound to specific sites on rDNA and localized into the nucleoli during the G1 phase of cell cycle to activate rDNA transcription. It facilitated the recruitment of Pol I pre-initiation complex and impeded the binding of nucleolar remodeling complex (NoRC) to rDNA resulting in the formation of euchromatin active state. More importantly, Sp1 also orchestrated the site-specific binding of Gadd45a-nucleotide excision repair (NER) complex resulting in active demethylation and transcriptional activation of rDNA. Interestingly, knockdown of Sp1 impaired rDNA transcription due to reduced engagement of the Gadd45a-NER complex and hypermethylation of rDNA. Thus, the present study unveils a novel role of Sp1 in rDNA transcription involving promoter demethylation. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. CNS germinomas are characterized by global demethylation, chromosomal instability and mutational activation of the Kit-, Ras/Raf/Erk- and Akt-pathways

    Science.gov (United States)

    Schulte, Simone Laura; Waha, Andreas; Steiger, Barbara; Denkhaus, Dorota; Dörner, Evelyn; Calaminus, Gabriele; Leuschner, Ivo; Pietsch, Torsten

    2016-01-01

    CNS germinomas represent a unique germ cell tumor entity characterized by undifferentiated tumor cells and a high response rate to current treatment protocols. Limited information is available on their underlying genomic, epigenetic and biological alterations. We performed a genome-wide analysis of genomic copy number alterations in 49 CNS germinomas by molecular inversion profiling. In addition, CpG dinucleotide methylation was studied by immunohistochemistry for methylated cytosine residues. Mutational analysis was performed by resequencing of candidate genes including KIT and RAS family members. Ras/Erk and Akt pathway activation was analyzed by immunostaining with antibodies against phospho-Erk, phosho-Akt, phospho-mTOR and phospho-S6. All germinomas coexpressed Oct4 and Kit but showed an extensive global DNA demethylation compared to other tumors and normal tissues. Molecular inversion profiling showed predominant genomic instability in all tumors with a high frequency of regional gains and losses including high level gene amplifications. Activating mutations of KIT exons 11, 13, and 17 as well as a case with genomic KIT amplification and activating mutations or amplifications of RAS gene family members including KRAS, NRAS and RRAS2 indicated mutational activation of crucial signaling pathways. Co-activation of Ras/Erk and Akt pathways was present in 83% of germinomas. These data suggest that CNS germinoma cells display a demethylated nuclear DNA similar to primordial germ cells in early development. This finding has a striking coincidence with extensive genomic instability. In addition, mutational activation of Kit-, Ras/Raf/Erk- and Akt- pathways indicate the biological importance of these pathways and their components as potential targets for therapy. PMID:27391150

  8. Gadd45a promotes DNA demethylation through TDG

    OpenAIRE

    Li, Zheng; Gu, Tian-Peng; Weber, Alain R.; Shen, Jia-Zhen; Li, Bin-Zhong; Xie, Zhi-Guo; Yin, Ruichuan; Guo, Fan; Liu, Xiaomeng; Tang, Fuchou; Wang, Hailin; Sch?r, Primo; Xu, Guo-Liang

    2015-01-01

    Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)?initiated oxidative demethylation. The conn...

  9. Exploring Representativeness and Informativeness for Active Learning.

    Science.gov (United States)

    Du, Bo; Wang, Zengmao; Zhang, Lefei; Zhang, Liangpei; Liu, Wei; Shen, Jialie; Tao, Dacheng

    2017-01-01

    How can we find a general way to choose the most suitable samples for training a classifier? Even with very limited prior information? Active learning, which can be regarded as an iterative optimization procedure, plays a key role to construct a refined training set to improve the classification performance in a variety of applications, such as text analysis, image recognition, social network modeling, etc. Although combining representativeness and informativeness of samples has been proven promising for active sampling, state-of-the-art methods perform well under certain data structures. Then can we find a way to fuse the two active sampling criteria without any assumption on data? This paper proposes a general active learning framework that effectively fuses the two criteria. Inspired by a two-sample discrepancy problem, triple measures are elaborately designed to guarantee that the query samples not only possess the representativeness of the unlabeled data but also reveal the diversity of the labeled data. Any appropriate similarity measure can be employed to construct the triple measures. Meanwhile, an uncertain measure is leveraged to generate the informativeness criterion, which can be carried out in different ways. Rooted in this framework, a practical active learning algorithm is proposed, which exploits a radial basis function together with the estimated probabilities to construct the triple measures and a modified best-versus-second-best strategy to construct the uncertain measure, respectively. Experimental results on benchmark datasets demonstrate that our algorithm consistently achieves superior performance over the state-of-the-art active learning algorithms.

  10. Spatial control of protein phosphatase 2A (de)methylation

    International Nuclear Information System (INIS)

    Longin, Sari; Zwaenepoel, Karen; Martens, Ellen; Louis, Justin V.; Rondelez, Evelien; Goris, Jozef; Janssens, Veerle

    2008-01-01

    Reversible methylation of the protein phosphatase 2A catalytic subunit (PP2A C ) is an important regulatory mechanism playing a crucial role in the selective recruitment of regulatory B subunits. Here, we investigated the subcellular localization of leucine carboxyl methyltransferase (LCMT1) and protein phosphatase methylesterase (PME-1), the two enzymes catalyzing this process. The results show that PME-1 is predominantly localized in the nucleus and harbors a functional nuclear localization signal, whereas LCMT1 is underrepresented in the nucleus and mainly localizes to the cytoplasm, Golgi region and late endosomes. Indirect immunofluorescence with methylation-sensitive anti-PP2A C antibodies revealed a good correlation with the methylation status of PP2A C , demethylated PP2A C being substantially nuclear. Throughout mitosis, demethylated PP2A C is associated with the mitotic spindle and during cytokinesis with the cleavage furrow. Overexpression of PME-1, but not of an inactive mutant, results in increased demethylation of PP2A C in the nucleus, whereas overexpression of a cytoplasmic PME-1 mutant lacking the NLS results in increased demethylation in the cytoplasm-in all cases, however, without any obvious functional consequences. PME-1 associates with an inactive PP2A population, regardless of its esterase activity or localization. We propose that stabilization of this inactive, nuclear PP2A pool is a major in vivo function of PME-1

  11. Gender Differences in Global but Not Targeted Demethylation in iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Inês Milagre

    2017-01-01

    Full Text Available Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.

  12. Demethylating agent, 5-azacytidine, reverses differentiation of embryonic stem cells

    International Nuclear Information System (INIS)

    Tsuji-Takayama, Kazue; Inoue, Toshiya; Ijiri, Yoshihiro; Otani, Takeshi; Motoda, Ryuichi; Nakamura, Shuji; Orita, Kunzo

    2004-01-01

    The de novo methylation activity is essential for embryonic development as well as embryonic stem (ES) cell differentiation, where the intensive and extensive DNA methylation was detected. In this study, we investigated the effects of a demethylating agent, 5-azacytidine (5-AzaC), on differentiated ES cells in order to study the possibility of reversing the differentiation process. We first induced differentiation of ES cells by forming embryoid bodies, and then the cells were treated with 5-AzaC. The cells showed some undifferentiated features such as stem cell-like morphology with unclear cell-to-cell boundary and proliferative responsiveness to LIF. Moreover, 5-AzaC increased the expressions of ES specific markers, SSEA-1, and alkaline phosphatase activity as well as ES specific genes, Oct4, Nanog, and Sox2. We also found that 5-AzaC demethylated the promoter region of H19 gene, a typical methylated gene during embryonic differentiation. These results indicate that 5-AzaC reverses differentiation state of ES cells through its DNA demethylating activity to differentiation related genes

  13. Recent activities of the Seismology Division Early Career Representative(s)

    Science.gov (United States)

    Agius, Matthew; Van Noten, Koen; Ermert, Laura; Mai, P. Martin; Krawczyk, CharLotte

    2016-04-01

    The European Geosciences Union is a bottom-up-organisation, in which its members are represented by their respective scientific divisions, committees and council. In recent years, EGU has embarked on a mission to reach out for its numerous 'younger' members by giving awards to outstanding young scientists and the setting up of Early Career Scientists (ECS) representatives. The division representative's role is to engage in discussions that concern students and early career scientists. Several meetings between all the division representatives are held throughout the year to discuss ideas and Union-wide issues. One important impact ECS representatives have had on EGU is the increased number of short courses and workshops run by ECS during the annual General Assembly. Another important contribution of ECS representatives was redefining 'Young Scientist' to 'Early Career Scientist', which avoids discrimination due to age. Since 2014, the Seismology Division has its own ECS representative. In an effort to more effectively reach out for young seismologists, a blog and a social media page dedicated to seismology have been set up online. With this dedicated blog, we'd like to give more depth to the average browsing experience by enabling young researchers to explore various seismology topics in one place while making the field more exciting and accessible to the broader community. These pages are used to promote the latest research especially of young seismologists and to share interesting seismo-news. Over the months the pages proved to be popular, with hundreds of views every week and an increased number of followers. An online survey was conducted to learn more about the activities and needs of early career seismologists. We present the results from this survey, and the work that has been carried out over the last two years, including detail of what has been achieved so far, and what we would like the ECS representation for Seismology to achieve. Young seismologists are

  14. Active Learning by Querying Informative and Representative Examples.

    Science.gov (United States)

    Huang, Sheng-Jun; Jin, Rong; Zhou, Zhi-Hua

    2014-10-01

    Active learning reduces the labeling cost by iteratively selecting the most valuable data to query their labels. It has attracted a lot of interests given the abundance of unlabeled data and the high cost of labeling. Most active learning approaches select either informative or representative unlabeled instances to query their labels, which could significantly limit their performance. Although several active learning algorithms were proposed to combine the two query selection criteria, they are usually ad hoc in finding unlabeled instances that are both informative and representative. We address this limitation by developing a principled approach, termed QUIRE, based on the min-max view of active learning. The proposed approach provides a systematic way for measuring and combining the informativeness and representativeness of an unlabeled instance. Further, by incorporating the correlation among labels, we extend the QUIRE approach to multi-label learning by actively querying instance-label pairs. Extensive experimental results show that the proposed QUIRE approach outperforms several state-of-the-art active learning approaches in both single-label and multi-label learning.

  15. Representing cognitive activities and errors in HRA trees

    International Nuclear Information System (INIS)

    Gertman, D.I.

    1992-01-01

    A graphic representation method is presented herein for adapting an existing technology--human reliability analysis (HRA) event trees, used to support event sequence logic structures and calculations--to include a representation of the underlying cognitive activity and corresponding errors associated with human performance. The analyst is presented with three potential means of representing human activity: the NUREG/CR-1278 HRA event tree approach; the skill-, rule- and knowledge-based paradigm; and the slips, lapses, and mistakes paradigm. The above approaches for representing human activity are integrated in order to produce an enriched HRA event tree -- the cognitive event tree system (COGENT)-- which, in turn, can be used to increase the analyst's understanding of the basic behavioral mechanisms underlying human error and the representation of that error in probabilistic risk assessment. Issues pertaining to the implementation of COGENT are also discussed

  16. Oxidative demethylation of monomethylmercury in sediments

    International Nuclear Information System (INIS)

    Oremland, R.S.

    1991-01-01

    Previous studies suggested that demethylation of monomethylmercury proceeds in nature by a simple organo-mercury lyase reaction resulting in the production of CH 4 and Hg 2+ , which is further reduced to Hg 0 . Addition of 14 CH 3 HgI to sediments resulted in the production of mainly 14 CO 2 and some 14 CH 4 . In the case of estuarine sediments, production of both these gases was only observed under anaerobiosis, and was totally inhibited by MoO 4 2- , which indicated the involvement of sulfate-reducing bacteria. In the case of anaerobic freshwater sediments, results with inhibitors indicated that both methanogens and sulfate reducers were involved in this oxidative demethylation. Aerobic incubation of estuarine sediments resulted in the production of only 14 CH 4 , indicating the importance of the organo-mercurial lyase reaction under this condition. However, in freshwater sediments, this reaction was not observed, and the oxidative demethylation reaction was predominant either under aerobic or anaerobic conditions. A methylotrophic methanogen (GS-16) was able to form traces of 14 CH 4 and 14 CO 2 from 14 CH 3 HgI, and some strains of sulfate-reducers formed traces of 14 CH 4 . Addition of methanol to anaerobic freshwater sediments partially inhibited production of 14 CH 4 and 14 CO 2 , but not CH 4 . These results suggest that oxidative demethylation proceeds by an established pathway for C-1 metabolism

  17. Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

    Science.gov (United States)

    Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

    2013-12-01

    Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

  18. Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma.

    Science.gov (United States)

    Bao, Xing; Ren, Tingting; Huang, Yi; Wang, Shidong; Zhang, Fan; Liu, Kuisheng; Zheng, Bingxin; Guo, Wei

    2016-08-30

    In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the underlying molecular mechanisms remain unclear. The effects of ATO on the migratory and invasive capacities of chondrosarcoma cells were investigated by Wound healing, Transwell and EMT assays. The expression of miR-125b in human chondrosarcoma tissues and cell lines was detected by real-time PCR analysis. Bisulfite sequencing analysis (BSP) was used to detect the effects of ATO on the expression of miR-125b. The gain-of-function and loss-of-function experiments were performed on chondrosarcoma cell lines to investigate the effects of miR-125b on chondrosarcoma invasion, and to determine whether signal transducer and activator of transcription 3(Stat3) mediates these effects. Dual-luciferase reporter assay was used to identify whether Stat3 is a direct target of miR-125b. MiR-125b was significantly downregulated in human metastatic chondrosarcoma tissues and cell lines but not in non-metastatic chondrosarcoma tissues. ATO up-regulates the expression of miR-125b by the demethylation of DNA. ATO induces MET and attenuates the invasive capacities of chondrosarcoma cells through miR-125b. Stat3 was verified as a direct target of miR-125b, which is involved in ATO regulating EMT-associated traits. These findings, for the first time, provides evidence that the miR-125b-mediated inhibition of Stat3 is involved in the ATO-induced attenuation of metastasis in chondrosarcoma cells.

  19. Ligand Binding Affinities of Arctigenin and Its Demethylated Metabolites to Estrogen Receptor Alpha

    Directory of Open Access Journals (Sweden)

    Masao Hattori

    2013-01-01

    Full Text Available Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (−-arctigenin, the aglycone of arctiin, was demethylated to (−-dihydroxyenterolactone (DHENL by Eubacterium (E. sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (−-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (−-arctigenin using a ligand binding screen assay method. The IC50 value of (2R,3R-2-(4-hydroxy-3-methoxybenzyl-3-(3,4-dihydroxybenzyl-butyrolactone was 7.9 × 10−4 M.

  20. Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Palumbo, Fabrizio [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); Garcia-Lainez, Guillermo [Instituto de Investigación Sanitaria (IIS) La Fe, Hospital Universitari i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia (Spain); Limones-Herrero, Daniel [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); Coloma, M. Dolores; Escobar, Javier [Instituto de Investigación Sanitaria (IIS) La Fe, Hospital Universitari i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia (Spain); Jiménez, M. Consuelo [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); Miranda, Miguel A., E-mail: mmiranda@qim.upv.es [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); and others

    2016-12-15

    Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound. In this case, the metabolites selected for the study are demethylchlorpromazine (DMCPZ), didemethylchlorpromazine (DDMCPZ) and chlorpromazine sulfoxide (CPZSO). The demethylated CPZ metabolites DMCPZ and DDMCPZ maintain identical chromophore to the parent drug. In this work, it has been found that the nature of the aminoalkyl side chain modulates the hydrophobicity and the photochemical properties (for instance, the excited state lifetimes), but it does not change the photoreactivity pattern, which is characterized by reductive photodehalogenation, triggered by homolytic carbon-chlorine bond cleavage with formation of highly reactive aryl radical intermediates. Accordingly, these metabolites are phototoxic to cells, as revealed by the 3T3 NRU assay; their photo-irritation factors are even higher than that of CPZ. The same trend is observed in photogenotoxicity studies, both with isolated and with cellular DNA, where DMCPZ and DDMCPZ are more active than CPZ itself. In summary, side-chain demethylation of CPZ, as a consequence of Phase I biotransformation, does not result a photodetoxification. Instead, it leads to metabolites that exhibit in an even enhanced photo(geno)toxicity. - Highlights: • Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. • Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. • DNA single strand breaks formation is observed on agarose gel electrophoresis.

  1. Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

    International Nuclear Information System (INIS)

    Palumbo, Fabrizio; Garcia-Lainez, Guillermo; Limones-Herrero, Daniel; Coloma, M. Dolores; Escobar, Javier; Jiménez, M. Consuelo; Miranda, Miguel A.

    2016-01-01

    Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound. In this case, the metabolites selected for the study are demethylchlorpromazine (DMCPZ), didemethylchlorpromazine (DDMCPZ) and chlorpromazine sulfoxide (CPZSO). The demethylated CPZ metabolites DMCPZ and DDMCPZ maintain identical chromophore to the parent drug. In this work, it has been found that the nature of the aminoalkyl side chain modulates the hydrophobicity and the photochemical properties (for instance, the excited state lifetimes), but it does not change the photoreactivity pattern, which is characterized by reductive photodehalogenation, triggered by homolytic carbon-chlorine bond cleavage with formation of highly reactive aryl radical intermediates. Accordingly, these metabolites are phototoxic to cells, as revealed by the 3T3 NRU assay; their photo-irritation factors are even higher than that of CPZ. The same trend is observed in photogenotoxicity studies, both with isolated and with cellular DNA, where DMCPZ and DDMCPZ are more active than CPZ itself. In summary, side-chain demethylation of CPZ, as a consequence of Phase I biotransformation, does not result a photodetoxification. Instead, it leads to metabolites that exhibit in an even enhanced photo(geno)toxicity. - Highlights: • Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. • Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. • DNA single strand breaks formation is observed on agarose gel electrophoresis.

  2. Stereoselectivity of the demethylation of nicotine piperidine homologues by Nicotiana plumbaginifolia cell suspension cultures.

    Science.gov (United States)

    Bartholomeusz, Trixie Ann; Molinié, Roland; Roscher, Albrecht; Felpin, François-Xavier; Gillet, Françoise; Lebreton, Jacques; Mesnard, François; Robins, Richard J

    2005-08-01

    The metabolism of (R,S)-N-methylanabasine and (R,S)-N-methylanatabine has been studied in a cell suspension culture of Nicotiana plumbaginifolia. Both substrates are effectively demethylated, anabasine or anatabine, respectively, accumulating in the medium. Similarly, there is strong stereoselectivity for the (R)-isomers of both substrates. The kinetics of metabolism of (R,S)-N-methylanabasine differ significantly from those of nicotine in that no further degradation of the initial demethylation product occurs. (R,S)-N-Methylanatabine, however, shows kinetics closer to those of nicotine, with loss of alkaloid from the system. Further more, (R,S)-N-methylanabasine does not diminish (S)-nicotine demethylation, indicating a lack of competition. However, the metabolism of (S)-nicotine is affected by the presence of (R,S)-N-methylanabasine. Hence, the demethylation of the piperidine homologues of nicotine is seen to be similar but not identical to that of the pyridine analogues. The implications of these different metabolic profiles in relation to the demethylation activity are discussed.

  3. EG-13GENOME-WIDE METHYLATION ANALYSIS IDENTIFIES GENOMIC DNA DEMETHYLATION DURING MALIGNANT PROGRESSION OF GLIOMAS

    Science.gov (United States)

    Saito, Kuniaki; Mukasa, Akitake; Nagae, Genta; Aihara, Koki; Otani, Ryohei; Takayanagi, Shunsaku; Omata, Mayu; Tanaka, Shota; Shibahara, Junji; Takahashi, Miwako; Momose, Toshimitsu; Shimamura, Teppei; Miyano, Satoru; Narita, Yoshitaka; Ueki, Keisuke; Nishikawa, Ryo; Nagane, Motoo; Aburatani, Hiroyuki; Saito, Nobuhito

    2014-01-01

    Low-grade gliomas often undergo malignant progression, and these transformations are a leading cause of death in patients with low-grade gliomas. However, the molecular mechanisms underlying malignant tumor progression are still not well understood. Recent evidence indicates that epigenetic deregulation is an important cause of gliomagenesis; therefore, we examined the impact of epigenetic changes during malignant progression of low-grade gliomas. Specifically, we used the Illumina Infinium Human Methylation 450K BeadChip to perform genome-wide DNA methylation analysis of 120 gliomas and four normal brains. This study sample included 25 matched-pairs of initial low-grade gliomas and recurrent tumors (temporal heterogeneity) and 20 of the 25 recurring tumors recurred as malignant progressions, and one matched-pair of newly emerging malignant lesions and pre-existing lesions (spatial heterogeneity). Analyses of methylation profiles demonstrated that most low-grade gliomas in our sample (43/51; 84%) had a CpG island methylator phenotype (G-CIMP). Remarkably, approximately 50% of secondary glioblastomas that had progressed from low-grade tumors with the G-CIMP status exhibited a characteristic partial demethylation of genomic DNA during malignant progression, but other recurrent gliomas showed no apparent change in DNA methylation pattern. Interestingly, we found that most loci that were demethylated during malignant progression were located outside of CpG islands. The information of histone modifications patterns in normal human astrocytes and embryonal stem cells also showed that the ratio of active marks at the site corresponding to DNA demethylated loci in G-CIMP-demethylated tumors was significantly lower; this finding indicated that most demethylated loci in G-CIMP-demethylated tumors were likely transcriptionally inactive. A small number of the genes that were upregulated and had demethylated CpG islands were associated with cell cycle-related pathway. In

  4. [Fundamental role of the workers' representative in preventive safety activity].

    Science.gov (United States)

    Ossicini, A; Bindi, L; Casale, M C

    2003-01-01

    With the arrival of Legislative Decree 626/94 which brought into Italian law the EU directives on workers' health and safety at the workplace, our country has also introduced rules that make a break with the past in this area, with the creation of new professional roles. The workers' safety representative takes on a fundamentally important role in the management of prevention, safety and health for workers in their place of employment in accordance with article 19. In fact, before the introduction of this Legislative Decree, the "protection" of workers' health was essentially based on rules and regulations the application of which was left to the exclusive and direct responsibility of the relationship between the employer and doctor, leaving out any participation by the worker. Whereas in the past workers could only be considered the final receivers of instructions about the security measures to apply, with Law 626 the workers themselves became active participants in the assessment of risks at work and consequently in the implementing of all the safety and hygiene measures contributing to the reduction of risk levels. The new regulations now in force assign important tasks to the workers' safety representative; all tasks and responsibilities associated with that role are examined and discussed, especially those relating to rights to information and training, consultation and participation in the process of designing and promoting safety measures. The job of workers' representative today takes on a fundamentally important meaning and role in a self-regulating system of work safety, where he or she has a proper area responsibility, so becoming a reference point for the workers generally.

  5. Methylmercury decomposition in sediments and bacterial cultures: Involvement of methanogens and sulfate reducers in oxidative demethylation

    International Nuclear Information System (INIS)

    Oremland, R.S.; Culbertson, C.W.; Winfrey, M.R.

    1991-01-01

    The biogeochemical cycling of mercury has received considerable attention because of the toxicity of methylmercury, its bioaccumulation in biota, and its biomagnification in aquatic food chains. The formation of methylmercury is mediated primarily by microorganisms. Demethylation of monomethylmercury in freshwater and estuarine sediments and in bacterial cultures was investigated with 14 CH 3 HgI. Under anaerobiosis, results with inhibitors indicated partial involvement of both sulfate reducers and methanogens, the former dominated estuarine sediments, while both were active in freshwaters. Aerobes were the most significant demethylators in estuarine sediments, but were unimportant in freshwater sediments. Products of anaerobic demthylation were mainly 14 CO 2 as well as lesser amounts of 14 CH 4 . Acetogenic activity resulted in fixation of some 14 CO 2 produced from 14 CH 3 HgI into acetate. Aerobic demethylation in estuarine sediments produced only 14 CH 4 , while aerobic demethylation in freshwater sediments produced small amounts of both 14 CH 4 and 14 CO 2 . Two species of Desulfovibrio produced only traces of 14 CH 4 from 14 CH 3 HgI, while a culture of a methylotrophic methanogen formed traces of 14 CO 2 and 14 CH 4 when grown on trimethylamine in the presence of the 14 CH 3 HgI. These results indicate that both aerobes and anaerobes demethylate mercury in sediments, but that either group may dominate in a particular sediment type. Aerobic demethylation in the estuarine sediments appeared to proceed by the previously characterized organomercurial-lyase pathway, because methane was the sole product. This indicates the presence of an oxidative pathway, possibly one in which methylmercury serves as an analog of one-carbon substrates

  6. Engineering activities on the ITER representative diagnostic equatorial port plug

    International Nuclear Information System (INIS)

    Meunier, L.; Doceul, L.; Salasca, S.; Martins, J.-P.; Jullien, F.; Dechelle, Christian; Bidaud, Pierre; Pilard, Vincent; Terra, Alexis; Ogea, Mathieu; Ciattaglia, Emanuela; Walker, Christopher

    2009-01-01

    Most of ITER diagnostic systems are integrated in port plugs, which are water cooled stainless steel structures inserted into the vacuum vessel ports. The port plug must provide basic functions such as neutron and gamma shielding, supporting the first wall armour (BSM), closing the vacuum vessel ports, while supporting the diagnostic equipments. ITER diagnostic port plug must resist a severe environment like high temperature due to neutron interaction with the structures and high electromechanical loading during disruptions events. CEA has contributed to the design and integration tasks in the frame of the representative equatorial port plug EQ no. 01, in particular on the engineering, structural and thermal finite element analysis. These detailed analyses have highlighted some design issues which were worked out through different solutions. This paper contains a description of the engineering activities performed such as: -The static mechanical calculations of the top plate closure system under disruption load. -The static mechanical calculations of the BSM attachment to the port plug. These two first studies led to design changes proposals which significantly improved the behaviour of the structures but also showed that the safety margin with respect to design limits is quite low. -The design of a Diagnostic Shield Module (DSM) integrated inside the port plug and a proposition of attachment scheme, with respect to disruption loads. The manufacturing of the DSM has been taken into account, as well as diagnostic integration inside the structure and maintenance aspects. -The thermal assessment of the port plug under neutronic load during normal operation, with the optimization of the cooling system. The maximum temperature calculated in normal operation has been reduced from 900 deg. C to less than 400 deg. C in the front plate; and the cooling arrangement at the back of the port plug has been simplified without important temperature increase.

  7. Engineering activities on the ITER representative diagnostic equatorial port plug

    Energy Technology Data Exchange (ETDEWEB)

    Meunier, L. [Association Euratom CEA, CEA/DSM/IRFM (France)], E-mail: lmeunier@cea.fr; Doceul, L.; Salasca, S.; Martins, J.-P.; Jullien, F.; Dechelle, Christian; Bidaud, Pierre; Pilard, Vincent; Terra, Alexis; Ogea, Mathieu [Association Euratom CEA, CEA/DSM/IRFM (France); Ciattaglia, Emanuela [EFDA CSU, Garching (Germany); Walker, Christopher [ITER International Organisation (France)

    2009-06-15

    Most of ITER diagnostic systems are integrated in port plugs, which are water cooled stainless steel structures inserted into the vacuum vessel ports. The port plug must provide basic functions such as neutron and gamma shielding, supporting the first wall armour (BSM), closing the vacuum vessel ports, while supporting the diagnostic equipments. ITER diagnostic port plug must resist a severe environment like high temperature due to neutron interaction with the structures and high electromechanical loading during disruptions events. CEA has contributed to the design and integration tasks in the frame of the representative equatorial port plug EQ no. 01, in particular on the engineering, structural and thermal finite element analysis. These detailed analyses have highlighted some design issues which were worked out through different solutions. This paper contains a description of the engineering activities performed such as: -The static mechanical calculations of the top plate closure system under disruption load. -The static mechanical calculations of the BSM attachment to the port plug. These two first studies led to design changes proposals which significantly improved the behaviour of the structures but also showed that the safety margin with respect to design limits is quite low. -The design of a Diagnostic Shield Module (DSM) integrated inside the port plug and a proposition of attachment scheme, with respect to disruption loads. The manufacturing of the DSM has been taken into account, as well as diagnostic integration inside the structure and maintenance aspects. -The thermal assessment of the port plug under neutronic load during normal operation, with the optimization of the cooling system. The maximum temperature calculated in normal operation has been reduced from 900 deg. C to less than 400 deg. C in the front plate; and the cooling arrangement at the back of the port plug has been simplified without important temperature increase.

  8. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

    Directory of Open Access Journals (Sweden)

    Benitez-Bribiesca Luis

    2006-08-01

    Full Text Available Abstract Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.

  9. Mining and representing recommendations in actively evolving recommender systems

    DEFF Research Database (Denmark)

    Assent, Ira

    2010-01-01

    Recommender systems provide an automatic means of filtering out interesting items, usually based on past similarity of user ratings. In previous work, we have suggested a model that allows users to actively build a recommender network. Users express trust, obtain transparency, and grow (anonymous......) recommender connections. In this work, we propose mining such active systems to generate easily understandable representations of the recommender network. Users may review these representations to provide active feedback. This approach further enhances the quality of recommendations, especially as topics...... of interest change over time. Most notably, it extends the amount of control users have over the model that the recommender network builds of their interests....

  10. Theoretical study on the N-demethylation mechanism of theobromine catalyzed by P450 isoenzyme 1A2.

    Science.gov (United States)

    Tao, Jing; Kang, Yuan; Xue, Zhiyu; Wang, Yongting; Zhang, Yan; Chen, Qiu; Chen, Zeqin; Xue, Ying

    2015-09-01

    Theobromine, a widely consumed pharmacological active substance, can cause undesirable muscle stiffness, nausea and anorexia in high doses ingestion. The main N-demethylation metabolic mechanism of theobromine catalyzed by P450 isoenzyme 1A2 (CYP1A2) has been explored in this work using the unrestricted hybrid density functional method UB3LYP in conjunction with the LACVP(Fe)/6-31G (H, C, N, O, S, Cl) basis set. Single-point calculations including empirical dispersion corrections were carried out at the higher 6-311++G** basis set. Two N-demethylation pathways were characterized, i.e., 3-N and 7-N demethylations, which involve the initial N-methyl hydroxylation to form carbinolamines and the subsequent carbinolamines decomposition to yield monomethylxanthines and formaldehydes. Our results have shown that the rate-limiting N-methyl hydroxylation occurs via a hydrogen atom transfer (HAT) mechanism, which proceeds in a spin-selective mechanism (SSM) in the gas phase. The carbinolamines generated are prone to decomposition via the contiguous heteroatom-assisted proton-transfer. Strikingly, 3-N demethylation is more favorable than 7-N demethylation due to its lower free energy barrier and 7-methylxanthine therefore is the optimum product reported for the demethylation of theobromine catalyzed by CYP1A2, which are in good agreement with the experimental observation. This work has first revealed the detail N-demethylation mechanisms of theobromine at the theoretical level. It can offer more significant information for the metabolism of purine alkaloid. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion

    OpenAIRE

    Carnesecchi, Julie; Forcet, Christelle; Zhang, Ling; Tribollet, Violaine; Barenton, Bruno; Boudra, Rafik; Cerutti, Catherine; Billas, Isabelle M. L.; Sérandour, Aurélien A.; Carroll, Jason S.; Beaudoin, Claude; Vanacker, Jean-Marc

    2017-01-01

    Dynamic demethylation of histone residues plays a crucial role in the regulation of gene expression. Lysine Specific Demethylase 1 (LSD1) can remove both transcriptionally permissive and repressive histone marks. How these activities are controlled is not clearly understood. Here, we show that the estrogen-related receptor α (ERRα) induces LSD1 to erase repressive marks in vitro. Through such a mechanism, LSD1 and ERRα commonly activate a set of transcriptional targets that include genes invo...

  12. [Antiviral activity of representatives of the family Crassulaceae].

    Science.gov (United States)

    Shirobokov, V P; Evtushenko, A I; Lapchik, V F; Shirobokova, D N; Suptel', E A

    1981-12-01

    The antiviral properties of the juice of 11 species of the orpine family were studied. 8 of them belonged to the genera Kalanchoe, i. e. Kalanchoe diagremontiona R. Hamet, K. pinnata (Zam.) Persoon, K. Peteri Werd., K. prolifera (Bovie) R. Hamet, K. marnierriana (Mann. et Boit) Jacobs; K. blossfeldiana v. Poelln, K. beharensis Drake del Gastillo, K. waldheimii R. Hamet et Perr and 3 belonged to the Sedum genera, i. e. Sedum telephium L., S. spectabile Boreau, S. acre L. A high virus neutralizing activity of the juice from 4 species of Kalanchoe, i. e. K. blossfeldiana, K. waldheimii, K. pinnata and K. beharensis was shown. Inhibition of the virus infecting activity was observed at the juice dilutions from 1-2 to 1-8000 and higher. The viricidal factor of Kalanchoe is stable. It is not destroyed by ether, alcohol and potassium periodate. It is not absorbed by bentonite at the acid pH values. Addition of cattle serum or purified proteins to the juice resulted in their precipitation which suppressed the viricidal activity of the juice.

  13. Promoter demethylation of Keap1 gene in human diabetic cataractous lenses

    Energy Technology Data Exchange (ETDEWEB)

    Palsamy, Periyasamy [Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE (United States); Ayaki, Masahiko [Shizuoka National Hospital, Saitama (Japan); Elanchezhian, Rajan [Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE (United States); Shinohara, Toshimichi, E-mail: tshinohara@unmc.edu [Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE (United States)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer We found significant Keap1 promoter demethylation in diabetic cataractous lenses. Black-Right-Pointing-Pointer Demethylation of Keap1 gene upregulated the expression of Keap1 mRNA and protein. Black-Right-Pointing-Pointer Elevated levels of Keap1 are known to decrease the levels of Nrf2. Black-Right-Pointing-Pointer Thereby, the levels of antioxidant enzymes are suppressed by decreased Nrf2 level. -- Abstract: Age-related cataracts (ARCs) are the major cause of visual impairments worldwide, and diabetic adults tend to have an earlier onset of ARCs. Although age is the strongest risk factor for cataracts, little is known how age plays a role in the development of ARCs. It is known that oxidative stress in the lens increases with age and more so in the lenses of diabetics. One of the central adaptive responses against the oxidative stresses is the activation of the nuclear transcriptional factor, NF-E2-related factor 2 (Nrf2), which then activates more than 20 different antioxidative enzymes. Kelch-like ECH associated protein 1 (Keap1) targets and binds to Nrf2 for proteosomal degradation. We hypothesized that hyperglycemia will lead to a dysfunction of the Nrf2-dependent antioxidative protection in the lens of diabetics. We studied the methylation status of the CpG islands in 15 clear and 21 diabetic cataractous lenses. Our results showed significant levels of demethylated DNA in the Keap1 promoter in the cataractous lenses from diabetic patients. In contrast, highly methylated DNA was found in the clear lens and tumorized human lens epithelial cell (HLEC) lines (SRA01/04). HLECs treated with a demethylation agent, 5-aza-2 Prime deoxycytidine (5-Aza), had a 10-fold higher levels of Keap1 mRNA, 3-fold increased levels of Keap1 protein, produced higher levels of ROS, and increased cell death. Our results indicated that demethylation of the CpG islands in the Keap1 promoter will activate the expression of Keap1 protein, which

  14. Promoter demethylation of Keap1 gene in human diabetic cataractous lenses

    International Nuclear Information System (INIS)

    Palsamy, Periyasamy; Ayaki, Masahiko; Elanchezhian, Rajan; Shinohara, Toshimichi

    2012-01-01

    Highlights: ► We found significant Keap1 promoter demethylation in diabetic cataractous lenses. ► Demethylation of Keap1 gene upregulated the expression of Keap1 mRNA and protein. ► Elevated levels of Keap1 are known to decrease the levels of Nrf2. ► Thereby, the levels of antioxidant enzymes are suppressed by decreased Nrf2 level. -- Abstract: Age-related cataracts (ARCs) are the major cause of visual impairments worldwide, and diabetic adults tend to have an earlier onset of ARCs. Although age is the strongest risk factor for cataracts, little is known how age plays a role in the development of ARCs. It is known that oxidative stress in the lens increases with age and more so in the lenses of diabetics. One of the central adaptive responses against the oxidative stresses is the activation of the nuclear transcriptional factor, NF-E2-related factor 2 (Nrf2), which then activates more than 20 different antioxidative enzymes. Kelch-like ECH associated protein 1 (Keap1) targets and binds to Nrf2 for proteosomal degradation. We hypothesized that hyperglycemia will lead to a dysfunction of the Nrf2-dependent antioxidative protection in the lens of diabetics. We studied the methylation status of the CpG islands in 15 clear and 21 diabetic cataractous lenses. Our results showed significant levels of demethylated DNA in the Keap1 promoter in the cataractous lenses from diabetic patients. In contrast, highly methylated DNA was found in the clear lens and tumorized human lens epithelial cell (HLEC) lines (SRA01/04). HLECs treated with a demethylation agent, 5-aza-2′deoxycytidine (5-Aza), had a 10-fold higher levels of Keap1 mRNA, 3-fold increased levels of Keap1 protein, produced higher levels of ROS, and increased cell death. Our results indicated that demethylation of the CpG islands in the Keap1 promoter will activate the expression of Keap1 protein, which then increases the targeting of Nrf2 for proteosomal degradation. Decreased Nrf2 activity represses the

  15. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion

    Science.gov (United States)

    Carnesecchi, Julie; Forcet, Christelle; Zhang, Ling; Tribollet, Violaine; Barenton, Bruno; Boudra, Rafik; Cerutti, Catherine; Billas, Isabelle M. L.; Sérandour, Aurélien A.; Carroll, Jason S.; Beaudoin, Claude; Vanacker, Jean-Marc

    2017-01-01

    Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERRα is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERRα coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERRα reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion. PMID:28348226

  16. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.

    Science.gov (United States)

    Carnesecchi, Julie; Forcet, Christelle; Zhang, Ling; Tribollet, Violaine; Barenton, Bruno; Boudra, Rafik; Cerutti, Catherine; Billas, Isabelle M L; Sérandour, Aurélien A; Carroll, Jason S; Beaudoin, Claude; Vanacker, Jean-Marc

    2017-04-11

    Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERRα is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERRα coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERRα reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion.

  17. Representing cognitive activities and errors in HRA trees

    International Nuclear Information System (INIS)

    Gertman, D.I.

    1992-01-01

    This paper discusses development of a means by which to present cognitive information in human reliability assessment (HRA) event trees. The descriptions found in probabilistic risk assessments (PRAs) regarding the demands on, and the resulting performance of, nuclear power plant (NPP) crews often make use of the technique for human error rate prediction (THERP), which provides a mechanism, the HRA event tree, for presenting the analyst's conceptualization of the activities underlying performance and the errors associated with that performance. When using THERP, analysts have often omitted the more complex elements of human cognition from these trees. There has yet to be a concerted effort to take theory, principles, and data from cognitive psychology and wed it to the logic structure of the HRA event tree. This paper attempts to do so. The COGENT modeling scheme (cognitively based HRA event trees) adds two taxonomies to the HRA event tree proposed by Swain and Guttman. The first taxonomy, the one proposed by Norman and Reason, describes the type of error committed and implies something about the underlying cognition as well. The second of these, the Rasmussen taxonomy, provides description regarding the skill-based, rule-based, or knowledge-based behavior underlying the execution of tasks. It is not apparent and must be deduced from the pattern of errors exhibited by personnel

  18. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells

    DEFF Research Database (Denmark)

    Kirkin, Alexei F.; Dzhandzhugazyan, Karine N.; Guldberg, Per

    2018-01-01

    In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4+ T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT...... antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25...... patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can...

  19. Fast Curing Bio-Based Phenolic Resins via Lignin Demethylated under Mild Reaction Condition

    OpenAIRE

    Jiongjiong Li; Jizhi Zhang; Shifeng Zhang; Qiang Gao; Jianzhang Li; Wei Zhang

    2017-01-01

    Demethylation technique has been used to enhance lignin reactivity for preparation of phenolic resins. However, the demethylation efficiency and the demethylated lignin (DL) reactivity were still unsatisfactory. To improve the demethylation efficiency, alkali lignin was demethylated under different mild conditions using sodium sulfite as a catalyst. Lignin and DL were characterized by 1H-NMR (nuclear magnetic resonance) and Fourier transform infrared (FT-IR) spectroscopy to determine the deme...

  20. Simultaneous determination of the novel tyrosine kinase inhibitor meditinib and its active metabolite demethylation meditinib in monkey plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies.

    Science.gov (United States)

    Liang, Feng; Kong, Qi; Guo, Yongqi; Wang, Yu; Sun, Dejie; Liu, Shi; Cai, Jinling; Guan, Yongbiao; Ding, Rigao

    2015-08-01

    Meditinib (ME) is a novel tyrosine kinase inhibitor used as an antichronic myeloid leukemia drug. A simple, sensitive and specific LC/MS/MS method was developed and validated for the analysis of ME and its metabolite demethylation meditinib (PI) in monkey plasma using naltrexone as the internal standard. Sample preparation involved protein precipitation with methanol. The analysis was carried out on an Agilent C8 column (3.5 µm, 2.1 × 50 mm). Elution was achieved with a mobile phase gradient varying the proportion of a water solution containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol solution (solvent B) at a flow rate of 300 μL/min. The method had a linear calibration curve over the concentration range of 2-1000 ng/mL for ME and 2-1000 ng/mL for PI. The lower limits of quantification of ME and PI were 2 and 2 ng/mL, respectively. The intra- and inter-day precision values were 85%. The assay has been successfully used for pharmacokinetic evaluation of ME and PI using the monkey as an animal model, and those data are reported for the first time. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Demethylation of arsenic limits its volatilization in fungi

    International Nuclear Information System (INIS)

    Su, Shiming; Zeng, Xibai; Feng, Qiufen; Bai, Lingyu; Zhang, Lili; Jiang, Sheng; Li, Aiguo; Duan, Ran; Wang, Xiurong; Wu, Cuixia; Wang, Yanan

    2015-01-01

    Arsenic (As) biomethylation is increasingly being regarded as a promising method to volatize As from the environment; however, the As volatilization efficiency of most microorganisms is low. Here, the speciation transformation of dimethylarsinic acid (DMA) as an important methylation intermediate in the cells of Fusarium oxysporum CZ-8F1, Penicillium janthinellum SM-12F4, and Trichoderma asperellum SM-12F1 were investigated. These fungal strains have been certified to volatilize As from As-loaded environment. In situ X-ray absorption near edge structure (XANES) indicated that demethylation of DMA with methylarsonic acid (MMA), arsenate [As(V)], and arsenite [As(III)] as intermediates or products occurred in fungal cells after exposure to DMA for 15 days. 36.7–55.7% of the original DMA could lose one or two methyl groups and be changed into MMA or inorganic As. Chromatographic separation of the cell lysates also supported these findings. Thus it comes that demethylation might be a remarkable internal factor limiting As volatilization efficiency. - Highlights: • XAS and chromatographic separation were used to study the speciation change of DMA. • DMA demethylation with MMA, As(V), and As(III) as products occurred in fungal cells. • Demethylation might be responsible for the limited volatilization efficiency of As. - Demethylation might be responsible for the limited methylation efficiency of As

  2. (/sup 125/I) 7-iodo-6-demethyl-6-deoxytetracycline HCl: its use in the study of bone mineralization

    Energy Technology Data Exchange (ETDEWEB)

    Belbeck, L W; Bowen, B M; Garnett, E S [McMaster Univ., Hamilton, Ontario (Canada); Porter, J K; Teare, F W

    1979-06-01

    /sup 125/I 7-iodo-6-demethyl-6-deoxytetracycline can be used in a non-invasive method to indicate sites of active bone mineralization. Sequential doses of this agent have been used to follow bone repair in a fractured femur of a dog without resorting to bone biopsy. Metabolic problems that involve bone may also be studied with this potentially useful radiopharmaceutical.

  3. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    International Nuclear Information System (INIS)

    Matsukura, Hiroshi; Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun; Muramatsu, Masaaki; Sudo, Katsuko; Sato, Noriko

    2011-01-01

    Highlights: → Genistein (GEN) is a phytoestrogen found in soy products. → GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. → GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. → A high-resolution melting assay was used to screen for epigenetic change. → We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  4. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsukura, Hiroshi, E-mail: hmatsukura.epi@mri.tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun [Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Muramatsu, Masaaki [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Sudo, Katsuko [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Animal Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Sato, Noriko, E-mail: nsato.epi@tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)

    2011-08-26

    Highlights: {yields} Genistein (GEN) is a phytoestrogen found in soy products. {yields} GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. {yields} GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. {yields} A high-resolution melting assay was used to screen for epigenetic change. {yields} We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  5. Targeted DNA demethylation of the Arabidopsis genome using the human TET1 catalytic domain

    Science.gov (United States)

    Gallego-Bartolomé, Javier; Gardiner, Jason; Liu, Wanlu; Papikian, Ashot; Ghoshal, Basudev; Kuo, Hsuan Yu; Zhao, Jenny Miao-Chi; Jacobsen, Steven E.

    2018-01-01

    DNA methylation is an important epigenetic modification involved in gene regulation and transposable element silencing. Changes in DNA methylation can be heritable and, thus, can lead to the formation of stable epialleles. A well-characterized example of a stable epiallele in plants is fwa, which consists of the loss of DNA cytosine methylation (5mC) in the promoter of the FLOWERING WAGENINGEN (FWA) gene, causing up-regulation of FWA and a heritable late-flowering phenotype. Here we demonstrate that a fusion between the catalytic domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and an artificial zinc finger (ZF) designed to target the FWA promoter can cause highly efficient targeted demethylation, FWA up-regulation, and a heritable late-flowering phenotype. Additional ZF–TET1cd fusions designed to target methylated regions of the CACTA1 transposon also caused targeted demethylation and changes in expression. Finally, we have developed a CRISPR/dCas9-based targeted demethylation system using the TET1cd and a modified SunTag system. Similar to the ZF–TET1cd fusions, the SunTag–TET1cd system is able to target demethylation and activate gene expression when directed to the FWA or CACTA1 loci. Our study provides tools for targeted removal of 5mC at specific loci in the genome with high specificity and minimal off-target effects. These tools provide the opportunity to develop new epialleles for traits of interest, and to reactivate expression of previously silenced genes, transgenes, or transposons. PMID:29444862

  6. TET1 promotes cisplatin-resistance via demethylating the vimentin promoter in ovarian cancer.

    Science.gov (United States)

    Han, Xi; Zhou, Yuanyuan; You, Yuanyi; Lu, Jiaojiao; Wang, Lijie; Hou, Huilian; Li, Jing; Chen, Wei; Zhao, Le; Li, Xu

    2017-04-01

    The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells. Ectopic expression of TET1 in A2780 cells promoted cisplatin resistance and decreased cytotoxicity induced by cisplatin, while inhibition of TET1 by siRNA transfection in CP70 cells attenuated cisplatin resistance and enhanced cytotoxicity of cisplatin. Increased TET1 induced re-expression of vimentin through active DNA demethylation, and cause partial epithelial-to-mesenchymal (EMT) in A2780 cells. Contrarily, knocking down of TET1 in CP70 cells reduced vimentin expression and reversed EMT process. Immunohistochemical analysis of TET1 in human ovarian cancer tissues revealed that TET1 existed in nucleus and cytoplasm in ovarian cancer tissues. And the expression of nuclear TET1 was positively correlated with residual tumor and chemotherapeutic response. Thus, TET1 expression causes resistance to cisplatin and one of the targets of TET1 action is vimentin in ovarian cancer. © 2017 International Federation for Cell Biology.

  7. Biochemistry and occurrence of O-demethylation in plant metabolism

    Directory of Open Access Journals (Sweden)

    Jillian Hagel

    2010-07-01

    Full Text Available Demethylases play a pivitol role in numerous biological processes from covalent histone modification and DNA repair to specialized metabolism in plants and microorganisms. Enzymes that catalyze O- and N-demethylation include 2-oxoglutarate (2OG/Fe(II-dependent dioxygenases, cytochromes P450, Rieske-domain proteins and flavin adenine dinucleotide (FAD-dependent oxidases. Proposed mechanisms for demethylation by 2OG/Fe(II-dependent enzymes involve hydroxylation at the O- or N-linked methyl group followed by formaldehyde elimination. Members of this enzyme family catalyze a wide variety of reactions in diverse plant metabolic pathways. Recently, we showed that 2OG/Fe(II-dependent dioxygenases catalyze the unique O-demethylation steps of morphine biosynthesis in opium poppy, which provides a rational basis for the widespread occurrence of demethylases in benzylisoquinoline alkaloid metabolism.

  8. A New Synthetic Route to Dihydrobenzopyran Via Tandem Demethylation Cyclisation

    Directory of Open Access Journals (Sweden)

    G. Shanmugam

    2000-06-01

    Full Text Available A tandem demethylation-cyclisation reaction resulting in the formation of pyran rings using AlCl3/EtSH reagent under mild reaction conditions is reported. X-ray diffraction studies on the intermediate support the suggested mechanism.

  9. Participation of the Neighborhood Representatives (Mukhtars into Managerial Activities in Local Level: Burdur Case

    Directory of Open Access Journals (Sweden)

    Mustafa LAMBA

    2017-05-01

    Full Text Available Neighborhood representatives (mukhtars are the nearest administrative units to citizens in local level. It is required to take advantage of that the neighborhood representatives know their districts and residents better than central and local government authorities. In addition, it will be appropriate to the principles of subsidiarity and the European Charter of Local Self Government to determine problems and demands of neighborhoods by their representatives. It is necessary to maintain communication channels and keep close relations with neighborhood representatives by local governments to use that advantage efficiently. It is aimed in this study to determine the participation level of neighborhood representatives into managerial activities in local level. For that purpose, the neighborhood representatives in the center of Burdur province are included in the research. According to the findings, it has been determined that the neighborhood representatives have participated into various activities without experiencing any difficulty, and they have been informed about the services regarding to their neighborhoods, and they have kept close relationship with central and local administrations, and most of them could communicate with local authorities directly. Therefore, it has been concluded that the neighborhood representatives have been influential enough in decision-making mechanisms in local level in Burdur.

  10. Early de novo DNA methylation and prolonged demethylation in the muscle lineage.

    Science.gov (United States)

    Tsumagari, Koji; Baribault, Carl; Terragni, Jolyon; Varley, Katherine E; Gertz, Jason; Pradhan, Sirharsa; Badoo, Melody; Crain, Charlene M; Song, Lingyun; Crawford, Gregory E; Myers, Richard M; Lacey, Michelle; Ehrlich, Melanie

    2013-03-01

    Myogenic cell cultures derived from muscle biopsies are excellent models for human cell differentiation. We report the first comprehensive analysis of myogenesis-specific DNA hyper- and hypo-methylation throughout the genome for human muscle progenitor cells (both myoblasts and myotubes) and skeletal muscle tissue vs. 30 non-muscle samples using reduced representation bisulfite sequencing. We also focused on four genes with extensive hyper- or hypo-methylation in the muscle lineage (PAX3, TBX1, MYH7B/MIR499 and OBSCN) to compare DNA methylation, DNaseI hypersensitivity, histone modification, and CTCF binding profiles. We found that myogenic hypermethylation was strongly associated with homeobox or T-box genes and muscle hypomethylation with contractile fiber genes. Nonetheless, there was no simple relationship between differential gene expression and myogenic differential methylation, rather only for subsets of these genes, such as contractile fiber genes. Skeletal muscle retained ~30% of the hypomethylated sites but only ~3% of hypermethylated sites seen in myogenic progenitor cells. By enzymatic assays, skeletal muscle was 2-fold enriched globally in genomic 5-hydroxymethylcytosine (5-hmC) vs. myoblasts or myotubes and was the only sample type enriched in 5-hmC at tested myogenic hypermethylated sites in PAX3/CCDC140 andTBX1. TET1 and TET2 RNAs, which are involved in generation of 5-hmC and DNA demethylation, were strongly upregulated in myoblasts and myotubes. Our findings implicate de novo methylation predominantly before the myoblast stage and demethylation before and after the myotube stage in control of transcription and co-transcriptional RNA processing. They also suggest that, in muscle, TET1 or TET2 are involved in active demethylation and in formation of stable 5-hmC residues.

  11. JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for Development of Hematopoietic Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Sihui Li

    2018-04-01

    Full Text Available Summary: The arginine methylation status of histones dynamically changes during many cellular processes, including hematopoietic stem/progenitor cell (HSPC development. The arginine methyltransferases and the readers that transduce the histone codes have been defined. However, whether arginine demethylation actively occurs in cells and what enzyme demethylates the methylarginine residues during various cellular processes are unknown. We report that JMJD1B, previously identified as a lysine demethylase for H3K9me2, mediates arginine demethylation of H4R3me2s and its intermediate, H4R3me1. We show that demethylation of H4R3me2s and H3K9me2s in promoter regions is correlated with active gene expression. Furthermore, knockout of JMJD1B blocks demethylation of H4R3me2s and/or H3K9me2 at distinct clusters of genes and impairs the activation of genes important for HSPC differentiation and development. Consequently, JMJD1B−/− mice show defects in hematopoiesis. Altogether, our study demonstrates that demethylase-mediated active arginine demethylation process exists in eukaryotes and that JMJD1B demethylates both H4R3me2s and H3K9me2 for epigenetic programming during hematopoiesis. : Li et al. identify the arginine demethylase (RDM activity of JMJD1B, a known lysine demethylase (KDM. They reveal that JMJD1B actively mediates demethylation of histone markers H4R3me2s and H3K9me2 in hematopoietic stem/progenitor cells (HSPCs. Keywords: JMJD1B, KDM3B, PRMT5, arginine demethylase, histone, epigenetic programming, gene expression, hematopoiesis

  12. Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging.

    Science.gov (United States)

    Wei, Shu; Hua, Hai-Rong; Chen, Qian-Quan; Zhang, Ying; Chen, Fei; Li, Shu-Qing; Li, Fan; Li, Jia-Li

    2017-03-18

    Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews ( Tupaia belangeri chinensis ). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

  13. Representing and estimating interactions between activities in a need-based model of activity generation

    NARCIS (Netherlands)

    Nijland, L.; Arentze, T.; Timmermans, H.

    2013-01-01

    Although several activity-based models made the transition to practice in recent years, modeling dynamic activity generation and especially, the mechanisms underlying activity generation are not well incorporated in the current activity-based models. For instance, current models assume that

  14. Representing and estimating interactions between activities in a need-based model of activity generation

    NARCIS (Netherlands)

    Nijland, E.W.L.; Arentze, T.A.; Timmermans, H.J.P.

    2011-01-01

    Although several activity-based models made the transition to practice in recent years, modelling dynamic activity generation and especially, the mechanisms underlying activity generation are not well incorporated in the current activity-based models. For example, current models assume that

  15. Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b.

    Science.gov (United States)

    Ebata, Kevin T; Mesh, Kathryn; Liu, Shichong; Bilenky, Misha; Fekete, Alexander; Acker, Michael G; Hirst, Martin; Garcia, Benjamin A; Ramalho-Santos, Miguel

    2017-01-01

    Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells. Vitamin C treatment reduces global levels of H3K9me2, but not other histone methylation marks analyzed, as measured by western blot, immunofluorescence and mass spectrometry. Vitamin C leads to widespread loss of H3K9me2 at large chromosomal domains as well as gene promoters and repeat elements. Vitamin C-induced loss of H3K9me2 occurs rapidly within 24 h and is reversible. Importantly, we found that the histone demethylases Kdm3a and Kdm3b are required for vitamin C-induced demethylation of H3K9me2. Moreover, we show that vitamin C-induced Kdm3a/b-mediated H3K9me2 demethylation and Tet-mediated DNA demethylation are independent processes at specific loci. Lastly, we document Kdm3a/b are partially required for the upregulation of germline genes by vitamin C. These results reveal a specific role for vitamin C in histone demethylation in ES cells and document that DNA methylation and H3K9me2 cooperate to silence germline genes in pluripotent cells.

  16. Non-Relative Value Unit-Generating Activities Represent One-Fifth of Academic Neuroradiologist Productivity.

    Science.gov (United States)

    Wintermark, M; Zeineh, M; Zaharchuk, G; Srivastava, A; Fischbein, N

    2016-07-01

    A neuroradiologist's activity includes many tasks beyond interpreting relative value unit-generating imaging studies. Our aim was to test a simple method to record and quantify the non-relative value unit-generating clinical activity represented by consults and clinical conferences, including tumor boards. Four full-time neuroradiologists, working an average of 50% clinical and 50% academic activity, systematically recorded all the non-relative value unit-generating consults and conferences in which they were involved during 3 months by using a simple, Web-based, computer-based application accessible from smartphones, tablets, or computers. The number and type of imaging studies they interpreted during the same period and the associated relative value units were extracted from our billing system. During 3 months, the 4 neuroradiologists working an average of 50% clinical activity interpreted 4241 relative value unit-generating imaging studies, representing 8152 work relative value units. During the same period, they recorded 792 non-relative value unit-generating study reviews as part of consults and conferences (not including reading room consults), representing 19% of the interpreted relative value unit-generating imaging studies. We propose a simple Web-based smartphone app to record and quantify non-relative value unit-generating activities including consults, clinical conferences, and tumor boards. The quantification of non-relative value unit-generating activities is paramount in this time of a paradigm shift from volume to value. It also represents an important tool for determining staffing levels, which cannot be performed on the basis of relative value unit only, considering the importance of time spent by radiologists on non-relative value unit-generating activities. It may also influence payment models from medical centers to radiology departments or practices. © 2016 by American Journal of Neuroradiology.

  17. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: Role of Jumonji C-domain containing protein 6 in RHA demethylation

    International Nuclear Information System (INIS)

    Lawrence, Paul; Conderino, Joseph S.; Rieder, Elizabeth

    2014-01-01

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication. - Highlights: • We examined the role of JMJD6 in FMDV-induced RHA demethylation process. • Using an arginine demethylation assay showed that JMJD6 is involved in RHA demethylation. • A demethylases inhibitor reduced cytoplasmic accumulation of RHA and FMDV titers

  18. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: Role of Jumonji C-domain containing protein 6 in RHA demethylation

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, Paul; Conderino, Joseph S.; Rieder, Elizabeth, E-mail: elizabeth.rieder@ars.usda.gov

    2014-03-15

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided with nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication. - Highlights: • We examined the role of JMJD6 in FMDV-induced RHA demethylation process. • Using an arginine demethylation assay showed that JMJD6 is involved in RHA demethylation. • A demethylases inhibitor reduced cytoplasmic accumulation of RHA and FMDV titers.

  19. A non-heme iron-mediated chemical demethylation in DNA and RNA.

    Science.gov (United States)

    Yi, Chengqi; Yang, Cai-Guang; He, Chuan

    2009-04-21

    DNA methylation is arguably one of the most important chemical signals in biology. However, aberrant DNA methylation can lead to cytotoxic or mutagenic consequences. A DNA repair protein in Escherichia coli, AlkB, corrects some of the unwanted methylations of DNA bases by a unique oxidative demethylation in which the methyl carbon is liberated as formaldehyde. The enzyme also repairs exocyclic DNA lesions--that is, derivatives in which the base is augmented with an additional heterocyclic subunit--by a similar mechanism. Two proteins in humans that are homologous to AlkB, ABH2 and ABH3, repair the same spectrum of lesions; another human homologue of AlkB, FTO, is linked to obesity. In this Account, we describe our studies of AlkB, ABH2, and ABH3, including our development of a general strategy to trap homogeneous protein-DNA complexes through active-site disulfide cross-linking. AlkB uses a non-heme mononuclear iron(II) and the cofactors 2-ketoglutarate (2KG) and dioxygen to effect oxidative demethylation of the DNA base lesions 1-methyladenine (1-meA), 3-methylcytosine (3-meC), 1-methylguanine (1-meG), and 3-methylthymine (3-meT). ABH3, like AlkB, works better on single-stranded DNA (ssDNA) and is capable of repairing damaged bases in RNA. Conversely, ABH2 primarily repairs lesions in double-stranded DNA (dsDNA); it is the main housekeeping enzyme that protects the mammalian genome from 1-meA base damage. The AlkB-family proteins have moderate affinities for their substrates and bind DNA in a non-sequence-specific manner. Knowing that these proteins flip the damaged base out from the duplex DNA and insert it into the active site for further processing, we first engineered a disulfide cross-link in the active site to stabilize the Michaelis complex. Based on the detailed structural information afforded by the active-site cross-linked structures, we can readily install a cross-link away from the active site to obtain the native-like structures of these complexes

  20. ERRα protein is stabilized by LSD1 in a demethylation-independent manner.

    Directory of Open Access Journals (Sweden)

    Julie Carnesecchi

    Full Text Available The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue may be a key event to increase ERRα protein, independently of its corresponding mRNA.

  1. ERRα protein is stabilized by LSD1 in a demethylation-independent manner.

    Science.gov (United States)

    Carnesecchi, Julie; Cerutti, Catherine; Vanacker, Jean-Marc; Forcet, Christelle

    2017-01-01

    The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα) induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue) may be a key event to increase ERRα protein, independently of its corresponding mRNA.

  2. Spatiotemporally Representative and Cost-Efficient Sampling Design for Validation Activities in Wanglang Experimental Site

    Directory of Open Access Journals (Sweden)

    Gaofei Yin

    2017-11-01

    Full Text Available Spatiotemporally representative Elementary Sampling Units (ESUs are required for capturing the temporal variations in surface spatial heterogeneity through field measurements. Since inaccessibility often coexists with heterogeneity, a cost-efficient sampling design is mandatory. We proposed a sampling strategy to generate spatiotemporally representative and cost-efficient ESUs based on the conditioned Latin hypercube sampling scheme. The proposed strategy was constrained by multi-temporal Normalized Difference Vegetation Index (NDVI imagery, and the ESUs were limited within a sampling feasible region established based on accessibility criteria. A novel criterion based on the Overlapping Area (OA between the NDVI frequency distribution histogram from the sampled ESUs and that from the entire study area was used to assess the sampling efficiency. A case study in Wanglang National Nature Reserve in China showed that the proposed strategy improves the spatiotemporally representativeness of sampling (mean annual OA = 74.7% compared to the single-temporally constrained (OA = 68.7% and the random sampling (OA = 63.1% strategies. The introduction of the feasible region constraint significantly reduces in-situ labour-intensive characterization necessities at expenses of about 9% loss in the spatiotemporal representativeness of the sampling. Our study will support the validation activities in Wanglang experimental site providing a benchmark for locating the nodes of automatic observation systems (e.g., LAINet which need a spatially distributed and temporally fixed sampling design.

  3. Why eicosanoids could represent a new class of tocolytics on uterine activity in pregnant women.

    Science.gov (United States)

    Corriveau, Stéphanie; Berthiaume, Maryse; Rousseau, Eric; Pasquier, Jean-Charles

    2009-10-01

    The purpose of this study was to assess the effects of exogenous eicosanoids on spontaneous uterine contractile activity. Eight uterine biopsies were performed from women who were undergoing elective cesarean delivery. Tension measurements were performed in vitro on myometrial strips. Contractile activities were quantified by the calculation of the area under the curve. The effects of eicosanoids and specific enzyme inhibitors were assessed. Fractions from various uterine tissues were analyzed by Western blot. Data demonstrate the presence, in some tested tissues, of cytochrome P-450 epoxygenase and soluble epoxide hydrolase, which respectively produce and degrade epoxyeicosatrienoic acid regioisomers. Inhibition of soluble epoxide hydrolase with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid or omega-hydroxylase with N-methylsulfonyl-12,12-dibromododec-11-enamide resulted in a tocolytic effect; N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide, which is an epoxygenase inhibitor, had no effect. Exogenous epoxyeicosatrienoic acids displayed significant tocolytic effects on spontaneous contractile activities. Epoxy- and hydroxyeicosanoids represent new bioactive, arachidonic acid by-products with in vitro tocolytic activities. These findings suggest that cytochrome P-450 isozymes may represent relevant pharmacologic targets under physiopathologic conditions.

  4. Consideration of statistical uncertainties for the determination of representative values of the specific activity of wastes

    International Nuclear Information System (INIS)

    Barthel, R.

    2008-01-01

    The German Radiation Protection Commission has recommended 'Principles and Methods for the Consideration of Statistical Uncertainties for the Determination of Representative Values of the Specific Activity of NORM wastes' concerning the proof of compliance with supervision limits or dose standards according to paragraph 97 and paragraph 98 of the Radiation Protection Ordinance, respectively. The recommendation comprises a method ensuring the representativeness of estimates for the specific activity of NORM wastes, which also assures the required evidence for conformity with respect to supervision limits or dose standards, respectively. On the basis of a sampling survey, confidence limits for expectation values of specific activities are determined, which will be used to show that the supervision limit or the dose standard is met or exceeded with certainty, or that the performed sampling is not sufficient for the intended assessment. The sampling effort depends on the type and the width of the distribution of specific activities and is determined by the position of the confidence interval with respect to the supervision limit or of the resulting doses with respect to the dose standard. The statistical uncertainties that are described by confidence limits may be reduced by an optimised extension of the sample number, as far as necessary. (orig.)

  5. Chemical groups and structural characterization of lignin via thiol-mediated demethylation

    Science.gov (United States)

    Lihong Hu; Hui Pan; Yonghong Zhou; Chung-Yun Hse; Chengguo Liu; Baofang Zhang; Bin Xu

    2014-01-01

    A new approach to increase the reactivity of lignin by thiol-mediated demethylation was investigated in this study. Demethylated lignin was characterized by the changes in its hydroxyl and methoxyl groups, molecular weight, and other properties using titration and spectroscopy methods including FT-IR, 1H NMR, UV,and GPC. The total...

  6. Fast Curing Bio-Based Phenolic Resins via Lignin Demethylated under Mild Reaction Condition

    Directory of Open Access Journals (Sweden)

    Jiongjiong Li

    2017-09-01

    Full Text Available Demethylation technique has been used to enhance lignin reactivity for preparation of phenolic resins. However, the demethylation efficiency and the demethylated lignin (DL reactivity were still unsatisfactory. To improve the demethylation efficiency, alkali lignin was demethylated under different mild conditions using sodium sulfite as a catalyst. Lignin and DL were characterized by 1H-NMR (nuclear magnetic resonance and Fourier transform infrared (FT-IR spectroscopy to determine the demethylation mechanism. With the demethylation of lignin, the methoxyl group content decreased from 1.93 m mol/g to 1.09 m mol/g, and the phenolic hydroxyl group content increased from 0.56 m mol/g to 0.82 m mol/g. These results revealed that methoxyl groups were attacked by SO32−, and some methoxyl groups were converted to phenolic hydroxyl groups by a nucleophilic substitution reaction, generating DL with high reactivity. The chemical properties of lignin-based phenolic resins were studied by 13C-NMR and FT-IR spectroscopy, and their physical properties were also investigated. The results indicated that lignin-based phenolic resins exhibited faster curing rate and shorter gel time. In addition, the bonding strength increased from 0.92 MPa to 1.07 MPa, and the formaldehyde emission decreased from 0.58 mg/L to 0.22 mg/L after lignin demethylated at the optimum condition.

  7. A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways.

    Science.gov (United States)

    Äijö, Tarmo; Huang, Yun; Mannerström, Henrik; Chavez, Lukas; Tsagaratou, Ageliki; Rao, Anjana; Lähdesmäki, Harri

    2016-03-14

    We present a generative model, Lux, to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications. Analysis of targeted data from Tet2-knockdown embryonic stem cells and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in putative regulatory regions.

  8. Physical activity, sedentary behavior, and body mass index in the Czech Republic: a nationally representative survey.

    Science.gov (United States)

    Mitáš, Josef; Ding, Ding; Frömel, Karel; Kerr, Jacqueline

    2014-07-01

    Post-communist countries have experienced rapid economic development and social changes, which have been accompanied by changes in health-related lifestyle behaviors, such as physical activity. The purpose of this study was to examine the associations of domain-specific physical activity and total sedentary time with BMI among adults in the Czech Republic. We surveyed a nationally representative sample (n = 4097) of the Czech Republic in fall 2007 using the International Physical Activity Questionnaire (long form). Multiple linear regression analyses were used to examine associations of physical activity, sedentary time and sociodemographic characteristics with BMI. Older age, lower educational attainment, and lower levels of leisure-time physical activity were associated with higher BMI. Compared with those living in large cities, men living in small towns and women living in small villages had higher BMI. This study has identified correlates of BMI in the Czech Republic. Although more evidence from longitudinal studies is needed, findings from the current study can inform interventions to prevent the rising obesity epidemic.

  9. Urease Activity Represents an Alternative Pathway for Mycobacterium tuberculosis Nitrogen Metabolism

    Science.gov (United States)

    Lin, Wenwei; Mathys, Vanessa; Ang, Emily Lei Yin; Koh, Vanessa Hui Qi; Martínez Gómez, Julia María; Ang, Michelle Lay Teng; Zainul Rahim, Siti Zarina; Tan, Mai Ping; Pethe, Kevin

    2012-01-01

    Urease represents a critical virulence factor for some bacterial species through its alkalizing effect, which helps neutralize the acidic microenvironment of the pathogen. In addition, urease serves as a nitrogen source provider for bacterial growth. Pathogenic mycobacteria express a functional urease, but its role during infection has yet to be characterized. In this study, we constructed a urease-deficient Mycobacterium tuberculosis strain and confirmed the alkalizing effect of the urease activity within the mycobacterium-containing vacuole in resting macrophages but not in the more acidic phagolysosomal compartment of activated macrophages. However, the urease-mediated alkalizing effect did not confer any growth advantage on M. tuberculosis in macrophages, as evidenced by comparable growth profiles for the mutant, wild-type (WT), and complemented strains. In contrast, the urease-deficient mutant exhibited impaired in vitro growth compared to the WT and complemented strains when urea was the sole source of nitrogen. Substantial amounts of ammonia were produced by the WT and complemented strains, but not with the urease-deficient mutant, which represents the actual nitrogen source for mycobacterial growth. However, the urease-deficient mutant displayed parental colonization profiles in the lungs, spleen, and liver in mice. Together, our data demonstrate a role for the urease activity in M. tuberculosis nitrogen metabolism that could be crucial for the pathogen's survival in nutrient-limited microenvironments where urea is the sole nitrogen source. Our work supports the notion that M. tuberculosis virulence correlates with its unique metabolic versatility and ability to utilize virtually any carbon and nitrogen sources available in its environment. PMID:22645285

  10. O2 -independent demethylation of trimethylamine N-oxide by Tdm of Methylocella silvestris.

    Science.gov (United States)

    Zhu, Yijun; Ksibe, Amira Z; Schäfer, Hendrik; Blindauer, Claudia A; Bugg, Timothy D H; Chen, Yin

    2016-11-01

    Bacterial trimethylamine N-oxide (TMAO) demethylase, Tdm, carries out an unusual oxygen-independent demethylation reaction, resulting in the formation of dimethylamine and formaldehyde. In this study, site-directed mutagenesis, homology modelling and metal analyses by inorganic mass spectrometry have been applied to gain insight into metal stoichiometry and underlying catalytic mechanism of Tdm of Methylocella silvestris BL2. Herein, we demonstrate that active Tdm has 1 molar equivalent of Zn 2+ and 1 molar equivalent of non-haem Fe 2+ . We further investigated Zn 2+ - and Fe 2+ -binding sites through homology modelling and site-directed mutagenesis and found that Zn 2+ is coordinated by a 3-sulfur-1-O motif. An aspartate residue (D198) likely bridges Fe 2+ and Zn 2+ centres, either directly or indirectly via H-bonding through a neighbouring H 2 O molecule. H276 contributes to Fe 2+ binding, mutation of which results in an inactive enzyme, and the loss of iron, but not zinc. Site-directed mutagenesis of Tdm also led to the identification of three hydrophobic aromatic residues likely involved in substrate coordination (F259, Y305, W321), potentially through a cation-π interaction. Furthermore, a crossover experiment using a substrate analogue gave direct evidence that a trimethylamine-alike intermediate was produced during the Tdm catalytic cycle, suggesting TMAO has a dual role of being both a substrate and an oxygen donor for formaldehyde formation. Together, our results provide novel insight into the role of Zn 2+ and Fe 2+ in the catalysis of TMAO demethylation by this unique oxygen-independent enzyme. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  11. FOXP3 Expression in GARP-Transduced Helper T Cells Is Not Associated with FOXP3 TSDR Demethylation.

    Science.gov (United States)

    Kehrmann, Jan; Zeschnigk, Michael; Buer, Jan; Probst-Kepper, Michael

    2011-10-01

    AIM: Glycoprotein A repetitions predominant (GARP or LRRC32) represents a human regulatory CD4+ CD25(hi) FOXP3+ T (T(reg)) cell-specific receptor that controls FOXP3. Ectopic expression of GARP in helper T (T(h)) cells has been shown to be sufficient for the induction of FOXP3 and generation of a stable regulatory phenotype. Since expression of FOXP3 in Treg cells is epigenetically controlled by a conserved motif, the so-called T(reg)-specific demethylated region (TSDR), we asked whether GARP-mediated upregulation of FOXP3 in Th cells is similarly accompanied by demethylation of the TSDR. METHODS: DNA methylation of the FOXP3 TSDR was analyzed by direct sequencing of polymerase chain reaction (PCR) products from bisulfite-treated genomic DNA. RESULTS: Although GARP-transduced T(h) cells exhibit constitutive FOXP3 expression and a regulatory phenotype, the FOXP3 TSDR is completely methylated as in naive T(h) cells. GARP-mediated FOXP3 upregulation in T(h) cells is not associated with T(reg)-specific demethylation of the FOXP3 TSDR. CONCLUSION: Although GARP-engineered T(h) cells exhibit stable FOXP3 expression and a phenotypic reprogramming towards T(reg) cells in vitro, these cells do not completely mimic the epigenotype of natural T(reg) cells. Thus, concepts based on the genetic modification of T(h) cells as cellular therapies to treat autoimmune diseases or to control transplantation tolerance should be critically tested before any clinical application.

  12. Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes.

    Science.gov (United States)

    Matern, Andreas; Pedrolli, Danielle; Großhennig, Stephanie; Johansson, Jörgen; Mack, Matthias

    2016-12-01

    The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B 2 ), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8-demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8-aminoriboflavin adenine dinucleotide (AFAD). In vivo reporter gene assays and in vitro transcription/translation experiments show that the L. monocytogenes FMN riboswitch Rli96, which controls expression of the riboflavin transport gene lmo1945, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of L. monocytogenes with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in L. monocytogenes IMPORTANCE: The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are small molecules which are produced by Streptomyces davawensis and Streptomyces cinnabarinus

  13. Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro

    NARCIS (Netherlands)

    Lirk, P.; Hollmann, M. W.; Fleischer, M.; Weber, N. C.; Fiegl, H.

    2014-01-01

    Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of

  14. Physical activity and coronary artery calcification in two cohorts of women representing early and late postmenopause.

    Science.gov (United States)

    Storti, Kristi L; Pettee Gabriel, Kelley K; Underwood, Darcy A; Kuller, Lewis H; Kriska, Andrea M

    2010-01-01

    The aim of this study was to examine the association between physical activity (PA) and coronary artery calcification (CAC) among two cohorts of postmenopausal (PM) women representing early and late postmenopause. The cross-sectional relationship between PA and CAC was examined in 173 younger PM women (mean age ± SD, 56.8 ± 2.9 y) from the Women on the Move Through Activity and Nutrition (WOMAN) study and 121 older PM women (mean age ± SD, 73.9 ± 3.8 y) from the Walking Women Follow-up (WWF) study who had complete PA and CAC data. PA was measured objectively using a pedometer over a 7-day period in both cohorts. CAC was assessed using electron beam tomography. Descriptive statistics were used to describe median levels of PA and CAC, as well as proportions of detectable CAC (0 vs > 0). Fifty-seven percent of WOMAN study participants and 74% of WWF study participants had detectable CAC. The median (interquartile range) CAC score was 1.4 (0-23.3) for participants in the WOMAN study and 38.8 (0-264.4) among WWF study participants. Median (interquartile range) step counts were 6,447 (4,823-8,722) steps per day in the WOMAN study and 5,466 (3,610-7,576) steps per day for WWF study participants. Among WWF study participants, there was a statistically significant inverse association between pedometer steps and CAC (P for trend = 0.002); no association was found among WOMAN study participants. Among older PM women, higher levels of PA were associated with lower CAC. However, the relationship was not observed in PM women, likely due to the lower prevalence of CAC in this age group.

  15. Arsenic Demethylation by a C·As Lyase in Cyanobacterium Nostoc sp. PCC 7120.

    Science.gov (United States)

    Yan, Yu; Ye, Jun; Xue, Xi-Mei; Zhu, Yong-Guan

    2015-12-15

    Arsenic, a ubiquitous toxic substance, exists mainly as inorganic forms in the environment. It is perceived that organoarsenicals can be demethylated and degraded into inorganic arsenic by microorganisms. Few studies have focused on the mechanism of arsenic demethylation in bacteria. Here, we investigated arsenic demethylation in a typical freshwater cyanobacterium Nostoc sp. PCC 7120. This bacterium was able to demethylate monomethylarsenite [MAs(III)] rapidly to arsenite [As(III)] and also had the ability to demethylate monomethylarsenate [MAs(V)] to As(III). The NsarsI encoding a C·As lyase responsible for MAs(III) demethylation was cloned from Nostoc sp. PCC 7120 and heterologously expressed in an As-hypersensitive strain Escherichia coli AW3110 (ΔarsRBC). Expression of NsarsI was shown to confer MAs(III) resistance through arsenic demethylation. The purified NsArsI was further identified and functionally characterized in vitro. NsArsI existed mainly as the trimeric state, and the kinetic data were well-fit to the Hill equation with K0.5 = 7.55 ± 0.33 μM for MAs(III), Vmax = 0.79 ± 0.02 μM min(-1), and h = 2.7. Both of the NsArsI truncated derivatives lacking the C-terminal 10 residues (ArsI10) or 23 residues (ArsI23) had a reduced ability of MAs(III) demethylation. These results provide new insights for understanding the important role of cyanobacteria in arsenic biogeochemical cycling in the environment.

  16. Do Public Involvement Activities in Biomedical Research and Innovation Recruit Representatively? A Systematic Qualitative Review.

    Science.gov (United States)

    Lander, Jonas; Hainz, Tobias; Hirschberg, Irene; Bossert, Sabine; Strech, Daniel

    2016-01-01

    Public involvement activities (PIAs) may contribute to the governance of ethically challenging biomedical research and innovation by informing, consulting with and engaging the public in developments and decision-making processes. For PIAs to capture a population's preferences (e.g. on issues in whole genome sequencing, biobanks or genome editing), a central methodological requirement is to involve a sufficiently representative subgroup of the general public. While the existing literature focusses on theoretical and normative aspects of 'representation', this study assesses empirically how such considerations are implemented in practice. It evaluates how PIA reports describe representation objectives, the recruitment process and levels of representation achieved. PIA reports were included from a systematic literature search if they directly reported a PIA conducted in a relevant discipline such as genomics, biobanks, biotechnology or others. PIA reports were analyzed with thematic text analysis. The text analysis was guided by an assessment matrix based on PIA-specific guidelines and frameworks. We included 46 relevant reports, most focusing on issues in genomics. 27 reports (59%) explicitly described representation objectives, though mostly without adjusting eligibility criteria and recruiting methods to the specific objective. 11 reports (24%) explicitly reported to have achieved the intended representation; the rest either reported failure or were silent on this issue. Representation of study samples in PIAs in biomedical research and innovation is currently not reported systematically. Improved reporting on representation would not only improve the validity and value of PIAs, but could also contribute to PIA results being used more often in relevant policy and decision-making processes. © 2016 S. Karger AG, Basel.

  17. Fiscal years 2007 and 2008 : representative examples of completed RD&T projects and activities

    Science.gov (United States)

    2009-06-01

    The tables in this document correspond to major offices and initiatives at the Federal Highway Administration's Office of Research, Development, and Technology (RD&T), located at the Turner-Fairbank Highway Research Center. The tables provide represe...

  18. Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients.

    Science.gov (United States)

    Coller, Janet K; Michalakas, Jennifer R; James, Heather M; Farquharson, Aaron L; Colvill, Joel; White, Jason M; Somogyi, Andrew A

    2012-11-01

    Management of pain in opioid dependent individuals is problematic due to numerous issues including cross-tolerance to opioids. Hence there is a need to find alternative analgesics to classical opioids and tramadol is potentially one such alternative. Methadone inhibits CYP2D6 in vivo and in vitro. We aimed to investigate the effect of methadone on the pathways of tramadol metabolism: O-demethylation (CYP2D6) to the opioid-active metabolite M1 and N-demethylation (CYP3A4) to M2 in subjects maintained on methadone or buprenorphine as a control. Compared with subjects on buprenorphine, methadone reduced the clearance of tramadol to active O-desmethyl-tramadol (M1) but had no effect on N-desmethyltramadol (M2) formation. Similar to other analgesics whose active metabolites are formed by CYP2D6 such as codeine, reduced formation of O-desmethyltramadol (M1) is likely to result in reduced analgesia for subjects maintained on methadone. Hence alternative analgesics whose metabolism is independent of CYP2D6 should be utilized in this patient population. To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine methadone and seven buprenorphine maintained subjects received a single 100 mg dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites. The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012-0.103)] compared with those taking buprenorphine [0.192 (0.108-0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower

  19. The Cell Cycle: An Activity Using Paper Plates to Represent Time Spent in Phases of the Cell Cycle

    Science.gov (United States)

    Scherer, Yvette D.

    2014-01-01

    In this activity, students are given the opportunity to combine skills in math and geometry for a biology lesson in the cell cycle. Students utilize the data they collect and analyze from an online onion-root-tip activity to create a paper-plate time clock representing a 24-hour cell cycle. By dividing the paper plate into appropriate phases of…

  20. Mitochondrial control through nutritionally regulated global histone H3 lysine-4 demethylation.

    Science.gov (United States)

    Soloveychik, Maria; Xu, Mengshu; Zaslaver, Olga; Lee, Kwanyin; Narula, Ashrut; Jiang, River; Rosebrock, Adam P; Caudy, Amy A; Meneghini, Marc D

    2016-11-29

    Histone demethylation by Jumonji-family proteins is coupled with the decarboxylation of α-ketoglutarate (αKG) to yield succinate, prompting hypotheses that their activities are responsive to levels of these metabolites in the cell. Consistent with this paradigm we show here that the Saccharomyces cerevisiae Jumonji demethylase Jhd2 opposes the accumulation of H3K4me3 in fermenting cells only when they are nutritionally manipulated to contain an elevated αKG/succinate ratio. We also find that Jhd2 opposes H3K4me3 in respiratory cells that do not exhibit such an elevated αKG/succinate ratio. While jhd2∆ caused only limited gene expression defects in fermenting cells, transcript profiling and physiological measurements show that JHD2 restricts mitochondrial respiratory capacity in cells grown in non-fermentable carbon in an H3K4me-dependent manner. In association with these phenotypes, we find that JHD2 limits yeast proliferative capacity under physiologically challenging conditions as measured by both replicative lifespan and colony growth on non-fermentable carbon. JHD2's impact on nutrient response may reflect an ancestral role of its gene family in mediating mitochondrial regulation.

  1. Mitochondrial control through nutritionally regulated global histone H3 lysine-4 demethylation

    Science.gov (United States)

    Soloveychik, Maria; Xu, Mengshu; Zaslaver, Olga; Lee, Kwanyin; Narula, Ashrut; Jiang, River; Rosebrock, Adam P.; Caudy, Amy A.; Meneghini, Marc D.

    2016-01-01

    Histone demethylation by Jumonji-family proteins is coupled with the decarboxylation of α-ketoglutarate (αKG) to yield succinate, prompting hypotheses that their activities are responsive to levels of these metabolites in the cell. Consistent with this paradigm we show here that the Saccharomyces cerevisiae Jumonji demethylase Jhd2 opposes the accumulation of H3K4me3 in fermenting cells only when they are nutritionally manipulated to contain an elevated αKG/succinate ratio. We also find that Jhd2 opposes H3K4me3 in respiratory cells that do not exhibit such an elevated αKG/succinate ratio. While jhd2∆ caused only limited gene expression defects in fermenting cells, transcript profiling and physiological measurements show that JHD2 restricts mitochondrial respiratory capacity in cells grown in non-fermentable carbon in an H3K4me-dependent manner. In association with these phenotypes, we find that JHD2 limits yeast proliferative capacity under physiologically challenging conditions as measured by both replicative lifespan and colony growth on non-fermentable carbon. JHD2’s impact on nutrient response may reflect an ancestral role of its gene family in mediating mitochondrial regulation. PMID:27897198

  2. Comparatives of Expressive Activities of Junior High School Students with Different Types of Representative Systems

    Directory of Open Access Journals (Sweden)

    Geydebrekht N.A.

    2017-08-01

    Full Text Available The article presents data from a study of drawings of children of primary school age to identify the сcomparative diagnostic parameters that allow to define the leading representative system in the child. 164 drawings of 51 persons under test of the two grades of primary school were analyzed. The observation and modified in relation to primary school age version of the method «Representational systems bias test» (Lewis A., Puselik R., 2012 were used as elements of the diagnostic unit. Based on these results it is concluded that the drawings of children of primary school age with different types of representative systems have differences, sufficient to justify their diagnostic informative value. The results of the study make comparative profiles of children of primary school age with different types of representational systems to facilitate the diagnostic part of the work with children's drawings.

  3. Synergistic Cytotoxic Effect of L-Asparaginase Combined with Decitabine as a Demethylating Agent in Pediatric T-ALL, with Specific Epigenetic Signature

    Directory of Open Access Journals (Sweden)

    Salvatore Serravalle

    2016-01-01

    Full Text Available T-Acute Lymphoblastic Leukemia (T-ALL remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients’ outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment. Hence we treated different T-ALL cell lines with L-asparaginase and correlated different responses to the treatment with ASNS expression. Then we demonstrated that the ASNS expression was dependent on the methylation status of the promoter. Finally we showed that, despite the demethylating effect on the ASNS gene expression, the combined treatment with the demethylating agent Decitabine could synergistically improve the L-asparaginase sensitivity in those T-ALL cell lines characterized by hypermethylation of the ASNS gene. In conclusion, this preclinical study identified an unexpected synergistic activity of L-asparaginase and Decitabine in the subgroup of T-ALL with low ASNS expression due to hypermethylation of the ASNS promoter, while it did not restore sensitivity in the resistant cell lines characterized by higher ASNS expression.

  4. Fire activity and severity in the western US vary along proxy gradients representing fuel amount and fuel moisture.

    Directory of Open Access Journals (Sweden)

    Sean A Parks

    Full Text Available Numerous theoretical and empirical studies have shown that wildfire activity (e.g., area burned at regional to global scales may be limited at the extremes of environmental gradients such as productivity or moisture. Fire activity, however, represents only one component of the fire regime, and no studies to date have characterized fire severity along such gradients. Given the importance of fire severity in dictating ecological response to fire, this is a considerable knowledge gap. For the western US, we quantify relationships between climate and the fire regime by empirically describing both fire activity and severity along two climatic water balance gradients, actual evapotranspiration (AET and water deficit (WD, that can be considered proxies for fuel amount and fuel moisture, respectively. We also concurrently summarize fire activity and severity among ecoregions, providing an empirically based description of the geographic distribution of fire regimes. Our results show that fire activity in the western US increases with fuel amount (represented by AET but has a unimodal (i.e., humped relationship with fuel moisture (represented by WD; fire severity increases with fuel amount and fuel moisture. The explicit links between fire regime components and physical environmental gradients suggest that multivariable statistical models can be generated to produce an empirically based fire regime map for the western US. Such models will potentially enable researchers to anticipate climate-mediated changes in fire recurrence and its impacts based on gridded spatial data representing future climate scenarios.

  5. An active learning representative subset selection method using net analyte signal

    Science.gov (United States)

    He, Zhonghai; Ma, Zhenhe; Luan, Jingmin; Cai, Xi

    2018-05-01

    To guarantee accurate predictions, representative samples are needed when building a calibration model for spectroscopic measurements. However, in general, it is not known whether a sample is representative prior to measuring its concentration, which is both time-consuming and expensive. In this paper, a method to determine whether a sample should be selected into a calibration set is presented. The selection is based on the difference of Euclidean norm of net analyte signal (NAS) vector between the candidate and existing samples. First, the concentrations and spectra of a group of samples are used to compute the projection matrix, NAS vector, and scalar values. Next, the NAS vectors of candidate samples are computed by multiplying projection matrix with spectra of samples. Scalar value of NAS is obtained by norm computation. The distance between the candidate set and the selected set is computed, and samples with the largest distance are added to selected set sequentially. Last, the concentration of the analyte is measured such that the sample can be used as a calibration sample. Using a validation test, it is shown that the presented method is more efficient than random selection. As a result, the amount of time and money spent on reference measurements is greatly reduced.

  6. Participation in Leisure Activities among Canadian Children with Arthritis: Results from a National Representative Sample.

    Science.gov (United States)

    Cavallo, Sabrina; Majnemer, Annette; Mazer, Barbara; Chilingaryan, Gevorg; Ehrmann Feldman, Debbie

    2015-06-01

    To describe the level of participation in leisure activities among children and youth with arthritis, as well as to identify the sociodemographic (age, sex, family income), disease-related (functional limitations, disease duration, pain, medication use, child's need for assistance), and contextual factors (use of rehabilitation services, proximity of local recreation facilities, cost of activities) that may be associated. Data from the Participation and Activity Limitation Survey (PALS) 2006, a Canadian postcensus survey, was analyzed. Bivariate and multivariable linear regression analyses were applied to examine the associations between the sample's level of participation in leisure activities, and sociodemographic, disease-related, and contextual characteristics. In Canada in 2006, an estimated 4350 children ranging in age from 5 to 14 years were living with arthritis. Fifty-six percent of parents reported that arthritis restricted their child's participation in leisure activities. Bivariate analysis showed that the availability of local recreational facilities, the affordability of activities, and the child not requiring any assistance were all associated (modified Bonferroni correction α leisure activities. Multiple linear regressions showed that higher family income (β 0.47, 95% CI 0.09, 0.85) and greater perceived pain (β 0.59, 95% CI 0.07, 1.10) were positively associated with involvement in informal leisure. Our findings underline the importance of considering contextual factors in developing treatment plans aimed at improving participation in leisure activities among children with arthritis. Future longitudinal studies targeting children living with arthritis could provide pertinent information on participation over fluctuations in disease status.

  7. Distance to green space and physical activity: a danish national representative survey

    DEFF Research Database (Denmark)

    Toftager, Mette; Ekholm, Ola; Schipperijn, Jasper

    2011-01-01

    This study examines the relationship between distance to green space and the level of physical activity among the population of Denmark. In addition, the relationship between distance to green space and obesity is investigated.......This study examines the relationship between distance to green space and the level of physical activity among the population of Denmark. In addition, the relationship between distance to green space and obesity is investigated....

  8. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    Science.gov (United States)

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful “thoughtless emptiness (TE),” a “focused attention,” and an “open monitoring” task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  9. Knowledge Activation versus Sentence Mapping When Representing Fictional Characters' Emotional States.

    Science.gov (United States)

    Gernsbacher, Morton Ann; Robertson, Rachel R. W.

    1992-01-01

    In a study of knowledge activation and sentence mapping, subjects read stories that described concrete actions, and then the content of the stories was manipulated (i.e. stories were written that implied different emotional states). It is suggested that the more emotionally evoking situations one encounters the more memory traces are stored and…

  10. An equivalent body surface charge model representing three-dimensional bioelectrical activity

    Science.gov (United States)

    He, B.; Chernyak, Y. B.; Cohen, R. J.

    1995-01-01

    A new surface-source model has been developed to account for the bioelectrical potential on the body surface. A single-layer surface-charge model on the body surface has been developed to equivalently represent bioelectrical sources inside the body. The boundary conditions on the body surface are discussed in relation to the surface-charge in a half-space conductive medium. The equivalent body surface-charge is shown to be proportional to the normal component of the electric field on the body surface just outside the body. The spatial resolution of the equivalent surface-charge distribution appears intermediate between those of the body surface potential distribution and the body surface Laplacian distribution. An analytic relationship between the equivalent surface-charge and the surface Laplacian of the potential was found for a half-space conductive medium. The effects of finite spatial sampling and noise on the reconstruction of the equivalent surface-charge were evaluated by computer simulations. It was found through computer simulations that the reconstruction of the equivalent body surface-charge from the body surface Laplacian distribution is very stable against noise and finite spatial sampling. The present results suggest that the equivalent body surface-charge model may provide an additional insight to our understanding of bioelectric phenomena.

  11. The Roles of a Flavone-6-Hydroxylase and 7-O-Demethylation in the Flavone Biosynthetic Network of Sweet Basil*

    Science.gov (United States)

    Berim, Anna; Gang, David R.

    2013-01-01

    Lipophilic flavonoids found in the Lamiaceae exhibit unusual 6- and 8-hydroxylations whose enzymatic basis is unknown. We show that crude protein extracts from peltate trichomes of sweet basil (Ocimum basilicum L.) cultivars readily hydroxylate position 6 of 7-O-methylated apigenin but not apigenin itself. The responsible protein was identified as a P450 monooxygenase from the CYP82 family, a family not previously reported to be involved in flavonoid metabolism. This enzyme prefers flavones but also accepts flavanones in vitro and requires a 5-hydroxyl in addition to a 7-methoxyl residue on the substrate. A peppermint (Mentha × piperita L.) homolog displayed identical substrate requirements, suggesting that early 7-O-methylation of flavones might be common in the Lamiaceae. This hypothesis is further substantiated by the pioneering discovery of 2-oxoglutarate-dependent flavone demethylase activity in basil, which explains the accumulation of 7-O-demethylated flavone nevadensin. PMID:23184958

  12. Demethylation of host-cell DNA at the site of avian retrovirus integration

    Czech Academy of Sciences Publication Activity Database

    Hejnar, Jiří; Elleder, Daniel; Hájková, P.; Walter, J.; Blažková, Jana; Svoboda, Jan

    2003-01-01

    Roč. 2003, č. 311 (2003), s. 641-648 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915 Keywords : DNA methylation and demethylation * integration of retroviruses * gene silencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.836, year: 2003

  13. Raman spectroscopic characterisations and analytical discrimination between caffeine and demethylated analogues of pharmaceutical relevance

    Science.gov (United States)

    Edwards, H. G. M.; Munshi, T.; Anstis, M.

    2005-05-01

    The FT Raman spectrum of caffeine was analysed along with that of its demethylated analogues, theobromine and theophylline. The similar but not identical structures of these three compounds allowed a more detailed assignment of the Raman bands. Noticeable differences in the Raman spectra of these compounds were apparent and key marker bands have been identified for the spectroscopic identification of these three compounds.

  14. Oxidative demethylation of lanosterol in cholesterol biosynthesis: accumulation of sterol intermediates

    International Nuclear Information System (INIS)

    Shafiee, A.; Trzaskos, J.M.; Paik, Y.K.; Gaylor, J.L.

    1986-01-01

    With [ 3 H-24,25]-dihydrolanosterol as substrate, large-scale metabolic formation of intermediates of lanosterol demethylation was carried out to identify all compounds in the metabolic process. Utilizing knowledge of electron transport of lanosterol demethylation, we interrupted the demethylation reaction allowing accumulation and confirmation of the structure of the oxygenated intermediates lanost-8-en-3 beta,32-diol and 3 beta-hydroxylanost-8-en-32-al, as well as the demethylation product 4,4-dimethyl-cholesta-8,14-dien-3 beta-ol. Further metabolism of the delta 8.14-diene intermediate to a single product 4,4-dimethyl-cholest-8-en-3 beta-ol occurs under interruption conditions in the presence of 0.5 mM CN-1. With authentic compounds, each intermediate has been rigorously characterized by high performance liquid chromatography and gas-liquid chromatography plus mass spectral analysis of isolated and derivatized sterols. Intermediates that accumulated in greater abundance were further characterized by ultraviolet, 1 H-NMR, and infrared spectroscopy of the isolated sterols

  15. Demethylation of methylated arsenic species during generation of arsanes with tetrahydridoborate(1−) in acidic media

    Czech Academy of Sciences Publication Activity Database

    Marschner, Karel; Musil, Stanislav; Dědina, Jiří

    2016-01-01

    Roč. 88, č. 12 (2016), s. 6366-6373 ISSN 0003-2700 R&D Projects: GA ČR GA14-23532S Institutional support: RVO:68081715 Keywords : arsenic speciation analysis * hydride generation * demethylation Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 6.320, year: 2016

  16. Synthesis and characterization of N-demethylated metabolites of malachite green and leucomalachite green.

    Science.gov (United States)

    Cho, Bongsup P; Yang, Tianle; Blankenship, Lonnie R; Moody, Joanna D; Churchwell, Mona; Beland, Frederick A; Culp, Sandra J

    2003-03-01

    Malachite green (MG), a triphenylmethane dye used to treat fungal and protozoan infections in fish, undergoes sequential oxidation to produce various N-demethylated derivatives (monodes-, dides(sym)-, dides(unsym)-, trides-, and tetrades-) both before and after reduction to leucomalachite green (LMG). The close structure resemblance of the metabolites with aromatic amine carcinogens implicates a potential genotoxicity from exposure to MG. The availability of the synthetic standards is important for metabolic and DNA adduct studies of MG. This paper describes a simple and versatile method for the synthesis of MG, LMG, and their N-demethylated metabolites. The synthesis involves a coupling of 4-(dimethylamino)benzophenone or 4-nitrobenzophenone with the aryllithium reagents derived from appropriately substituted 4-bromoaniline derivatives, followed by treatment with HCl in methanol. The resulting cationic MG and their leuco analogues showed systematic UV/vis spectral and tandem mass fragmentation patterns consistent with sequential N-demethylation. The extensive (1)H and (13)C spectral assignments of the metabolites were aided by the availability of (13)C(7)-labeled MG and LMG. The results indicate the existence of a resonance structure with the cationic charge located in the central methane carbon (C(7)). The synthetic procedure is general in scope so that it can be extended to the preparation of N-demethylated metabolites of other structurally related N-methylated triphenylmethane dyes.

  17. Base-oxidant promoted metal-free N-demethylation of arylamines

    Indian Academy of Sciences (India)

    A metal-free oxidative N-demethylation of arylamines with triethylamine as a base and tert-butyl hydroperoxide (TBHP) as oxidant is reported in this paper. The reaction is general, practical, inexpensive, non-toxic, and the method followed is environmentally benign, with moderate to good yields.

  18. BOLD data representing activation and connectivity for rare no-go versus frequent go cues

    Directory of Open Access Journals (Sweden)

    Harma Meffert

    2016-06-01

    Full Text Available The neural circuitry underlying response control is often studied using go/no-go tasks, in which participants are required to respond as fast as possible to go cues and withhold from responding to no-go stimuli. In the current task, response control was studied using a fully counterbalanced design in which blocks with a low frequency of no-go cues (75% go, 25% no-go were alternated with blocks with a low frequency of go cues (25% go, 75% no-go; see also “Segregating attention from response control when performing a motor inhibition task: Segregating attention from response control” [1]. We applied a whole brain corrected, paired t-test to the data assessing for regions differentially activated by low frequency no-go cues relative to high frequency go cues. In addition, we conducted a generalized psychophysiological interaction analysis on the data using a right inferior frontal gyrus seed region. This region was identified through the BOLD response t-test and was chosen because right inferior gyrus is highly implicated in response inhibition.

  19. Eriosema (Fabaceae) Species Represent a Rich Source of Flavonoids with Interesting Pharmacological Activities.

    Science.gov (United States)

    Awouafack, Maurice Ducret; Tane, Pierre; Spiteller, Michael; Eloff, Jacobus Nicolaas

    2015-07-01

    Many flavonoids have so far been isolated as main secondary metabolites in plant species of the genus Eriosema (Fabaceae), which contains approximately 160 species. A total of 52 flavonoids including isoflavones, dihydroflavonols, flavonols, flavanones, dihydrochalcones, isoflavanone and their pyrano or glucoside derivatives were isolated and characterized from the five species of this genus investigated to date. Total synthesis and semi-synthesis (acetylation, methylation, hydrogenation, and cyclization) of some isolated flavonoids were reported. Due to several significant pharmacological properties (antimicrobial, cytotoxicity, anti-mycobacterial, antioxidant, antiviral, erectile-dysfunction, vasodilatory and hypoglycemic) of the isolated flavonoids and derivatives, more scientists should be interested in investigating Eriosema species. The present review is the first to document all flavonoids that have been reported from the genus Eriosema to date together with their synthetic and semi-synthetic derivatives, and their pharmacological properties. Dihydrochalcones, which are precursors of other classes of flavonoids, are very rare in natural sources and their isolation from Eriosema species may explain the large number of flavonoids found in this genus. It appears that isoflavone could be a marker for species in this genus. The 83 flavonoids (1-83) documented include 52 isolates, 31 semi-synthetic and 3 totally synthetic derivatives. Data were obtained from Google scholar, Pubmed, Scifinder, Sciencedirect, and Scopus. With 52 different flavonoids isolated from only 5 of the approximately 160 species it shows the remarkable chemical diversity of this genus. This compilation of the biological activities and chemical composition may renew the interest of pharmacologists and phytochemists in this genus.

  20. Demethylation of methylmercury in growing rice plants: An evidence of self-detoxification

    International Nuclear Information System (INIS)

    Xu, Xiaohan; Zhao, Jiating; Li, Yunyun; Fan, Yuqin; Zhu, Nali; Gao, Yuxi; Li, Bai; Liu, Hanyu; Li, Yu-Feng

    2016-01-01

    Mercury (Hg) is a global pollutant that poses a serious threat to human and the environment. Rice was found as an important source for human exposure to Hg in some areas. In this study, the transportation and transformation of IHg and MeHg in rice plants exposed to IHg or MeHg were investigated. The IHg and MeHg concentrations in rice roots and shoots collected every five days were analyzed by HPLC-ICP-MS and SR-XANES. When exposed to MeHg, the percent of IHg in rice roots and shoots increased while MeHg decreased significantly, suggesting prominent demethylation of MeHg occurred. However no notable MeHg was found in both roots and shoots of rice plant when exposed to IHg. SR-XANES analysis further confirmed the demethylation of MeHg with rice. This study provides a new finding that demethylation of MeHg could occur in growing rice, which may be a self-defense process of rice plant. - Graphical abstract: Inorganic mercury in Rice (Oryza sativa L.) plants exposed to methylmercury was detected: An evidence of rice plant against methylmercury phytotoxicity. Display Omitted - Highlights: • Demethylation of MeHg in rice plant was found in rice root. • Hg in rice roots mainly present as MeHg-SR or RS-Hg-SR form. • MeHg-SR in roots can be gradually transformed to RS-Hg-SR with rice growth. - Demethylation of MeHg in growing rice.

  1. SET oncoprotein accumulation regulates transcription through DNA demethylation and histone hypoacetylation.

    Science.gov (United States)

    Almeida, Luciana O; Neto, Marinaldo P C; Sousa, Lucas O; Tannous, Maryna A; Curti, Carlos; Leopoldino, Andreia M

    2017-04-18

    Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation. DNA methylation profile of 24 tumour suppressors evidenced that SET accumulation decreased DNA methylation in association with loss of 5-methylcytidine, formation of 5-hydroxymethylcytosine and increased TET1 levels, indicating an active DNA demethylation mechanism. However, the expression of some suppressor genes was lowered in cells with high SET levels, suggesting that loss of methylation is not the main mechanism modulating gene expression. SET accumulation also downregulated the expression of 32 genes of a panel of 84 transcription factors, and SET directly interacted with chromatin at the promoter of the downregulated genes, decreasing histone acetylation. Gene expression analysis after cell treatment with 5-aza-2'-deoxycytidine (5-AZA) and Trichostatin A (TSA) revealed that histone acetylation reversed transcription repression promoted by SET. These results suggest a new function for SET in the regulation of chromatin dynamics. In addition, TSA diminished both SET protein levels and SET capability to bind to gene promoter, suggesting that administration of epigenetic modifier agents could be efficient to reverse SET phenotype in cancer.

  2. Learning in later life: participation in formal, non-formal and informal activities in a nationally representative Spanish sample.

    Science.gov (United States)

    Villar, Feliciano; Celdrán, Montserrat

    2013-06-01

    This article examines the participation of Spanish older people in formal, non-formal and informal learning activities and presents a profile of participants in each kind of learning activity. We used data from a nationally representative sample of Spanish people between 60 and 75 years old ( n  = 4,703). The data were extracted from the 2007 Encuesta sobre la Participación de la Población Adulta en Actividades de Aprendizaje (EADA, Survey on Adult Population Involvement in Learning Activities). Overall, only 22.8 % of the sample participated in a learning activity. However, there was wide variation in the participation rates for the different types of activity. Informal activities were far more common than formal ones. Multivariate logistic regression indicated that education level and involvement in social and cultural activities were associated with likelihood of participating, regardless of the type of learning activity. When these variables were taken into account, age did not predict decreasing participation, at least in non-formal and informal activities. Implications for further research, future trends and policies to promote older adult education are discussed.

  3. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

    Science.gov (United States)

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2) and the match-activity profile were examined using Pearson’s correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98) and straight line running speed (ES = 1.03–1.18) than inside players, and also covered greater very high-speed running (VHSR) distance/min (ES = 0.67) and reached higher peak running speeds (ES = 0.95) during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE) bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69–1.15) and mean RHIE bout recovery (ES = 0.56). Inside and outside players also reported small to moderate differences (ES = 0.43–0.80) for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions. PMID:26642320

  4. Association Between Objectively Measured Physical Activity and Erectile Dysfunction among a Nationally Representative Sample of American Men.

    Science.gov (United States)

    Loprinzi, Paul D; Edwards, Meghan

    2015-09-01

    Emerging work suggests an inverse association between physical activity and erectile dysfunction (ED). The majority of this cross-sectional research comes from convenience samples and all studies on this topic have employed self-report physical activity methodology. Therefore, the purpose of this brief-report, confirmatory research study was to examine the association between objectively measured physical activity and ED in a national sample of Americans. Data from the 2003-2004 National Health and Nutrition Examination Survey were used. Six hundred ninety-two adults between the ages of 50 and 85 years (representing 33.2 million adults) constituted the analytic sample. Participants wore an ActiGraph 7164 accelerometer (ActiGraph, Pensacola, FL, USA) for up to 7 days with ED assessed via self-report. The main outcome measure used was ED assessed via self-report. After adjustments, for every 30 min/day increase in moderate-to-vigorous physical activity, participants had a 43% reduced odds of having ED (odds ratioadjusted  = 0.57; 95% confidence interval: 0.40-0.81; P = 0.004). This confirmatory study employing an objective measure of physical activity in a national sample suggests an inverse association between physical activity and ED. © 2015 International Society for Sexual Medicine.

  5. A new mechanism for reduced sensitivity to demethylation-inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis

    NARCIS (Netherlands)

    Díaz-Trujillo, C.; Chong, P.; Stergiopoulos, I.; Meijer, H.J.G.; Wit, de P.J.G.M.; Kema, G.H.J.

    2018-01-01

    The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications with a major share for sterol demethylation-inhibitors

  6. A new mechanism for reduced sensitivity to demethylation-inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis

    NARCIS (Netherlands)

    Díaz-Trujillo, C.; Chong, P.; Stergiopoulos, I.; Meijer, H.J.G.; Wit, de P.J.G.M.; Kema, G.H.J.

    2017-01-01

    The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications with a major share for sterol demethylation-inhibitors

  7. Sensory rhodopsins I and II modulate a methylation/demethylation system in Halobacterium halobium phototaxis

    International Nuclear Information System (INIS)

    Spudich, E.N.; Takahashi, T.; Spudich, J.L.

    1989-01-01

    This work demonstrates that phototaxis stimuli in the archaebacterium Halobacterium halobium control a methylation/demethylation system in vivo through photoactivation of sensory rhodopsin I (SR-I) in either its attractant or repellent signaling form as well as through the repellent receptor sensory rhodopsin II (SR-II, also called phoborhodopsin). The effects of positive stimuli that suppress swimming reversals (i.e., an increase in attractant or decrease in repellent light) and negative stimuli that induce swimming reversals (i.e., a decrease in attractant or increase in repellent light) through each photoreceptor were monitored by assaying release of volatile [3H]methyl groups. This assay has been used to measure [3H]methanol produced during the process of adaptation to chemotactic stimuli in eubacteria. In H. halobium positive photostimuli produce a transient increase in the rate of demethylation followed by a decrease below the unstimulated value, whereas negative photostimuli cause an increase followed by a rate similar to that of the unstimulated value. Photoactivation of the SR-I attractant and simultaneous photoactivation of the SR-II repellent receptors cancel in their effects on demethylation, demonstrating the methylation system is regulated by an integrated signal. Analysis of mutants indicates that the source for the volatile methyl groups is intrinsic membrane proteins distinct from the chromoproteins that share the membrane. A methyl-accepting protein (94 kDa) previously correlated in amount with the SR-I chromoprotein (25 kDa) is shown here to be missing in a recently isolated SR-I-SR-II+ mutant (Flx3b), thus confirming the association of this protein with SR-I. Photoactivated SR-II in mutant Flx3b controls demethylation, predicting the existence of a photomodulated methyl-accepting component distinct from the 94-kDa protein of SR-I

  8. The autoradiolytic and the γ-induced demethylation of solid thymine-(methyl-14C)

    International Nuclear Information System (INIS)

    Merwitz, O.

    1980-01-01

    The autoradiolytic and the γ-induced demethylation of solid thymine were measured qualitatively and quantitatively for the first time with specially purified thymine-(methyl- 14 C). Analogous experiments with thymine-(methyl- 3 H) and radio-gaschromatographic analysis provided proof for the formation of molecular hydrogen and methane. Ethane was not detected. The results are discussed in connection with e.s.r.-spectroscopic studies. (author)

  9. Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter.

    Science.gov (United States)

    Yang, Ruili; Yu, Tingting; Kou, Xiaoxing; Gao, Xiang; Chen, Chider; Liu, Dawei; Zhou, Yanheng; Shi, Songtao

    2018-06-01

    Ten-eleven translocation (Tet) family-mediated DNA oxidation represents an epigenetic modification capable of converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), which regulates various biological processes. However, it is unknown whether Tet family affects mesenchymal stem cells (MSCs) or the skeletal system. Here we show that depletion of Tet1 and Tet2 results in impaired self-renewal and differentiation of bone marrow MSCs (BMMSCs) and a significant osteopenia phenotype. Tet1 and Tet2 deficiency reduces demethylation of the P2rX7 promoter and downregulates exosome release, leading to intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p. These miRNAs inhibit Runx2 signaling to impair BMMSC function. We show that overexpression of P2rX7 rescues the impaired BMMSCs and osteoporotic phenotype in Tet1 and Tet2 double knockout mice. These results indicate that Tet1 and Tet2 play a critical role in maintaining BMMSC and bone homeostasis through demethylation of P2rX7 to control exosome and miRNA release. This Tet/P2rX7/Runx2 cascade may serve as a target for the development of novel therapies for osteopenia disorders.

  10. Representing Development

    DEFF Research Database (Denmark)

    Representing Development presents the different social representations that have formed the idea of development in Western thinking over the past three centuries. Offering an acute perspective on the current state of developmental science and providing constructive insights into future pathways, ...

  11. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Putnik, Milica, E-mail: milica.putnik@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Zhao, Chunyan, E-mail: chunyan.zhao@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Gustafsson, Jan-Ake, E-mail: jan-ake.gustafsson@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden); Department of Biology and Biochemistry, Science and Engineering Research Center Bldg, University of Houston, Houston, TX 77204-5056 (United States); Dahlman-Wright, Karin, E-mail: karin.dahlman-wright@ki.se [Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-14183 (Sweden)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Estrogen signaling and demethylation can both control gene expression in breast cancers. Black-Right-Pointing-Pointer Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. Black-Right-Pointing-Pointer 137 genes are influenced by both 17{beta}-estradiol and demethylating agent 5-aza-2 Prime -deoxycytidine. Black-Right-Pointing-Pointer A set of genes is identified as targets of both estrogen signaling and demethylation. Black-Right-Pointing-Pointer There is no direct molecular interplay of mediators of estrogen and epigenetic signaling. -- Abstract: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17{beta}-estradiol (E2) and a demethylating agent 5-aza-2 Prime -deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of

  12. Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Putnik, Milica; Zhao, Chunyan; Gustafsson, Jan-Åke; Dahlman-Wright, Karin

    2012-01-01

    Highlights: ► Estrogen signaling and demethylation can both control gene expression in breast cancers. ► Cross-talk between these mechanisms is investigated in human MCF-7 breast cancer cells. ► 137 genes are influenced by both 17β-estradiol and demethylating agent 5-aza-2′-deoxycytidine. ► A set of genes is identified as targets of both estrogen signaling and demethylation. ► There is no direct molecular interplay of mediators of estrogen and epigenetic signaling. -- Abstract: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17β-estradiol (E2) and a demethylating agent 5-aza-2′-deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of these genes in MCF-7 cells. In a further analysis of the potential interplay between estrogen signaling and DNA methylation, E2 treatment

  13. Association of Physical Activity with Alcohol Abuse and Dependence in a Nationally-Representative U.S. Sample.

    Science.gov (United States)

    Damian, April Joy; Mendelson, Tamar

    2017-11-10

    Alcohol use is a pervasive and costly public health problem in the United States. Relapse rates from alcohol use disorders are high. Although exercise has been proposed as a strategy to prevent relapse, lifestyle modification is the least studied aspect of relapse prevention programs, especially among racial/ethnic minority populations. The current study assessed whether being physically active was associated with remission from alcohol abuse or dependence among Black (African American and Afro Caribbean) adults in the U.S. We utilized data on Black adult participants (n = 4,828) from the nationally representative National Survey of American Life (NSAL) conducted in 2001-2003. Logistic regression models were estimated to assess the odds of being in 12-month remission or currently meeting DSM-IV criteria for alcohol abuse or dependence based on level of physical activity, adjusting for socio-demographic and neighborhood characteristics. People who endorsed being physically active had higher odds of being in 12-month remission from alcohol use problems (OR: 1.67, 95% CI: 1.28, 2.17) than people who were physically inactive, adjusting for individual- and neighborhood-level characteristics. People who were physically active did not differ significantly from those who were inactive with respect to odds of currently meeting DSM-IV criteria for alcohol abuse or dependence. Conclusions/Importance: Physical activity was positively associated with being in 12-month remission from alcohol use problems. Longitudinal studies are needed to establish temporal ordering and to explore exercise as a potential relapse prevention strategy for alcohol use problems.

  14. A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice

    KAUST Repository

    La, Honggui; Ding, Bo; Mishra, Gyan Prakash; Zhou, Bo; Yang, Hongmei; Bellizzi, Maria Del Rosario; Chen, Songbiao; Meyers, Blake C.; Peng, Zhaohua; Zhu, Jian-Kang; Wang, Guoliang

    2011-01-01

    DNA 5-methylcytosine (5-meC) is an important epigenetic mark for transcriptional gene silencing in many eukaryotes. In Arabidopsis, 5-meC DNA glycosylase/lyases actively remove 5-meC to counter-act transcriptional gene silencing in a locus-specific manner, and have been suggested to maintain the expression of transposons. However, it is unclear whether plant DNA demethylases can promote the transposition of transposons. Here we report the functional characterization of the DNA glycosylase/lyase DNG701 in rice. DNG701 encodes a large (1,812 amino acid residues) DNA glycosylase domain protein. Recombinant DNG701 protein showed 5-meC DNA glycosylase and lyase activities in vitro. Knockout or knockdown of DNG701 in rice plants led to DNA hypermethylation and reduced expression of the retrotransposon Tos17. Tos17 showed less transposition in calli derived from dng701 knockout mutant seeds compared with that in wild-type calli. Overexpression of DNG701 in both rice calli and transgenic plants substantially reduced DNA methylation levels of Tos17 and enhanced its expression. The overexpression also led to more frequent transposition of Tos17 in calli. Our results demonstrate that rice DNG701 is a 5-meC DNA glycosylase/lyase responsible for the demethylation of Tos17 and this DNA demethylase plays a critical role in promoting Tos17 transposition in rice calli.

  15. A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice

    KAUST Repository

    La, Honggui

    2011-09-06

    DNA 5-methylcytosine (5-meC) is an important epigenetic mark for transcriptional gene silencing in many eukaryotes. In Arabidopsis, 5-meC DNA glycosylase/lyases actively remove 5-meC to counter-act transcriptional gene silencing in a locus-specific manner, and have been suggested to maintain the expression of transposons. However, it is unclear whether plant DNA demethylases can promote the transposition of transposons. Here we report the functional characterization of the DNA glycosylase/lyase DNG701 in rice. DNG701 encodes a large (1,812 amino acid residues) DNA glycosylase domain protein. Recombinant DNG701 protein showed 5-meC DNA glycosylase and lyase activities in vitro. Knockout or knockdown of DNG701 in rice plants led to DNA hypermethylation and reduced expression of the retrotransposon Tos17. Tos17 showed less transposition in calli derived from dng701 knockout mutant seeds compared with that in wild-type calli. Overexpression of DNG701 in both rice calli and transgenic plants substantially reduced DNA methylation levels of Tos17 and enhanced its expression. The overexpression also led to more frequent transposition of Tos17 in calli. Our results demonstrate that rice DNG701 is a 5-meC DNA glycosylase/lyase responsible for the demethylation of Tos17 and this DNA demethylase plays a critical role in promoting Tos17 transposition in rice calli.

  16. Quaternary ammonium oxidative demethylation: X-ray crystallographic, resonance Raman, and UV-visible spectroscopic analysis of a Rieske-type demethylase.

    Science.gov (United States)

    Daughtry, Kelly D; Xiao, Youli; Stoner-Ma, Deborah; Cho, Eunsun; Orville, Allen M; Liu, Pinghua; Allen, Karen N

    2012-02-08

    Herein, the structure resulting from in situ turnover in a chemically challenging quaternary ammonium oxidative demethylation reaction was captured via crystallographic analysis and analyzed via single-crystal spectroscopy. Crystal structures were determined for the Rieske-type monooxygenase, stachydrine demethylase, in the unliganded state (at 1.6 Å resolution) and in the product complex (at 2.2 Å resolution). The ligand complex was obtained from enzyme aerobically cocrystallized with the substrate stachydrine (N,N-dimethylproline). The ligand electron density in the complex was interpreted as proline, generated within the active site at 100 K by the absorption of X-ray photon energy and two consecutive demethylation cycles. The oxidation state of the Rieske iron-sulfur cluster was characterized by UV-visible spectroscopy throughout X-ray data collection in conjunction with resonance Raman spectra collected before and after diffraction data. Shifts in the absorption band wavelength and intensity as a function of absorbed X-ray dose demonstrated that the Rieske center was reduced by solvated electrons generated by X-ray photons; the kinetics of the reduction process differed dramatically for the liganded complex compared to unliganded demethylase, which may correspond to the observed turnover in the crystal.

  17. Representing dispositions

    Directory of Open Access Journals (Sweden)

    Röhl Johannes

    2011-08-01

    Full Text Available Abstract Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

  18. Representing time

    Directory of Open Access Journals (Sweden)

    Luca Poncellini

    2010-06-01

    Full Text Available The analysis of natural phenomena applied to architectural planning and design is facing the most fascinating and elusive of the four dimensions through which man attempts to define life within the universe: time. We all know what time is, said St. Augustine, but nobody knows how to describe it. Within architectural projects and representations, time rarely appears in explicit form. This paper presents the results of a research conducted by students of NABA and of the Polytechnic of Milan with the purpose of representing time considered as a key element within architectural projects. Student investigated new approaches and methodologies to represent time using the two-dimensional support of a sheet of paper.

  19. Position of coordination of the lithium ion determines the regioselectivity of demethylations of 3,4-dimethoxymorphinans with L-selectride.

    Science.gov (United States)

    Wu, Huifang; Thatcher, Linn N; Bernard, Denzil; Parrish, Damon A; Deschamps, Jeffrey R; Rice, Kenner C; MacKerell, Alexander D; Coop, Andrew

    2005-06-23

    [reaction: see text] L-Selectride is an efficient agent for the 3-O-demethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-demethylation, rather than cleavage of the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion.

  20. A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes

    International Nuclear Information System (INIS)

    Zambrano, Pilar; Sandoval, Karina; Trejo-Becerril, Catalina; Chanona-Vilchis, Jose; Duenas-González, Alfonso; Segura-Pacheco, Blanca; Perez-Cardenas, Enrique; Cetina, Lucely; Revilla-Vazquez, Alma; Taja-Chayeb, Lucía; Chavez-Blanco, Alma; Angeles, Enrique; Cabrera, Gustavo

    2005-01-01

    The antihypertensive compound hydralazine is a known demethylating agent. This phase I study evaluated the tolerability and its effects upon DNA methylation and gene reactivation in patients with untreated cervical cancer. Hydralazine was administered to cohorts of 4 patients at the following dose levels: I) 50 mg/day, II) 75 mg/day, III) 100 mg/day and IV) 150 mg/day. Tumor biopsies and peripheral blood samples were taken the day before and after treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RARβ, FHIT and p16 were evaluated pre and post-treatment for DNA promoter methylation and gene expression by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor samples. Methylation of the imprinted H19 gene and the 'normally methylated' sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by capillary electrophoresis and cytosine extension assay. Toxicity was evaluated using the NCI Common Toxicity Criteria. Hydralazine was well tolerated. Toxicities were mild being the most common nausea, dizziness, fatigue, headache and palpitations. Overall, 70% of the pretreatment samples and all the patients had at least one methylated gene. Rates of demethylation at the different dose levels were as follows: 50 mg/day, 40%; 75 mg/day, 52%, 100 mg/day, 43%, and 150 mg/day, 32%. Gene expression analysis showed only 12 informative cases, of these 9 (75%) re-expressed the gene. There was neither change in the methylation status of H19 and clone 1.2 nor changes in global DNA methylation. Hydralazine at doses between 50 and 150 mg/day is well tolerated and effective to demethylate and reactivate the expression of tumor suppressor genes without affecting global DNA methylation

  1. LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture.

    Science.gov (United States)

    Wang, Jun; Ti, Yunfan; Wang, Yicun; Guo, Guodong; Jiang, Hui; Chang, Menghan; Qian, Hongbo; Zhao, Jianning; Sun, Guojing

    2018-04-19

    The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4 + T cells in patients with long bone fracture. We found that LAG-3 + cells represented approximately 13% of peripheral blood CD4 + T cells on average. Compared to LAG-3 - CD4 + T cells, LAG-3 + CD4 + T cells presented significantly higher Foxp3 and CTLA-4 expression. Directly ex vivo or with TCR stimulation, LAG-3 + CD4 + T cells expressed significantly higher levels of IL-10 and TGF-β than LAG-3 - CD4 + T cells. Interestingly, blocking the LAG-3-MHC class II interaction actually increased the IL-10 expression by LAG-3 + CD4 + T cells. The frequency of LAG-3 + CD4 + T cell was positively correlated with restoration of healthy bone function in long bone fracture patients. These results together suggested that LAG-3 is a marker of CD4 + T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells.

  2. Gender differences in the associations of gambling activities and suicidal behaviors with problem gambling in a nationally representative French sample.

    Science.gov (United States)

    Husky, Mathilde M; Michel, Grégory; Richard, Jean-Baptiste; Guignard, Romain; Beck, François

    2015-06-01

    The objectives of the present study are to describe gender differences in factors associated with moderate risk and problem gambling. Data were extracted from the 2010 Health Barometer, a large survey on a representative sample of the general population aged 15-85 years living in France (n=27,653), carried out by the National Institute for Health Promotion and Health Education. Data were collected between October 2009 and July 2010. A computer-assisted telephone interview system was used. The findings indicate that men are three times more likely to experience problems with gambling. Men and women have different patterns of gambling activities. Men were more involved with Rapido, internet gambling, sports and racetrack betting, poker, and casino tables, whereas women gambled more often on scratch games. Both men and women engaging in immediate reward games were significantly more likely to experience difficulties with gambling. This association, however, was stronger in women. Furthermore, suicidal ideation and behaviors were more likely to be associated with gambling problems in women as compared to men. The study underscores the importance of considering gender-related differences in the study of gambling behaviors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Green synthesis of low-toxicity graphene-fulvic acid with an open band gap enhances demethylation of methylmercury.

    Science.gov (United States)

    Hu, Xiangang; Mu, Li; Lu, Kaicheng; Kang, Jia; Zhou, Qixing

    2014-06-25

    The demethylation of methylmercury has received substantial attention. Here, a novel chemical method for the demethylation of methylmercury is proposed. The low-toxicity graphene-fulvic acid (FA, a ubiquitous material in the environment) was synthesized without the use of a chemical reagent. The hybridized graphene-FA presented an indirect open band gap of 2.25-2.87 eV as well as adequate aqueous dispersion. More importantly, the hybridized graphene-FA exhibited 6- and 10-fold higher photocatalytic efficiencies for the demethylation of methylmercury than FA and free FA with graphene, respectively. This result implies that immobilized, rather than free, FA accelerated the catalysis. Furthermore, inorganic mercuric ion, elemental mercury, and mercuric oxide were identified as the primary demethylation products. For free FA with graphene, graphene quenches the excited-state FA, inhibiting the demethylation by electron transfer. In contrast, the graphene of the self-assembled graphene-FA serves as an electron reservoir, causing electron-hole pair separation. Graphene-FA showed a negligible toxicity toward microalgae compared to graphene. The above results reveal that the green synthesis of graphene and organic molecules is a convenient strategy for obtaining effective cocatalysts.

  4. A Convenient and Efficient Method for Demethylation of Aryl Methyl Ethers with Magnesium Iodide in Ionic Liquid

    International Nuclear Information System (INIS)

    Lee, Kwan Soo; Kim, Kee D.

    2010-01-01

    We have developed a new and efficient method for the demethylation of various types of aryl methyl ethers using readily available, stable, and easily handled magnesium iodide in [BMIM]BF 4 ionic liquid. Owing to its simplicity and mild reaction conditions the protocol reported herein may serve as a useful alternative to the existing methods for the deprotection of aryl methyl ethers to the corresponding phenolic derivatives. Demethylation of aryl methyl ethers to the corresponding phenols are very important reactions in organic synthesis. A number of methods have been reported for the cleavage of highly stable aryl methyl ethers utilizing strong acids or bases such as aluminum chloride, boron tribromide, cerium chloride, alkaline thiolate, methyl magnesium iodide, and L-Selectride. However, all of these methods invariably suffered from one or more drawbacks such as harsh reaction conditions, long reaction times, difficulty of manipulation, use of exotic reagents, and low reaction yields. Furthermore, in the most of known methods for demethylation of aryl methyl ethers, use of large excess amounts of demethylating agents have been generally required. Thus, it is highly desirable to develop an improved convenient and efficient procedure for demethylation reactions of aryl methyl ethers

  5. A Convenient and Efficient Method for Demethylation of Aryl Methyl Ethers with Magnesium Iodide in Ionic Liquid

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kwan Soo [KAIST, Daejeon (Korea, Republic of); Kim, Kee D. [Sangji University, Wonju (Korea, Republic of)

    2010-12-15

    We have developed a new and efficient method for the demethylation of various types of aryl methyl ethers using readily available, stable, and easily handled magnesium iodide in [BMIM]BF{sub 4} ionic liquid. Owing to its simplicity and mild reaction conditions the protocol reported herein may serve as a useful alternative to the existing methods for the deprotection of aryl methyl ethers to the corresponding phenolic derivatives. Demethylation of aryl methyl ethers to the corresponding phenols are very important reactions in organic synthesis. A number of methods have been reported for the cleavage of highly stable aryl methyl ethers utilizing strong acids or bases such as aluminum chloride, boron tribromide, cerium chloride, alkaline thiolate, methyl magnesium iodide, and L-Selectride. However, all of these methods invariably suffered from one or more drawbacks such as harsh reaction conditions, long reaction times, difficulty of manipulation, use of exotic reagents, and low reaction yields. Furthermore, in the most of known methods for demethylation of aryl methyl ethers, use of large excess amounts of demethylating agents have been generally required. Thus, it is highly desirable to develop an improved convenient and efficient procedure for demethylation reactions of aryl methyl ethers.

  6. Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labeled aminopyrine in man

    International Nuclear Information System (INIS)

    Schneider, J.F.; Schoeller, D.A.; Nemchausky, B.; Bayer, J.L.; Klein, P.

    1978-01-01

    Interval sampling of expired breath as a simple, non-invasive assessment of the effect of liver disease upon hepatic microsomal drug metabolism, has been demonstrated with [ 14 C] dimethylaminoantipyrine (aminopyrine). In order to eliminate radiation risk the authors have validated the use of aminopyrine labeled with the stable, non-radioactive isotope 13 C. Simultaneous oral administration of both [ 14 C]- and [ 13 C] aminopyrine to five adult subjects without liver disease as well as five patients with known liver disease, resulted in the excretion of label at nearly identical rates in both individual time collections (r=0.94) as well as cumulative excretion for three hours (r=0.97). An oral dose of 2-mg/kg of [ 13 C) aminopyrine resulted in rates of production of 13 CO 2 significantly greater than baseline variations in 13 CO 2 production in the fasting, resting subject. Measurements of a single peak value at one half hour correlated closely with the determination of cumulative appearance over three hours (r=0.96). A consistent reproducible increase in the peak production of 13 CO 2 was observed when five patients received phenobarbital. Stable isotope labeled aminopyrine may be used to detect the effects of disease and treatment upon hepatic N-demethylation activity in human subjects without incurring any risk from radiation. Furthermore, the availability of another isotopic carbon label should make possible the study of direct drug-drug interaction utilizing CO 2 analysis. (Auth.)

  7. Dioxygenases Catalyze O-Demethylation and O,O-Demethylenation with Widespread Roles in Benzylisoquinoline Alkaloid Metabolism in Opium Poppy*

    Science.gov (United States)

    Farrow, Scott C.; Facchini, Peter J.

    2013-01-01

    In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy. PMID:23928311

  8. Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy.

    Science.gov (United States)

    Farrow, Scott C; Facchini, Peter J

    2013-10-04

    In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy.

  9. Association of Dietary Behaviors with Physical Activity in a Nationally Representative Sample of Children and Adolescents: the CASPIAN- IV Study

    Directory of Open Access Journals (Sweden)

    Saeid Safiri

    2016-03-01

    Full Text Available Background: Nutritional health and adequate physical activity (PA, especially in childhood and grow periods, have a substantial role in health. This study assessed the association of dietary behaviors (main courses and snacks intake with PA in children and adolescents. Materials and Methods: Using multistage random cluster sampling method, a representative sample of 14,880 school students were selected from urban and rural areas of 30 provinces of Iran. Through a validated questionnaire, daily consumption of main course ( breakfast, lunch, and dinner as well as daily consumption of different snacks and health foods ( fast foods, milk, vegetables, dry fruits, fresh fruits, sweetened beverages, salty snacks and sweets were recorded for every participants. Information of past week weekly frequency of leisure time PA was collected. Results: Overall, 13,486 out of 14,880 students (response rate: 90.6% participated in this survey. Participants consisted of 6,640 (49.2% girls and 75.6% urban residents; their mean and standard deviation (SD age was 12.47 (3.36 years. Daily consumption of fresh fruits (odds ratio [OR]: 1.35, 95%confidence interval [CI]: 1.20-1.52, dried fruits (OR: 1.21; 95%CI: 1.06-1.40, vegetable (OR: 1.39; 95% CI: 1.24-1.56, and milk (OR: 1.35; 95% CI: 1.21-1.52 increased the odds of high PA compare to low PA in adjusted model.  Skipping the breakfast, lunch and dinner decreased the odds of moderate and high PA compare to low PA (P

  10. Herbivore-Induced DNA Demethylation Changes Floral Signalling and Attractiveness to Pollinators in Brassica rapa.

    Directory of Open Access Journals (Sweden)

    Roman T Kellenberger

    Full Text Available Plants have to fine-tune their signals to optimise the trade-off between herbivore deterrence and pollinator attraction. An important mechanism in mediating plant-insect interactions is the regulation of gene expression via DNA methylation. However, the effect of herbivore-induced DNA methylation changes on pollinator-relevant plant signalling has not been systematically investigated. Here, we assessed the impact of foliar herbivory on DNA methylation and floral traits in the model crop plant Brassica rapa. Methylation-sensitive amplified fragment length polymorphism (MSAP analysis showed that leaf damage by the caterpillar Pieris brassicae was associated with genome-wide methylation changes in both leaves and flowers of B. rapa as well as a downturn in flower number, morphology and scent. A comparison to plants with jasmonic acid-induced defence showed similar demethylation patterns in leaves, but both the floral methylome and phenotype differed significantly from P. brassicae infested plants. Standardised genome-wide demethylation with 5-azacytidine in five different B. rapa full-sib groups further resulted in a genotype-specific downturn of floral morphology and scent, which significantly reduced the attractiveness of the plants to the pollinator bee Bombus terrestris. These results suggest that DNA methylation plays an important role in adjusting plant signalling in response to changing insect communities.

  11. DNA demethylation upregulated Nrf2 expression in Alzheimer's disease cellular model

    Directory of Open Access Journals (Sweden)

    Huimin eCao

    2016-01-01

    Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is an important transcription factor in the defense against oxidative stress. Cumulative evidence has shown that oxidative stress plays a key role in the pathogenesis of Alzheimer's disease (AD. Previous animal and clinical studies had observed decreased expression of Nrf2 in AD. However, the underlying regulation mechanisms of Nrf2 in AD remain unclear. Here, we used the DNA methyltransferases (Dnmts inhibitor 5-aza-2′-deoxycytidine (5-Aza to test whether Nrf2 expression was regulated by methylation in N2a cells characterizing by expressing human Swedish mutant amyloid precursor protein (N2a/APPswe. We found 5-Aza treatment increased Nrf2 at both mRNA and protein levels via down-regulating the expression of Dnmts and DNA demethylation. In addition, 5-Aza mediated upregulation of Nrf2 expression was concomitant with increased nuclear translocation of Nrf2 and higher expression of Nrf2 downstream target gene NAD(PH:quinone oxidoreductas (NQO1. Our study showed that DNA demethylation promoted the Nrf2 cell signaling pathway, which may enhance the antioxidant system against AD development.

  12. Nicotine demethylation in Nicotiana cell suspension cultures: N'-formylnornicotine is not involved.

    Science.gov (United States)

    Bartholomeusz, Trixie Ann; Bhogal, Ramneek K; Molinié, Roland; Felpin, François-Xavier; Mathé-Allainmat, Monique; Meier, Anna-Carolin; Dräger, Birgit; Lebreton, Jacques; Roscher, Albrecht; Robins, Richard J; Mesnard, François

    2005-10-01

    Nicotine or nornicotine enriched with stable isotopes in either the N'-methyl group or the pyrrolidine-N were fed to Nicotiana plumbaginifolia suspension cell cultures that do not form endogenous nicotine. The metabolism of these compounds was investigated by analysing the incorporation of isotope into other alkaloids using gas chromatography-mass spectroscopy (GC-MS). Nicotine metabolism primarily resulted in the accumulation of nornicotine, the N'-demethylation product. In addition, six minor metabolites appeared during the course of nicotine metabolism, four of which were identified as cotinine, myosmine, N'-formylnornicotine and N'-carboethoxynornicotine. While cotinine was formed from [(13)C,(2)H(3)-methyl]nicotine without dilution of label, N'-formylnornicotine was labelled at only about 6% of the level of nicotine and N'-carboethoxynornicotine was unlabelled. Feeding with [1'-(15)N]nornicotine resulted in incorporation without dilution of label into both N'-formylnornicotine and N'-carboethoxynornicotine. This pattern strongly indicates that, while nornicotine and cotinine are derived directly from nicotine, N'-formylnornicotine and N'-carboethoxynornicotine are metabolites of nornicotine. Thus, it is directly demonstrated that N'-formylnornicotine is not an intermediate in nicotine demethylation.

  13. Escitalopram is a weak inhibitor of the CYP2D6 catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain

    DEFF Research Database (Denmark)

    Noehr-Jensen, L; Zwisler, S T; Larsen, F

    2009-01-01

    Tramadol is O–demethylated to the active metabolite (+)–O–desmethyltramadol ((+)–M1) via CYP2D6, an enzyme that is weakly inhibited by escitalopram. We investigated the possibility of a pharmacokinetic (PK) and pharmacodynamic (PD) effect of escitalopram on tramadol metabolism. Fifteen healthy...... subjects completed this randomized, double–blind, three–phase, crossover trial. Combinations of escitalopram 20 mg/day or placebo together with tramadol 150 mg or placebo were used. Blood samples for pharmacokinetics were drawn at 0–24 h after medication. The analgesic effect of (+)–M was assessed...... AUEC1–12 of CPT were 4,140 and 4,388 cm·s after placebo and escitalopram, respectively (P = 0.71). Although escitalopram is a weak inhibitor of CYP2D6, it does not impair the analgesic effect of tramadol....

  14. KDM1A triggers androgen-induced miRNA transcription via H3K4me2 demethylation and DNA oxidation.

    Science.gov (United States)

    Yang, Shu; Zhang, Jiyuan; Zhang, Yalong; Wan, Xuechao; Zhang, Congzhe; Huang, Xiaohui; Huang, Wenhua; Pu, Honglei; Pei, Chaohan; Wu, Hai; Huang, Yan; Huang, Shengdong; Li, Yao

    2015-06-15

    Androgen receptor (AR) is a ligand dependent transcription factor that regulates the transcription of target genes. AR activity is closely involved in the maintenance and progression of prostate cancer. After the binding with androgen, AR moves into nucleus and binds to DNA sequence containing androgen response elements (ARE). Flavin-dependent monoamine oxidase KDM1A is necessary for AR driven transcription while the mechanism remains unclear. The association between androgen-dependent transcription and oxidation was tested through pharmaceutical inhibitions and siRNA knockdown of DNA oxidation repair components in prostate cancer cells. The recruitment of involved proteins and the histone methylation dynamics on ARE region was explored by chromatin immunoprecipitation (ChIP). Oxidation inhibition reduced AR dependent expression of KLK3, TMPRSS2, hsa-miR-125b2, and hsa-miR-133b. And such reduction could be restored by H2 O2 treatment. KDM1A recruitment and H3K4me2 demethylation on ARE regions, which produce H2 O2 , are associated with AR targets transcription. AR targets transcription and coupled oxidation recruit 8-oxoguanine-DNA glycosylase (OGG1) and the nuclease APEX1 to ARE regions. Such recruitment depends on KDM1A, and is necessary for AR targets transcription. Our work underlined the importance of histone demethylation and DNA oxidation/repairing machinery in androgen-dependent transcription. The present finds have implications for research into new druggable targets for prostate cancer relying on the cascade of AR activity regulation. © 2015 Wiley Periodicals, Inc.

  15. Production of 17-O-demethyl-geldanamycin, a cytotoxic ansamycin polyketide, by Streptomyces hygroscopicus DEM20745.

    Science.gov (United States)

    Baksh, Aron; Kepplinger, Bernhard; Isah, Hadiza A; Probert, Michael R; Clegg, William; Wills, Corinne; Goodfellow, Michael; Errington, Jeff; Allenby, Nick; Hall, Michael J

    2017-08-01

    The actinomycete DEM20745, collected from non-rhizosphere soil adjacent to Paraserianthes falactaria trees (Cangkringan, Indonesia), is an efficient producer of the anticancer ansamycin polyketide 17-O-demethyl-geldanamycin (17-O-DMG), a biosynthetic precursor of the Hsp90 inhibitor geldanamycin (GDM). In DEM20745, 17-O-DMG is the major ansamycin product observed reaching a maximum titre of 17 mg/L in the fermentation broth. 17-O-DMG has the potential to be a key starting material for the semi-synthesis of GDM analogues for use in anticancer therapy. Thus, this preferential biosynthesis of 17-O-DMG facilitates easy access to this important molecule and provides further insight in the biosynthesis of the geldanamycins.

  16. Aerosol azacytidine inhibits orthotopic lung cancers in mice through Its DNA demethylation and gene reactivation effects.

    Directory of Open Access Journals (Sweden)

    Xuan Qiu

    Full Text Available We devised an aerosol based demethylation therapy to achieve therapeutic efficacy in premalignant or in situ lesions of lung cancer, without systemic toxicity. Optimum regimens of aerosolized azacytidine (Aza were designed and used in orthotopic human non-small cell lung cancer xenograft models. The therapeutic efficacy and toxicity of aerosol Aza were compared with intravenously administered Aza. We observed that 80% of the droplets of the aerosol Aza measured ∼0.1-5 microns, which resulted in deposition in the lower bronchial airways. An animal model that phenocopies field carcinogeneisis in humans was developed by intratracheal inoculation of the human lung cancer cells in mice, thus resulting in their distribution throughout the entire airway space. Aerosolized Aza significantly prolonged the survival of mice bearing endo-bronchial lung tumors. The aerosol treatment did not cause any detectable lung toxicity or systemic toxicity. A pre-pharmacokinetic study in mice demonstrated that lung deposition of aerosolized Aza was significantly higher than the intravenous route. Lung tumors were resected after aerosol treatment and the methylation levels of 24 promoters of tumor-suppresser genes related to lung cancer were analyzed. Aerosol Aza significantly reduced the methylation level in 9 of these promoters and reexpressed several genes tested. In conclusion, aerosol Aza at non-cytotoxic doses appears to be effective and results in DNA demethylation and tumor suppressor gene re-expression. The therapeutic index of aerosol Aza is >100-fold higher than that of intravenous Aza. These results provide a preclinical rationale for a phase I clinical trial of aerosol Aza to be initiated at our Institution.

  17. "Are Thai children and youth sufficiently active? prevalence and correlates of physical activity from a nationally representative cross-sectional study".

    Science.gov (United States)

    Amornsriwatanakul, Areekul; Lester, Leanne; Bull, Fiona C; Rosenberg, Michael

    2017-05-30

    Children and youth gain multiple health benefits from regular participation in physical activity (PA). However, in Thailand there is limited national data on children and youth's PA behaviors and recent reports suggest that Thai children and youth have low levels of PA. Furthermore, there is almost no data on the factors associated with inactivity to support the development of a Thai National PA Plan. The purpose of this paper is to investigate Thai children and youth's participation in PA and its correlates across sociodemographic characteristics and different PA domains. This study applied a cross-sectional study design with a multi-stage stratified cluster sampling. A national representative sample of 13,255 children and youth aged 6-17 years were used for data analysis. A previously validated questionnaire was used to assess PA prevalence. Logistic regression was conducted to examine the relationships of socio-demographic factors, and participation in different PA domains with overall PA. Only 23.4% of Thai children and youth met recommended levels of PA and there were large gender and regional differences. PA levels generally declined with age, although the level observed in the 10-13 year group was slightly higher than other year groups. A majority of children and youth engaged in a large number of different activities across PA domains. Sex, age, BMI, geographical regions, organized sports, participation in sport and recreational activities were significant predictors of meeting the global PA guidelines, whereas participation in physical education, active transport, and the number of screen time activities had no association. Girls were less likely to achieve sufficient PA levels (OR = 0.49, 95%CI; 0.45-0.54, p Thai children and youth is low, despite the high levels of engagement in a large number of PA. The results indicate that policy and interventions aimed at increasing PA are needed with special attention required to address specific groups less

  18. Consequences of daily corticosteroid dosing with or without pre-treatment with quinidine on the in vivo cytochrome P450 2D (CYP2D) enzyme in rats: effect on O-demethylation activity of dextromethorphan and expression levels of CYP2D1 mRNA.

    Science.gov (United States)

    Giri, Poonam; Delvadia, Prashant; Gupta, Laxmikant; Patel, Nirmal; Trivedi, Priyal; Lad, Krishna; Patel, Hiren M; Srinivas, Nuggehally R

    2018-01-01

    1. Present investigation was carried out in rats to study influence of corticosteroids after repeated dosing with/without pre-treatment with CYP2D inhibitor quinidine on the CYP2D1 mRNA levels and CYP2D enzyme activity using dextromethorphan as probe substrate. 2. CYP2D1 mRNA was measured in liver homogenate using quantitative real-time polymerase chain reaction [qRT-PCR] and enzymatic reaction was studied ex vivo in liver S-9 fractions of rats treated with oral 10 mg/kg dexamethasone or prednisolone for five days or pre-treated with quinidine and followed by treatment with oral 10 mg/kg corticosteroids for five days. 3. Five days repeat dosing of dexamethasone or prednisolone decreased the activity of the rat liver CYP2D by 37% and 34%, at 30 min incubation and decreased CYP2D1 mRNA levels by 62% and 61%, respectively. 4. Pre-treatment of quinidine decreased the enzymatic activity of rat CYP2D by 58% and did not potentiate CYP2D inhibition by corticosteroids. This observation was further complemented by qRT-PCR data. 5. Corticosteroids caused CYP2D inhibition in rats vs. literature evidence of CYP2D induction in human hepatocytes/pregnant humans demonstrating lack of concordance. In vivo inhibition should be factored for interpretation of pharmacokinetic data of CYP2D substrates when treated with corticosteroids in rats.

  19. Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis

    Science.gov (United States)

    Bradley, Elizabeth W.; Carpio, Lomeli R.; McGee-Lawrence, Meghan E.; Becerra, Clara Castillejo; Amanatullah, Derek F.; Ta, Lauren E.; Otero, Miguel; Goldring, Mary B.; Kakar, Sanjeev; Westendorf, Jennifer J.

    2016-01-01

    OBJECTIVE Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in osteoarthritis progression in a murine model. We also assessed PHLPP1 expression and promoter methylation. DESIGN Knee joints of WT and Phlpp1−/− mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression was evaluated in human articular cartilage and chondrocyte cell lines. RESULTS Following DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1−/− mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures. Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines. CONCLUSION Phlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory responses promote PHLPP1 expression. PMID:26746148

  20. Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2015-01-01

    of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on E max model with three...... concentrations, and this decline was greater in susceptible strains than resistant strains. The lag phase, defined as the time needed for the strain to reach an OD600 value of 0.01, increased exponentially with increasing tetracycline concentration. The pharmacodynamic parameters confirmed that the [Formula: see...

  1. Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4).

    Science.gov (United States)

    Hassani, Saeed; Khaleghian, Ali; Ahmadian, Shahin; Alizadeh, Shaban; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

    2018-01-01

    PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.

  2. LECTINS OF REPRESENTATIVES OF THE ECHINACEA GENUS (ECHINACEA MOENCH). 3. RESEARCH OF ACTIVITY IN ONTOGENESIS ECHINACEA PALLIDA (NUTT.) NUTT

    OpenAIRE

    Поспелов, Сергей Викторович

    2013-01-01

    For the first time research of dynamics of lectins activity of pale purple coneflower (Echinacea pallida (Nutt.) Nutt) in ontogenesis. It has been established that on the first year of vegetation the highest level of phytolectins observed in herbs at the second part of vegetation (14,0–16,0 point). In the roots with rhizomes lectins were appears only at the end of vegetation (up to 2,0 point). In the second year in the genesic period some high activity was observed of leave’s extracts at the ...

  3. Geological activity of humans represented in the world heritage sites of India, Italy, and Russia: Evidence of the anthropocene

    Directory of Open Access Journals (Sweden)

    Ansari M K.

    2016-01-01

    Full Text Available The idea of the Anthropocene attracts attention of scientists, policy-makers, and broad public to the geological activity of humans and poses new important questions for the modern stratigraphy. The growth of the Anthropocene-related knowledge and its promotion can be based potentially on the UNESCO World Heritage Sites (WHS. On the one hand, many of these sites provide spectacular evidence of the human activity. On the other hand, these are remarkable tourist attractions. The WHSs of three heritage-rich countries, namely India, Italy, and Russia, have been assessed with regard to how these reflect the geological activity of humans. It is established that 65-90% of all WHSs in each country provide direct and indirect evidence of such an activity (artificial caves, terrace building, etc., which appears to be enough for the general discussion of the idea of the Anthropocene. However, the distribution of the WHSs by their age allows focusing only on the “early” (before 1800 AD start of the Anthropocene, which is not enough for full discussion of the lower limit of this unit. The examples considered in the present study imply that some WHSs alone provide very important pieces of the Anthropocene-related knowledge.

  4. Activity in neurons of a putative protocerebral circuit representing information about a ten component plant odour blend in Heliothis virescens.

    Directory of Open Access Journals (Sweden)

    Bjarte Bye Løfaldli

    2012-09-01

    Full Text Available The olfactory pathway in the insect brain is anatomically well described from the antennal lobe to the mushroom bodies and the lateral protocerebrum in several species. Less is known about the further connections of the olfactory network in protocerebrum and how information about relevant plant odorants and mixtures are represented in this network, resulting in output information mediated by descending neurons. In the present study we have recorded intracellularly followed by dye injections from neurons in the lateral- and superior protocerebrum of the moth, Heliothis virescens. As relevant stimuli, we have used selected primary plant odorants and mixtures of them. The results provide the morphology and physiological responses of neurons involved in a putative circuit connecting the mushroom body lobes, the superior and the lateral protocerebrum, as well as input to superior and lateral protocerebrum by one multiglomerular antennal lobe neuron and output from the lateral protocerebrum by one descending neuron. All neurons responded to one particular mixture of ten primary plant odorants, some of them also to single odorants of the mixture. Altogether, the physiological data indicate integration in protocerebral neurons of information from several of the receptor neuron types functionally described in this species.

  5. Radical Scavenging and Anti-Inflammatory Activities of Representative Anthocyanin Groupings from Pigment-Rich Fruits and Vegetables

    Directory of Open Access Journals (Sweden)

    Federica Blando

    2018-01-01

    Full Text Available Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interest because of their potential health effects. With the aim of contributing to major insights into their structure–activity relationship (SAR, we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant and two vegetables (black carrot and “Sun Black” tomato, differing in anthocyanin content (ranging from 4.9 to 38.5 mg/g DW and molecular structure of the predominant anthocyanins. PASs from the abovementioned plant materials have been evaluated for their antioxidant capacity using Trolox Equivalent Antioxidant Capacity (TEAC and Oxygen Radical Absorbance Capacity (ORAC assays. In human endothelial cells, we analysed the anti-inflammatory activity of different PASs by measuring their effects on the expression of endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables, even though this order was slightly reversed when ORAC assay values were expressed on a molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection.

  6. Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities.

    Science.gov (United States)

    Kamal, Susan; Holmberg, Christine; Russell, Jean; Bochenek, Tomasz; Tobiasz-Adamczyk, Beata; Fischer, Christiane; Tinnemann, Peter

    2015-01-01

    Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country. To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt. Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software. The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health. Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians.

  7. Evaluation of Antioxidant Activity, Polyphenolic Compounds, Amino Acids and Mineral Elements of Representative Genotypes of Lonicera edulis

    Directory of Open Access Journals (Sweden)

    Jiri Sochor

    2014-05-01

    Full Text Available The aim of this study was to evaluate the bioactive substances in 19 berry cultivars of edible honeysuckle (Lonicera edulis. A statistical evaluation was used to determine the relationship between the content of selected bioactive substances and individual cultivars. Regarding mineral elements, the content of sodium was measured using potentiometry and spectrophotometry. The content of selected polyphenolic compounds with high antioxidant activity was determined by a HPLC–UV/ED method. The total amount of polyphenols was determined by the Folin-Ciocalteu method. The antioxidant activity was determined using five methods (DPPH, FRAP, ABTS, FR and DMPD that differ in their principles. The content of 13 amino acids was determined by ion-exchange chromatography. The experimental results obtained for the different cultivars were evaluated and compared by statistical and bioinformatic methods. A unique feature of this study lies in the exhaustive analysis of the chosen parameters (amino acids, mineral elements, polyphenolic compounds and antioxidant activity during one growing season.

  8. Homogeneous ice nucleation from aqueous inorganic/organic particles representative of biomass burning: water activity, freezing temperatures, nucleation rates.

    Science.gov (United States)

    Knopf, Daniel A; Rigg, Yannick J

    2011-02-10

    Homogeneous ice nucleation plays an important role in the formation of cirrus clouds with subsequent effects on the global radiative budget. Here we report on homogeneous ice nucleation temperatures and corresponding nucleation rate coefficients of aqueous droplets serving as surrogates of biomass burning aerosol. Micrometer-sized (NH(4))(2)SO(4)/levoglucosan droplets with mass ratios of 10:1, 1:1, 1:5, and 1:10 and aqueous multicomponent organic droplets with and without (NH(4))(2)SO(4) under typical tropospheric temperatures and relative humidities are investigated experimentally using a droplet conditioning and ice nucleation apparatus coupled to an optical microscope with image analysis. Homogeneous freezing was determined as a function of temperature and water activity, a(w), which was set at droplet preparation conditions. The ice nucleation data indicate that minor addition of (NH(4))(2)SO(4) to the aqueous organic droplets renders the temperature dependency of water activity negligible in contrast to the case of aqueous organic solution droplets. The mean homogeneous ice nucleation rate coefficient derived from 8 different aqueous droplet compositions with average diameters of ∼60 μm for temperatures as low as 195 K and a(w) of 0.82-1 is 2.18 × 10(6) cm(-3) s(-1). The experimentally derived freezing temperatures and homogeneous ice nucleation rate coefficients are in agreement with predictions of the water activity-based homogeneous ice nucleation theory when taking predictive uncertainties into account. However, the presented ice nucleation data indicate that the water activity-based homogeneous ice nucleation theory overpredicts the freezing temperatures by up to 3 K and corresponding ice nucleation rate coefficients by up to ∼2 orders of magnitude. A shift of 0.01 in a(w), which is well within the uncertainty of typical field and laboratory relative humidity measurements, brings experimental and predicted freezing temperatures and homogeneous ice

  9. Protection motivation theory and physical activity: a longitudinal test among a representative population sample of Canadian adults.

    Science.gov (United States)

    Plotnikoff, Ronald C; Rhodes, Ryan E; Trinh, Linda

    2009-11-01

    The purpose of this study was to examine the Protection Motivation Theory (PMT) to predict physical activity (PA) behaviour in a large, population-based sample of adults. One thousand six hundred and two randomly selected individuals completed two telephone interviews over two consecutive six-month periods assessing PMT constructs. PMT explained 35 per cent and 20 per cent of the variance in intention and behaviour respectively. Coping cognitions as moderators of threat explained 1 per cent of the variance in intention and behaviour. Age and gender as moderators of threat did not provide additional variance in the models. We conclude that salient PMT predictors (e.g. self-efficacy) may guide the development of effective PA interventions in the general population.

  10. In vitro antiviral activity of a series of wild berry fruit extracts against representatives of Picorna-, Orthomyxo- and Paramyxoviridae.

    Science.gov (United States)

    Nikolaeva-Glomb, Lubomira; Mukova, Luchia; Nikolova, Nadya; Badjakov, Ilian; Dincheva, Ivayla; Kondakova, Violeta; Doumanova, Lyuba; Galabov, Angel S

    2014-01-01

    Wild berry species are known to exhibit a wide range of pharmacological activities. They have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. The aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in Bulgaria: strawberry (Fragaria vesca L.) and raspberry (Rubus idaeus L.) of the Rosaceae plant family, and bilberry (Vaccinium myrtillis L.) and lingonberry (Vaccinium vitis-idaea L) of the Ericaceae. The antiviral effect has been tested against viruses that are important human pathogens and for which chemotherapy and/or chemoprophylaxis is indicated, namely poliovirus type 1 (PV-1) and coxsackievirus B1 (CV-B1) from the Picornaviridae virus family, human respiratory syncytial virus A2 (HRSV-A2) from the Paramyxoviridae and influenza virus A/H3N2 of Orthomyxoviridae. Wild berry fruits are freeze-dried and ground, then total methanol extracts are prepared. Further the extracts are fractioned by solid phase extraction and the non-anthocyanin and anthocyanin fractions are eluted. The in vitro antiviral effect is examined by the virus cytopathic effect (CPE) inhibition test. The results reveal that the total extracts of all tested berry fruits inhibit the replication of CV-B1 and influenza A virus. CV-B1 is inhibited to the highest degree by both bilberry and strawberry, as well as by lingonberry total extracts, and influenza A by bilberry and strawberry extracts. Anthocyanin fractions of all wild berries strongly inhibit the replication of influenza virus A/H3N2. Given the obtained results it is concluded that wild berry species are a valuable resource of antiviral substances and the present study should serve as a basis for further detailed research on the matter.

  11. Cell-based DNA demethylation detection system for screening of epigenetic drugs in 2D, 3D and xenograft models

    Czech Academy of Sciences Publication Activity Database

    Agrawal, K.; Das, V.; Otmar, Miroslav; Krečmerová, Marcela; Džubák, P.; Hajdúch, M.

    2015-01-01

    Roč. 14, Suppl 2 (2015), B72 ISSN 1535-7163. [AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics. 05.11.2015-09.11.2015, Boston] R&D Projects: GA MPO(CZ) FR-TI4/625; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : demethylation * epigenetic drugs * fluorescence detection system Subject RIV: CC - Organic Chemistry

  12. Cell-based DNA demethylation detection system for screening of epigenetic drugs in 2D, 3D, and xenograft models

    Czech Academy of Sciences Publication Activity Database

    Agrawal, K.; Das, V.; Otmar, Miroslav; Krečmerová, Marcela; Džubák, P.; Hajdúch, M.

    91A, č. 2 (2017), s. 133-143 ISSN 1552-4922 R&D Projects: GA MZd(CZ) NV15-31984A; GA MŠk(CZ) LO1304; GA MŠk(CZ) LM2015064; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : DNA methylation * DNA methylation inhibitors * demethylation detection system * epigenetic drugs * high content screening Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.222, year: 2016

  13. Stable knockdown of PASG enhances DNA demethylation but does not accelerate cellular senescence in TIG-7 human fibroblasts.

    Science.gov (United States)

    Suzuki, Toshikazu; Farrar, Jason E; Yegnasubramanian, Srinivasan; Zahed, Muhammed; Suzuki, Nobuo; Arceci, Robert J

    2008-09-01

    Demethylation of 5-methylcytosine in genomic DNA is believed to be one of the mechanisms underlying replicative life-span of mammalian cells. Both proliferation associated SNF2-like gene (PASG, also termed Lsh) and DNA methyltransferase 3B (Dnmt3b) knockout mice result in embryonic genomic hypomethylation and a replicative senescent phenotype. However, it is unclear whether gradual demethylation of DNA during somatic cell division is directly involved in senescence. In this study, we retrovirally transduced TIG-7 human fibroblasts with a shRNA against PASG and compared the rate of change in DNA methylation as well as the replicative life-span to control cells under low (3%) and ambient (20%) oxygen. Expression of PASG protein was decreased by approximately 80% compared to control cells following transduction of PASG shRNA gene. The rate of cell growth was the same in both control and PASG-suppressed cells. The rate of demethylation of DNA was significantly increased in PASG-suppressed cells as compared control cells. However, decreased PASG expression did not shorten the replicative life-span of TIG-7 cells. Culture under low oxygen extended the life-span of TIG-7 cells but did not alter the rate of DNA demethylation. While knockout of PASG during development results in genomic hypomethylation and premature senescence, our results show that while downregulation of PASG expression in a somatic cell also leads to DNA hypomethylation, there is no associated senescent phenotype. These results suggest differences in cellular consequences of hypomethylation mediated by PASG during development compared to that in somatic cells.

  14. Photography by Cameras Integrated in Smartphones as a Tool for Analytical Chemistry Represented by an Butyrylcholinesterase Activity Assay.

    Science.gov (United States)

    Pohanka, Miroslav

    2015-06-11

    Smartphones are popular devices frequently equipped with sensitive sensors and great computational ability. Despite the widespread availability of smartphones, practical uses in analytical chemistry are limited, though some papers have proposed promising applications. In the present paper, a smartphone is used as a tool for the determination of cholinesterasemia i.e., the determination of a biochemical marker butyrylcholinesterase (BChE). The work should demonstrate suitability of a smartphone-integrated camera for analytical purposes. Paper strips soaked with indoxylacetate were used for the determination of BChE activity, while the standard Ellman's assay was used as a reference measurement. In the smartphone-based assay, BChE converted indoxylacetate to indigo blue and coloration was photographed using the phone's integrated camera. A RGB color model was analyzed and color values for the individual color channels were determined. The assay was verified using plasma samples and samples containing pure BChE, and validated using Ellmans's assay. The smartphone assay was proved to be reliable and applicable for routine diagnoses where BChE serves as a marker (liver function tests; some poisonings, etc.). It can be concluded that the assay is expected to be of practical applicability because of the results' relevance.

  15. Photography by Cameras Integrated in Smartphones as a Tool for Analytical Chemistry Represented by an Butyrylcholinesterase Activity Assay

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2015-06-01

    Full Text Available Smartphones are popular devices frequently equipped with sensitive sensors and great computational ability. Despite the widespread availability of smartphones, practical uses in analytical chemistry are limited, though some papers have proposed promising applications. In the present paper, a smartphone is used as a tool for the determination of cholinesterasemia i.e., the determination of a biochemical marker butyrylcholinesterase (BChE. The work should demonstrate suitability of a smartphone-integrated camera for analytical purposes. Paper strips soaked with indoxylacetate were used for the determination of BChE activity, while the standard Ellman’s assay was used as a reference measurement. In the smartphone-based assay, BChE converted indoxylacetate to indigo blue and coloration was photographed using the phone’s integrated camera. A RGB color model was analyzed and color values for the individual color channels were determined. The assay was verified using plasma samples and samples containing pure BChE, and validated using Ellmans’s assay. The smartphone assay was proved to be reliable and applicable for routine diagnoses where BChE serves as a marker (liver function tests; some poisonings, etc.. It can be concluded that the assay is expected to be of practical applicability because of the results’ relevance.

  16. Determination of parameters influencing methylation and demethylation in tropical lakes in Brazil and Nicaragua

    International Nuclear Information System (INIS)

    Hylander, Lars D.; Ahlgren, Ingemar; Erikson, Rolf; Lantz, Peter; Toernblom, Erik; Forsberg, Bruce R.; Guimaraes, Jean R.D.; Meili, Markus; Montenegro Guillen, Salvador; Vammen, Katherine; Altamirano, Maximina; Zelaya, Argentina; Sarria Sacasa, Karla; Jimenez, Mario

    2001-01-01

    Increased awareness about the toxicity of mercury (Hg) has during the latest decades resulted in reduced Hg use in industrialised countries. Developing countries, on the contrary, have largely increased their anthropogenic Hg emissions caused by its use in gold mining, transfer of Hg emitting factories from developed countries, and increased burning of coal without appropriate flue gas cleaning. These increased emissions occur mainly in the tropics, where the fate of Hg is not well documented. The aim of the present study is to increase the knowledge about Hg levels and transformations in two tropical areas affected by anthropogenic Hg emissions - the Pantanal wetland in Brazil, housing gold miners using the amalgamation method, and Lake Xolotilan (Managua) in Nicaragua, where a chlor-alkali plant relocated from the USA has emitted much Hg. Actual Hg content in water, biota, and sediment will be determined by atomic fluorescence spectrophotometry and atomic absorption spectrophotometry. Mercury inethylation capacity in sediments and selected biota will be determined with in-situ incubations with 203 Hg and subsequent radiological measurements. Factors affecting the methylation and demethylation rates will be identified by varying environmental conditions such as pH, redox potential, conductivity, light, temperature, geochemical factors and population of bacteria. Sediment turnover will be studied by determining fallout cesium ( 137 Cs) in sediment profiles. The study is expected to increase the knowledge about Hg-transformations in the tropics and point out proper measures to reduce health hazards due to Hg-exposure. (author)

  17. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5

    Science.gov (United States)

    Huang, Yue; Yan, Jingli; Li, Qi; Li, Jiafei; Gong, Shouzhe; Zhou, Hu; Gan, Jianhua; Jiang, Hualiang; Jia, Gui-Fang; Luo, Cheng; Yang, Cai-Guang

    2015-01-01

    Two human demethylases, the fat mass and obesity-associated (FTO) enzyme and ALKBH5, oxidatively demethylate abundant N6-methyladenosine (m6A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains a challenge, however. Here, we have identified meclofenamic acid (MA) as a highly selective inhibitor of FTO. MA is a non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with FTO binding for the m6A-containing nucleic acid. The structure of FTO/MA has revealed much about the inhibitory function of FTO. Our newfound understanding, revealed herein, of the part of the nucleotide recognition lid (NRL) in FTO, for example, has helped elucidate the principles behind the selectivity of FTO over ALKBH5. Treatment of HeLa cells with the ethyl ester form of MA (MA2) has led to elevated levels of m6A modification in mRNA. Our collective results highlight the development of functional probes of the FTO enzyme that will (i) enable future biological studies and (ii) pave the way for the rational design of potent and specific inhibitors of FTO for use in medicine. PMID:25452335

  18. Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

    Science.gov (United States)

    He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

    2014-12-01

    Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

  19. Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites.

    Science.gov (United States)

    Lee, Seung-Tae; Wiemels, Joseph L

    2016-02-18

    The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as 'backbone', largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Survey by senior NRC management to obtain veiwpoints on the safety impact of regulatory activities from representative utilities operating and constructing nuclear power plants

    International Nuclear Information System (INIS)

    1981-08-01

    A survey of licensee staff members representing the several organizational elements in different licensee corporate and plant staffs was conducted by senior NRC management to obtain licensee views on the potential safety consequences and impact of NRC regulatory activities. The comments received addressed the full scope of NRC activities and the negative impact of agency actions on licensee resources, staff performance, planning and scheduling, and organizational effectiveness. The findings of the survey is that the pace and nature of regulatory actions have created a potential safety problem which deserves further evaluation by the agency

  1. [Physical movement - is it good for the back? Nationwide representative study on different effects of physical activity at the workplace and in leisure time].

    Science.gov (United States)

    Schneider, S; Zoller, S

    2009-10-01

    Physical activity is an important component of primary and secondary prevention of orthopedic complaints such as back pain as well as for many other syndromes. This epidemiologic research project investigated the multifactorial interaction between physical leisure activities and back pain and also the question whether regular physical activity at the workplace can be equated with the effect of regular leisure activity. From a patients point of view this could be construed as an"excuse" to refrain from leisure and fitness sports. Within the framework of a cooperative project between the Orthopedic University Clinic in Heidelberg and the Robert-Koch Institute in Berlin, representative data were gathered for the first time in Germany on physical activity at the workplace and in leisure time as well as the prevalence of back pain. Within the first national health survey a random sample of 3,488 employed German citizens aged 18-69 years old was investigated with multiple logistic regression analyses.The prevalence of 7-day back pain in Germany was 34% and the prevalence for 1-year was 60%. Physical activity at the workplace was associated with a significantly higher risk for back pain whilst leisure sport activity was accompanied by a lower prevalence of back pain. Although 39% of all persons who were inactive in sport and physical activities claimed to have felt back pain at least once in a retrospective 7-day period, the corresponding values for persons active in sport were 33% (1-2 h sport/week), 27% (2-4 h sport/week) and 30% (>4 h sport/week).This study provides population-based epidemiologic data on the prevalence of back pain among employed German citizens for the first time since the reunification. Although causal conclusions cannot principally be derived from cross-sectional data, the results of this analysis allow the multifactorial conditional structure to be unraveled. Our data demonstrate that manual physical employment does not represent a substitute for

  2. Demethylation of Circulating Estrogen Receptor Alpha Gene in Cerebral Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Hsiu-Fen Lin

    Full Text Available Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα. Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients.The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted.The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011, but not in men (adjusted p = 0.300.Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

  3. Caffeine demethylation measured by breath analysis in experimental liver injury in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schaad, H.J.; Renner, E.L.; Wietholtz, H.; Preisig, R. [University of Berne, Department of Clinical Pharmaceology, Berne (Switzerland); Arnaud, M.J. [Nestle Research Center, Nestec Ltd., Vevey (Switzerland)

    1995-01-01

    To assess the effect of experimental liver injury on caffeine metabolism, 1 {mu}{sup C}i/kg b.w. of [3-methyl{sup 14}C]-caffeine (together with 5 mg/kg b.w. of the cold compound) was injected i.p. to four different experimental groups and respective controls of unanesthetized male Sprague-Dawley rats. Exhaled {sup 14}CO{sub 2} was completely collected during 4 h and peak exhalation rate and fraction of dose recovered were calculated. 1/3 hepatectomy affected {sup 14}CO{sub 2} exhalation to a limited extent, decreasing solely peak exhalation rate (p<0.05 compared to sham-operated control). 2/3 hepatectomy, on the other hand, resulted in significant reduction (p<0.01) in both peak exhalation rate (by 59%) and fraction of dose recovered (by 47%), that were proportionate to the loss of liver mass (50%). End-to-side portocaval shunt led to the well-documented hepatic `atrophy`, liver weight being diminished on average to 50% within 2 weeks of surgery; however, reductions in peak exhalation rate (by 75%) and fraction of dose recovered (by 64%) were even more pronounced. Finally, 48 h bile duct ligation was equivalent to `functional 2/3 hepatectomy`, peak exhalation rate (by 65%) and fraction of dose recovered (by 56%) being markedly diminished despite increased liver weight. These results indicate that {sup 14}CO{sub 2} exhalation curves following administration of specifically labelled caffeine are quantitative indicators of acute or chronic loss of functioning liver mass. In addition, the 3-demethylation pathway appears to be particularly sensitive to the inhibitory effects of cholestasis on microsomal function. (au) (30 refs.).

  4. Determination of parameters influencing methylation and demethylation in tropical lakes in Brazil and Nicaragua

    International Nuclear Information System (INIS)

    Hylander, Lars D.; Ahlgren, Ingemar; Broberg, Anders; Lantz, Peter; Tornblom, Erik; Forsberg, Bruce R.; Guimaraes, Jean R.D.; Mauro, Jane; Markus, Meili; Guillen Montenegro, Salvador; Vammen, Katherine; Sacasa, Sarria Karla; Regnell, Olof

    2002-01-01

    Increased awareness about the toxicity of mercury (Hg) has during the latest decades resulted in reduced use of Hg in industrialised countries. Developing countries, on the contrary, have largely increased their anthropogenic Hg emissions caused by its use in gold mining, transfer of Hg emitting factories from developed countries, and increased burning of coal without appropriate flue gas cleaning. The contribution of global Hg sources and the importance of other parameters to increased Hg levels encountered in hydroelectric reservoirs and other areas after flooding is not well understood, especially not in the tropics. The aim of the present study is to increase the knowledge about Hg transformations in tropical areas. Total Hg content in water, biota, and sediment will be determined by atomic absorption and fluorescence spectrophotometry and methyl Hg content in biota by gaschromatography after extraction with acids, hydroxides, and organic solvents. Mercury methylation capacity in sediments, water, and selected biota will be determined with 203 Hg and subsequent radiological measurements of insitu incubations. Factors affecting the methylation and demethylation rates will be identified with laboratory incubations with 203 Hg at varying environmental conditions such as organic matter, pH, redox potential, conductivity, light, temperature, geochemical factors and populations of bacteria. The populations of bacteria will be determined to quantity by isotope techniques. The first experiments indicate markedly larger methylation capacity as well as bacterial production of incubated samples of Eichhornia crassipes, originating from Brazil, compared to Myriophyllum spicatum from Sweden. The results are the first step to better understand the importance of environmental parameters and bacterial production for methylation of Hg. (author)

  5. The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers

    Directory of Open Access Journals (Sweden)

    Choi Sang-Wook

    2010-11-01

    Full Text Available Abstract Background The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with Helicobacter pylori (H. pylori and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements. Methods The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the H. pylori-negative gastric mucosa. Results The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the H. pylori-positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the H. pylori-positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner. Conclusions The overmethylated genes under the influence of retroelement methylation in the H. pylori-infected stomach are demethylated in the gastric cancers influenced by LOH.

  6. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Min [Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072 (China); Wu, Junjie, E-mail: wujunjiesh@126.com [Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433 (China); Cai, Yong, E-mail: dryongcai@126.com [Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433 (China)

    2013-09-06

    Highlights: •Dnmt3A and Dnmt3B are involved in the down-regulation of WIF-1 expression in non-small-cell lung cancer. •MiR-29 family members could restore WIF-1 expression through demethylation. •MiR-29s suppress Wnt/β-catenin signaling pathway and inhibit tumor growth. •The expression of miR-29a and miR-29b could be regulated partially in a positive feedback loop. -- Abstract: Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC.

  7. Selection of appropriate Chinese terms to represent intensity and types of physical activity terms for use in the Taiwan version of IPAQ.

    Science.gov (United States)

    Liou, Yiing Mei; Jwo, Clark J C; Yao, Kaiping Grace; Chiang, Li-Chi; Huang, Lian-Hua

    2008-12-01

    In order to analyze the health risks of insufficient activity by international comparisons, the first author obtained the permission to translate and develop a Taiwan version of the International Physical Activity Questionnaire (IPAQ). The objective was to determine culturally sensitive Chinese translations for the terms "moderate", "vigorous" and "physical activity" as well as to identify representative types of physical activity for Taiwanese. This study used discussions by 12 expert focus groups, 6 expert audits, a scale survey, field study, Cognitive Aspect Survey Methodology (CASM), dual independent translation and back-translation to establish a consensus on physical activity-related concepts, terminologies and types that define the intensity of common activities of Taiwanese by integrating both local and foreign studies. The Chinese terms "fei li", "zhong deng fei li" and "shen ti huo dong", respectively, were identified as suitable and adequate translations for the English terms "vigorous", "moderate" and "physical activity". The common Taiwanese activities were accurately categorized and listed in questionnaires, forming culturally sensitive scales. Taiwan versions of IPAQ's self-administered long version (SL), self-administered short version (SS), and telephone interview short version (TS) were developed. Their content validity indices were .992, .994, and .980, as well as .994, .992, and .994 for language equivalence and meaning similarity between the English and Chinese versions of the IPAQ-LS, IPAQ-SS, and IPAQ-TS, respectively. Consistency values for the English and Chinese versions in terms of intraclass correlation coefficients were .945, .704, and .894, respectively. The IPAQ-Taiwan is not only a sensitive and precise tool, but also shows the effectiveness of the methodology (CASM) used in tool development. Subjects who did not regularly exercise and had an education less than a junior high school level underestimated the moderate

  8. Grip strength, postural control, and functional leg power in a representative cohort of British men and women: associations with physical activity, health status, and socioeconomic conditions.

    Science.gov (United States)

    Kuh, Diana; Bassey, E Joan; Butterworth, Suzanne; Hardy, Rebecca; Wadsworth, Michael E J

    2005-02-01

    Understanding the health, behavioral, and social factors that influence physical performance in midlife may provide clues to the origins of frailty in old age and the future health of elderly populations. The authors evaluated muscle strength, postural control, and chair rise performance in a large representative prospective cohort of 53-year-old British men and women in relation to functional limitations, body size, health and activity, and socioeconomic conditions. Nurses interviewed 2984 men and women in their own homes in England, Scotland, and Wales and conducted physical examinations in 2956 of them. Objective measures were height, weight, and three physical performance tests: handgrip strength, one-legged standing balance time, and time to complete 10 chair rises. Functional limitations (difficulties walking, stair climbing, gripping, and falls), health status, physical activity, and social class were obtained using a structured questionnaire. Those with the worst scores on the physical performance tests had higher rates of functional limitations for both upper and lower limbs. Women had much weaker handgrip strength, somewhat poorer balance time, and only slightly poorer chair rise time compared with men. In women, health problems and low levels of physical activity contributed to poor physical performance on all three measures. In men, physical activity was the predominant influence. Heavier weight and poorer socioeconomic conditions contributed to poorer balance and chair rise times. In this representative middle-aged group, physical performance levels varied widely, and women were seriously disadvantaged compared with men. In general, physical performance was worse for men and women living in poorer socioeconomic conditions with greater body weight, poorer health status, and inactive lifestyles. These findings support recommendations for controlling excess body weight, effective health interventions, and the maintenance of active lifestyles during aging.

  9. Differential Activity of Voltage- and Ca2+-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case

    Directory of Open Access Journals (Sweden)

    Salvador Valle-Reyes

    2018-05-01

    Full Text Available Activation of resting T cells relies on sustained Ca2+ influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca2+- or voltage-activated K+ channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3. Voltage dependence of activation and inactivation of Kv1.3 current were shifted up to by 15 mV to more negative potentials upon a prolonged incubation in the whole cell mode and displayed little difference at a stable state in all cell lines but CEM, where the activation curve was biphasic, with a high and low potential components. In Jurkat, KCa currents were dominated by apamine-sensitive KCa2.2 channels, whereas only KCa3.1 current was detected in healthy T and leukemic CEM and MOLT-3 cells. Despite a high proliferation potential of Jurkat cells, Kv and KCa currents were unexpectedly small, more than 10-fold lesser as compared to activated healthy human T cells, CEM and MOLT-3, which displayed characteristic Kv1.3high:KCa3.1high phenotype. Our results suggest that Jurkat cells represent perhaps a singular case and call for more extensive studies on primary leukemic T cell lines as well as a verification of the therapeutic potential of specific KCa3.1 blockers to combat acute lymphoblastic T leukemias.

  10. The applicability of activities in kinetic expressions: a more fundamental approach to represent the kinetics of the system CO2-OH- in terms of activities

    NARCIS (Netherlands)

    Haubrock, J.; Hogendoorn, Kees; Versteeg, Geert

    2005-01-01

    In this paper the applicability of using activities instead of concentrations in kinetic expressions has been investigated using the reaction of CO2 with various hydroxide solutions as a model system. For this system it is known that when the reaction rate constant is based on the use of

  11. The applicability of activities in kinetic expressions : A more fundamental approach to represent the kinetics of the system CO2-OH- in terms of activities

    NARCIS (Netherlands)

    Haubrock, J.; Hogendoorn, J. A.; Versteeg, G. F.

    2005-01-01

    In this paper the applicability of using activities instead of concentrations in kinetic expressions has been investigated using the reaction of CO2 with various hydroxide solutions as a model system. For this system it is known that when the reaction rate constant is based on the use of

  12. The applicability of activities in kinetic expressions: A more fundamental approach to represent the kinetics of the system CO2–OH-salt in terms of activities

    NARCIS (Netherlands)

    Haubrock, J.; Hogendoorn, Kees; Versteeg, Geert

    2007-01-01

    The applicability of utilizing activities instead of concentrations in kinetic expressions has been investigated using the reaction of CO2 in sodium hydroxide solutions also containing different neutral salts (LiCl, KCl and NaCl) as model system. For hydroxide systems it is known that when the

  13. Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.

    Directory of Open Access Journals (Sweden)

    Christopher A Hamm

    Full Text Available Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.

  14. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo

    International Nuclear Information System (INIS)

    Toribio E, E.

    2005-01-01

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  15. ?Are Thai children and youth sufficiently active? prevalence and correlates of physical activity from a nationally representative cross-sectional study?

    OpenAIRE

    Amornsriwatanakul, Areekul; Lester, Leanne; Bull, Fiona C.; Rosenberg, Michael

    2017-01-01

    Background Children and youth gain multiple health benefits from regular participation in physical activity (PA). However, in Thailand there is limited national data on children and youth?s PA behaviors and recent reports suggest that Thai children and youth have low levels of PA. Furthermore, there is almost no data on the factors associated with inactivity to support the development of a Thai National PA Plan. The purpose of this paper is to investigate Thai children and youth?s participati...

  16. Characterizing the context of sedentary lifestyles in a representative sample of adults: a cross-sectional study from the physical activity measurement study project.

    Science.gov (United States)

    Kim, Youngwon; Welk, Gregory J

    2015-12-09

    Research has clearly demonstrated that excess time spent on sedentary behavior (SB) increases health risks in the population. However, the lack of information on the context of SB in the population prevents a detailed understanding of sedentary lifestyles. The purpose of this study was to characterize the context of SB in a representative sample of adults and to examine differences across various socio-demographic indicators. A diverse sample of 1442 adults (ages 20-71 year) completed an interviewer-administered 24-h activity recall to provide detailed information about the time, type and location of the previous day's activities. All reported activities were matched with MET scores from the Compendium of Physical Activity but only SB (i.e., METS Work: 27.5%, Community: 24.8%, Home/Indoor: 20.5%, Home/Outdoor: 15.8%, and Transportation: 11.3%). Patterns of SB allocations varied considerably across different socio-demographic indicators indicating the extreme variability in SB in the population. The findings provide unique insights about the context of SB at the population level, and can serve as a guide for developing intervention/policy studies to reduce sedentary time and minimize disparities in SB.

  17. Synergism between demethylation inhibitor fungicides or gibberellin inhibitor plant growth regulators and bifenthrin in a pyrethroid-resistant population of Listronotus maculicollis (Coleoptera: Curculionidae).

    Science.gov (United States)

    Ramoutar, D; Cowles, R S; Requintina, E; Alm, S R

    2010-10-01

    In 2007-2008, the "annual bluegrass weevil," Listronotus maculicollis Kirby (Coleoptera: Curculionidae), a serious pest of Poa annua L. (Poales: Poaceae) on U.S. golf courses, was shown to be resistant to two pyrethroids, bifenthrin and lambda-cyhalothrin. In 2008, we showed that bifenthrin resistance was principally mediated by oxidase detoxification (cytochrome P450 [P450]). P450s can be inhibited by demethylation inhibitor fungicides and gibberellin inhibitor plant growth regulators, both of which are commonly used on golf courses. We tested these compounds for synergistic activity with bifenthin against a pyrethroid-resistant population of L. maculicollis. The LD50 value for bifenthrin was significantly reduced from 87 ng per insect (without synergists) to 9.6-40 ng per insect after exposure to the fungicides fenarimol, fenpropimorph, prochloraz, propiconazole, and pyrifenox and the plant growth regulators flurprimidol, paclobutrazol, and trinexapac-ethyl. Simulated field exposure with formulated products registered for use on turf revealed enhanced mortality when adult weevils were exposed to bifenthrin (25% mortality, presented alone) combined with field dosages of propiconizole, fenarimol, flurprimidol, or trinexapac-ethyl (range, 49-70% mortality).

  18. MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation.

    Science.gov (United States)

    Huang, M-Y; Xuan, F; Liu, W; Cui, H-J

    2017-01-19

    It is generally known that histone demethylases regulate gene transcription by altering the methylate status on histones, but their roles in cancers and the underlying molecular mechanisms still remain unclear. MYC-induced nuclear antigen (MINA) is reported to be a histone demethylase and highly expressed in many cancers. Here, for the first time, we show that MINA is involved in glioblastoma carcinogenesis and reveal the probable mechanisms of it in cell-cycle control. Kaplan-Meier analysis of progression-free survival showed that high MINA expression was strongly correlated with poor outcome and advancing tumor stage. MINA knockdown significantly repressed the cell proliferation and tumorigenesis abilities of glioblastoma cells in vitro and in vivo that were rescued by overexpressing the full-length MINA afterwards. Microarray analysis after knockdown of MINA revealed that MINA probably regulated glioblastoma carcinogenesis through the predominant cell-cycle pathways. Further investigation showed that MINA deficiency led to a cell-cycle arrest in G1 and G2 phases. And among the downstream genes, we found that cyclins and cyclin-dependent kinases were directly activated by MINA via the demethylation of H3K9me3.

  19. Active play and screen time in US children aged 4 to 11 years in relation to sociodemographic and weight status characteristics: a nationally representative cross-sectional analysis

    Directory of Open Access Journals (Sweden)

    Must Aviva

    2008-10-01

    Full Text Available Abstract Background The high prevalence of childhood obesity underscores the importance of monitoring population trends in children's activity and screen time, and describing associations with child age, gender, race/ethnicity, and weight status. Our objective was to estimate the proportion of young children in the US who have low levels of active play or high levels of screen time, or who have both these behaviors, and to describe associations with age, gender, race/ethnicity, and weight status. Methods We analyzed data collected during the National Health and Nutrition Examination Surveys 2001–2004, a US nationally representative cross-sectional study. We studied 2964 children aged 4.00 to 11.99 years. Our main outcomes were reported weekly times that the child played or exercised hard enough to sweat or breathe hard (active play, daily hours the child watched television/videos, used computers, or played computer games (screen time, and the combination of low active play and high screen time. Low active play was defined as active play 6 times or less per week. High screen time was defined as more than 2 hours per day. We accounted for the complex survey design in analyses and report proportions and 95% confidence intervals. We used Wald Chi-square to test for differences between proportions. To identify factors associated with low active play and high screen time, we used multivariate logistic regression. Results Of US children aged 4 to 11 years, 37.3% (95% confidence interval, 34.1% to 40.4% had low levels of active play, 65.0% (95% CI, 61.4% to 68.5% had high screen time, and 26.3% (95% CI, 23.8% to 28.9% had both these behaviors. Characteristics associated with a higher probability of simultaneously having low active play and high screen time were older age, female gender, non-Hispanic black race/ethnicity, and having a BMI-for-age ≥95th percentile of the CDC growth reference. Conclusion Many young children in the US are reported to

  20. Social Modulation or Hormonal Causation? Linkages of Testosterone with Sexual Activity and Relationship Quality in a Nationally Representative Longitudinal Sample of Older Adults.

    Science.gov (United States)

    Das, Aniruddha; Sawin, Nicole

    2016-11-01

    This study used population-representative longitudinal data from the 2005-2006 and 2010-2011 waves of the National Social Life, Health and Aging Project-a probability sample of US adults aged 57-85 at baseline (N = 650 women and 620 men)-to examine the causal direction in linkages of endogenous testosterone (T) with sexual activity and relationship quality. For both genders, our autoregressive effects indicated a large amount of temporal stability, not just in individual-level attributes (T, masturbation) but also dyadic ones (partnered sex, relationship quality)-indicating that a need for more nuanced theories of relational processes. Cross-lagged results suggested gender-specific effects-generally more consistent with sexual or relational modulation of T than with hormonal causation. Specifically, men's findings indicated their T might be elevated by their sexual (masturbatory) activity but not vice versa, although androgen levels did lower men's subsequent relationship quality. Women's T, in contrast, was negatively influenced not just by their higher relationship quality but also by their more frequent partnered sex-perhaps reflecting a changing function of sexual activity in late life.

  1. [Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell Line and 2 MDS Patients].

    Science.gov (United States)

    Kang, Hui-Yuan; Wang, Xin-Rong; Gao, Li; Wang, Wei; Li, Mian-Yang; Wang, Li-Li; Wang, Cheng-Bin; Yu, Li

    2015-04-01

    To evaluate significance of ID4 gene mehtylation in demethylating myelodysplastic syndrome(MDS) cell Line MUTZ1 and 2 patients with MDS. The methylation-specific PCR (MS-PCR) and reverse transcription-PCR (RT-PCR) were applied to identify the methylation status and gene expression of ID4 gene in MDS cell line MUTZ1, a patient with aplastic anemia(AA) and a donor with normal bone marrow (NBM). RT-PCR was applied to detect the ID4 gene expression status in MUTZ1 cell line treated with decitabine at 3 different concentrations. Then bisulfite sequencing PCR (BSP) was applied to detect ID4 gene methylation status in 2 MDS parients treated with decitabine. The MDS cell line MUTZ-1 displayed a complete methylation of ID4 gene promoter with little mRNA expression. Inversely, bone marrow of an AA patient and NBM showed complete unmethylation of this gene with intensity mRNA expression. With the increase of decitabine concentration, ID4 gene mRNA expression was more and more increased. After decitabine treatment, ID4 gene methylation-positive frequencies of both the 2 MDS patients were much more decreased than that of the first treatment. So, ID4 gene mRNA expression inhibited by promoter hypemethylation could be recovered by using demethylation medicine. ID4 as a new potential anti-oncogene suggests that its methylation may become a marker for selection and assessment of therapeutic schedules in patients with MDS.

  2. Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, de M.A.

    2003-01-01

    Modulators known to reduce multidrug resistance in tumour cells were tested for their potency to synergize the fungitoxic activity of the fungicide oxpoconazole, a sterol demethylation inhibitor (DMI), against Botrytis cinerea Pers. Chlorpromazine, a phenothiazine compound known as a calmodulin

  3. Perceived and Objective Measures of Neighborhood Walkability and Physical Activity among Adults in Japan: A Multilevel Analysis of a Nationally Representative Sample.

    Science.gov (United States)

    Hanibuchi, Tomoya; Nakaya, Tomoki; Yonejima, Mayuko; Honjo, Kaori

    2015-10-23

    Although associations between a person's neighborhood and their health have been studied internationally, most studies have been limited to a few cities or towns. Therefore, we used a nationally representative sample to explore whether perceived and objective neighborhood walkability was associated with the physical activity of residents. Data were analyzed from the Japanese General Social Surveys of 2010 (n = 2395; 1114 men and 1281 women). Perceived walkability was scored using factor analysis for the respondents' perceptions of neighborhood conditions, while objective walkability was measured using the geographic information system approach. Finally, multilevel logistic regression analysis was performed to examine whether neighborhood walkability was associated with the frequency of leisure-time physical activity (LTPA) among respondents. We found that perceived walkability was positively associated with the frequency of LTPA (odds ratio of the highest quartile was 1.53 (1.14-2.05) compared with the lowest quartile); however, objective walkability showed no association. When stratified by gender, an association between perceived walkability and LTPA was observed among women, but only a marginally significant association was present between objective walkability and LTPA among men. We conclude that the association between neighborhood walkability and LTPA can be partially generalized across Japan.

  4. Nodulation of legumes, nitrogenase activity of roots and occurrence of nitrogen-fixing Azospirillum spp. In representative soils of central Amazonia

    Energy Technology Data Exchange (ETDEWEB)

    Sylvester-Bradley, R; De Oliverira, L A; De Podesta Filho, J A; John, T V

    1980-12-01

    Leguminosae do not predominate in the Brazilian Amazon rain forest, although they are among the five best represented families. Plant roots from various soils were examined for the presence of nodules, acetylene-reducing activity and N/sub 2/-fixing Azospirillum spp. Abundant nodulation was found in black earth (''terra preta dos indios'') and in one case on sandy soil under campinarana vegetation along a tributary of the upper Rio Negro. In sandy latosol some nodules occurred in secondary forest and fewer in primary forest. Legumes in disturbed clayey or sandy latosol showed more frequent nodulation. Primary forest on alluvial (''varzea'') soil, and in Bahia coastal rain forest on sandy latosol and Erythrina glauca used for shading cacao plantations were abundantly nodulated. Acetylene reduction assays showed no, or very little, nitrogenase activity of roots from primary or secondary forest on clayey latosol near Manaus. Nodulated roots from secondary forest on sandy latosol showed acetylene-reducing activity. High rates of acetylene reduction were observed in nodulated roots of primary forest on alluvial ''varzea'' soil. Root samples showed ethylene absorption in controls without acetylene which might interfere with the results of acetylene reduction tests. The incidence of Azospirillum was also higher in black earth than the other soils examined, and in soils with higher pH. The hypothesis that Azospirillum is associated with Trema micantha roots was refuted. Roots and soils collected under cultivated grasses showed a higher incidence of Azospirillum when fertilized with phosphorus and lime. Results indicate that nitrogen fixation did occur in association with roots in some soils, but not with roots of primary or secondary forest on clayey latosol in the vicinity of Manaus, which is the most common soil in Central Amazonia. The possible reasons for this are discussed.

  5. TSA-induced DNMT1 down-regulation represses hTERT expression via recruiting CTCF into demethylated core promoter region of hTERT in HCT116.

    Science.gov (United States)

    Choi, Jee-Hye; Min, Na Young; Park, Jina; Kim, Jin Hong; Park, Soo Hyun; Ko, Young Jong; Kang, Yoonsung; Moon, Young Joon; Rhee, Sangmyung; Ham, Seung Wook; Park, Ae Ja; Lee, Kwang-Ho

    2010-01-01

    Trichostatin A (TSA), an inhibitor of histone deacetylase, is a well-known antitumor agent that effectively and selectively induces tumor growth arrest and apoptosis. Recently, it was reported that hTERT is one of the primary targets for TSA-induced apoptosis in cancer cells but the mechanism of which has not yet been elucidated. In the present study, to better understand the epigenetic regulation mechanism responsible for the repression of hTERT by TSA, we examined expression of hTERT in the HCT116 colon cancer cell line after treatment with TSA and performed site-specific CpG methylation analysis of the hTERT promoter. We found that TSA-induced the demethylation of site-specific CpGs on the promoter of hTERT, which was caused by down-regulation of DNA methyltransferase 1 (DNMT1). Among the demethylated region, the 31st-33rd CpGs contained a binding site for CTCF, an inhibitor of hTERT transcription. ChIP analysis revealed that TSA-induced demethylation of the 31st-33rd CpGs promoted CTCF binding on hTERT promoter, leading to repression of hTERT. Taken together, down-regulation of DNMT1 by TSA caused demethylation of a CTCF binding site on the hTERT promoter, the result of which was repression of hTERT via recruitment of CTCF to the promoter. Copyright 2009 Elsevier Inc. All rights reserved.

  6. Analysis of acylcarnitines as their N-demethylated ester derivatives by gas chromatography-chemical ionization mass spectrometry.

    Science.gov (United States)

    Huang, Z H; Gage, D A; Bieber, L L; Sweeley, C C

    1991-11-15

    A novel approach to the analysis of acylcarnitines has been developed. It involves a direct esterification using propyl chloroformate in aqueous propanol followed by ion-pair extraction with potassium iodide into chloroform and subsequent on-column N-demethylation of the resulting acylcarnitine propyl ester iodides. The products, acyl N-demethylcarnitine propyl esters, are volatile and are easily analyzed by gas chromatography-chemical ionization mass spectrometry. For medium-chain-length (C4-C12) acylcarnitine standards, detection limits are demonstrated to be well below 1 ng starting material using selected ion monitoring. Well-separated gas chromatographic peaks and structure-specific mass spectra are obtained with samples of synthetic and biological origin. Seven acylcarnitines have been characterized in the urine of a patient suffering from medium-chain acyl-CoA dehydrogenase deficiency.

  7. Nutrition and physical activity related school environment/policy factors and child obesity in China: a nationally representative study of 8573 students in 110 middle schools.

    Science.gov (United States)

    Li, M; Xue, H; Wen, M; Wang, W; Wang, Y

    2017-12-01

    Obesity is a serious threat to global health. School is a key setting for obesity intervention. Research on school risk factors for child obesity is limited in developing countries. To examine regional variations in obesity and school environments/policies and their associations among students in China. Analyses were based on the first nationally representative sample of 8573 9 th graders in 110 middle schools from 28 regions across China. Multilevel models tested associations between school factors and child self-reported weight outcomes and by school urbanicity setting (urban, rural). Overweight/obesity rate is higher among boys and in urban areas. Schools in rural areas, or less developed regions, promote longer on-campus life, as is indicated by the presence of school cafeterias, night study sessions and longer class hours. Multilevel models show that (i) school cafeterias (OR = 2.53, 95% CI = 1.35-4.75) and internet bars close to school (OR = 1.63, 95% CI = 1.15-2.30) are associated with increased overweight/obesity risk in rural areas, especially for boys; (ii) school night study sessions are associated with lower overweight/obesity risk (OR = 0.69, 95% CI = 0.50-0.96) in rural areas. China has large regional disparities in school environment/policies related to nutrition and physical activity. Some school factors are associated with students' weight status, which vary across gender and areas. Future school-based interventions should attend to diverse regional contexts. © 2016 World Obesity Federation.

  8. Representative of the municipality

    International Nuclear Information System (INIS)

    Castellnou Barcelo, J.

    2007-01-01

    Full text of publication follows. The decommissioning of the Vandellos-I nuclear power plant was a big challenge for the host community of Vandellos i l'Hospitalet de l'Infant and the close-by region. Closing down of the facility resulted in a rise of unemployment and a decrease of municipal income. The public was concerned with three issues: safety, transparency and information about the decommissioning, and economic future. Therefore, from the very beginning, municipal governments entered into negotiations with ENRESA on socio-economic benefits, including local employment in dismantling activities, and other types of financial and non-financial compensation. The ADE business association, i.e. a network of business organisations was created that guided the allotment of work to local firms. To satisfy public demand, local municipalities focused on the triad of safety, dialogue and local development, considered the three 'pillars of trust'. A Municipal Monitoring Commission was created, made up of representatives of affected municipalities, the regional government, the ADE business association, trade unions, the local university, the NPP management and ENRESA to monitor the dismantling process and regularly inform the local public. Items that were handled by this Commission included: - Work process monitoring. - Workers. - Materials Control. - Conventional and radioactive or contaminated waste management. - Emanation waste management (liquid and gas) - Safety (training and accidents). - Surveillance (radiological and environmental: dust, noise). - Effects. - Fulfillment of agreed conditions. A number of communication tools and channels were used, e.g., public information meetings, an information centre, the municipal magazine, the municipal radio station, and meetings with representatives of the local press. Particularly innovative was the idea to ask academics from the University of Tarragona to help with 'translating' technical information into language that could

  9. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample

    Directory of Open Access Journals (Sweden)

    Phuong Thi Vo

    2015-08-01

    Full Text Available Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957, the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions, Social Cognitive Theory (self-efficacy, outcome expectancies, and the Transtheoretical Model (behavioral processes of change, and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks – the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model – termed the Disposition-Belief-Motivation model – is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement.

  10. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample

    Science.gov (United States)

    Vo, Phuong T.; Bogg, Tim

    2015-01-01

    Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks – the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model – termed the Disposition-Belief-Motivation model– is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement. PMID:26300811

  11. Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample.

    Science.gov (United States)

    Vo, Phuong T; Bogg, Tim

    2015-01-01

    Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks - the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model - termed the Disposition-Belief-Motivation model- is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement.

  12. DNA methylation in porcine preimplantation embryos developed in vivo and produced by in vitro fertilization, parthenogenetic activation and somatic cell nuclear transfer

    DEFF Research Database (Denmark)

    Deshmukh, Rahul Shahaji; Østrup, Olga; Østrup, Esben

    2011-01-01

    DNA demethylation and remethylation are crucial for reprogramming of the differentiated parental/somatic genome in the recipient ooplasm upon somatic cell nuclear transfer. Here, we analyzed the DNA methylation dynamics during porcine preimplantation development. Porcine in vivo developed (IV......), in vitro fertilized (IVF), somatic cell nuclear transfer (SCNT) and parthenogenetically activated (PA) embryos were evaluated for DNA methylation quantification at different developmental stages. Fertilized (IV and IVF) one-cell stages lacked a substantial active demethylation of the paternal genome...

  13. DNA methylation in porcine preimplantation embryos developed in-vivo or produced by in-vitro fertilization, parthenogenetic activation and somatic cell nuclear transfer

    DEFF Research Database (Denmark)

    Deshmukh, Rahul Shahaji; Østrup, Olga; Østrup, Esben

    2011-01-01

    DNA demethylation and remethylation are crucial for reprogramming of the differentiated parental/somatic genome in the recipient ooplasm upon somatic cell nuclear transfer. Here, we analyzed the DNA methylation dynamics during porcine preimplantation development. Porcine in vivo developed (IV......), in vitro fertilized (IVF), somatic cell nuclear transfer (SCNT) and parthenogenetically activated (PA) embryos were evaluated for DNA methylation quantification at different developmental stages. Fertilized (IV and IVF) one-cell stages lacked a substantial active demethylation of the paternal genome...

  14. Resolution, configurational assignment, and enantiopharmacology at glutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA

    DEFF Research Database (Denmark)

    Johansen, T N; Stensbøl, T B; Nielsen, B

    2001-01-01

    We have previously described (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) as a potent agonist at the (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of (S)-glutamic acid (Glu) receptors. We now report the chromatographic resolution...... of ACPA and (RS)-2-amino-3-(3-carboxy-4-isoxazolyl)propionic acid (demethyl-ACPA) using a Sumichiral OA-5000 column. The configuration of the enantiomers of both compounds have been assigned based on X-ray crystallographic analyses, supported by circular dichroism spectra and elution orders on chiral HPLC...... columns. Furthermore, the enantiopharmacology of ACPA and demethyl-ACPA was investigated using radioligand binding and cortical wedge electrophysiological assay systems and cloned metabotropic Glu receptors. (S)-ACPA showed high affinity in AMPA binding (IC(50) = 0.025 microM), low affinity in kainic acid...

  15. Mercury methylation and demethylation by periphyton biofilms and their host in a fluvial wetland of the St. Lawrence River (QC, Canada)

    International Nuclear Information System (INIS)

    Hamelin, Stéphanie; Planas, Dolors; Amyot, Marc

    2015-01-01

    Wetlands in large rivers are important sites of production of the neurotoxin methylmercury (MeHg), and the periphyton growing on wetland macrophytes are increasingly recognized as key players in this production and transfer in food webs. Information is lacking about mercury methylation (K m ) and demethylation (K d ) rates in periphytic biofilms from the Northern Hemisphere, as well as about the drivers of net MeHg production, hampering ecosystem modeling of Hg cycling. Mercury methylation and demethylation rates were measured in periphytic biofilms growing on submerged plants in a shallow fluvial lake located in a temperate cold region (St. Lawrence River, Quebec, Canada). Incubations were performed in situ within macrophyte beds using low-level spikes of 199 HgO and Me 200 Hg stable isotopes as tracers. A direct relationship was observed between K m (0.002 to 0.137 d −1 ) and [MeHg] in periphyton. A similar relationship was found between K d (0.096 to 0.334 d −1 ) and [inorganic Hg]. Periphyton of Lake St. Pierre reached high levels of net MeHg production that were two orders of magnitude higher than those found in local sediment. This production varied through the plant growing season and was mainly driven by environmental variables such as depth of growth, available light, dissolved oxygen, temperature, plant community structure, and productivity of the habitat. - Highlights: • Periphyton Hg methylation and demethylation were studied in a large fluvial lake. • Addition of stable Hg isotopes was used to obtain in situ rates for these processes. • Net methylation was higher in periphyton than in local sediments. • Methylation and demethylation rates fluctuated during the summer. • Key drivers of rates were depth, light, temperature, and community structure

  16. Mercury methylation and demethylation by periphyton biofilms and their host in a fluvial wetland of the St. Lawrence River (QC, Canada)

    Energy Technology Data Exchange (ETDEWEB)

    Hamelin, Stéphanie; Planas, Dolors [GRIL, Département de sciences biologiques, Université du Québec à Montréal, C.P. 8888, Succursale Centre-Ville, Montreal, Quebec H3C 3P8 (Canada); Amyot, Marc [GRIL, Département de sciences biologiques, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Quebec H3C 3J7 (Canada)

    2015-04-15

    Wetlands in large rivers are important sites of production of the neurotoxin methylmercury (MeHg), and the periphyton growing on wetland macrophytes are increasingly recognized as key players in this production and transfer in food webs. Information is lacking about mercury methylation (K{sub m}) and demethylation (K{sub d}) rates in periphytic biofilms from the Northern Hemisphere, as well as about the drivers of net MeHg production, hampering ecosystem modeling of Hg cycling. Mercury methylation and demethylation rates were measured in periphytic biofilms growing on submerged plants in a shallow fluvial lake located in a temperate cold region (St. Lawrence River, Quebec, Canada). Incubations were performed in situ within macrophyte beds using low-level spikes of {sup 199}HgO and Me{sup 200}Hg stable isotopes as tracers. A direct relationship was observed between K{sub m} (0.002 to 0.137 d{sup −1}) and [MeHg] in periphyton. A similar relationship was found between K{sub d} (0.096 to 0.334 d{sup −1}) and [inorganic Hg]. Periphyton of Lake St. Pierre reached high levels of net MeHg production that were two orders of magnitude higher than those found in local sediment. This production varied through the plant growing season and was mainly driven by environmental variables such as depth of growth, available light, dissolved oxygen, temperature, plant community structure, and productivity of the habitat. - Highlights: • Periphyton Hg methylation and demethylation were studied in a large fluvial lake. • Addition of stable Hg isotopes was used to obtain in situ rates for these processes. • Net methylation was higher in periphyton than in local sediments. • Methylation and demethylation rates fluctuated during the summer. • Key drivers of rates were depth, light, temperature, and community structure.

  17. List of Accredited Representatives

    Data.gov (United States)

    Department of Veterans Affairs — VA accreditation is for the sole purpose of providing representation services to claimants before VA and does not imply that a representative is qualified to provide...

  18. Deferasirox and vitamin D improves overall survival in elderly patients with acute myeloid leukemia after demethylating agents failure.

    Directory of Open Access Journals (Sweden)

    Etienne Paubelle

    Full Text Available The prognosis of acute myeloid leukemia (AML in elderly (≥65 years patients is poor and treatment remains non-consensual especially for those who are not eligible for intensive therapies. Our group has shown that in vitro the iron chelator deferasirox (DFX synergizes with vitamin D (VD to promote monocyte differentiation in primary AML cells. Herein, we present results from a retrospective case-control study in which the association of DFX (1-2 g/d and 25-hydroxycholecalciferol (100,000 IU/week (DFX/VD was proposed to patients following demethylating agents failure. Median survival of patients treated with DFX/VD combination (n = 17 was significantly increased in comparison with matched patients receiving best supportive care (BSC alone (n = 13 (10.4 versus 4 months respectively. In addition, the only factor associated to an increased overall survival in DFX/VD-treated patients was serum VD levels. We conclude that DFX/VD treatment correlated with increased overall survival of AML patients in this retrospective cohort of elderly patients.

  19. Effects of emodin on the demethylation of tumor-suppressor genes in pancreatic cancer PANC-1 cells.

    Science.gov (United States)

    Zhang, Hao; Chen, Liang; Bu, He-Qi; Yu, Qing-Jiang; Jiang, Dan-Dan; Pan, Feng-Ping; Wang, Yu; Liu, Dian-Lei; Lin, Sheng-Zhang

    2015-06-01

    Emodin, a natural anthraquinone derivative isolated from Rheum palmatum, has been reported to inhibit the growth of pancreatic cancer cells through different modes of action; yet, the detailed mechanism remains unclear. In the present study, we hypothesized that emodin exerts its antitumor effect by participating in the regulation of the DNA methylation level. Our research showed that emodin inhibited the growth of pancreatic cancer PANC-1 cells in a dose- and time-dependent manner. Dot-blot results showed that 40 µM emodin significantly inhibited genomic 5 mC expression in the PANC-1 cells, and mRNA-Seq showed that different concentrations of emodin could alter the gene expression profile in the PANC-1 cells. BSP confirmed that the methylation levels of P16, RASSF1A and ppENK were decreased, while concomitantly the unmethylated status was increased. RT-PCR and western blotting results confirmed that the low expression or absence of expression of mRNA and protein in the PANC-1 cells was re-expressed following treatment with emodin. In conclusion, our study for the first time suggests that emodin inhibits pancreatic cancer cell growth, which may be related to the demethylation of tumor-suppressor genes. The related mechanism may be through the inhibition of methyltransferase expression.

  20. Demethylation of induced pluripotent stem cells from type 1 diabetic patients enhances differentiation into functional pancreatic β cells.

    Science.gov (United States)

    Manzar, Gohar S; Kim, Eun-Mi; Zavazava, Nicholas

    2017-08-25

    Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield. The cells responded to high-glucose stimulation by secreting insulin in vitro The shape, size, and number of their granules, as observed by transmission electron microscopy, were identical to those found in cadaveric β cells. When the IPCs were transplanted into immunodeficient mice that had developed streptozotocin-induced diabetes, they promoted a dramatic decrease in hyperglycemia, causing the mice to become normoglycemic within 28 days. None of the mice died or developed teratomas. Because the cells are derived from "self," immunosuppression is not required, providing a much safer and reliable treatment option for T1D patients. Moreover, these cells can be used for drug screening, thereby accelerating drug discovery. In conclusion, our approach eliminates the need for cadaveric pancreatic tissue.

  1. Quantification of citalopram or escitalopram and their demethylated metabolites in neonatal hair samples by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Frison, Giampietro; Favretto, Donata; Vogliardi, Susanna; Terranova, Claudio; Ferrara, Santo Davide

    2008-08-01

    Citalopram and escitalopram are highly selective serotonin reuptake inhibitors widely used in the treatment of depression. They exhibit adverse drug reactions and side effects, however, and the development of specific methods for their determination is of great interest in clinical and forensic toxicology. A liquid chromatography-tandem mass spectrometry method has been developed and validated for the assay of citalopram, escitalopram, and their demethylated metabolites in 10-mg hair samples. The analytes were extracted by incubation in methanol and liquid/liquid extraction with diethyl ether/dichloromethane. Gradient elution on a narrow bore C18 column was realized using clomipramine-d3 as an internal standard. Positive ion electrospray ionization and tandem mass spectrometry determination by collision-induced dissociation were performed in an ion trap mass spectrometer. The method exhibited a linear range of 25 to 2000 pg/mg, a quantification limit of 25 pg/mg for all analytes, relative standard deviations in the range of 12.10 to 9.80 (intraassay), and 13.80 to 11.78 (interassay), and accuracies (as percent recovery of the spiked standards) in the range of 90% to 110%; it was applied to the determination of citalopram and escitalopram and their metabolites in hair samples of two newborns to document their in utero exposure to the drugs. The method proved suitable for neonatal hair analysis of citalopram or escitalopram and was applied to two real cases of gestational exposure.

  2. Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.

    Science.gov (United States)

    Chen, Lili; Jiang, Bowen; Zhong, Chunge; Guo, Jun; Zhang, Lihao; Mu, Teng; Zhang, Qiuhua; Bi, Xiuli

    2018-03-08

    Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.

  3. Intramolecular Oxidative O-Demethylation of an Oxoferryl Porphyrin Complexed with a Per-O-methylated β-Cyclodextrin Dimer.

    Science.gov (United States)

    Kitagishi, Hiroaki; Kurosawa, Shun; Kano, Koji

    2016-11-22

    The intramolecular oxidation of ROCH 3 to ROCH 2 OH, where the latter compound spontaneously decomposed to ROH and HCHO, was observed during the reaction of the supramolecular complex (met-hemoCD3) with cumene hydroperoxide in aqueous solution. Met-hemoCD3 is composed of meso-tetrakis(4-sulfonatophenyl)porphinatoiron(III) (Fe III TPPS) and a per-O-methylated β-cyclodextrin dimer having an -OCH 2 PyCH 2 O- linker (Py=pyridine-3,5-diyl). The O=Fe IV TPPS complex was formed by the reaction of met-hemoCD3 with cumene hydroperoxide, and isolated by gel-filtration chromatography. Although the isolated O=Fe IV TPPS complex in the cyclodextrin cage was stable in aqueous solution at 25 °C, it was gradually converted to Fe II TPPS (t 1/2 =7.6 h). This conversion was accompanied by oxidative O-demethylation of an OCH 3 group in the cyclodextrin dimer. The results indicated that hydrogen abstraction by O=Fe IV TPPS from ROCH 3 yields HO-Fe III TPPS and ROCH 2 . . This was followed by radical coupling to afford Fe II TPPS and ROCH 2 OH. The hemiacetal (ROCH 2 OH) immediately decomposed to ROH and HCHO. This study revealed the ability of oxoferryl porphyrin to induce two-electron oxidation. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Are Immigrants More Physically Active Than Native-Born Australians and Does it Changes Over Time? Evidence From a Nationally Representative Longitudinal Survey.

    Science.gov (United States)

    Joshi, Suresh; Jatrana, Santosh; Paradies, Yin

    2017-02-01

    We investigated the differences and over time changes in recommended physical activity among foreign-born (FB) from English speaking countries (ESC) and non-English speaking countries (NESC) relative to native-born (NB) Australians, and whether the association between nativity and duration of residence (DoR) and physical activity is mediated by English language proficiency, socioeconomic status and social engagement/membership. This study applies multilevel group-meancentered mixed (hybrid) logistic regression models to 12 waves of longitudinal data (12,634 individuals) from the Household, Income and Labor Dynamics in Australia survey with engagement in physical activities for more than 3 times a week as the outcome variable. Immigrants from ESC had higher odds of physical activity, while immigrants from NESC had significantly lower odds of physical activity than NB Australians, after adjusting for covariates. There was no evidence that these differences changed by DoR among immigrants from NESC, whereas ESC immigrants had higher odds of physical activity when their DoR was more than 20 years. We also found a mediating role of English language proficiency on immigrants physical activities. Appropriate health promotion interventions should be implemented to foster physical activities among NESC immigrants, considering English language proficiency as an important factor in designing interventions.

  5. Representing vision and blindness.

    Science.gov (United States)

    Ray, Patrick L; Cox, Alexander P; Jensen, Mark; Allen, Travis; Duncan, William; Diehl, Alexander D

    2016-01-01

    There have been relatively few attempts to represent vision or blindness ontologically. This is unsurprising as the related phenomena of sight and blindness are difficult to represent ontologically for a variety of reasons. Blindness has escaped ontological capture at least in part because: blindness or the employment of the term 'blindness' seems to vary from context to context, blindness can present in a myriad of types and degrees, and there is no precedent for representing complex phenomena such as blindness. We explore current attempts to represent vision or blindness, and show how these attempts fail at representing subtypes of blindness (viz., color blindness, flash blindness, and inattentional blindness). We examine the results found through a review of current attempts and identify where they have failed. By analyzing our test cases of different types of blindness along with the strengths and weaknesses of previous attempts, we have identified the general features of blindness and vision. We propose an ontological solution to represent vision and blindness, which capitalizes on resources afforded to one who utilizes the Basic Formal Ontology as an upper-level ontology. The solution we propose here involves specifying the trigger conditions of a disposition as well as the processes that realize that disposition. Once these are specified we can characterize vision as a function that is realized by certain (in this case) biological processes under a range of triggering conditions. When the range of conditions under which the processes can be realized are reduced beyond a certain threshold, we are able to say that blindness is present. We characterize vision as a function that is realized as a seeing process and blindness as a reduction in the conditions under which the sight function is realized. This solution is desirable because it leverages current features of a major upper-level ontology, accurately captures the phenomenon of blindness, and can be

  6. Epigenetic Changes during Hepatic Stellate Cell Activation.

    Directory of Open Access Journals (Sweden)

    Silke Götze

    Full Text Available Hepatic stellate cells (HSC, which can participate in liver regeneration and fibrogenesis, have recently been identified as liver-resident mesenchymal stem cells. During their activation HSC adopt a myofibroblast-like phenotype accompanied by profound changes in the gene expression profile. DNA methylation changes at single genes have been reported during HSC activation and may participate in the regulation of this process, but comprehensive DNA methylation analyses are still missing. The aim of the present study was to elucidate the role of DNA methylation during in vitro activation of HSC.The analysis of DNA methylation changes by antibody-based assays revealed a strong decrease in the global DNA methylation level during culture-induced activation of HSC. To identify genes which may be regulated by DNA methylation, we performed a genome-wide Methyl-MiniSeq EpiQuest sequencing comparing quiescent and early culture-activated HSC. Approximately 400 differentially methylated regions with a methylation change of at least 20% were identified, showing either hypo- or hypermethylation during activation. Further analysis of selected genes for DNA methylation and expression were performed revealing a good correlation between DNA methylation changes and gene expression. Furthermore, global DNA demethylation during HSC activation was investigated by 5-bromo-2-deoxyuridine assay and L-mimosine treatment showing that demethylation was independent of DNA synthesis and thereby excluding a passive DNA demethylation mechanism.In summary, in vitro activation of HSC initiated strong DNA methylation changes, which were associated with gene regulation. These results indicate that epigenetic mechanisms are important for the control of early HSC activation. Furthermore, the data show that global DNA demethylation during activation is based on an active DNA demethylation mechanism.

  7. Determination of total and organic mercury and evaluation of methylation and demethylation processes in sediments of the Rio Grande Reservoir, State of Sao Paulo, Brazil

    International Nuclear Information System (INIS)

    Franklin, Robson Leocadio

    2010-01-01

    The Rio Grande reservoir is located in the metropolitan area of Sao Paulo and it is a very important water supply for this region. In the present study bottom waters and sediment samples collected in this reservoir, in four sampling points, in four campaigns, from September 2008 to January 2010, were analyzed. Firstly total Hg was determined in sediment and bottom waters by cold vapor atomic absorption technique (CV AAS). Following, the analytical methodology for organic Hg was adapted from literature, where the organomercurial compounds were extracted with dichloromethane in acid medium and subsequent destruction of organic compounds by bromine chloride. The validation of this methodology, in terms of precision and accuracy, was performed by means of IAEA 405 and BCR-CRM 580 reference materials analyses. For methylation and demethylation processes evaluation in this environment, the following physical and chemical parameters were assessed, in situ: pH, water temperature, redox potential (EH), transparency and depth. For the sediment samples, granulometry, total organic carbon, sulphate-reducing bacteria, total N and P, besides the metals Co, Cu, Fe and Mn were evaluated. The selection of these parameters was related to the factors that influence the behavior of MeHg in the sediments and its transition zone. Total Hg ranging from 1.0 to 71.0 mg kg'- 1 and organic mercury from -1 in sediments and methylation rates from 0.06 to 1.4% were found, along the reservoir. Different methylation conditions along the reservoir and its influences were also discussed. As supplementary study the concentration of some metals and trace elements in the sediments by neutron activation analysis technique was determined. As, Ba, Br, Co, Cr, Cs, Hf, Fe, Na, Rb, Sb, Sc and Zn and rare earth elements Ce, Eu, La, Lu, Nd, Sm and Yb were determined. The enrichment factor in relation to earth crust values using Sc as normalizer element reached values higher than 2.0 for the elements As, Br

  8. Highly invasive alien plant Reynoutria japonica Houtt. represents a novel source for pharmaceutical industry - evidence from phenolic profile and biological activity

    Directory of Open Access Journals (Sweden)

    Božin Biljana

    2017-01-01

    Full Text Available Reynoutria japonica is on the IUCN list of the Worlds’100 worst invasive species, but it is also, especially its rhizome, an integral part of traditional chinese medicine. The objective of this study was to determine the amount of selected phenolic compounds in rhizome, stems, leaves and inflorescence methanol extracts of this plant, their antioxidant and anticholinesterase activity. The chemical profile of the examined extracts was obtained by a high-performance liquid chromatography. In vitro assays on DPPH, OH and NO radicals were used to estimate antioxidant potential and Ellman’s method was applied for the determination of anticholinesterase activity. Leaves and rhizome extracts were found to be rich in rosmarinic and chlorogenic acid, and selected flavonoids. Resveratrol was exclusively present in rhizome and stems extracts. All the investigated extracts expressed certain antioxidant activity, where leaves extract was the most active. However, rhizome extract was the strongest inhibitor of acetylcholinesterase. These findings indicate that there is a possibility of R. japonica exploitation for the isolation of biologically active phenolic compounds used in pharmaceutical and food industry.

  9. Lactococcus lactis TrxD represents a subgroup of thioredoxins prevalent in Gram-positive bacteria containing WCXDC active site motifs

    DEFF Research Database (Denmark)

    Björnberg, Olof; Efler, Petr; Epie, Denis Ebong

    2014-01-01

    Three protein disulfide reductases of the thioredoxin superfamily from the industrially important Gram-positive Lactococcus lactis (LlTrxA, LlTrxD and LlNrdH) are compared to the "classical" thioredoxin from Escherichia coil (EcTrx1). LlTrxA resembles EcTrx1 with a WCGPC active site motif and other...... capacity to reduce insulin disulfides and their exposed active site thiol is alkylated at a similar rate at pH 7.0. LlTrxD on the other hand, is alkylated by iodoacetamide at almost 100 fold higher rate and shows no activity towards insulin disulfides. LlTrxA, LlTrxD and L1NrdH are all efficiently reduced...

  10. Shuttle Rocket Motor Program: NASA should delay awarding some construction contracts. Report to the Chair, Subcommittee on Government Activities and Transportation, Committee on Government Operations, House of Representatives

    Science.gov (United States)

    1992-01-01

    Even though the executive branch has proposed terminating the Advanced Solid Rocket Motor (ASRM) program, NASA is proceeding with all construction activity planned for FY 1992 to avoid schedule slippage if the program is reinstated by Congress. However, NASA could delay some construction activities for at least a few months without affecting the current launch data schedule. For example, NASA could delay Yellow Creek's motor storage and dock projects, Stennis' dock project, and Kennedy's rotation processing and surge facility and dock projects. Starting all construction activities as originally planned could result in unnecessarily incurring additional costs and termination liability if the funding for FY 1993 is not provided. If Congress decides to continue the program, construction could still be completed in time to avoid schedule slippage.

  11. One nuclear calcium transient induced by a single burst of action potentials represents the minimum signal strength in activity-dependent transcription in hippocampal neurons.

    Science.gov (United States)

    Yu, Yan; Oberlaender, Kristin; Bengtson, C Peter; Bading, Hilmar

    2017-07-01

    Neurons undergo dramatic changes in their gene expression profiles in response to synaptic stimulation. The coupling of neuronal excitation to gene transcription is well studied and is mediated by signaling pathways activated by cytoplasmic and nuclear calcium transients. Despite this, the minimum synaptic activity required to induce gene expression remains unknown. To address this, we used cultured hippocampal neurons and cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) that allows detection of nascent transcripts in the cell nucleus. We found that a single burst of action potentials, consisting of 24.4±5.1 action potentials during a 6.7±1.9s depolarization of 19.5±2.0mV causing a 9.3±0.9s somatic calcium transient, is sufficient to activate transcription of the immediate early gene arc (also known as Arg3.1). The total arc mRNA yield produced after a single burst-induced nuclear calcium transient was very small and, compared to unstimulated control neurons, did not lead to a significant increase in arc mRNA levels measured using quantitative reverse transcriptase PCR (qRT-PCR) of cell lysates. Significantly increased arc mRNA levels became detectable in hippocampal neurons that had undergone 5-8 consecutive burst-induced nuclear calcium transients at 0.05-0.15Hz. These results indicate that a single burst-induced nuclear calcium transient can activate gene expression and that transcription is rapidly shut off after synaptic stimulation has ceased. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A new mechanism for reduced sensitivity to demethylation-inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis.

    Science.gov (United States)

    Diaz-Trujillo, Caucasella; Chong, Pablo; Stergiopoulos, Ioannis; Cordovez, Viviane; Guzman, Mauricio; De Wit, Pierre J G M; Meijer, Harold J G; Scalliet, Gabriel; Sierotzki, Helge; Lilia Peralta, Esther; Arango Isaza, Rafael E; Kema, Gerrit H J

    2017-11-04

    The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications, with a major contribution from sterol demethylation-inhibitors (DMIs). The continued use of DMIs places considerable selection pressure on natural P. fijiensis populations, enabling the selection of novel genotypes with reduced sensitivity. The hitherto explanatory mechanism for this reduced sensitivity was the presence of non-synonymous point mutations in the target gene Pfcyp51, encoding the sterol 14α-demethylase enzyme. Here, we demonstrate a second mechanism involved in DMI sensitivity of P. fijiensis. We identified a 19-bp element in the wild-type (wt) Pfcyp51 promoter that concatenates in strains with reduced DMI sensitivity. A polymerase chain reaction (PCR) assay identified up to six Pfcyp51 promoter repeats in four field populations of P. fijiensis in Costa Rica. We used transformation experiments to swap the wt promoter of a sensitive field isolate with a promoter from a strain with reduced DMI sensitivity that comprised multiple insertions. Comparative in vivo phenotyping showed a functional and proportional up-regulation of Pfcyp51, which consequently decreased DMI sensitivity. Our data demonstrate that point mutations in the Pfcyp51 coding domain, as well as promoter inserts, contribute to the reduced DMI sensitivity of P. fijiensis. These results provide new insights into the importance of the appropriate use of DMIs and the need for the discovery of new molecules for black Sigatoka management. © 2017 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.

  13. Enantiomeric separation of some demethylated analogues of clofibric acid by capillary zone electrophoresis and nano-liquid chromatography.

    Science.gov (United States)

    Fantacuzzi, Marialuigia; Bettoni, Giancarlo; D'Orazio, Giovanni; Fanali, Salvatore

    2006-03-01

    The enantiomeric separation of some demethylated analogues of clofibric acid, namely 2-(6-chloro-benzothiazol-2-ylsulfanyl)-, 2-(6-methoxy-benzothiazol-2-ylsulfanyl)-, 2-(quinolin-2-yloxy)-, 2-(6-chloro-quinolin-2-yloxy)-, 2-(7-chloro-quinolin-4-yloxy)-propionic acid (compounds A-E, respectively), has been studied by CZE and nano-LC using for the first technique two beta-CD derivatives and vancomycin added to the BGE and vancomycin-modified silica particles for the second one, with the aim to find the optimum experimental conditions for the baseline resolution. The type and the concentration of the chiral selector added to the BGE, the buffer pH, the type of organic modifier and its concentration, the capillary temperature and the applied voltage played a very important role in the enantioresolution of the analysed compounds. The use of 6-monodeoxy-6-monoamino-beta-CD allowed to achieve baseline resolution of four of five clofibric acid derivatives in less than 10 min while heptakis-(2,3,6-tri-O-methyl)-beta-CD partially resolved the same compounds in their enantiomers. Employing vancomycin as the chiral selector in CZE, the counter-current partial filling method was chosen achieving baseline resolution of four analytes. All the studied compounds were enantioresolved employing a capillary column packed with vancomycin stationary phase by nano-LC, and the resolution was strongly influenced by the concentration of the organic modifier and by the pH of the mobile phase. The best results were achieved at pH 4.5 in presence of 60% of methanol (MeOH). However, longer analysis times were observed in the experiments carried out by nano-LC.

  14. Selective inhibition of the demethylation at C-14 in ergosterol biosynthesis by the fungicide, Denmert (S-1358)

    International Nuclear Information System (INIS)

    Kato, Toshiro; Kawase, Yasuo

    1976-01-01

    A direct evidence of the inhibitory effect in a cell-free system of S. cerevisiae was experimentally studied, and the site of action of Denmert (S-n-butyl S'-p-tert-butylbenzyl N-3-pyridyldithiocarbon-imidate) in sterol biosynthesis was examined. 14 C-labeled lanosterol and 14-desmethyl-lanosterol were biosynthetically prepared. DL-mevalonate-2- 14 C was incubated with yeast cell-free homogenates for 3 hr at 28 deg C while being shaked vigorously in atmospheric oxygen. The resultant 14 C-labeled sterol was extracted and chromatographed on a silicic acid-Hyflo Super Cel column. 4,4-dimethyl sterol thus obtained was acetylated with acetic anhydride and pyridine. The separation of lanosteryl acetate and 14-desmethyl lanosteryl acetate was accomplished on alumina thin-layer plates. After the saponification of each steryl acetate, the quantity of the sterol was assessed by gas chromatography with cholesterol as an internal standard. The incubation of the 14 C-labeled sterol was achieved under the same conditions as those for the DL-mevalonate-2- 14 C except the addition of the substrate which was dispersed in 0.1M phosphate buffer. Denmert inhibited the conversion of 14 C-labeled lanosterol to 4-desmethyl sterol, while the conversion of 14 C-labeled 14-desmethyl lanosterol to 4-desmethyl sterol was hardly affected by the fungicide. Therefore, Denmert is a potent selective inhibitor of the demethylation at the C-14 position in ergosterol biosynthesis. The fungicide, triarimol, exhibited the same effect on sterol biosynthesis as that of Denmert. (Iwakiri, K.)

  15. Representing Color Ensembles.

    Science.gov (United States)

    Chetverikov, Andrey; Campana, Gianluca; Kristjánsson, Árni

    2017-10-01

    Colors are rarely uniform, yet little is known about how people represent color distributions. We introduce a new method for studying color ensembles based on intertrial learning in visual search. Participants looked for an oddly colored diamond among diamonds with colors taken from either uniform or Gaussian color distributions. On test trials, the targets had various distances in feature space from the mean of the preceding distractor color distribution. Targets on test trials therefore served as probes into probabilistic representations of distractor colors. Test-trial response times revealed a striking similarity between the physical distribution of colors and their internal representations. The results demonstrate that the visual system represents color ensembles in a more detailed way than previously thought, coding not only mean and variance but, most surprisingly, the actual shape (uniform or Gaussian) of the distribution of colors in the environment.

  16. Using Graph Components Derived from an Associative Concept Dictionary to Predict fMRI Neural Activation Patterns that Represent the Meaning of Nouns.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Akama

    Full Text Available In this study, we introduce an original distance definition for graphs, called the Markov-inverse-F measure (MiF. This measure enables the integration of classical graph theory indices with new knowledge pertaining to structural feature extraction from semantic networks. MiF improves the conventional Jaccard and/or Simpson indices, and reconciles both the geodesic information (random walk and co-occurrence adjustment (degree balance and distribution. We measure the effectiveness of graph-based coefficients through the application of linguistic graph information for a neural activity recorded during conceptual processing in the human brain. Specifically, the MiF distance is computed between each of the nouns used in a previous neural experiment and each of the in-between words in a subgraph derived from the Edinburgh Word Association Thesaurus of English. From the MiF-based information matrix, a machine learning model can accurately obtain a scalar parameter that specifies the degree to which each voxel in (the MRI image of the brain is activated by each word or each principal component of the intermediate semantic features. Furthermore, correlating the voxel information with the MiF-based principal components, a new computational neurolinguistics model with a network connectivity paradigm is created. This allows two dimensions of context space to be incorporated with both semantic and neural distributional representations.

  17. OSMOSE experiment representativity studies.

    Energy Technology Data Exchange (ETDEWEB)

    Aliberti, G.; Klann, R.; Nuclear Engineering Division

    2007-10-10

    The OSMOSE program aims at improving the neutronic predictions of advanced nuclear fuels through measurements in the MINERVE facility at the CEA-Cadarache (France) on samples containing the following separated actinides: Th-232, U-233, U-234, U-235, U-236, U-238, Np-237, Pu-238, Pu-239, Pu-240, Pu-241, Pu-242, Am-241, Am-243, Cm-244 and Cm-245. The goal of the experimental measurements is to produce a database of reactivity-worth measurements in different neutron spectra for the separated heavy nuclides. This database can then be used as a benchmark for integral reactivity-worth measurements to verify and validate reactor analysis codes and integral cross-section values for the isotopes tested. In particular, the OSMOSE experimental program will produce very accurate sample reactivity-worth measurements for a series of actinides in various spectra, from very thermalized to very fast. The objective of the analytical program is to make use of the experimental data to establish deficiencies in the basic nuclear data libraries, identify their origins, and provide guidelines for nuclear data improvements in coordination with international programs. To achieve the proposed goals, seven different neutron spectra can be created in the MINERVE facility: UO2 dissolved in water (representative of over-moderated LWR systems), UO2 matrix in water (representative of LWRs), a mixed oxide fuel matrix, two thermal spectra containing large epithermal components (representative of under-moderated reactors), a moderated fast spectrum (representative of fast reactors which have some slowing down in moderators such as lead-bismuth or sodium), and a very hard spectrum (representative of fast reactors with little moderation from reactor coolant). The different spectra are achieved by changing the experimental lattice within the MINERVE reactor. The experimental lattice is the replaceable central part of MINERVE, which establishes the spectrum at the sample location. This configuration

  18. Representing distance, consuming distance

    DEFF Research Database (Denmark)

    Larsen, Gunvor Riber

    Title: Representing Distance, Consuming Distance Abstract: Distance is a condition for corporeal and virtual mobilities, for desired and actual travel, but yet it has received relatively little attention as a theoretical entity in its own right. Understandings of and assumptions about distance...... are being consumed in the contemporary society, in the same way as places, media, cultures and status are being consumed (Urry 1995, Featherstone 2007). An exploration of distance and its representations through contemporary consumption theory could expose what role distance plays in forming...

  19. Comparison of the EPIC Physical Activity Questionnaire with Combined Heart Rate and Movement Sensing in a Nationally Representative Sample of Older British Adults

    Science.gov (United States)

    España-Romero, Vanesa; Golubic, Rajna; Martin, Kathryn R.; Hardy, Rebecca; Ekelund, Ulf; Kuh, Diana; Wareham, Nicholas J.; Cooper, Rachel; Brage, Soren

    2014-01-01

    Objectives To compare physical activity (PA) subcomponents from EPIC Physical Activity Questionnaire (EPAQ2) and combined heart rate and movement sensing in older adults. Methods Participants aged 60–64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life) during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE), sedentary behaviour, light (LPA) and moderate-to-vigorous PA (MVPA) were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women). Results EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement) in men and women were 32.3 (−61.5 to 122.6) and 29.0 (−39.2 to 94.6) kJ/kg/day for PAEE; −4.6 (−10.6 to 1.3) and −6.0 (−10.9 to −1.0) h/day for sedentary time; −171.8 (−454.5 to 110.8) and −60.4 (−367.5 to 246.6) min/day for LPA; 91.1 (−159.5 to 341.8) and 55.4 (−117.2 to 228.0) min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho  = 0.12 to 0.36); the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women) and PAEE (rho = 0.26 men; rho = 0.25 women). Conclusion EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population. PMID:24516543

  20. Comparison of the EPIC Physical Activity Questionnaire with combined heart rate and movement sensing in a nationally representative sample of older British adults.

    Directory of Open Access Journals (Sweden)

    Vanesa España-Romero

    Full Text Available To compare physical activity (PA subcomponents from EPIC Physical Activity Questionnaire (EPAQ2 and combined heart rate and movement sensing in older adults.Participants aged 60-64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE, sedentary behaviour, light (LPA and moderate-to-vigorous PA (MVPA were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women.EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement in men and women were 32.3 (-61.5 to 122.6 and 29.0 (-39.2 to 94.6 kJ/kg/day for PAEE; -4.6 (-10.6 to 1.3 and -6.0 (-10.9 to -1.0 h/day for sedentary time; -171.8 (-454.5 to 110.8 and -60.4 (-367.5 to 246.6 min/day for LPA; 91.1 (-159.5 to 341.8 and 55.4 (-117.2 to 228.0 min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho= 0.12 to 0.36; the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women and PAEE (rho = 0.26 men; rho = 0.25 women.EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population.

  1. Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

    Directory of Open Access Journals (Sweden)

    Isabelle Benz-de Bretagne

    2011-01-01

    Full Text Available MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III. Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (=.04 than those carrying the C allele. This higher UCP I/(I + III ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient.

  2. Representing AIDS in Comics.

    Science.gov (United States)

    Czerwiec, M K

    2018-02-01

    Matthew P. McAllister wrote: "Comic books can and have contributed positively to the discourse about AIDS: images that encourage true education, understanding and compassion can help cope with a biomedical condition which has more than a biomedical relevance" [1]. With this in mind, I combined a 23-narrator oral history and my personal memoir about an inpatient Chicago AIDS hospital unit in my book, Taking Turns: Stories from HIV/AIDS Care Unit 371. In doing so, I built upon the existing rich history of HIV/AIDS in comics, which this article will briefly describe. Although not a comprehensive review of the intersection of AIDS and comics, the book is a tour through influences that proved useful to me. In addition, in making my book, I faced a distinct ethical issue with regard to representing patient experiences with HIV/AIDS, and I describe here how I addressed it. © 2018 American Medical Association. All Rights Reserved.

  3. Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes

    Czech Academy of Sciences Publication Activity Database

    Vlková, Veronika; Štěpánek, Ivan; Hrušková, Veronika; Šenigl, Filip; Mayerová, Veronika; Šrámek, Martin; Šímová, Jana; Bieblová, Jana; Indrová, Marie; Hejhal, Tomáš; Dérian, N.; Klatzmann, D.; Six, A.; Reiniš, Milan

    2014-01-01

    Roč. 5, č. 16 (2014), s. 6923-35 ISSN 1949-2553 R&D Projects: GA ČR GAP301/10/2174; GA MZd NT14461 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:French state funds within the Investissements d’Avenir program(FR) ANR-11-IDEX-0004-02 Institutional support: RVO:68378050 Keywords : IFNγ signalling pathway * DNA demethylation * tumour Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.359, year: 2014

  4. A Simple, Rapid and Mild One Pot Synthesis of Benzene Ring Acylated and Demethylated Analogues of Harmine under Solvent-free Conditions

    Directory of Open Access Journals (Sweden)

    Bina S. Siddiqui

    2008-08-01

    Full Text Available A simple, rapid, solvent-free, room temperature one pot synthesis of benzene ring acylated and demethylated analogues of harmine using acyl halides/acid anhydrides and AlCl3 has been developed. Eight different acyl halides/acid anhydrides were used in the synthesis. The resulting mixture of products was separated by column chromatography to afford 10- and 12-monoacyl analogues, along with 10,12-diacyl-11-hydroxy products. In five cases the corresponding 10-acyl-11-hydroxy analogues were also obtained. Yields from the eight syntheses (29 products in total were in the 6-34% range and all compounds were fully characterized.

  5. Potential Mechanism of Action of 3′-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Juan Manuel J. Favela-Hernández

    2015-07-01

    Full Text Available Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3′-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3′-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR. The genetic profile expression results showed that lignan 3′-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

  6. Potential Mechanism of Action of 3'-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus.

    Science.gov (United States)

    Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María del Rayo

    2015-07-08

    Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

  7. Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma.

    Science.gov (United States)

    Altman, Matthew C; Whalen, Elizabeth; Togias, Alkis; O'Connor, George T; Bacharier, Leonard B; Bloomberg, Gordon R; Kattan, Meyer; Wood, Robert A; Presnell, Scott; LeBeau, Petra; Jaffee, Katy; Visness, Cynthia M; Busse, William W; Gern, James E

    2018-03-05

    Childhood asthma in inner-city populations is a major public health burden, and understanding early-life immune mechanisms that promote asthma onset is key to disease prevention. Children with asthma demonstrate a high prevalence of aeroallergen sensitization and T H 2-type inflammation; however, the early-life immune events that lead to T H 2 skewing and disease development are unknown. We sought to use RNA sequencing of PBMCs collected at age 2 years to determine networks of immune responses that occur in children with allergy and asthma. In an inner-city birth cohort with high asthma risk, we compared gene expression using RNA sequencing in PBMCs collected at age 2 years between children with 2 or more aeroallergen sensitizations, including dust mite, cockroach, or both, by age 3 years and asthma by age 7 years (cases) and matched control subjects who did not have any aeroallergen sensitization or asthma by age 7 years. PBMCs from the cases showed higher levels of expression of natural killer (NK) cell-related genes. After cockroach or dust mite allergen but not tetanus antigen stimulation, PBMCs from the cases compared with the control subjects showed differential expression of 244 genes. This gene set included upregulation of a densely interconnected NK cell-like gene network reflecting a pattern of cell activation and induction of inflammatory signaling molecules, including the key T H 2-type cytokines IL9, IL13, and CCL17, as well as a dendritic cell-like gene network, including upregulation of CD1 lipid antigen presentation molecules. The NK cell-like response was reproducible in an independent group of children with later-onset allergic sensitization and asthma and was found to be specific to only those children with both aeroallergen sensitization and asthma. These findings provide important mechanistic insight into an early-life immune pathway involved in T H 2 polarization, leading to the development of allergic asthma. Copyright © 2018 American

  8. Hypomethylation of the Treg-Specific Demethylated Region in FOXP3 Is a Hallmark of the Regulatory T-cell Subtype in Adult T-cell Leukemia.

    Science.gov (United States)

    Shimazu, Yayoi; Shimazu, Yutaka; Hishizawa, Masakatsu; Hamaguchi, Masahide; Nagai, Yuya; Sugino, Noriko; Fujii, Sumie; Kawahara, Masahiro; Kadowaki, Norimitsu; Nishikawa, Hiroyoshi; Sakaguchi, Shimon; Takaori-Kondo, Akifumi

    2016-02-01

    Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1. Because of its immunosuppressive property and resistance to treatment, patients with ATL have poor prognoses. ATL cells possess the regulatory T cell (Treg) phenotype, such as CD4 and CD25, and usually express forkhead box P3 (FOXP3). However, the mechanisms of FOXP3 expression and its association with Treg-like characteristics in ATL remain unclear. Selective demethylation of the Treg-specific demethylated region (TSDR) in the FOXP3 gene leads to stable FOXP3 expression and defines natural Tregs. Here, we focus on the functional and clinical relationship between the epigenetic pattern of the TSDR and ATL. Analysis of DNA methylation in specimens from 26 patients with ATL showed that 15 patients (58%) hypomethylated the TSDR. The FOXP3(+) cells were mainly observed in the TSDR-hypomethylated cases. The TSDR-hypomethylated ATL cells exerted more suppressive function than the TSDR-methylated ATL cells. Thus, the epigenetic analysis of the FOXP3 gene identified a distinct subtype with Treg properties in heterogeneous ATL. Furthermore, we observed that the hypomethylation of TSDR was associated with poor outcomes in ATL. These results suggest that the DNA methylation status of the TSDR is an important hallmark to define this heterogeneous disease and to predict ATL patient prognosis. ©2015 American Association for Cancer Research.

  9. Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein (VCP).

    Science.gov (United States)

    Long, Xin Hua; Zhou, Yun Fei; Peng, Ai Fen; Zhang, Zhi Hong; Chen, Xuan Yin; Chen, Wen Zhao; Liu, Jia Ming; Huang, Shan Hu; Liu, Zhi Li

    2015-05-01

    Previous studies demonstrated that increased Homo sapiens valosin-containing protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the underlying mechanism of VCP over-expression in OS remains unknown. In the present study, we found a significantly negative correlation between miR-129-5p and VCP protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = -0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p. In addition, three CPG islands in the region of miR-129-5p promoter were detected by bioinformatical prediction, and significantly higher expression of miR-129-5p and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2'-deoxycytidine (a potent DNA demethylating agent) than in those untreated cells were observed. Furthermore, lower migratory and invasive ability was found in cells with elevated miR-129-5p than in those with decreased miR-129-5p. These findings indicated that increased miR-129-5p may be mediated by demethylation and inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS management, although further studies will be necessary.

  10. Representative of the Media

    International Nuclear Information System (INIS)

    Domenech, F.

    2007-01-01

    Francesc Domenech recalled that the Vandellos-I accident created a very difficult situation for the nuclear industry. During the crisis the nuclear sector decided not to participate in any media activities. Finally, the industry realised that not being open only exacerbated the credibility crisis. The closure of the Vandellos -I power plant decreased the stress and offered an opportunity for the nuclear sector to change its attitude and public relations. In Mr. Domenech's view the Vandellos-I decommissioning project is a technical challenge undertaken by society. ENRESA made great efforts to rebuild mutual trust between the nuclear industry and the media. For the first time, journalists were provided with fluid data, some of them very complex, which the media had to render more understandable for the public. Finally, Mr. Domenech observed that nowadays it is the regulator which most needs to gain credibility. (author)

  11. Screening and identification of metabolites of two kinds of main active ingredients and hepatotoxic pyrrolizidine alkaloids in rat after lavage Farfarae Flos extract by UHPLC-Q-TOF-MS mass spectrometry.

    Science.gov (United States)

    Cheng, Xiaoye; Liao, Man; Diao, Xinpeng; Sun, Yupeng; Zhang, Lantong

    2018-02-01

    Farfarae Flos, the dried flower buds of Tussilago farfara L., is usually used to treat coughs, bronchitic and asthmatic conditions as an important traditional Chinese medicine. Tussilagone and methl butyric acid tussilagin ester are seen as representatives of two kinds of active substances. In addition, the pyrrolizidine alkaloids, mainly senkirkine and senecionine, present in the herb can be hepatoxic. In this study, a rapid and sensitive ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry method was successfully applied to identify the metabolites of tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine. A total of 35, 37, 18 and nine metabolites of tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine in rats were tentatively identified. Hydrolysis, oxidation, reduction and demethylation were the major metabolic reactions for tussilagone and methl butyric acid tussilagin ester. The main biotransformation routes of senkirkine and senecionine were identified as demethylation, N-methylation, oxidation and reduction. This study is the first reported analysis and characterization of the metabolites and the proposed metabolic pathways might provide further understanding of the metabolic fate of the chemical constituents after oral administration of Farfarae Flos extract in vivo. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Tet1 Oxidase Regulates Neuronal Gene Transcription, Active DNA Hydroxy-methylation, Object Location Memory, and Threat Recognition Memory.

    Science.gov (United States)

    Kumar, Dinesh; Aggarwal, Milan; Kaas, Garrett A; Lewis, John; Wang, Jing; Ross, Daniel L; Zhong, Chun; Kennedy, Andrew; Song, Hongjun; Sweatt, J David

    2015-10-01

    A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this equilibrium remain elusive. Tet1 oxidase has been shown to play a key role in the active DNA demethylation in the CNS. In this study, we used Tet1 gene knockout (Tet1KO) mice to examine the involvement of Tet1 in memory consolidation and storage in the adult brain. We found that Tet1 ablation leads to: altered expression of numerous neuronal activity-regulated genes, compensatory upregulation of active demethylation pathway genes, and upregulation of various epigenetic modifiers. Moreover, Tet1KO mice showed an enhancement in the consolidation and storage of threat recognition (cued and contextual fear conditioning) and object location memories. We conclude that Tet1 plays a critical role in regulating neuronal transcription and in maintaining the epigenetic state of the brain associated with memory consolidation and storage.

  13. Tet1 oxidase regulates neuronal gene transcription, active DNA hydroxymethylation, object location memory, and threat recognition memory

    Directory of Open Access Journals (Sweden)

    Dinesh Kumar

    2015-10-01

    Full Text Available A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this equilibrium remain elusive. Tet1 oxidase has been shown to play a key role in the active DNA demethylation in the central nervous system. In this study, we used Tet1 gene knockout (Tet1KO mice to examine the involvement of Tet1 in memory consolidation and storage in the adult brain. We found that Tet1 ablation leads to altered expression of numerous neuronal activity-regulated genes, compensatory upregulation of active demethylation pathway genes, and upregulation of various epigenetic modifiers. Moreover, Tet1KO mice showed an enhancement in the consolidation and storage of threat recognition (cued and contextual fear conditioning and object location memories. We conclude that Tet1 plays a critical role in regulating neuronal transcription and in maintaining the epigenetic state of the brain associated with memory consolidation and storage.

  14. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    International Nuclear Information System (INIS)

    Mossman, David; Kim, Kyu-Tae; Scott, Rodney J

    2010-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

  15. Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

    Science.gov (United States)

    Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

    2016-07-01

    Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Carbon-cycle effects of differences in soil moisture and soil extracellular enzyme activity at sites representing different land-use histories in high-elevation Ecuadorian páramo landscapes

    Science.gov (United States)

    McKnight, J.; Harden, C. P.; Schaeffer, S. M.

    2016-12-01

    Ecuadorian páramo grasslands are important regional soil carbon sinks. In the páramo of the Mazar Wildlife Reserve, differences in soil carbon content among different types of land use may reflect changes in soil carbon-acquisition related microbial enzyme activity after land cover and soil moisture are altered; however, this hypothesis has not been tested explicitly for Ecuadorian páramos. This study used a fluorescence enzyme assay to assess the activities of four different extracellular enzymes representing carbon acquisition: α-glucosidase, β-glucosidase, β-D-cellulobiohydrolase, and β-xylosidase in Andean páramo soils. Acquisition activities were also measured for nitrogen (N-acetyl-β-glucosidase and leucine aminopeptidase) and phosphorus (phosphatase) to assess stoichiometric differences between land-uses, which can affect soil microbial activity related to carbon acquisition. Soils were analyzed from four land uses: native forest, grass páramo, recently burned grass páramo, and non-native pine plantation. Carbon acquisition activity was highest at the pine site (678 nmol h-1 g-1) and lowest at the recently burned páramo site (252 nmol h-1 g-1), indicating the lowest and highest available soil carbon, respectively. Carbon-acquisition EE activity was significantly higher at the grass páramo site (595 nmol h-1 g-1) than at the recently burned páramo and native forest sites. At the grass páramo site, a history of burning as a management strategy and high carbon-acquisition EE activity could indicate the presence of pyrogenic soil organic matter, which is more resistant to microbial decomposition. Soils at the native forest and both grassland sites were phosphorus limited, and soil at the pine site had higher nitrogen-acquisition activity, indicative of a shift to nitrogen-limited soil stoichiometric conditions. To our knowledge these are the first data reported for soil extracellular enzyme activities for Ecuadorian páramos.

  17. Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation

    International Nuclear Information System (INIS)

    Miller, Mitchell D.; Aravind, L.; Bakolitsa, Constantina; Rife, Christopher L.; Carlton, Dennis; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structure of the first representative of DUF364 family reveals a combination of enolase N-terminal-like and C-terminal Rossmann-like folds. Analysis of the interdomain cleft combined with sequence and genome context conservation among homologs, suggests a unique catalytic site likely involved in the synthesis of a flavin or pterin derivative. The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

  18. Potential Mechanism of Action of 3′-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus

    OpenAIRE

    Favela-Hernández, Juan; Clemente-Soto, Aldo; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María

    2015-01-01

    Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3′-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from L...

  19. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition

    Science.gov (United States)

    Rodríguez-Cortez, Virginia C.; del Pino-Molina, Lucia; Rodríguez-Ubreva, Javier; Ciudad, Laura; Gómez-Cabrero, David; Company, Carlos; Urquiza, José M.; Tegnér, Jesper; Rodríguez-Gallego, Carlos; López-Granados, Eduardo; Ballestar, Esteban

    2015-01-01

    Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals. PMID:26081581

  20. Identification of three new phase II metabolites of a designer drug methylone formed in rats by N-demethylation followed by conjugation with dicarboxylic acids.

    Science.gov (United States)

    Židková, Monika; Linhart, Igor; Balíková, Marie; Himl, Michal; Dvořáčková, Veronika; Lhotková, Eva; Páleníček, Tomáš

    2018-06-01

    1. Methylone (3,4-methylenedioxy-N-methylcathinone, MDMC), which appeared on the illicit drug market in 2004, is a frequently abused synthetic cathinone derivative. Known metabolic pathways of MDMC include N-demethylation to normethylone (3,4-methylenedioxycathinone, MDC), aliphatic chain hydroxylation and oxidative demethylenation followed by monomethylation and conjugation with glucuronic acid and/or sulphate. 2. Three new phase II metabolites, amidic conjugates of MDC with succinic, glutaric and adipic acid, were identified in the urine of rats dosed subcutaneously with MDMC.HCl (20 mg/kg body weight) by LC-ESI-HRMS using synthetic reference standards to support identification. 3. The main portion of administered MDMC was excreted unchanged. Normethylone, was a major urinary metabolite, of which a minor part was conjugated with dicarboxylic acids. 4. Previously identified ring-opened metabolites 4-hydroxy-3-methoxymethcathinone (4-OH-3-MeO-MC), 3-hydroxy-4-methoxymeth-cathinone (3-OH-4-MeO-MC) and 3,4-dihydroxymethcathinone (3,4-di-OH-MC) mostly in conjugated form with glucuronic and/or sulphuric acids were also detected. 5. Also, ring-opened metabolites derived from MDC, namely, 4-hydroxy-3-methoxycathinone (4-OH-3-MeO-C), 3-hydroxy-4-methoxycathinone (3-OH-4-MeO-C) and 3,4-dihydroxycathinone (3,4-di-OH-C) were identified for the first time in vivo.

  1. Abundance, genetic diversity and sensitivity to demethylation inhibitor fungicides of Aspergillus fumigatus isolates from organic substrates with special emphasis on compost.

    Science.gov (United States)

    Santoro, Karin; Matić, Slavica; Gisi, Ulrich; Spadaro, Davide; Pugliese, Massimo; Gullino, Maria L

    2017-12-01

    Aspergillus fumigatus is a widespread fungus that colonizes dead organic substrates but it can also cause fatal human diseases. Aspergilloses are treated with demethylation inhibitor (DMI) fungicides; however, resistant isolates appeared recently in the medical and also environmental area. The present study aims at molecular characterizing and quantifying A. fumigatus in major environmental habitats and determining its sensitivity to medical and agricultural DMI fungicides. A. fumigatus was isolated only rarely from soil and meadow/forest organic matter but high concentrations (10 3 to 10 7  cfu/g) were detected in substrates subjected to elevated temperatures, such as compost and silage. High genetic diversity of A. fumigatus from compost was found based on SSR markers, distinguishing among fungal isolates even when coming from the same substrate sample, while subclustering was observed based on mutations in cyp51A gene. Several cyp51A amino acid substitutions were found in 15 isolates, although all isolates were fully sensitive to the tested DMI fungicides, with exception of one isolate in combination with one fungicide. This study suggests that the tested A. fumigatus isolates collected in Italy, Spain and Hungary from the fungus' major living habitats (compost) and commercial growing substrates are not potential carriers for DMI resistance in the environment. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. Representative process sampling - in practice

    DEFF Research Database (Denmark)

    Esbensen, Kim; Friis-Pedersen, Hans Henrik; Julius, Lars Petersen

    2007-01-01

    Didactic data sets representing a range of real-world processes are used to illustrate "how to do" representative process sampling and process characterisation. The selected process data lead to diverse variogram expressions with different systematics (no range vs. important ranges; trends and....../or periodicity; different nugget effects and process variations ranging from less than one lag to full variogram lag). Variogram data analysis leads to a fundamental decomposition into 0-D sampling vs. 1-D process variances, based on the three principal variogram parameters: range, sill and nugget effect...

  3. Marc Treib: Representing Landscape Architecture

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2008-01-01

    The editor of Representing Landscape Architecture, Marc Treib, argues that there is good reason to evaluate the standard practices of representation that landscape architects have been using for so long. In the rush to the promised land of computer design these practices are now in danger of being...

  4. Does representative wind information exist?

    NARCIS (Netherlands)

    Wieringa, J.

    1996-01-01

    Representativity requirements are discussed for various wind data users. It is shown that most applications can be dealt with by using data from wind stations when these are made to conform with WMO specifications. Methods to achieve this WMO normalization are reviewed, giving minimum specifications

  5. OAS :: Member States : Permanent Representatives

    Science.gov (United States)

    Rights Actions against Corruption C Children Civil Registry Civil Society Contact Us Culture Cyber Barbados Belize Bolivia Brazil Canada Chile Colombia Costa Rica Cuba 1 Dominica (Commonwealth of) Dominican Gutierez Ambassador, Permanent Representative of Belize Diego Pary Rodríguez Bolivia Diego Pary Rodríguez

  6. Judgments of and by Representativeness

    Science.gov (United States)

    1981-05-15

    p. 4i). This hy- pothesis was studied in several contexts, including intuitive statisti- cal judgments and the prediction of professional choice (Kahneman... professional choice . Here, X is representative of M either because it is frequently associated with M (e.g., high fever commonly accompanies pneumonia

  7. WIPP facility representative program plan

    International Nuclear Information System (INIS)

    1994-01-01

    This plan describes the Department of Energy (DOE), Carlsbad Area Office (CAO) facility representative (FR) program at the Waste Isolation Pilot Plant (WIPP). It provides the following information: (1) FR and support organization authorities and responsibilities; (2) FR program requirements; and (3) FR training and qualification requirements

  8. Yucca Mountain Climate Technical Support Representative

    International Nuclear Information System (INIS)

    Sharpe, Saxon E

    2007-01-01

    The primary objective of Project Activity ORD-FY04-012, 'Yucca Mountain Climate Technical Support Representative', was to provide the Office of Civilian Radioactive Waste Management (OCRWM) with expertise on past, present, and future climate scenarios and to support the technical elements of the Yucca Mountain Project (YMP) climate program. The Climate Technical Support Representative was to explain, defend, and interpret the YMP climate program to the various audiences during Site Recommendation and License Application. This technical support representative was to support DOE management in the preparation and review of documents, and to participate in comment response for the Final Environmental Impact Statement, the Site Recommendation Hearings, the NRC Sufficiency Comments, and other forums as designated by DOE management. Because the activity was terminated 12 months early and experience a 27% reduction in budget, it was not possible to complete all components of the tasks as originally envisioned. Activities not completed include the qualification of climate datasets and the production of a qualified technical report. The following final report is an unqualified summary of the activities that were completed given the reduced time and funding

  9. Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

    International Nuclear Information System (INIS)

    Araújo, E.S.S. de; Vasques, L.R.; Stabellini, R.; Krepischi, A.C.V.; Pereira, L.V.

    2014-01-01

    DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A

  10. Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

    Energy Technology Data Exchange (ETDEWEB)

    Araújo, E.S.S. de [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Vasques, L.R. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Stabellini, R.; Krepischi, A.C.V. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Pereira, L.V. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-10-17

    DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.

  11. Burnout in Customer Service Representatives

    Directory of Open Access Journals (Sweden)

    Tariq Jalees

    2008-09-01

    Full Text Available The purpose and aim of this research was to (1 identify the factors that contributes towards job burnout in sales service representative (2 What are the relationships of these factors (3 To empirically test the relationships of the determinants relating to burnout in customer service representatives. Based on literature survey six different variables related to burnout were identified. The variables were (1 Emotional exhaustion.(2 Reduced personal accomplishment.(3 Job induced tension.(4 Job satisfaction.(5 Workload (6 Job satisfaction.Each of the variables contained 3 sub-variables. Five different hypotheses were developed and tested through techniques such as Z-test, F-test and regression analysis. The questionnaire administered for the study contained 15 questions including personal data. The subject was Moblink company customers sales service representative in Karachi.The valid sample size was 98 drawn through multi-cluster technique. Techniques such as measure of dispersion and measure of central tendencies were used for analyzing the data. Regression, Z-test, and F-test were used for testing the developed hypothesis.According to the respondents’ opinions, the reduced personal accomplishment had a high rating with a mean of 3.75 and job induced tension has the lowest mean of 3.58. The standard deviation of respondents’ opinions was highest for dimension depersonalization and least for dimension work load. This indicates that there is a high polarization of the respondents’ opinions on the dimension depersonalization moral and least on the dimension work load.The Skew nesses for all the dimensions were in negative except the determinants emotional exhaustion and workload. This indicates that the majority of respondents’ opinions on all the dimensions were below the mean except in the case of emotional exhaustion and workload.Five hypotheses were developed and tested:a The hypothesis relating to low level of burnout in customers

  12. Partial demethylation of oligogalacturonides by pectin methyl esterase 1 is required for eliciting defence responses in wild strawberry (Fragaria vesca).

    Science.gov (United States)

    Osorio, Sonia; Castillejo, Cristina; Quesada, Miguel A; Medina-Escobar, Nieves; Brownsey, Geoff J; Suau, Rafael; Heredia, Antonio; Botella, Miguel A; Valpuesta, Victoriano

    2008-04-01

    In addition to the role of the cell wall as a physical barrier against pathogens, some of its constituents, such as pectin-derived oligogalacturonides (OGA), are essential components for elicitation of defence responses. To investigate how modifications of pectin alter defence responses, we expressed the fruit-specific Fragaria x ananassa pectin methyl esterase FaPE1 in the wild strawberry Fragaria vesca. Pectin from transgenic ripe fruits differed from the wild-type with regard to the degree and pattern of methyl esterification, as well as the average size of pectin polymers. Purified oligogalacturonides from the transgenic fruits showed a reduced degree of esterification compared to oligogalacturonides from wild-type fruits. This reduced esterification is necessary to elicit defence responses in strawberry. The transgenic F. vesca lines had constitutively activated pathogen defence responses, resulting in higher resistance to the necrotropic fungus Botrytis cinerea. Further studies in F. vesca and Nicotiana benthamiana leaves showed that the elicitation capacity of the oligogalacturonides is more specific than previously envisaged.

  13. Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Yu [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Zhan, Qian [The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xu, Hongying [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Li, Lili; Li, Chen [Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute (Hong Kong); Xiao, Qian; Xiang, Shili; Hui, Tianli [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xiang, Tingxiu, E-mail: larissaxiang@163.com [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rengs726@126.com [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2016-06-10

    The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

  14. Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

    International Nuclear Information System (INIS)

    Fan, Yu; Zhan, Qian; Xu, Hongying; Li, Lili; Li, Chen; Xiao, Qian; Xiang, Shili; Hui, Tianli; Xiang, Tingxiu; Ren, Guosheng

    2016-01-01

    The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

  15. Representing culture in interstellar messages

    Science.gov (United States)

    Vakoch, Douglas A.

    2008-09-01

    As scholars involved with the Search for Extraterrestrial Intelligence (SETI) have contemplated how we might portray humankind in any messages sent to civilizations beyond Earth, one of the challenges they face is adequately representing the diversity of human cultures. For example, in a 2003 workshop in Paris sponsored by the SETI Institute, the International Academy of Astronautics (IAA) SETI Permanent Study Group, the International Society for the Arts, Sciences and Technology (ISAST), and the John Templeton Foundation, a varied group of artists, scientists, and scholars from the humanities considered how to encode notions of altruism in interstellar messages . Though the group represented 10 countries, most were from Europe and North America, leading to the group's recommendation that subsequent discussions on the topic should include more globally representative perspectives. As a result, the IAA Study Group on Interstellar Message Construction and the SETI Institute sponsored a follow-up workshop in Santa Fe, New Mexico, USA in February 2005. The Santa Fe workshop brought together scholars from a range of disciplines including anthropology, archaeology, chemistry, communication science, philosophy, and psychology. Participants included scholars familiar with interstellar message design as well as specialists in cross-cultural research who had participated in the Symposium on Altruism in Cross-cultural Perspective, held just prior to the workshop during the annual conference of the Society for Cross-cultural Research . The workshop included discussion of how cultural understandings of altruism can complement and critique the more biologically based models of altruism proposed for interstellar messages at the 2003 Paris workshop. This paper, written by the chair of both the Paris and Santa Fe workshops, will explore the challenges of communicating concepts of altruism that draw on both biological and cultural models.

  16. Semantic Representatives of the Concept

    Directory of Open Access Journals (Sweden)

    Elena N. Tsay

    2013-01-01

    Full Text Available In the article concept as one of the principle notions of cognitive linguistics is investigated. Considering concept as culture phenomenon, having language realization and ethnocultural peculiarities, the description of the concept “happiness” is presented. Lexical and semantic paradigm of the concept of happiness correlates with a great number of lexical and semantic variants. In the work semantic representatives of the concept of happiness, covering supreme spiritual values are revealed and semantic interpretation of their functioning in the Biblical discourse is given.

  17. Conspicuous Waste and Representativeness Heuristic

    Directory of Open Access Journals (Sweden)

    Tatiana M. Shishkina

    2017-12-01

    Full Text Available The article deals with the similarities between conspicuous waste and representativeness heuristic. The conspicuous waste is analyzed according to the classic Veblen’ interpretation as a strategy to increase social status through conspicuous consumption and conspicuous leisure. In “The Theory of the Leisure Class” Veblen introduced two different types of utility – conspicuous and functional. The article focuses on the possible benefits of the analysis of conspicuous utility not only in terms of institutional economic theory, but also in terms of behavioral economics. To this end, the representativeness heuristics is considered, on the one hand, as a way to optimize the decision-making process, which allows to examine it in comparison with procedural rationality by Simon. On the other hand, it is also analyzed as cognitive bias within the Kahneman and Twersky’ approach. The article provides the analysis of the patterns in the deviations from the rational behavior strategy that could be observed in case of conspicuous waste both in modern market economies in the form of conspicuous consumption and in archaic economies in the form of gift-exchange. The article also focuses on the marketing strategies for luxury consumption’ advertisement. It highlights the impact of the symbolic capital (in Bourdieu’ interpretation on the social and symbolic payments that actors get from the act of conspicuous waste. This allows to perform a analysis of conspicuous consumption both as a rational way to get the particular kind of payments, and, at the same time, as a form of institutionalized cognitive bias.

  18. May 2013 Council of Chapter Representatives Notes

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2013-05-01

    Full Text Available No abstract available. Article truncated at 150 words. The Council of Chapter Representatives met in conjunction with the ATS meeting in Philadelphia on May 18, 2012.Roll Call. The meeting was called to order at 11 AM. Representatives from Arizona, California, DC Metro, Louisiana, Michigan, New Mexico, New York, Oregon, and Rhode Island were in attendance, and by telephone from Washington.Chapter Updates. Information on chapter activities and a chapter brochure. There are currently 19 active chapters. Most are having annual meetings. Advocacy. Gary Ewart from ATS Government Relations gave a presentation on Washington activities. Highlights included activities on the SGR, a number of air pollution regulations and a letter campaign advocating regulation of cigars. ATS President 2013-14-vision for the coming year. Patrician Finn gave a summary of what she hopes to accomplish over the next year. The theme of her presidency will be health equality. ATS Executive Director-update. Steve Crane gave a positive presentation on the …

  19. Representative mass reduction in sampling

    DEFF Research Database (Denmark)

    Petersen, Lars; Esbensen, Harry Kim; Dahl, Casper Kierulf

    2004-01-01

    We here present a comprehensive survey of current mass reduction principles and hardware available in the current market. We conduct a rigorous comparison study of the performance of 17 field and/or laboratory instruments or methods which are quantitatively characterized (and ranked) for accuracy...... dividers, the Boerner Divider, the ??spoon method??, alternate/fractional shoveling and grab sampling. Only devices based on riffle splitting principles (static or rotational) passes the ultimate representativity test (with minor, but significant relative differences). Grab sampling, the overwhelmingly...... most often used mass reduction method, performs appallingly?its use must be discontinued (with the singular exception for completely homogenized fine powders). Only proper mass reduction (i.e. carried out in complete compliance with all appropriate design principles, maintenance and cleaning rules) can...

  20. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Toribio E, E

    2005-07-01

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  1. Want change? Call your representative

    Science.gov (United States)

    Fischhoff, Ilya R.

    2011-07-01

    During my tenure as an AGU Congressional Science Fellow, which began in September 2010 and continues until November 2011, my time has been shared between working with the U.S. House of Representatives Natural Resource Committee Democratic staff and in the office of Rep. Ed Markey (D-Mass., ranking Democrat on the committee). I appreciate getting to work with staff, fellows, and interns who inspire me, make me laugh, and know their issues cold. Much of my work on the committee is related to fish, wildlife, oceans, lands, and water issues and is directly related to my background in ecology and evolutionary biology (I studied zebra ecology and behavior in Kenya). My assignments have included asking the Environmental Protection Agency (EPA) about why it has not changed the allowed usage of certain pesticides that the National Marine Fisheries Service has found to jeopardize the recovery of endangered Pacific salmon; helping to identify research needs and management options to combat the swiftly spreading and catastrophic white nose syndrome in North American bats; and inquiring as to whether a captive-ape welfare bill, if passed without amendment, could thwart development of a vaccine to stop the Ebola virus from continuing to cause mass mortality in endangered wild apes.

  2. Determination of the Proportion of Total Soil Extracellular Acid Phosphomonoesterase (E.C. 3.1.3.2 Activity Represented by Roots in the Soil of Different Forest Ecosystems

    Directory of Open Access Journals (Sweden)

    Klement Rejsek

    2012-01-01

    Full Text Available The aim of this study is to present a new method for determining the root-derived extracellular acid phosphomonoesterase (EAPM activity fraction within the total EAPM activity of soil. EAPM activity was determined for roots, organic and mineral soil. Samples were collected using paired PVC cylinders, inserted to a depth of 15 cm, within seven selected forest stands. Root-derived EAPM formed between 4 and18% of the total EAPM activity of soil from forests of differing maturity. A new approach, presented in this work, enables separation of root-derived EAPM activity from total soil EAPM. Separation of root-derived EAPM from soil provides a better understanding of its role in P-cycling in terrestrial ecosystems. The method presented in this work is a first step towards the separation of root- and microbe-derived EAPM in soils, which are thought to possess different kinetic properties and different sensitivity to environmental change.

  3. Agonists and partial agonists of rhodopsin: retinal polyene methylation affects receptor activation.

    Science.gov (United States)

    Vogel, Reiner; Lüdeke, Steffen; Siebert, Friedrich; Sakmar, Thomas P; Hirshfeld, Amiram; Sheves, Mordechai

    2006-02-14

    Using Fourier transform infrared (FTIR) difference spectroscopy, we have studied the impact of sites and extent of methylation of the retinal polyene with respect to position and thermodynamic parameters of the conformational equilibrium between the Meta I and Meta II photoproducts of rhodopsin. Deletion of methyl groups to form 9-demethyl and 13-demethyl analogues, as well as addition of a methyl group at C10 or C12, shifted the Meta I/Meta II equilibrium toward Meta I, such that the retinal analogues behaved like partial agonists. This equilibrium shift resulted from an apparent reduction of the entropy gain of the transition of up to 65%, which was only partially offset by a concomitant reduction of the enthalpy increase. The analogues produced Meta II photoproducts with relatively small alterations, while their Meta I states were significantly altered, which accounted for the aberrant transitions to Meta II. Addition of a methyl group at C14 influenced the thermodynamic parameters but had little impact on the position of the Meta I/Meta II equilibrium. Neutralization of the residue 134 in the E134Q opsin mutant increased the Meta II content of the 13-demethyl analogue, but not of the 9-demethyl analogue, indicating a severe impairment of the allosteric coupling between the conserved cytoplasmic ERY motif involved in proton uptake and the Schiff base/Glu 113 microdomain in the 9-demethyl analogue. The 9-methyl group appears therefore essential for the correct positioning of retinal to link protonation of the cytoplasmic motif with protonation of Glu 113 during receptor activation.

  4. Automated extraction of lysergic acid diethylamide (LSD) and N-demethyl-LSD from blood, serum, plasma, and urine samples using the Zymark RapidTrace with LC/MS/MS confirmation.

    Science.gov (United States)

    de Kanel, J; Vickery, W E; Waldner, B; Monahan, R M; Diamond, F X

    1998-05-01

    A forensic procedure for the quantitative confirmation of lysergic acid diethylamide (LSD) and the qualitative confirmation of its metabolite, N-demethyl-LSD, in blood, serum, plasma, and urine samples is presented. The Zymark RapidTrace was used to perform fully automated solid-phase extractions of all specimen types. After extract evaporation, confirmations were performed using liquid chromatography (LC) followed by positive electrospray ionization (ESI+) mass spectrometry/mass spectrometry (MS/MS) without derivatization. Quantitation of LSD was accomplished using LSD-d3 as an internal standard. The limit of quantitation (LOQ) for LSD was 0.05 ng/mL. The limit of detection (LOD) for both LSD and N-demethyl-LSD was 0.025 ng/mL. The recovery of LSD was greater than 95% at levels of 0.1 ng/mL and 2.0 ng/mL. For LSD at 1.0 ng/mL, the within-run and between-run (different day) relative standard deviation (RSD) was 2.2% and 4.4%, respectively.

  5. Efecto de actividades turísticas sobre el comportamiento de fauna representativa de las Islas Galápagos, Ecuador Short-term effects of tourism activities on the behavior of representative fauna on the Galapagos Islands, Ecuador

    Directory of Open Access Journals (Sweden)

    Fernanda González-Pérez

    2010-01-01

    Full Text Available Fueron consideradas clave para actividades turísticas en 16 sitios de las Islas Galápagos: la raya sartén marmoleada (Taeniura meyeri, raya águila (Aetobatus narinari, tiburón de aleta blanca (Triaenodon obesus, tortuga verde (Chelonia mydas, cormorán no volador (Phalacrocorax harrisi y lobo marino de Galápagos (Zalophus califórnianus, con el objetivo de analizar reacciones a corto plazo ante actividades de buceo apnea o "snorkeling", buceo autónomo o "scuba", paseos en bote o "panga-ride" y caminatas. Para cada especie se documentó su comportamiento al momento del encuentro con los turistas y su reacción ante dicha situación. El uso del Análisis de Correspondencias reveló que el tipo de reacción de las especies depende significativamente de la actividad turística, a excepción de las rayas sartén marmoleada y águila. Asimismo, los análisis indican que, a nivel de especie, cada actividad turística estuvo asociada significativamente con reacciones animales particulares. Esto sugiere que las especies analizadas son sensibles ante determinadas actividades turísticas, por lo que se deberían implementar recomendaciones de manejo a fin de garantizar la sustentabilidad del ecoturismo.This study focused on the short-term reactions of six key species (Taeniura meyeri, Aetobatus narinari, Triaendon obesus, Chelonia mydas, Phalacrocorax harrisi, and Zalophus califórnianus during tourism activities (SCUBA diving, panga-ride, snorkeling, and hiking at 16 tourist sites on the islands. For each species we recorded its behavior when first encountering tourists and its reaction following this encounter. A Correspondence Analysis revealed that the type of reaction of the species depended significantly on the type of touristic activity, with the exception of the black spotted and eagle rays. Moreover, the analysis showed that, for each species, the different tourist activities were significantly associated with particular animal activities

  6. NASA: Changes to the scope, schedule, and estimated cost of the Earth Observing System. Report to the Chair, Government Activities and Transportation Subcommittee, Committee on Government Operations, House of Representatives

    International Nuclear Information System (INIS)

    1992-07-01

    Congress funded the Earth Observing System (EOS) as a new NASA program beginning in fiscal year 1991. NASA proposed to launch about 30 types of earth observing instruments beginning in 1998. These instruments were intended to improve satellite data about the earth and to provide new data to support interdisciplinary studies of the earth. EOS is seen by NASA as the first step toward a future period of space-based scientific observation of the earth. The program is directly linked to the objectives of the U.S. Global Change Research Program and international efforts to observe and study the earth. The U.S. Global Change Research Program, which is funded by 11 agencies, is an attempt to achieve these objectives and to improve predictions of climate and other forms of global change. Within that program, EOS is intended to significantly improve scientists' abilities to model, and thereby predict, broad natural relationships among the sea, land, and atmosphere; to observe how water, carbon, and other substances move on the planet or are affected by variations in the sun's radiation; and to assess the impact of human activities on the earth's climate. Ultimately, EOS is to help determine the extent to which human activities are affecting the earth's environment and to provide policymakers with the information they will need to preserve the earth

  7. High-Mannose Specific Lectin and Its Recombinants from a Carrageenophyta Kappaphycus alvarezii Represent a Potent Anti-HIV Activity Through High-Affinity Binding to the Viral Envelope Glycoprotein gp120.

    Science.gov (United States)

    Hirayama, Makoto; Shibata, Hiromi; Imamura, Koji; Sakaguchi, Takemasa; Hori, Kanji

    2016-02-01

    We previously reported that a high-mannose binding lectin KAA-2 from the red alga Kappaphycus alvarezii, which is an economically important species and widely cultivated as a source of carrageenans, had a potent anti-influenza virus activity. In this study, the full-length sequences of two KAA isoforms, KAA-1 and KAA-2, were elucidated by a combination of peptide mapping and complementary DNA (cDNA) cloning. They consisted of four internal tandem-repeated domains, which are conserved in high-mannose specific lectins from lower organisms, including a cyanobacterium Oscillatoria agardhii and a red alga Eucheuma serra. Using an Escherichia coli expression system, an active recombinant form of KAA-1 (His-tagged rKAA-1) was successfully generated in the yield of 115 mg per liter of culture. In a detailed oligosaccharide binding analysis by a centrifugal ultrafiltration-HPLC method with 27 pyridylaminated oligosaccharides, His-tagged rKAA-1 and rKAA-1 specifically bound to high-mannose N-glycans with an exposed α1-3 mannose in the D2 arm as the native lectin did. Predicted from oligosaccharide binding specificity, a surface plasmon resonance analysis revealed that the recombinants exhibit strong interaction with gp120, a heavily glycosylated envelope glycoprotein of HIV with high association constants (1.48 - 1.61 × 10(9) M(-1)). Native KAAs and the recombinants inhibited the HIV-1 entry at IC50s of low nanomolar levels (7.3-12.9 nM). Thus, the recombinant proteins would be useful as antiviral reagents targeting the viral surface glycoproteins with high-mannose N-glycans, and the cultivated alga K. alvarezii could also be a good source of not only carrageenans but also this functional lectin(s).

  8. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Toribio E, E

    2005-07-01

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  9. Synthesis and antibacterial activity of insignin and its 8-methoxy- and 6-demethoxy derivatives

    Directory of Open Access Journals (Sweden)

    Aamer Saeed

    2006-06-01

    Full Text Available A short and efficient synthesis of insignin (8-hydroxy-6-methoxy-3-heptyl- isocoumarin (1, a metabolite of natural lichens, has been described. Reaction of 3,5-dimethoxyhomophthalic anhydride (2 with octanoyl chloride in the presence of 1,1,3,3-tetramethylguanidine (TMG and triethyl amine afforded the 6,8-dimethoxy-3-heptylisocoumarin (3 in high yield. Regioselective demethylation of the latter using anhydrous aluminum chloride furnished the 8-hydroxy-6-methoxy-3-heptylisocoumarin (1 whereas, the complete demethylation of (3 yielded 6,8-dihydroxy-3-heptylisocoumarin (4. The isocoumarins (1, 3, and 4 were examined in vitro for antibacterial activity and were shown to exhibit moderate activity.

  10. Physical activity and screen-based media use: cross-sectional associations with health-related quality of life and the role of body satisfaction in a representative sample of German adolescents.

    Science.gov (United States)

    Finne, Emily; Bucksch, Jens; Lampert, Thomas; Kolip, Petra

    2013-01-01

    Purpose : Although it is widely accepted that physical activity (PA) positively, and screen-based media use (SBM) negatively, affects well-being, there is a lack of studies relating PA and SBM to health-related quality of life (HRQoL) in adolescents. We examined these associations in German adolescents for different HRQoL subdomains and explored the role of body satisfaction as a possible mediator. Methods : The 11-17-year-old subsample of the German Health Interview and Examination Survey (2003-2006) was analysed ( N = 6813; 51.3% male). Cross-sectional associations of self-reported PA frequency and amount of daily SBM with HRQoL subscale scores (according to KINDL-R) were examined by hierarchical linear regression models, adjusting for the clustering of the sample and for a variety of possible confounders. The size and significance of indirect effects via body (dis)satisfaction (BDS) were examined by mediation analyses. Results : Higher PA frequency was significantly associated with higher HRQoL on nearly all subscales and dose-response-relationships were observable. Variations were greatest in terms of social well-being in boys (effect size d = 0.59) and physical well-being in girls ( d = 0.43). Higher SBM was related to lower HRQoL on all subscales in girls and on some subscales in boys, with the largest effects for school functioning in both genders ( d = 0.31 and 0.37, respectively). The mediated effects for PA and SBM were significant in both genders, but the sizes and the proportions of total effects mediated by body satisfaction were rather small. Conclusions : Higher PA frequency was associated with higher self-reported HRQoL, and higher SBM was associated with lower self-reported HRQoL in both genders, even after adjusting for relevant covariates. The results support the assumption of independent health impacts of both behaviours, although no causal relationship can be confirmed with these cross-sectional data. Mechanisms other than body satisfaction

  11. Activity of two chlorinated lincomycin analogues against chloroquine-resistant falciparum malaria in owl monkeys.

    Science.gov (United States)

    Powers, K G; Jacobs, R L

    1972-01-01

    The chloroquine-resistant Oak Knoll strain of Plasmodium falciparum, recently adapted to the owl monkey (Aotus trivirgatus), was insusceptible to chloroquine therapy. Two chlorinated lincomycin analogues tested in this host-parasite system cured blood-induced infections. Acute infections were treated orally for 7 consecutive days with either 15 or 75 mg of clindamycin hydrochloride (U-21) per kg per day, 10 or 50 mg of N-demethyl-4'-pentyl clindamycin hydrochloride (U-24) per kg per day, or 20 mg of chloroquine base per kg per day. These lincomycin analogues cleared trophozoites from the peripheral blood by the end of the 7-day treatment period. The speed of clearance of parasites was not dose-related, but curative activity appeared dependent upon the amount of drug given as well as the number of daily treatments. The efficacy of U-21 and U-24 is of particular interest since they represent major structural departures from compounds commonly used in the treatment of malaria.

  12. Activity of Two Chlorinated Lincomycin Analogues Against Chloroquine-Resistant Falciparum Malaria in Owl Monkeys1

    Science.gov (United States)

    Powers, Kendall G.; Jacobs, Richard L.

    1972-01-01

    The chloroquine-resistant Oak Knoll strain of Plasmodium falciparum, recently adapted to the owl monkey (Aotus trivirgatus), was insusceptible to chloroquine therapy. Two chlorinated lincomycin analogues tested in this host-parasite system cured blood-induced infections. Acute infections were treated orally for 7 consecutive days with either 15 or 75 mg of clindamycin hydrochloride (U-21) per kg per day, 10 or 50 mg of N-demethyl-4′-pentyl clindamycin hydrochloride (U-24) per kg per day, or 20 mg of chloroquine base per kg per day. These lincomycin analogues cleared trophozoites from the peripheral blood by the end of the 7-day treatment period. The speed of clearance of parasites was not dose-related, but curative activity appeared dependent upon the amount of drug given as well as the number of daily treatments. The efficacy of U-21 and U-24 is of particular interest since they represent major structural departures from compounds commonly used in the treatment of malaria. PMID:4207758

  13. OAS :: Authorities : Permanent Representatives to the OAS

    Science.gov (United States)

    Rights Actions against Corruption C Children Civil Registry Civil Society Contact Us Culture Cyber Representative of Belize Diego Pary Rodríguez Bolivia Diego Pary Rodríguez Ambassador, Permanent Representative of Bolivia José Luiz Machado Brazil José Luiz Machado e Costa Ambassador, Permanent Representative

  14. Represented Speech in Qualitative Health Research

    DEFF Research Database (Denmark)

    Musaeus, Peter

    2017-01-01

    Represented speech refers to speech where we reference somebody. Represented speech is an important phenomenon in everyday conversation, health care communication, and qualitative research. This case will draw first from a case study on physicians’ workplace learning and second from a case study...... on nurses’ apprenticeship learning. The aim of the case is to guide the qualitative researcher to use own and others’ voices in the interview and to be sensitive to represented speech in everyday conversation. Moreover, reported speech matters to health professionals who aim to represent the voice...... of their patients. Qualitative researchers and students might learn to encourage interviewees to elaborate different voices or perspectives. Qualitative researchers working with natural speech might pay attention to how people talk and use represented speech. Finally, represented speech might be relevant...

  15. Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts

    Directory of Open Access Journals (Sweden)

    Régis T. Costello

    2015-01-01

    Full Text Available Epigenetic drugs modify DNA methylation and are used in refractory anemia with excess of blasts (RAEB. These drugs may reactivate anti-oncogene expression and restore a normal phenotype instead of inducing antitumor toxicity, although they also have immunosuppressive effects on T-lymphocytes [1] In RAEB and acute myeloid leukemia, a defect in natural killer (NK cell cytotoxicity has been shown, which relies on abnormal expression of activating receptors. Previous study has shown that 5-azacytidine impaired mRNA synthesis and induced apoptosis in NK cells [2]. In this study we investigated the effect of the demethylating drug 5-azacytidine (Vidaza® on NK receptors with the hypothesis that demethylation of the promoters of activating NK receptor genes induces gene reactivation and thus may increase their expression.

  16. Representative Sampling for reliable data analysis

    DEFF Research Database (Denmark)

    Petersen, Lars; Esbensen, Kim Harry

    2005-01-01

    regime in order to secure the necessary reliability of: samples (which must be representative, from the primary sampling onwards), analysis (which will not mean anything outside the miniscule analytical volume without representativity ruling all mass reductions involved, also in the laboratory) and data...

  17. 14 CFR 1274.906 - Designation of New Technology Representative and Patent Representative.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Designation of New Technology... Conditions § 1274.906 Designation of New Technology Representative and Patent Representative. Designation of New Technology Representative and Patent Representative July 2002 (a) For purposes of administration...

  18. Verification of Representative Sampling in RI waste

    International Nuclear Information System (INIS)

    Ahn, Hong Joo; Song, Byung Cheul; Sohn, Se Cheul; Song, Kyu Seok; Jee, Kwang Yong; Choi, Kwang Seop

    2009-01-01

    For evaluating the radionuclide inventories for RI wastes, representative sampling is one of the most important parts in the process of radiochemical assay. Sampling to characterized RI waste conditions typically has been based on judgment or convenience sampling of individual or groups. However, it is difficult to get a sample representatively among the numerous drums. In addition, RI waste drums might be classified into heterogeneous wastes because they have a content of cotton, glass, vinyl, gloves, etc. In order to get the representative samples, the sample to be analyzed must be collected from selected every drum. Considering the expense and time of analysis, however, the number of sample has to be minimized. In this study, RI waste drums were classified by the various conditions of the half-life, surface dose, acceptance date, waste form, generator, etc. A sample for radiochemical assay was obtained through mixing samples of each drum. The sample has to be prepared for radiochemical assay and although the sample should be reasonably uniform, it is rare that a completely homogeneous material is received. Every sample is shredded by a 1 ∼ 2 cm 2 diameter and a representative aliquot taken for the required analysis. For verification of representative sampling, classified every group is tested for evaluation of 'selection of representative drum in a group' and 'representative sampling in a drum'

  19. Representing Uncertainty by Probability and Possibility

    DEFF Research Database (Denmark)

    of uncertain parameters. Monte Carlo simulation is readily used for practical calculations. However, an alternative approach is offered by possibility theory making use of possibility distributions such as intervals and fuzzy intervals. This approach is well suited to represent lack of knowledge or imprecision......Uncertain parameters in modeling are usually represented by probability distributions reflecting either the objective uncertainty of the parameters or the subjective belief held by the model builder. This approach is particularly suited for representing the statistical nature or variance...

  20. Understanding and Representing Changing Work Structures and Practices through Art

    Science.gov (United States)

    Wieland, Stacey M. B.

    2018-01-01

    Courses: Organizational Communication, Advanced Organizational Communication, Organizing Work, Management/Organizational History. Objectives: This activity will help students to understand major shifts in the organization of work and creatively represent changing work structures and practices. An optional follow-up assignment is included. A…

  1. Services Subcontract Technical Representative (STR) handbook

    International Nuclear Information System (INIS)

    Houston, D.H.

    1997-06-01

    The purpose of this handbook is to provide guidance to Bechtel Hanford, Inc. Subcontract Representatives in their assignments. It is the intention of this handbook to ensure that subcontract work is performed in accordance with the subcontract documents

  2. REFractions: The Representing Equivalent Fractions Game

    Science.gov (United States)

    Tucker, Stephen I.

    2014-01-01

    Stephen Tucker presents a fractions game that addresses a range of fraction concepts including equivalence and computation. The REFractions game also improves students' fluency with representing, comparing and adding fractions.

  3. Representing Boolean Functions by Decision Trees

    KAUST Repository

    Chikalov, Igor

    2011-01-01

    A Boolean or discrete function can be represented by a decision tree. A compact form of decision tree named binary decision diagram or branching program is widely known in logic design [2, 40]. This representation is equivalent to other forms

  4. Request by the Resident Representative of Iraq

    International Nuclear Information System (INIS)

    1990-01-01

    The attached clarification by a spokesman of the Iraqi Ministry of Foreign Affairs is being circulated for the information of Member States pursuant to a request made by the Resident Representative of Iraq

  5. Crisis Relocation Workshops for Transportation Industry Representatives

    Science.gov (United States)

    1979-12-01

    executive, two National Guard members, one Air Force transporta- _a ,tion representative, two Red Cross representatives, one school bus z coordinators...manaaers, local transitCD operator, and miiltary busingA authorityA Local Governa-ient 2 Fire chief, assistantI Air Force 3 Liaison Support D CPA :z...to attend the workshop. Majur trans- portation problems anticipated during crisis relocation include: 1. Transportation of carless residents; 2. The

  6. Genomic sequencing and in vivo footprinting of an expression-specific DNase I-hypersensitive site of avian vitellogenin II promoter reveal a demethylation of a mCpG and a change in specific interactions of proteins with DNA.

    Science.gov (United States)

    Saluz, H P; Feavers, I M; Jiricny, J; Jost, J P

    1988-01-01

    Genomic sequencing was used to study the in vivo methylation pattern of two CpG sites in the promoter region of the avian vitellogenin gene. The CpG at position +10 was fully methylated in DNA isolated from tissues that do not express the gene but was unmethylated in the liver of mature hens and estradiol-treated roosters. In the latter tissue, this site became demethylated and DNase I hypersensitive after estradiol treatment. A second CpG (position -52) was unmethylated in all tissues examined. In vivo genomic footprinting with dimethyl sulfate revealed different patterns of DNA protection in silent and expressed genes. In rooster liver cells, at least 10 base pairs of DNA, including the methylated CpG, were protected by protein(s). Gel-shift assays indicated that a protein factor, present in rooster liver nuclear extract, bound at this site only when it was methylated. In hen liver cells, the same unmethylated CpG lies within a protected region of approximately equal to 20 base pairs. In vitro DNase I protection and gel-shift assays indicate that this sequence is bound by a protein, which binds both double- and single-stranded DNA. For the latter substrate, this factor was shown to bind solely the noncoding (i.e., mRNA-like) strand. Images PMID:3413118

  7. Investigations into the post-natal development of demethylating enzyme systems by determination of carbon dioxide 14 in the air exhaled by mice after applications of carbon 14 dimethyl amino-antipyrine

    International Nuclear Information System (INIS)

    Schmidt, H.

    1982-01-01

    Albino mice were subcutaneously injected with carbon 14 dimethyl aminopyrines, the methyl group of which can be metabolised in the organism into carbon dioxide 14. The following results were obtained: In the carbon dioxide 14 exhalation of neonate, young and adult animals after administration of carbon 14 aminopyrine, distinct differences were noted. The maximum of elimination via the lungs occurs after 20-30 minutes in grown-up mice, in neonates or young animals distinctly later (60-90 min). The carbon dioxide 14 exhalation was also measured after additional subcutaneous application of methrotrexate. In mice aged 8 and 10 days a distinct decrease in carbon dioxide 14 exhalation was found. By contrast, a rise in carbon dioxide 14 exhaled was found in mice aged 2 days. The orientating experiments with folic acid and carbon 14 dimethyl aminopyrine show that leucovorin leads to a distinct increase in carbon dioxide 14 exhalation during the first 30 minutes. As a cause of the different degrees of stimulation respectively inhibition of demethylation, different biochemical ways of formaldehyde formation are pointed out. One of these probably includes the folate-dependent reaction. (orig./MG) [de

  8. 48 CFR 1852.227-72 - Designation of new technology representative and patent representative.

    Science.gov (United States)

    2010-10-01

    ... CONTRACT CLAUSES Texts of Provisions and Clauses 1852.227-72 Designation of new technology representative... of New Technology Representative and Patent Representative (JUL 1997) (a) For purposes of administration of the clause of this contract entitled “New Technology” or “Patent Rights—Retention by the...

  9. 14 CFR 1260.58 - Designation of new technology representative and patent representative.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Designation of new technology... of new technology representative and patent representative. Designation of New Technology... of this grant entitled “New Technology,” the following named representatives are hereby designated by...

  10. 40 CFR 60.4112 - Changing Hg designated representative and alternate Hg designated representative; changes in...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Changing Hg designated representative and alternate Hg designated representative; changes in owners and operators. 60.4112 Section 60.4112... Generating Units Hg Designated Representative for Hg Budget Sources § 60.4112 Changing Hg designated...

  11. Representing uncertainty on model analysis plots

    Directory of Open Access Journals (Sweden)

    Trevor I. Smith

    2016-09-01

    Full Text Available Model analysis provides a mechanism for representing student learning as measured by standard multiple-choice surveys. The model plot contains information regarding both how likely students in a particular class are to choose the correct answer and how likely they are to choose an answer consistent with a well-documented conceptual model. Unfortunately, Bao’s original presentation of the model plot did not include a way to represent uncertainty in these measurements. I present details of a method to add error bars to model plots by expanding the work of Sommer and Lindell. I also provide a template for generating model plots with error bars.

  12. Representative Democracy in Australian Local Government

    Directory of Open Access Journals (Sweden)

    Colin Hearfield

    2009-01-01

    Full Text Available In an assessment of representative democracy in Australian local government, this paper considers long-run changes in forms of political representation, methods of vote counting, franchise arrangements, numbers of local government bodies and elected representatives, as well as the thorny question of constitutional recognition. This discussion is set against the background of ongoing tensions between the drive for economic efficiency and the maintenance of political legitimacy, along with more deep-seated divisions emerging from the legal relationship between local and state governments and the resultant problems inherent in local government autonomy versus state intervention.

  13. Enhancing policy innovation by redesigning representative democracy

    DEFF Research Database (Denmark)

    Sørensen, Eva

    2016-01-01

    Policy innovation is a key aspect of public innovation, which has been largely overlooked. Political leadership, competition and collaboration are key drivers of policy innovation. It is a barrier in traditional models of representative democracy that they provide weak conditions for collaboration....... Two Danish case studies indicate that collaboration between politicians and relevant and affected stakeholders can promote policy innovation, but also that a redesign of representative democracy is needed in order to establish a productive combination of political leadership, competition...... and collaboration in political life....

  14. Representativeness elements of an hybrid reactor demonstrator

    International Nuclear Information System (INIS)

    Kerdraon, D.; Billebaud, A.; Brissot, R.; David, S.; Giorni, A.; Heuer, D.; Loiseaux, J.M.; Meplan, O.

    2000-11-01

    This document deals with the quantification of the minimum thermal power level for a demonstrator and the definition of the physical criteria which define the representative character of a demonstrator towards a power reactor. Solutions allowing to keep an acceptable flow in an industrial core, have also been studied. The document is divided in three parts: the representativeness elements, the considered solutions and the characterization of the neutrons flows at the interfaces and the dose rates at the outer surface of the vessel. (A.L.B.)

  15. Molecular dynamics analysis reveals structural insights into mechanism of nicotine N-demethylation catalyzed by tobacco cytochrome P450 mono-oxygenase.

    Directory of Open Access Journals (Sweden)

    Shan Wang

    Full Text Available CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys-trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase.

  16. Attributes Heeded When Representing an Osmosis Problem.

    Science.gov (United States)

    Zuckerman, June Trop

    Eighteen high school science students were involved in a study to determine what attributes in the problem statement they need when representing a typical osmosis problem. In order to realize this goal students were asked to solve problems aloud and to explain their answers. Included as a part of the results are the attributes that the students…

  17. Representing Uncertainty on Model Analysis Plots

    Science.gov (United States)

    Smith, Trevor I.

    2016-01-01

    Model analysis provides a mechanism for representing student learning as measured by standard multiple-choice surveys. The model plot contains information regarding both how likely students in a particular class are to choose the correct answer and how likely they are to choose an answer consistent with a well-documented conceptual model.…

  18. Strong imploding shock, the representative curve

    International Nuclear Information System (INIS)

    Mishkin, E.A.; Alejaldre, C.

    1981-01-01

    The representative curve of the ideal gas behind the front of a spherically, or cylindrically, symmetric strong imploding shock is shown to pass through the point where the reduced pressure is maximum, P(xisub(m)) = Psub(m)sub(a)sub(x). (orig.)

  19. 28 CFR 104.4 - Personal Representative.

    Science.gov (United States)

    2010-07-01

    ... addition, as provided in § 104.21(b)(5) of this part, the Special Master may publish a list of individuals... Special Master may, in his discretion, determine that the Personal Representative for purposes of... administrator of the decedent's estate. In the event no will exists, the Special Master may, in his discretion...

  20. Adjustment Following Disability: Representative Case Studies.

    Science.gov (United States)

    Heinemann, Allen W.; Shontz, Franklin C.

    1984-01-01

    Examined adjustment following physical disability using the representative case method with two persons with quadriplegia. Results highlighted the importance of previously established coping styles as well as the role of the environment in adjustment. Willingness to mourn aided in later growth. (JAC)

  1. Representative parameter of immunostimulatory ginseng polysaccharide to predict radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Son, Hyeog Jin; Shim, Ji Young; Ahn, Ji Yeon; Yun, Yeon Sook; Song, Jie Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-09-15

    According to the increase in the use of radiotherapy to cancer patients, many approaches have been tried to develop new agents for the protection of surrounding normal tissues. However, it is still few applied in the clinic as a radioprotector. We aim to find a representative parameter for radioprotection to easily predict the activity of in vivo experiment from the results of in vitro screening. The polysaccharide extracted from Panax ginseng was used in this study because the immunostimulator has been regarded as one of the radioprotective agent category and was already reported having a promising radioprotective activity through the increase of hematopoietic cells and the production of several cytokines. Mitogenic activity, AK cells activity and nitric oxide production were monitored for the in vitro immunological assay, and endogenous Colony-Forming Unit (e-CFU) was measured as in vivo radioprotective parameter. The immunological activity was increased by the galactose contents of ginseng polysaccharide dependently. The result of this study suggests that mitogenic activity of splenocytes demonstrated a good correlation with in vivo radioprotective effect, and may be used as a representative parameter to screen the candidates for radioprotector.

  2. Representing Boolean Functions by Decision Trees

    KAUST Repository

    Chikalov, Igor

    2011-01-01

    A Boolean or discrete function can be represented by a decision tree. A compact form of decision tree named binary decision diagram or branching program is widely known in logic design [2, 40]. This representation is equivalent to other forms, and in some cases it is more compact than values table or even the formula [44]. Representing a function in the form of decision tree allows applying graph algorithms for various transformations [10]. Decision trees and branching programs are used for effective hardware [15] and software [5] implementation of functions. For the implementation to be effective, the function representation should have minimal time and space complexity. The average depth of decision tree characterizes the expected computing time, and the number of nodes in branching program characterizes the number of functional elements required for implementation. Often these two criteria are incompatible, i.e. there is no solution that is optimal on both time and space complexity. © Springer-Verlag Berlin Heidelberg 2011.

  3. Climate Change and the Representative Agent

    Energy Technology Data Exchange (ETDEWEB)

    Howarth, R.B. [Environmental Studies Program, Dartmouth College, Hanover, New Hampshire 03755 (United States)

    2000-02-01

    The artifice of an infinitely-lived representative agent is commonly invoked to balance the present costs and future benefits of climate stabilization policies. Since actual economies are populated by overlapping generations of finite-lived persons, this approach begs important questions of welfare aggregation. This paper compares the results of representative agent and overlapping generations models that are numerically calibrated based on standard assumptions regarding climate economy interactions. Under two social choice rules - Pareto efficiency and classical utilitarianism - the models generate closely similar simulation results. In the absence of policies to redistribute income between present and future generations, efficient rates of carbon dioxide emissions abatement rise from 15 to 20% between the years 2000 and 2105. Under classical utilitarianism, in contrast, optimal control rates rise from 48 to 79% this same period. 23 refs.

  4. Meeting staff representatives of the European Agencies

    CERN Multimedia

    Staff Association

    2014-01-01

      The AASC (Assembly of Agency Staff Committee) held its 27th Meeting of the specialized European Agencies on 26 and 27 May on the premises of the OHIM (Office for Harmonization in the Internal Market) in Alicante, Spain. Two representatives of the CERN Staff Association, in charge of External Relations, attended as observers. This participation is a useful complement to regular contacts we have with FICSA (Federation of International Civil Servants' Associations), which groups staff associations of the UN Agencies, and the annual CSAIO conferences (Conference of Staff Associations of International Organizations), where each Autumn representatives of international organizations based in Europe meet to discuss themes of common interest to better promote and defend the rights of the international civil servants. All these meetings allow us to remain informed on items that are directly or indirectly related to employment and social conditions of our colleagues in other international and Europ...

  5. Data structures and apparatuses for representing knowledge

    Science.gov (United States)

    Hohimer, Ryan E; Thomson, Judi R; Harvey, William J; Paulson, Patrick R; Whiting, Mark A; Tratz, Stephen C; Chappell, Alan R; Butner, Robert S

    2014-02-18

    Data structures and apparatuses to represent knowledge are disclosed. The processes can comprise labeling elements in a knowledge signature according to concepts in an ontology and populating the elements with confidence values. The data structures can comprise knowledge signatures stored on computer-readable media. The knowledge signatures comprise a matrix structure having elements labeled according to concepts in an ontology, wherein the value of the element represents a confidence that the concept is present in an information space. The apparatus can comprise a knowledge representation unit having at least one ontology stored on a computer-readable medium, at least one data-receiving device, and a processor configured to generate knowledge signatures by comparing datasets obtained by the data-receiving devices to the ontologies.

  6. Using semantics for representing experimental protocols.

    Science.gov (United States)

    Giraldo, Olga; García, Alexander; López, Federico; Corcho, Oscar

    2017-11-13

    An experimental protocol is a sequence of tasks and operations executed to perform experimental research in biological and biomedical areas, e.g. biology, genetics, immunology, neurosciences, virology. Protocols often include references to equipment, reagents, descriptions of critical steps, troubleshooting and tips, as well as any other information that researchers deem important for facilitating the reusability of the protocol. Although experimental protocols are central to reproducibility, the descriptions are often cursory. There is the need for a unified framework with respect to the syntactic structure and the semantics for representing experimental protocols. In this paper we present "SMART Protocols ontology", an ontology for representing experimental protocols. Our ontology represents the protocol as a workflow with domain specific knowledge embedded within a document. We also present the S ample I nstrument R eagent O bjective (SIRO) model, which represents the minimal common information shared across experimental protocols. SIRO was conceived in the same realm as the Patient Intervention Comparison Outcome (PICO) model that supports search, retrieval and classification purposes in evidence based medicine. We evaluate our approach against a set of competency questions modeled as SPARQL queries and processed against a set of published and unpublished protocols modeled with the SP Ontology and the SIRO model. Our approach makes it possible to answer queries such as Which protocols use tumor tissue as a sample. Improving reporting structures for experimental protocols requires collective efforts from authors, peer reviewers, editors and funding bodies. The SP Ontology is a contribution towards this goal. We build upon previous experiences and bringing together the view of researchers managing protocols in their laboratory work. Website: https://smartprotocols.github.io/ .

  7. The local brand representative in reseller networks

    OpenAIRE

    Gupta, Suraksha; Malhotra, Naresh K; Czinkota, Michael; Foroudi, Pantea

    2016-01-01

    This study investigates the characteristics of local individuals who represent a brand to its resellers by first conceptualizing these characteristics by employing complexity theory and then testing the conceptualization. This research revealed that four characteristics ‘native’, ‘entrepreneurial’, ‘advisor’, and ‘compatible’ are the main ones that influence reseller brand preferences. The study finds a link between reseller brand preference and reseller brand loyalty which is useful for mana...

  8. Citizen's initiatives and the representative system

    International Nuclear Information System (INIS)

    Guggenberger, B.; Kempf, U.

    1978-01-01

    This anthology containing contributions of 19 sociologists is a systematic investigation of the locality, the possibilities and the effective radius of citizen's initiatives under the functional conditions of the parliamentary - representative system. The intellectual and political surroundings, the sociologic context, the institutional, political and judical overall conditions as well as the consequences of this movement for the whole political system of the Federal Republic of Germany. (orig.) [de

  9. Representativeness of the IAGOS airborne measurements in the lower troposphere

    OpenAIRE

    Petetin, H.; Jeoffrion, M.; Sauvage, B.; Athier, G.; Blot, R.; Boulanger, D.; Clark, H.; Cousin, J.-M.; Gheusi, F.; Nedelec, P.; Steinbacher, M.; Thouret, V.

    2018-01-01

    In the framework of the In Service Aircraft for Global Observing System (IAGOS) program, airborne in-situ O3 and CO measurements are performed routinely using in-service aircraft, providing vertical profiles from the surface to about 10–12 km. Due to the specificity of IAGOS measurements (measurements around busy international airports), uncertainties exist on their representativeness in the lower troposphere as they may be impacted by emissions related to airport activities and/or other air...

  10. Diversity and representativeness: two key factors

    CERN Multimedia

    Staff Association

    2013-01-01

    In the past few weeks many of you have filled out the questionnaire for preparing the upcoming Five-yearly review. Similarly, Staff Association members have elected their delegates to the Staff Council for the coming two years. Once again we would like to thank all those who have taken the time and effort to make their voice heard on these two occasions. Elections to the Staff Council Below we publish the new Staff Council with its forty delegates who will represent in 2014 and 2015 all CERN staff in the discussions with Management and Member States in the various bodies and committees. Therefore it is important that the Staff Council represents as far as possible the diversity of the CERN population. By construction, the election process with its electoral colleges and two-step voting procedure guarantees that all Departments, even the small ones, and the various staff categories are correctly represented. Figure 1 shows the participation rate in the elections. The average rate is just above 52 %, with ...

  11. Total glucosides of paeony induces regulatory CD4(+)CD25(+) T cells by increasing Foxp3 demethylation in lupus CD4(+) T cells.

    Science.gov (United States)

    Zhao, Ming; Liang, Gong-ping; Tang, Mei-ni; Luo, Shuang-yan; Zhang, Jing; Cheng, Wen-jing; Chan, Tak-mao; Lu, Qian-jin

    2012-05-01

    Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4(+) T cells. Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down-regulating Foxp3 promoter methylation levels. However, we couldn't observe similar results in healthy control CD4(+) T cells treated by TGP. Moreover, our results also showed that IFN-γ and IL-2 expression was enhanced in TGP-treated lupus CD4(+) T cells. These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFN-γ and IL-2 signaling. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available It has been documented all-trans retinoic acid (atRA promotes the development of TGF-β-induced CD4(+Foxp3(+ regulatory T cells (iTreg that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs.Addition of atRA to naïve CD4(+CD25(- cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered.We have identified the cellular and molecular mechanism(s by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

  13. Identifying optimal models to represent biochemical systems.

    Directory of Open Access Journals (Sweden)

    Mochamad Apri

    Full Text Available Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.

  14. [Sensitivity of four representative angular cephalometric measures].

    Science.gov (United States)

    Xü, T; Ahn, J; Baumrind, S

    2000-05-01

    Examined the sensitivity of four representative cephalometric angles to the detection of different vectors of craniofacial growth. Landmark coordinate data from a stratified random sample of 48 adolescent subjects were used to calculate conventional values for changes between the pretreatment and end-of-treatment lateral cephalograms. By modifying the end-of-treatment coordinate values appropriately, the angular changes could be recalculated reflecting three hypothetical situations: Case 1. What if there were no downward landmark displacement between timepoints? Case 2. What if there were no forward landmark displacement between timepoints? Case 3. What if there were no Nasion change? These questions were asked for four representative cephalometric angles: SNA, ANB, NAPg and UI-SN. For Case 1, the associations (r) between the baseline and the modified measure for the three angles were very highly significant (P < 0.001) with r2 values no lower than 0.94! For Case 2, however, the associations were much weaker and no r value reached significance. These angular measurements are less sensitive for measuring downward landmark displacement than they are for measuring forward landmark displacement.

  15. Anthropomorphic Networks as Representatives of Global Consciousness

    Directory of Open Access Journals (Sweden)

    Sergii Yahodzinskyi

    2018-02-01

    Full Text Available There has been analyzed a phenomenon of global consciousness, and its cultural and historical, civilizational dimensions have been substantiated. There has been demonstrated that the concept of planetary consciousness, global thinking, noosphere was described for the first time in the philosophy of cosmism. However, in modern conditions ideas of representatives of the naturalistic philosophical direction of cosmism have not lost their heuristic potential. They can be reconsidered in a new fashion within the context of emerging anthropomorphic (human dimension networks. There has been proved that global consciousness is a component of the social and cultural potential of global information networks defining vectors to prospects of humanity progress in the 21st century. Relying on methodology of the structural and functional analysis, the author arrives at a conclusion about global networks obtaining the status of representatives of global consciousness. This is the area of networks where all relevant information is concentrated – from statistical data to scientific and technical information. Access to these data is limited by human abilities and is realized in the form of discrete requests with using heuristic algorithms of information procession. A suggestion is introduced considering the fact that modern society being a self-organized system seeks to gain stable condition. Anthropomorphic networks are means of decreasing social entropy, which is growing as a result of any kind of human intervention into social processes. Thus, for the first time a human is challenged by their intellect, ability to create, discover and control.

  16. How Are Feedbacks Represented in Land Models?

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2016-09-01

    Full Text Available Land systems are characterised by many feedbacks that can result in complex system behaviour. We defined feedbacks as the two-way influences between the land use system and a related system (e.g., climate, soils and markets, both of which are encompassed by the land system. Land models that include feedbacks thus probably more accurately mimic how land systems respond to, e.g., policy or climate change. However, representing feedbacks in land models is a challenge. We reviewed articles incorporating feedbacks into land models and analysed each with predefined indicators. We found that (1 most modelled feedbacks couple land use systems with transport, soil and market systems, while only a few include feedbacks between land use and social systems or climate systems; (2 equation-based land use models that follow a top-down approach prevail; and (3 feedbacks’ effects on system behaviour remain relatively unexplored. We recommend that land system modellers (1 consider feedbacks between land use systems and social systems; (2 adopt (bottom-up approaches suited to incorporating spatial heterogeneity and better representing land use decision-making; and (3 pay more attention to nonlinear system behaviour and its implications for land system management and policy.

  17. Metabolite Profiling of Eastern Teaberry (Gaultheria procumbens L. Lipophilic Leaf Extracts with Hyaluronidase and Lipoxygenase Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Piotr Michel

    2017-03-01

    Full Text Available The phytochemical profile and anti-inflammatory activity of Gaultheria procumbens dry lipophilic leaf extracts were evaluated. Forty compounds were identified by GC-MS, representing 86.36% and 81.97% of the petroleum ether (PE and chloroform (CHE extracts, respectively, with ursolic acid (28.82%, oleanolic acid (10.11%, methyl benzoate (10.03%, and methyl salicylate (6.88% dominating in CHE, and methyl benzoate (21.59%, docosane (18.86%, and octacosane (11.72% prevailing in PE. Three components of CHE were fully identified after flash chromatography isolation and spectroscopic studies as (6S,9R-vomifoliol (4.35%, 8-demethyl-latifolin (1.13%, and 8-demethylsideroxylin (2.25%. Hyaluronidase and lipoxygenase inhibitory activity was tested for CHE (IC50 = 282.15 ± 10.38 μg/mL and 899.97 ± 31.17 μg/mL, respectively, PE (IC50 = 401.82 ± 16.12 μg/mL and 738.49 ± 15.92 μg/mL, and nine of the main constituents versus heparin (IC50 = 366.24 ± 14.72 μg/mL and indomethacin (IC50 = 92.60 ± 3.71 μg/mL as positive controls. With the best activity/concentration relationships, ursolic and oleanolic acids were recommended as analytical markers for the extracts and plant material. Seasonal variation of both markers following foliar development was investigated by UHPLC-PDA. The highest levels of ursolic (5.36–5.87 mg/g DW of the leaves and oleanolic (1.14–1.26 mg/g DW acids were observed between August and October, indicating the optimal season for harvesting.

  18. Quantifying Heuristic Bias: Anchoring, Availability, and Representativeness.

    Science.gov (United States)

    Richie, Megan; Josephson, S Andrew

    2018-01-01

    Construct: Authors examined whether a new vignette-based instrument could isolate and quantify heuristic bias. Heuristics are cognitive shortcuts that may introduce bias and contribute to error. There is no standardized instrument available to quantify heuristic bias in clinical decision making, limiting future study of educational interventions designed to improve calibration of medical decisions. This study presents validity data to support a vignette-based instrument quantifying bias due to the anchoring, availability, and representativeness heuristics. Participants completed questionnaires requiring assignment of probabilities to potential outcomes of medical and nonmedical scenarios. The instrument randomly presented scenarios in one of two versions: Version A, encouraging heuristic bias, and Version B, worded neutrally. The primary outcome was the difference in probability judgments for Version A versus Version B scenario options. Of 167 participants recruited, 139 enrolled. Participants assigned significantly higher mean probability values to Version A scenario options (M = 9.56, SD = 3.75) than Version B (M = 8.98, SD = 3.76), t(1801) = 3.27, p = .001. This result remained significant analyzing medical scenarios alone (Version A, M = 9.41, SD = 3.92; Version B, M = 8.86, SD = 4.09), t(1204) = 2.36, p = .02. Analyzing medical scenarios by heuristic revealed a significant difference between Version A and B for availability (Version A, M = 6.52, SD = 3.32; Version B, M = 5.52, SD = 3.05), t(404) = 3.04, p = .003, and representativeness (Version A, M = 11.45, SD = 3.12; Version B, M = 10.67, SD = 3.71), t(396) = 2.28, p = .02, but not anchoring. Stratifying by training level, students maintained a significant difference between Version A and B medical scenarios (Version A, M = 9.83, SD = 3.75; Version B, M = 9.00, SD = 3.98), t(465) = 2.29, p = .02, but not residents or attendings. Stratifying by heuristic and training level, availability maintained

  19. Picturing and modelling catchments by representative hillslopes

    Science.gov (United States)

    Loritz, Ralf; Hassler, Sibylle; Jackisch, Conrad; Zehe, Erwin

    2016-04-01

    Hydrological modelling studies often start with a qualitative sketch of the hydrological processes of a catchment. These so-called perceptual models are often pictured as hillslopes and are generalizations displaying only the dominant and relevant processes of a catchment or hillslope. The problem with these models is that they are prone to become too much predetermined by the designer's background and experience. Moreover it is difficult to know if that picture is correct and contains enough complexity to represent the system under study. Nevertheless, because of their qualitative form, perceptual models are easy to understand and can be an excellent tool for multidisciplinary exchange between researchers with different backgrounds, helping to identify the dominant structures and processes in a catchment. In our study we explore whether a perceptual model built upon an intensive field campaign may serve as a blueprint for setting up representative hillslopes in a hydrological model to reproduce the functioning of two distinctly different catchments. We use a physically-based 2D hillslope model which has proven capable to be driven by measured soil-hydrological parameters. A key asset of our approach is that the model structure itself remains a picture of the perceptual model, which is benchmarked against a) geo-physical images of the subsurface and b) observed dynamics of discharge, distributed state variables and fluxes (soil moisture, matric potential and sap flow). Within this approach we are able to set up two behavioral model structures which allow the simulation of the most important hydrological fluxes and state variables in good accordance with available observations within the 19.4 km2 large Colpach catchment and the 4.5 km2 large Wollefsbach catchment in Luxembourg without the necessity of calibration. This corroborates, contrary to the widespread opinion, that a) lower mesoscale catchments may be modelled by representative hillslopes and b) physically

  20. Using resource graphs to represent conceptual change

    Directory of Open Access Journals (Sweden)

    Michael C. Wittmann

    2006-08-01

    Full Text Available We introduce resource graphs, a representation of linked ideas used when reasoning about specific contexts in physics. Our model is consistent with previous descriptions of coordination classes and resources. It represents mesoscopic scales that are neither knowledge-in-pieces nor large-scale concepts. We use resource graphs to describe several forms of conceptual change: incremental, cascade, wholesale, and dual construction. For each, we give evidence from the physics education research literature to show examples of each form of conceptual change. Where possible, we compare our representation to models used by other researchers. Building on our representation, we analyze another form of conceptual change, differentiation, and suggest several experimental studies that would help understand the differences between reform-based curricula.

  1. STATISTICAL MODELS OF REPRESENTING INTELLECTUAL CAPITAL

    Directory of Open Access Journals (Sweden)

    Andreea Feraru

    2016-06-01

    Full Text Available This article entitled Statistical Models of Representing Intellectual Capital approaches and analyses the concept of intellectual capital, as well as the main models which can support enterprisers/managers in evaluating and quantifying the advantages of intellectual capital. Most authors examine intellectual capital from a static perspective and focus on the development of its various evaluation models. In this chapter we surveyed the classical static models: Sveiby, Edvisson, Balanced Scorecard, as well as the canonical model of intellectual capital. Among the group of static models for evaluating organisational intellectual capital the canonical model stands out. This model enables the structuring of organisational intellectual capital in: human capital, structural capital and relational capital. Although the model is widely spread, it is a static one and can thus create a series of errors in the process of evaluation, because all the three entities mentioned above are not independent from the viewpoint of their contents, as any logic of structuring complex entities requires.

  2. Towards a representative periphytic diatom sample

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available The need to acquire a representative periphytic diatom sample for river water quality monitoring has been recognised in the development of existing diatom indices, important in the development and employment of diatom monitoring tools for the Water Framework Directive. In this study, a nested design with replication is employed to investigate the magnitude of variation in diatom biomass, composition and Trophic Diatom Index at varying scales within a small chalk river. The study shows that the use of artificial substrates may not result in diatom communities that are typical of the surrounding natural substrates. Periphytic diatom biomass and composition varies between artificial and natural substrates, riffles and glides and between two stretches of the river channel. The study also highlights the existence of high variation in diatom frustule frequency and biovolume at the individual replicate scale which may have implications for the use of diatoms in routine monitoring.

  3. Antecedents and Consequences of Sales Representatives' Relationship Termination Competence

    DEFF Research Database (Denmark)

    Geersbro, Jens; Ritter, Thomas

    2013-01-01

    . In addition, termination competence significantly affects the value of customer portfolios. Practical implications: The findings suggest that managers should more actively consider relationship termination as a legitimate option in customer relationship management. In order to increase the value of a firm......'s customer portfolio, managers must not only provide a clear definition of the types of customers the organization does not want to serve, but must also implement termination routines within the organization. Managers also need to establish incentives for sales representatives to terminate relationships......Purpose: Most firms have a number of unprofitable customer relationships that drain the firms' resources. However, firms in general and sales representatives in particular hesitate to address this problem and, ultimately, to terminate business relationships. This paper therefore aims to investigate...

  4. Probability & Perception: The Representativeness Heuristic in Action

    Science.gov (United States)

    Lu, Yun; Vasko, Francis J.; Drummond, Trevor J.; Vasko, Lisa E.

    2014-01-01

    If the prospective students of probability lack a background in mathematical proofs, hands-on classroom activities may work well to help them to learn to analyze problems correctly. For example, students may physically roll a die twice to count and compare the frequency of the sequences. Tools such as graphing calculators or Microsoft Excel®…

  5. Multicriteria analysis of ontologically represented information

    Science.gov (United States)

    Wasielewska, K.; Ganzha, M.; Paprzycki, M.; Bǎdicǎ, C.; Ivanovic, M.; Lirkov, I.

    2014-11-01

    Our current work concerns the development of a decision support system for the software selection problem. The main idea is to utilize expert knowledge to help the user in selecting the best software / method / computational resource to solve a computational problem. Obviously, this involves multicriterial decision making and the key open question is: which method to choose. The context of the work is provided by the Agents in Grid (AiG) project, where the software selection (and thus multicriterial analysis) is to be realized when all information concerning the problem, the hardware and the software is ontologically represented. Initially, we have considered the Analytical Hierarchy Process (AHP), which is well suited for the hierarchical data structures (e.g., such that have been formulated in terms of ontologies). However, due to its well-known shortcomings, we have decided to extend our search for the multicriterial analysis method best suited for the problem in question. In this paper we report results of our search, which involved: (i) TOPSIS (Technique for Order Preference by Similarity to Ideal Solution), (ii) PROMETHEE, and (iii) GRIP (Generalized Regression with Intensities of Preference). We also briefly argue why other methods have not been considered as valuable candidates.

  6. What does self rated mental health represent

    Directory of Open Access Journals (Sweden)

    Daphna Levinson

    2014-12-01

    Full Text Available Background. Unlike the widely used self rated health, the self rated mental health was found unsuitable as a proxy for mental illness. This paper analyses the relationships between the self ratings of physical health, mental health and overall health, and their association of with the objective indicators for physical and mental health. Design and methods. The study is a secondary analysis of data from a nationwide representative sample of the non-institutionalized adult residents of Israel in 2003 that was collected via computer-assisted personal interview methods [n=4859].Results. The self rated physical health and the self rated mental health were strongly related to each other yet the self rated mental health was not related to chronic physical conditions and the self rated physical health was not related to mental disorders. In a multiple logistic regression analysis, those with positive self rated mental health had 93 times the odds of reporting positive overall health whereas those with positive self rated physical health had 40 times the odds of reporting positive overall health. Conclusions. The self rating of mental health presents a qualitatively different dimension from mental illness. The self rated mental health is two times more important than the self rated physical health in predicting the self rated overall health

  7. The Two Sides of the Representative Coin

    Directory of Open Access Journals (Sweden)

    Keith Sutherland

    2011-12-01

    Full Text Available In Federalist 10 James Madison drew a functional distinction between “parties” (advocates for factional interests and “judgment” (decision-making for the public good and warned of the corrupting effect of combining both functions in a “single body of men.” This paper argues that one way of overcoming “Madisonian corruption” would be by restricting political parties to an advocacy role, reserving the judgment function to an allotted (randomly-selected microcosm of the whole citizenry, who would determine the outcome of parliamentary debates by secret ballot—a division of labour suggested by James Fishkin’s experiments in deliberative polling. The paper then defends this radical constitutional proposal against Bernard Manin’s (1997 claim that an allotted microcosm could not possibly fulfil the “consent” requirement of Natural Right theory. Not only does the proposal challenge Manin’s thesis, but a 28th Amendment implementing it would finally reconcile the competing visions that have bedevilled representative democracy since the Constitutional Convention of 1787.

  8. A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing Reduces Artifacts and False Positives in Lysine Demethylase Screening.

    Science.gov (United States)

    Wigle, Tim J; Swinger, Kerren K; Campbell, John E; Scholle, Michael D; Sherrill, John; Admirand, Elizabeth A; Boriack-Sjodin, P Ann; Kuntz, Kevin W; Chesworth, Richard; Moyer, Mikel P; Scott, Margaret Porter; Copeland, Robert A

    2015-07-01

    Demethylation of histones by lysine demethylases (KDMs) plays a critical role in controlling gene transcription. Aberrant demethylation may play a causal role in diseases such as cancer. Despite the biological significance of these enzymes, there are limited assay technologies for study of KDMs and few quality chemical probes available to interrogate their biology. In this report, we demonstrate the utility of self-assembled monolayer desorption/ionization (SAMDI) mass spectrometry for the investigation of quantitative KDM enzyme kinetics and for high-throughput screening for KDM inhibitors. SAMDI can be performed in 384-well format and rapidly allows reaction components to be purified prior to injection into a mass spectrometer, without a throughput-limiting liquid chromatography step. We developed sensitive and robust assays for KDM1A (LSD1, AOF2) and KDM4C (JMJD2C, GASC1) and screened 13,824 compounds against each enzyme. Hits were rapidly triaged using a redox assay to identify compounds that interfered with the catalytic oxidation chemistry used by the KDMs for the demethylation reaction. We find that overall this high-throughput mass spectrometry platform coupled with the elimination of redox active compounds leads to a hit rate that is manageable for follow-up work. © 2015 Society for Laboratory Automation and Screening.

  9. Musculoskeletal symptoms in pharmaceutical sales representatives.

    Science.gov (United States)

    Sang, Katherine; Gyi, Diane; Haslam, Cheryl

    2010-03-01

    Musculoskeletal disorders (MSDs) are a leading cause of work-related ill health. Existing literature indicates that pharmaceutical sales representatives (PSRs) report a high prevalence of MSDs, possibly exacerbated by the nature of work (prolonged driving and manual handling). In addition, they experience difficulty in accessing occupational health services. To assess the prevalence of musculoskeletal symptoms and associated risk factors among PSRs in order to assist their occupational health management through raising risk awareness. A self-completed questionnaire distributed to 205 PSRs within a UK pharmaceutical company was used to assess the prevalence of musculoskeletal symptoms, psychosocial factors, work tasks undertaken and company car use. To assist understanding of work tasks and organizational factors, semi-structured interviews were undertaken with a sample of 12 key personnel. The questionnaire response rate was 68%. PSRs reported high mileage and 100% reported working from the car in a typical day. Forty-seven per cent reported both manual handling for > or = 4 h/day and 'often' or 'sometimes' working from the car. Fifty-seven per cent reported low back symptoms in the last 12 months. Interview data revealed issues relating to car choice, storage in the boot and working from the car, which should be considered when developing priorities for preventive management of MSDs. Musculoskeletal symptoms appear to be a problem for PSRs, with risk factors reported as prolonged driving, sitting in the car, working from the car and manual handling. Interventions to facilitate their occupational health management should focus on raising awareness of the risks of prolonged driving and working from the car.

  10. HOW TO REPRESENT THE GENETIC CODE?

    Directory of Open Access Journals (Sweden)

    N.S. Santos-Magalhães

    2004-05-01

    Full Text Available The advent of molecular genetic comprises a true revolution of far-reaching consequences for human-kind, which evolved into a specialized branch of the modern-day Biochemistry. The analysis of specicgenomic information are gaining wide-ranging interest because of their signicance to the early diag-nosis of disease, and the discovery of modern drugs. In order to take advantage of a wide assortmentof signal processing (SP algorithms, the primary step of modern genomic SP involves convertingsymbolic-DNA sequences into complex-valued signals. How to represent the genetic code? Despitebeing extensively known, the DNA mapping into proteins is one of the relevant discoveries of genetics.The genetic code (GC is revisited in this work, addressing other descriptions for it, which can beworthy for genomic SP. Three original representations are discussed. The inner-to-outer map buildson the unbalanced role of nucleotides of a codon. A two-dimensional-Gray genetic representationis oered as a structured map that can help interpreting DNA spectrograms or scalograms. Theseare among the powerful visual tools for genome analysis, which depends on the choice of the geneticmapping. Finally, the world-chart for the GC is investigated. Evoking the cyclic structure of thegenetic mapping, it can be folded joining the left-right borders, and the top-bottom frontiers. As aresult, the GC can be drawn on the surface of a sphere resembling a world-map. Eight parallels oflatitude are required (four in each hemisphere as well as four meridians of longitude associated tofour corresponding anti-meridians. The tropic circles have 11.25o, 33.75o, 56.25o, and 78.5o (Northand South. Starting from an arbitrary Greenwich meridian, the meridians of longitude can be plottedat 22.5o, 67.5o, 112.5o, and 157.5o (East and West. Each triplet is assigned to a single point on thesurface that we named Nirenberg-Kohamas Earth. Despite being valuable, usual representations forthe GC can be

  11. Right Lateral Cerebellum Represents Linguistic Predictability.

    Science.gov (United States)

    Lesage, Elise; Hansen, Peter C; Miall, R Chris

    2017-06-28

    Mounting evidence indicates that posterolateral portions of the cerebellum (right Crus I/II) contribute to language processing, but the nature of this role remains unclear. Based on a well-supported theory of cerebellar motor function, which ascribes to the cerebellum a role in short-term prediction through internal modeling, we hypothesize that right cerebellar Crus I/II supports prediction of upcoming sentence content. We tested this hypothesis using event-related fMRI in male and female human subjects by manipulating the predictability of written sentences. Our design controlled for motor planning and execution, as well as for linguistic features and working memory load; it also allowed separation of the prediction interval from the presentation of the final sentence item. In addition, three further fMRI tasks captured semantic, phonological, and orthographic processing to shed light on the nature of the information processed. As hypothesized, activity in right posterolateral cerebellum correlated with the predictability of the upcoming target word. This cerebellar region also responded to prediction error during the outcome of the trial. Further, this region was engaged in phonological, but not semantic or orthographic, processing. This is the first imaging study to demonstrate a right cerebellar contribution in language comprehension independently from motor, cognitive, and linguistic confounds. These results complement our work using other methodologies showing cerebellar engagement in linguistic prediction and suggest that internal modeling of phonological representations aids language production and comprehension. SIGNIFICANCE STATEMENT The cerebellum is traditionally seen as a motor structure that allows for smooth movement by predicting upcoming signals. However, the cerebellum is also consistently implicated in nonmotor functions such as language and working memory. Using fMRI, we identify a cerebellar area that is active when words are predicted and

  12. Endeavors to Represent the Non-Representational

    DEFF Research Database (Denmark)

    Nørgård, Rikke Toft

    without seeming ‘meaningless’ to the research community. Therefore, I was forced to take on the additional task of developing a methodological framework that, on the one hand, was capable of connecting with the corporeal-locomotive dimension in gameplay activity and experience in a generative...... mix of ‘research music videos,’ ‘film strips,’ ‘photo montages,’ ‘collages,’ ‘poetic tales,’ ‘theoretical remixes,’ ‘aestheticized metaphorical writings,’ ‘fictionalized narratives,’ ‘narrative inquiries.’ This article presents the methodological side of the story through presenting the results...... dictate the exploration of the research field or subject – A circumstance that sets the methodological approach apart from more traditional approaches within media studies and game research....

  13. Application to Representative Structures. Other Representative Structures: Mutsu-Ogawara, Niigata East and West

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Burcharth, Hans F.

    1999-01-01

    Reliability analyses are performed for three Japanese vertical wall breakwaters in this chapter. Only the geotechnical failure modes described in chapter 3 are investigated. For none of the breakwaters detailed data are available for the wave climate and for the soil conditions. Therefore represe...

  14. Design and evaluation of representative indoor radon surveys

    International Nuclear Information System (INIS)

    Csige, I.; Csegzi, S.

    2004-01-01

    We have developed a procedure to design and evaluate representative indoor radon surveys. The procedure is based on random sampling of a population of houses and careful statistical analysis of measured indoor radon concentrations. The method is designed to estimate the fraction of houses in which annual average 222 Rn activity concentration may exceed a certain reference level. Measurements of annual average indoor 222 Rn activity concentration were done in sleeping rooms at pillow level using etched track type radon detectors. We applied the above procedure in an old fashioned village and in a fast developing small city in Transylvania, Romania. In the village almost all houses were single floor wooden made houses without cellar built with traditional technology on a geologically uniform area. The distribution of indoor 222 Rn activity concentration in a sample of 115 houses can almost perfectly be fitted with log-normal probability density function. The correlation coefficient of linear fitting on linearized scales was k = -0.9980. The percentages of houses expected to have annual average 222 Rn activity concentration higher than 400 Bq m -3 is less than 1 %, and of those higher than 600 Bq m -3 can be estimated to be around 0.1 %. The small city, on the other hand lies on a geologically inhomogeneous area, and house construction technology has also changed dramatically in past decades. The resulting distribution of measured indoor 222 Rn activity concentration in a sample of 116 houses cannot be fitted with any simple probability density function. Therefore the prediction of the fraction of houses in which the annual average 222 Rn activity concentration may exceed a certain reference level could not be done adequately. With certain assumptions we estimated that the percentages of houses expected to have annual average 222 Rn activity concentration higher than 400 Bq m -3 is between 3 and 7 %, and of those higher than 600 Bq m -3 can be estimated to be between

  15. Understanding and representing natural language meaning

    Science.gov (United States)

    Waltz, D. L.; Maran, L. R.; Dorfman, M. H.; Dinitz, R.; Farwell, D.

    1982-12-01

    During this contract period the authors have: (1) continued investigation of events and actions by means of representation schemes called 'event shape diagrams'; (2) written a parsing program which selects appropriate word and sentence meanings by a parallel process know as activation and inhibition; (3) begun investigation of the point of a story or event by modeling the motivations and emotional behaviors of story characters; (4) started work on combining and translating two machine-readable dictionaries into a lexicon and knowledge base which will form an integral part of our natural language understanding programs; (5) made substantial progress toward a general model for the representation of cognitive relations by comparing English scene and event descriptions with similar descriptions in other languages; (6) constructed a general model for the representation of tense and aspect of verbs; (7) made progress toward the design of an integrated robotics system which accepts English requests, and uses visual and tactile inputs in making decisions and learning new tasks.

  16. Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor

    DEFF Research Database (Denmark)

    Kristensen, Line Hyltoft; Nielsen, Anders Laerke; Helgstrand, Charlotte

    2012-01-01

    Dynamic methylations and demethylations of histone lysine residues are important for gene regulation and are facilitated by histone methyltransferases and histone demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2 specific lysine demethylase belonging to the family of JmjC domain containing...... lysine specific HDMs (JHDMs). Several studies have linked KDM5B to breast, prostate and skin cancer, highlighting its potential as a drug target. However, most inhibitor studies have focused on other JHDMs, and inhibitors for KDM5B remain to be explored. Here, we report the expression, purification...... and characterization of the catalytic core of recombinant KDM5B (residues 1-769, ccKDM5B). We show that ccKDM5B, recombinantly expressed in insect cells, demethylates H3K4me3 and H3K4me2 in vitro. The kinetic characterization showed that ccKDM5B has a K(m) (app) value of 0.5 µM for its tri-methylated substrate H3...

  17. Actividad física deportiva en una muestra representativa de la población de la Región de Murcia Physical sports activity in a representative sample of the population of Región de Murcia, Spain

    Directory of Open Access Journals (Sweden)

    M.T. Martínez-Ros

    2003-02-01

    the region of Murcia, Spain, and to analyze its association with major demographic and socioeconomic determinants and other cardiovascular risk factors. Methods: Survey of a representative sample of the population aged between 18 and 65 years from Murcia was performed using multistage random sampling with definition of the sample quotas. A total of 3091 individuals were surveyed. The frequency and duration of intense physical sports activity during the two weeks prior to the survey was obtained using a validated questionnaire. Information was also collected on socioeconomic variables, smoking, blood pressure, weight and height and a blood test was performed to determine plasma lipids. Intense or vigorous physical activity (≥ 6 Metabolic Equivalents [MET] was measured in kcal/day and reduced to hours/week to give three categories: no vigorous physical activity, less than 2 hours/week, and 2 hours/week or more. Results: Overall, 17.8% (95% CI: 16.6-19.0 of the adult population of the region of Murcia performed intense physical activity for ≥ 2 hours/week. The figures were twice as high in men (23.1%; 95% CI: 21.0-25.2 than in women (12.5%; 95% CI: 10.9-14.1. In the logistic regression analysis, a higher frequency of intense physical activity was associated with age, level of education and employment situation. In men it was also associated with occupation and residence in urban areas. Conclusions: During the study period, one in five adults in the region of Murcia took intense physical sports activity with a frequency and duration that were compatible with the prevention of episodes of coronary ischemia.

  18. Registration Appointment and Services for Representatives Management Information

    Data.gov (United States)

    Social Security Administration — A new internet/intranet application that collects all representative information and establishes the relationship between the claimant and the representative. Allow...

  19. Japanese practicing physicians' relationships with pharmaceutical representatives: a national survey.

    Directory of Open Access Journals (Sweden)

    Sayaka Saito

    Full Text Available BACKGROUND: Previous surveys on the relationship between physicians and pharmaceutical representatives (PRs have been of limited quality. The purpose of our survey of practicing physicians in Japan was to assess the extent of their involvement in pharmaceutical promotional activities, physician characteristics that predict such involvement, attitudes toward relationships with PRs, correlations between the extent of involvement and attitudes, and differences in the extent of involvement according to self-reported prescribing behaviors. METHODS AND FINDINGS: From January to March 2008, we conducted a national survey of 2621 practicing physicians in seven specialties: internal medicine, general surgery, orthopedic surgery, pediatrics, obstetrics-gynecology, psychiatry, and ophthalmology. The response rate was 54%. Most physicians met with PRs (98%, received drug samples (85% and stationery (96%, and participated in industry-sponsored continuing medical education (CME events at the workplace (80% and outside the workplace (93%. Half accepted meals outside the workplace (49% and financial subsidies to attend CME events (49%. Rules at the workplace banning both meetings with PRs and gifts predicted less involvement of physicians in promotional activities. Physicians valued information from PRs. They believed that they were unlikely to be influenced by promotional activities, but that their colleagues were more susceptible to such influence than themselves. They were divided about the appropriateness of low-value gifts. The extent of physician involvement in promotional activities was positively correlated with the attitudes that PRs are a valuable source of information and that gifts are appropriate. The extent of such involvement was higher among physicians who prefer to ask PRs for information when a new medication becomes available, physicians who are not satisfied with patient encounters ending only with advice, and physicians who prefer to

  20. Molecular basis of the activity of the phytopathogen pectin methylesterase

    Science.gov (United States)

    Fries, Markus; Ihrig, Jessica; Brocklehurst, Keith; Shevchik, Vladimir E; Pickersgill, Richard W

    2007-01-01

    We provide a mechanism for the activity of pectin methylesterase (PME), the enzyme that catalyses the essential first step in bacterial invasion of plant tissues. The complexes formed in the crystal using specifically methylated pectins, together with kinetic measurements of directed mutants, provide clear insights at atomic resolution into the specificity and the processive action of the Erwinia chrysanthemi enzyme. Product complexes provide additional snapshots along the reaction coordinate. We previously revealed that PME is a novel aspartic-esterase possessing parallel β-helix architecture and now show that the two conserved aspartates are the nucleophile and general acid-base in the mechanism, respectively. Other conserved residues at the catalytic centre are shown to be essential for substrate binding or transition state stabilisation. The preferential binding of methylated sugar residues upstream of the catalytic site, and demethylated residues downstream, drives the enzyme along the pectin molecule and accounts for the sequential pattern of demethylation produced by both bacterial and plant PMEs. PMID:17717531

  1. Representativeness of environmental impact assessment methods regarding Life Cycle Inventories.

    Science.gov (United States)

    Esnouf, Antoine; Latrille, Éric; Steyer, Jean-Philippe; Helias, Arnaud

    2018-04-15

    Life Cycle Assessment (LCA) characterises all the exchanges between human driven activities and the environment, thus representing a powerful approach for tackling the environmental impact of a production system. However, LCA practitioners must still choose the appropriate Life Cycle Impact Assessment (LCIA) method to use and are expected to justify this choice: impacts should be relevant facing the concerns of the study and misrepresentations should be avoided. This work aids practitioners in evaluating the adequacy between the assessed environmental issues and studied production system. Based on a geometrical standpoint of LCA framework, Life Cycle Inventories (LCIs) and LCIA methods were localized in the vector space spanned by elementary flows. A proximity measurement, the Representativeness Index (RI), is proposed to explore the relationship between those datasets (LCIs and LCIA methods) through an angular distance. RIs highlight LCIA methods that measure issues for which the LCI can be particularly harmful. A high RI indicates a close proximity between a LCI and a LCIA method, and highlights a better representation of the elementary flows by the LCIA method. To illustrate the benefits of the proposed approach, representativeness of LCIA methods regarding four electricity mix production LCIs from the ecoinvent database are presented. RIs for 18 LCIA methods (accounting for a total of 232 impact categories) were calculated on these LCIs and the relevance of the methods are discussed. RIs prove to be a criterion for distinguishing the different LCIA methods and could thus be employed by practitioners for deeper interpretations of LCIA results. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Solar Heliospheric and INterplanetary Environment (SHINE) Students - Student Representatives' Perspectives

    Science.gov (United States)

    Pahud, D. M.; Niembro, T.

    2014-12-01

    The SHINE workshop is an annual meeting of solar and heliospheric scientists which, in addition to aiming to improve understanding of solar disturbances and their propagation to, and effect, on the Earth (shinecon.org), is dedicated to actively supporting students. This dedication is substantiated in part through the National Science Foundation (NSF) providing funding for student attendance to the workshop, which enables student participation. Another example of SHINE's commitment to its student members is the incorporation of a Student Day prior to the workshop since 2003, entirely organized and run by two student representatives. While there are variations in format from year to year, Student Day consists of tutorials and research talks exclusively by student volunteers to an audience of only students. The day is intended to provide a low-stress environment for students to learn about the various topics addressed during the workshop, to ask questions freely, and to engage in scientific discussion with other students which hopefully is a catalyst for collaboration. As a result of positive experiences, over the past decade student attendance and participation in the workshop have increased. At the SHINE 2014 workshop, nearly a third of attendees were students. SHINE student visibility has increased over the years, with student posters being advertised at breakfast, inclusion of a student day summary by the student representatives during a plenary session, and continued support from the steering committee. Students are also promoting a broader impact of SHINE sciences via increased social media presence. From a student representative's perspective, SHINE has built and fostered a healthy student community and encourages students to engage in shaping the future of the field.

  3. 20 CFR 266.7 - Accountability of a representative payee.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Accountability of a representative payee. 266.7 Section 266.7 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT REPRESENTATIVE PAYMENT § 266.7 Accountability of a representative payee. (a) A representative...

  4. Type a behaviour pattern and performance as insurance representative

    Directory of Open Access Journals (Sweden)

    D. J. W. Strumpfer

    1991-06-01

    Full Text Available Participants were 155 insurance representatives and 116 of them who were still in the same position one year later. The performance criterion represented commission on policies and annuities sold; data were obtained for the year of testing and the next year. The Jenkins Activity Survey was administered. The Type A (M === 6.26; SD == 7.90 was not excessively high. The Factor H score correlated r (114 - 0,23, p = 0,05 with the criterion for the second year; no other score correlated significantly with criterion scores. Interventions to reduce Type A behaviour for health reasons seem unlikely to reduce business performance. Opsomming Die deelnemers was 155 assuransieverteenwoordigers en 116 van hulle wat een jaar later nog in dieselfde pos was. Die prestasiekriterium het kommissie op polisse en annuiteite verteenwoordig; gegewens is vir die jaar van toetsing en die volgende jaar verkry. Jenkins se Aktiviteitsvraelys is toegepas. Die Tipe A (X == 6.26; SA - 790 was nie buitengewoon hoog nie. Die Faktor H-telling het r (114 - 0,23, p - 0,05 met die kriterium vir die tweede jaar gekorreleer; geen ander tellings het beduidend met die kriteriumtellings gekorreleer nie. Dit lyk onwaarskynlik dat intervensies om Tipe A-gedrag om gesondheidsredes te verminder besigheidsprestasie sal verlaag.

  5. [Dangerous liaisons--physicians and pharmaceutical sales representatives].

    Science.gov (United States)

    Granja, Mónica

    2005-01-01

    Interactions between physicians and detailers (even when legitimate ones) raise scientific and ethical questions. In Portugal little thinking and discussion has been done on the subject and the blames for bribery have monopolized the media. This work intended to review what has been said in medical literature about these interactions. How do physicians see themselves when interacting with pharmaceutical companies and their representatives? Do these companies in fact change their prescriptive behaviour, and, if so, how do they change it? How can physicians interact with detailers and still keep their best practice? A Medline research, from 1966 till 2002, was performed using the key-words as follows. A database similar to Medline but concerning medical journals published in Portugal, Index das Revistas Médicas Portuguesas, was also researched from 1992 to 2002. Pharmaceutical companies are profit bound and they allot promoting activities, and detailing in particular, huge amounts of money. Most physicians hold firmly to the belief that they are able to resist and not be influenced by drug companies promotion activities. Nevertheless, all previous works on literature tell us the opposite. Market research also indicates that detailers effectively promote drug sales. Various works also suggest that the information detailers provide to physicians may be largely incorrect, even comparing it to the written information provided by the pharmaceutical companies they work for. The frequency at which portuguese physicians (especially family physicians) contact with pharmaceutical sales representatives is higher than the frequency reported in countries where the available studies come from (namely, Canada and the United States of America). This may put portuguese physicians at a higher risk, making it imperative that work and wide debate are initiated among the class.

  6. Representativeness of the IAGOS airborne measurements in the lower troposphere

    Directory of Open Access Journals (Sweden)

    H. Petetin

    2018-03-01

    Full Text Available In the framework of the In Service Aircraft for Global Observing System (IAGOS program, airborne in-situ O3 and CO measurements are performed routinely using in-service aircraft, providing vertical profiles from the surface to about 10–12 km. Due to the specificity of IAGOS measurements (measurements around busy international airports, uncertainties exist on their representativeness in the lower troposphere as they may be impacted by emissions related to airport activities and/or other aircraft. In this study, we thus investigate how the IAGOS measurements in the lower troposphere compare with nearby surface stations (from the local Air Quality monitoring network (AQN and more distant regional surface stations (from the Global Atmospheric Watch (GAW network. The study focuses on Frankfurt but some results at other European airports (Vienna, Paris are also discussed. Results indicate that the IAGOS observations close to the surface do not appear to be strongly impacted by local emissions related to airport activities. In terms of mixing ratio distribution, seasonal variations and trends, the CO and O3 mixing ratios measured by IAGOS in the first few hundred metres above the surface have similar characteristics to the mixing ratios measured at surrounding urban background stations. Higher in altitude, both the difference with data from the local AQN and the consistency with the GAW regional stations are higher, which indicates a larger representativeness of the IAGOS data. Despite few quantitative differences with Frankfurt, consistent results are obtained in the two other cities Vienna and Paris. Based on 11 years of data (2002–2012, this study thus demonstrates that IAGOS observations in the lowest troposphere can be used as a complement to surface stations to study the air quality in/around the agglomeration, providing important information on the vertical distribution of pollution.

  7. Marketing norm perception among medical representatives in Indian pharmaceutical industry.

    Science.gov (United States)

    Nagashekhara, Molugulu; Agil, Syed Omar Syed; Ramasamy, Ravindran

    2012-03-01

    Study of marketing norm perception among medical representatives is an under-portrayed component that deserves further perusal in the pharmaceutical industry. The purpose of this study is to find out the perception of marketing norms among medical representatives. The research design is quantitative and cross sectional study with medical representatives as unit of analysis. Data is collected from medical representatives (n=300) using a simple random and cluster sampling using a structured questionnaire. Results indicate that there is no difference in the perception of marketing norms among male and female medical representatives. But there is a difference in opinion among domestic and multinational company's medical representatives. Educational back ground of medical representatives also shows the difference in opinion among medical representatives. Degree holders and multinational company medical representatives have high perception of marketing norms compare to their counterparts. The researchers strongly believe that mandatory training on marketing norms is beneficial in decision making process during the dilemmas in the sales field.

  8. Representatives of religious education in the structure of Novorossiysk university

    Directory of Open Access Journals (Sweden)

    Г. П. Бахчиванжи

    2015-03-01

    Full Text Available History of the Departments of Theology, Ecclesiastical History and Ecclesiastical Law of Novorossiysk University as well as clarification of activities of professors who were the Heads of these Departments is the subject of the article. The objective of the research was to reveal the contribution to science these professors had made on basis of such material as “Records of Proceedings of the Board Meeting of Novorossiysk University”, “Teaching of Sciences at the Imperial Novorossiysk University Review” as well as the particular studies of the professors themselves. As a result of the research using the analytical approach generic aspects of existence of theological departments in educational structure of the University including the period of teaching the theological disciplines at the Richelieu Lycée were described. The basic legislative acts regulating the activity of such Departments were stated and the activity of such professors as Pavlovskiy M.K., Kudryavtsev A.N., Voytovskiy V.M., Klitin A.N., Krasnoseltsev N.F., Dobroklonskiy A.P., Almazov A.I., Pavlov F.S. who not only became the significant persons in the history of the University but also played the leading role in social and spiritual life of Odessa in general was elucidated. Such analysis of the activity of the representatives of religious education at Novorossiysk University provided an opportunity to conclude of the importance of the theological disciplines in educational structure of the University as it is them that are of great importance to the spiritual development of personality and society on the whole.

  9. Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

    Science.gov (United States)

    Bao, Beier; He, Yingzi; Tang, Dongmei; Li, Wenyan; Li, Huawei

    2017-01-01

    The H3K27 demethylases are involved in a variety of biological processes, including cell differentiation, proliferation, and cell death by regulating transcriptional activity. However, the function of H3K27 demethylation in the field of hearing research is poorly understood. Here, we investigated the role of H3K27me3 histone demethylase activity in hair cell regeneration using an in vivo animal model. Our data showed that pharmacologic inhibition of H3K27 demethylase activity with the specific small-molecule inhibitor GSK-J4 decreased the number of regenerated hair cells in response to neomycin damage. Furthermore, inhibition of H3K27me3 histone demethylase activity dramatically suppressed cell proliferation and activated caspase-3 levels in the regenerating neuromasts of the zebrafish lateral line. GSK-J4 administration also increased the expression of p21 and p27 in neuromast cells and inhibited the ERK signaling pathway. Collectively, our findings indicate that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss. PMID:28348517

  10. Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism.

    Science.gov (United States)

    De Filippis, Barbara; Giancristofaro, Antonella; Ammazzalorso, Alessandra; D'Angelo, Alessandra; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Petruzzelli, Michele; Amoroso, Rosa

    2011-10-01

    A new series of gemfibrozil analogues conjugated with α-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPARα agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPARα receptor and were also screened for their activity on PPARα-regulated gene CPT1A. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  11. Statistics On Title II Direct Payments To Claimant Representatives

    Data.gov (United States)

    Social Security Administration — Every person has the right to be represented by an attorney or other representative while pursuing a claim or other rights. This dataset contains data around Title...

  12. 20 CFR 416.1520 - Fee for a representative's services.

    Science.gov (United States)

    2010-04-01

    ... AGED, BLIND, AND DISABLED Representation of Parties § 416.1520 Fee for a representative's services. (a... you or your representative from contacting us in person or in writing. (B) There was a death or...

  13. 20 CFR 404.1720 - Fee for a representative's services.

    Science.gov (United States)

    2010-04-01

    ... DISABILITY INSURANCE (1950- ) Representation of Parties § 404.1720 Fee for a representative's services. (a... you or your representative from contacting us in person or in writing. (B) There was a death or...

  14. THE STRUCTURE OF HAPPINESS REPRESENTATION FOR RUSSIAN AND AMERICAN REPRESENTATIVES

    Directory of Open Access Journals (Sweden)

    S. Yu. Zhdanova

    2017-01-01

    Full Text Available Introduction. Emotional state of students exerts direct impact on their ability and readiness to cope with challenges when studying, gives rise to the success of educational process and its effectiveness. In this regard, the search of methods and determination of the tasks of psychological diagnostics is brought into focus. Above all, the teacher should consider mentality and valuable attitudes of representatives of various cultures, including their understanding of happiness and personal well-being in the activity against the background of the increasing scales of the international and interethnic mobility.The development of Russian psychology has recently acquired the direction of positive psychology, the focus of which is happiness and positive functioning of the individual. Modern research reveals significant differences in the indicators of happiness and satisfaction with life between representatives of different cultures. However, the diagnostic tools used in such studies are based primarily on the model of happiness image that has been developed in American psychology. In this connection, the question arises as to what extent the image of happiness in American culture correlates with the image of happiness in Russian culture.The aim of this work is to study the representation of happiness between representatives of American and Russian culture, the definition of invariable and variable components in the structure of representation.Methodology and research methods. The study included several stages. At the first stage, the theoretical analysis and development of the ontology of the subject area “Psychology of Happiness” was carried out. At the second stage, an empirical study of the representations of American and Russian respondents was carried out. The main method of data collection was a narrative interview; a method of early personal memories was used to obtain the narrative of happiness. Subsequent processing of verbal

  15. Invite your representative to work. Change the world. Here's how.

    Science.gov (United States)

    Montell, Denise J

    2018-02-15

    Today's political climate can seem hostile to science. Alternative facts, climate change denial, and relabeling of actual news as fake news are discouraging phenomena for sure. But these trends make it more important than ever to engage our politicians. Take heart! There is something you can do. You can show your representatives firsthand the amazing things you do, evidence of the economic engine that your activities generate, and the real people behind the discoveries. I did, and it was fun. We invited our congressman to the University of California, Santa Barbara (UCSB), and he accepted! For 2 hours, we explained and demonstrated efforts to cure blindness using stem cells, the medical implications of the discovery that cells can recover from the brink of death, a mosquito lab striving to eliminate insect-borne disease, and an Alzheimer's disease laboratory. Salud Carbajal peered through a microscope and met real scientists. Before his visit, he did not know what a postdoctoral fellow was, much less what stem cells look like. When he left he knew our names, how much money we bring into his district, and how important National Institutes of Health funding and international mobility are to our enterprise. Although I live in the United States, this approach should also apply to other democratic countries. If each of us converts one representative into a science champion, we can change the world. © 2018 Montell. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  16. 40 CFR 72.22 - Alternate designated representative.

    Science.gov (United States)

    2010-07-01

    ... designated representative is selected shall include a procedure for the owners and operators of the source and affected units at the source to authorize the alternate designated representative to act in lieu...) In the event of a conflict, any action taken by the designated representative shall take precedence...

  17. 22 CFR 23.4 - Representative value in exchange.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Representative value in exchange. 23.4 Section 23.4 Foreign Relations DEPARTMENT OF STATE FEES AND FUNDS FINANCE AND ACCOUNTING § 23.4 Representative value in exchange. Representative value in exchange for the collection of a fee means foreign...

  18. 40 CFR 60.4111 - Alternate Hg designated representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Alternate Hg designated representative... Times for Coal-Fired Electric Steam Generating Units Hg Designated Representative for Hg Budget Sources § 60.4111 Alternate Hg designated representative. (a) A certificate of representation under § 60.4113...

  19. High School Students' Perception of University Students as STEM Representatives

    DEFF Research Database (Denmark)

    Poulsen, Eva Lykkegaard

    ’ potential identities. It shows that the students preferred STEM representatives resembled themselves in some aspects (primarily social and health aspects) and fit their perceptions of a typical person working in STEM in other aspects (knowledge seeking, hard-working etc.). At least two different...... studies, it is important to introduce high school students to good STEM representatives to make possible the development of potential STEM identities. A potential identity within a specific subject area relies on at least a situation bound relation-ship to the subject area or the person representing it....... Some representatives transmit infor-mation and are thereby definers, whereas other representatives illustrates as personal examples and are thereby models. This study focuses on high school students’ views on STEM representatives and the impact these representatives have on the high school students...

  20. Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers

    Science.gov (United States)

    Sérandour, Aurélien A.; Avner, Stéphane; Percevault, Frédéric; Demay, Florence; Bizot, Maud; Lucchetti-Miganeh, Céline; Barloy-Hubler, Frédérique; Brown, Myles; Lupien, Mathieu; Métivier, Raphaël; Salbert, Gilles; Eeckhoute, Jérôme

    2011-01-01

    Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation. PMID:21233399

  1. Arctic indigenous peoples as representations and representatives of climate change.

    Science.gov (United States)

    Martello, Marybeth Long

    2008-06-01

    Recent scientific findings, as presented in the Arctic Climate Impact Assessment (ACIA), indicate that climate change in the Arctic is happening now, at a faster rate than elsewhere in the world, and with major implications for peoples of the Arctic (especially indigenous peoples) and the rest of the planet. This paper examines scientific and political representations of Arctic indigenous peoples that have been central to the production and articulation of these claims. ACIA employs novel forms and strategies of representation that reflect changing conceptual models and practices of global change science and depict indigenous peoples as expert, exotic, and at-risk. These portrayals emerge alongside the growing political activism of Arctic indigenous peoples who present themselves as representatives or embodiments of climate change itself as they advocate for climate change mitigation policies. These mutually constitutive forms of representation suggest that scientific ways of seeing the global environment shape and are shaped by the public image and voice of global citizens. Likewise, the authority, credibility, and visibility of Arctic indigenous activists derive, in part, from their status as at-risk experts, a status buttressed by new scientific frameworks and methods that recognize and rely on the local experiences and knowledges of indigenous peoples. Analyses of these relationships linking scientific and political representations of Arctic climate change build upon science and technology studies (STS) scholarship on visualization, challenge conventional notions of globalization, and raise questions about power and accountability in global climate change research.

  2. Interactions between physicians and pharmaceutical sales representatives in Saudi Arabia.

    Science.gov (United States)

    Alosaimi, Fahad Dakheel; Alkaabba, Abdulaziz; Qadi, Mahdi; Albahlal, Abdullah; Alabdulkarim, Yasir; Alabduljabbar, Mohammad; Alqahtani, Faisal

    2013-01-01

    Interaction between physicians and pharmaceutical sales representative (PR) is a major component of the promotional activities by pharmaceutical companies. The lack of studies examining the magnitude of this interaction in Saudi Arabia is evident. The objective of this study is to estimate the magnitude and associated characteristics of physician-PR interaction. A cross-sectional study was conducted among physicians working in the different regions of Saudi Arabia between March and July of 2012. A cross-sectional study was undertaken between March and July of 2012 in the different regions of Saudi Arabia. A self-administrated questionnaire was developed and handed to all participants, both in paper and electronic formats. A total of 663 participants completed the questionnaire. The participation rate was 66.3% (663/1000). The majority of the participants (72.9%) reported interaction with PRs. This was lower among residents/interns compared to higher ranking employees (55.6% vs 83.6%, P strategy to reduce negative impact.

  3. Representative Delay Measurements (RDM: Facing the Challenge of Modern Networks

    Directory of Open Access Journals (Sweden)

    Joachim Fabini

    2015-02-01

    Full Text Available Network access technologies have evolved significantly in the last years. They deploy novel mechanisms like reactive capacity allocation and time-slotted operation to optimize overall network capacity. From a single node's perspective, such optimizations decrease network determinism and measurement repeatability. Evolving application fields like machine to machine (M2M communications or real-time gaming often have strict real-time requirements to operate correctly. Highly accurate delay measurements are necessary to monitor network compliance with application demands or to detect deviations of normal network behavior, which may be caused by network failures, misconfigurations or attacks. This paper analyzes factors that challenge active delay measurements in modern networks. It introduces the Representative Delay Measurement tool (RDM that addresses these factors and proposes solutions that conform to requirements of the recently published RFC7312. Delay measurement results acquired using RDM in live networks confirm that advanced measurement methods can significantly improve the quality of measurement samples by isolating systematic network behavior. The resulting high-quality samples are one prerequisite for accurate statistics that support proper operation of subsequent algorithms and applications.

  4. High School Students' Perception of University Students as STEM Representatives

    DEFF Research Database (Denmark)

    Poulsen, Eva Lykkegaard

    The Danish government has an ambition to recruit more high school students into STEM edu-cations (science, technology, engineering and/or mathematics). The students’ choice of further education is based on the people and jobs they have knowledge of. Therefore, to recruit more students into STEM....... Some representatives transmit infor-mation and are thereby definers, whereas other representatives illustrates as personal examples and are thereby models. This study focuses on high school students’ views on STEM representatives and the impact these representatives have on the high school students...... studies, it is important to introduce high school students to good STEM representatives to make possible the development of potential STEM identities. A potential identity within a specific subject area relies on at least a situation bound relation-ship to the subject area or the person representing it...

  5. The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers.

    Directory of Open Access Journals (Sweden)

    Marumi Ohno

    Full Text Available Cytoplasmic constitutive active/androstane receptor (CAR retention protein (CCRP and also known as DNAJC7 is a co-chaperone previously characterized to retain nuclear receptor CAR in the cytoplasm of HepG2 cells. Here we have produced CCRP knockout (KO mice and demonstrated that CCRP regulates CAR at multiple steps in activation of the cytochrome (Cyp 2b10 gene in liver: nuclear accumulation, RNA polymerase II recruitment and epigenetic modifications. Phenobarbital treatment greatly increased nuclear CAR accumulation in the livers of KO males as compared to those of wild type (WT males. Despite this accumulation, phenobarbital-induced activation of the Cyp2b10 gene was significantly attenuated. In ChIP assays, a CAR/retinoid X receptor-α (RXRα heterodimer binding to the Cyp2b10 promoter was already increased before phenobarbital treatment and further pronounced after treatment. However, RNA polymerase II was barely recruited to the promoter even after phenobarbital treatment. Histone H3K27 on the Cyp2b10 promoter was de-methylated only after phenobarbital treatment in WT but was fully de-methylated before treatment in KO males. Thus, CCRP confers phenobarbital-induced de-methylation capability to the promoter as well as the phenobarbital responsiveness of recruiting RNA polymerase II, but is not responsible for the binding between CAR and its cognate sequence, phenobarbital responsive element module. In addition, KO males developed steatotic livers and increased serum levels of total cholesterol and high density lipoprotein in response to fasting. CCRP appears to be involved in various hepatic regulations far beyond CAR-mediated drug metabolism.

  6. Assessing Use of Cognitive Heuristic Representativeness in Clinical Reasoning

    OpenAIRE

    Payne, Velma L.; Crowley, Rebecca S.

    2008-01-01

    We performed a pilot study to investigate use of the cognitive heuristic Representativeness in clinical reasoning. We tested a set of tasks and assessments to determine whether subjects used the heuristics in reasoning, to obtain initial frequencies of heuristic use and related cognitive errors, and to collect cognitive process data using think-aloud techniques. The study investigates two aspects of the Representativeness heuristic - judging by perceived frequency and representativeness as ca...

  7. Determination of representative CANDU feeder dimensions for engineering simulator

    International Nuclear Information System (INIS)

    Cho, S.; Muzumdar, A.

    1996-01-01

    This paper describes a logic for selection of representative channel groups and a methodology for determination of representative CANDU feeder dimensions and the pressure drops between inlet/outlet header and fuel channel in the primary loop. A code, MEDOC, was developed based on this logic and methodology and helps perform a calculation of representative feeder dimensions for a selected channel group on the basis of feeder geometry data (fluid volume, mass flow rate, loss factor) and given property data (pressure, quality, density) at inlet/outlet header. The representative feeder dimensions calculated based on this methodology will be useful for the engineering simulator for the CANDU type reactor. (author)

  8. DFS Associates: Simple ways to become a good manufacturer's representative

    OpenAIRE

    Sandra K. Pharre

    2018-01-01

    Being one of the trusted manufacturer’s representative firms for RF and microwave products and services, DFS Associates wanted to impart a few insights to consider in becoming a good manufacturer’s representative with this article. Firstly, you need to understand what it does if you’re interested on becoming one where it could be an individual or a small business that can represent a manufacturer’s products and services effectively to the marketplace. You can choose between representing one m...

  9. Fiscal year 1986, Department of Energy authorization (magnetic fusion energy and departmental administration and supporting services activities). Volume V. Hearings before the Subcommittee on Energy Research and Production of the Committee on Science and Technology, House of Representatives, Ninety-Ninth Congress, First Session, March 8, 18, 1985

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    Volume V of the hearing record covers testimony given over two days on budgets for research on magnetic fusion energy and on the administration and support services of the DOE. The principal witness on the first day was Dr. Alvin Trivelpiece of DOE, who described adjustments in fusion funding that resulted from federal budget cuts. These led to delay and deferments in the program, and raised the issue of how to maintain balance in the program and still meet program goals. Trivelpiece emphasized that cuts for fusion research were consistent with other DOE reductions. Testimony on the second day came from representatives of fusion laboratories and the nuclear industry. Two appendices with additional questions and answers submitted for the record follow the testimony of the 16 witnesses

  10. Representing Young Children with Disabilities in Classroom Environments.

    Science.gov (United States)

    Favazza, Paddy C.; LaRoe, Joyce; Phillipsen, Leslie; Kumar, Poonam

    2000-01-01

    The "Inventory of Disability Representation" was administered to 92 teachers representing kindergarten, community child care, or preschool settings. Low scores across settings indicated that classrooms typically do not have materials that represent or depict children with diverse abilities. Reasons cited by teachers are noted as are benefits…

  11. 19 CFR 146.2 - Port director as Board representative.

    Science.gov (United States)

    2010-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES General Provisions § 146.2 Port director as Board representative. The appropriate port director shall be in charge of the zone as the representative of the Board. [T.D. 86-16, 51 FR 5049, Feb. 11, 1986, as amended by T.D. 99-27, 64 FR 13676, Mar. 22, 1999] ...

  12. 40 CFR 60.4114 - Objections concerning Hg designated representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Objections concerning Hg designated... Times for Coal-Fired Electric Steam Generating Units Hg Designated Representative for Hg Budget Sources § 60.4114 Objections concerning Hg designated representative. (a) Once a complete certificate of...

  13. 37 CFR 10.84 - Representing a client zealously.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Representing a client... Office Code of Professional Responsibility § 10.84 Representing a client zealously. (a) A practitioner shall not intentionally: (1) Fail to seek the lawful objectives of a client through reasonably available...

  14. 40 CFR Appendix I to Part 261 - Representative Sampling Methods

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Representative Sampling Methods I...—Representative Sampling Methods The methods and equipment used for sampling waste materials will vary with the form and consistency of the waste materials to be sampled. Samples collected using the sampling...

  15. 27 CFR 71.31 - Attorneys and other representatives.

    Science.gov (United States)

    2010-04-01

    ... representatives. 71.31 Section 71.31 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... applicant may be represented by an attorney, certified public accountant, or other person enrolled to practice before the Alcohol and Tobacco Tax and Trade Bureau under 31 CFR part 8—Practice before the...

  16. Calls to Teen Line: Representative Concerns of Adolescents.

    Science.gov (United States)

    Boehm, Kathryn E.; Schondel, Connie K.; Ivoska, William J.; Marlowe, Alison L.; Manke-Mitchell, Laurie

    1998-01-01

    Study examines whether the concerns of teenagers calling a peer listening service are representative of the concerns of teenagers in the area served. Results indicate that students' biggest concerns involve family problems, peer relationships, self-esteem, and school problems. Concludes that calls to the teen line are representative. (Author/GCP)

  17. [Experimental rationale for the parameters of a rapid method for oxidase activity determination].

    Science.gov (United States)

    Butorina, N N

    2010-01-01

    Experimental rationale is provided for the parameters of a rapid (1-2-min) test to concurrently determine the oxidase activity of all bacteria grown on the membrane filter after water filtration. Oxidase reagents that are the aqueous solutions of tetramethyl-p-phenylenediamine dihydrochloride and demethyl-p-phenylenediamine dihydrochloride have been first ascertained to exert no effect on the viability and enzymatic activity of bacteria after one-hour contact. An algorithm has been improved for the rapid oxidase activity test: the allowable time for bacteria to contact oxidase reagents and procedures for minimizing the effect on bacterial biochemical activity following the contact. An accelerated method based on lactose medium with tergitol 7 and Endo agar has been devised to determine coliform bacteria, by applying the rapid oxidase test: the time of a final response is 18-24 hours. The method has been included into GOST 52426-2005.

  18. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  19. Searches over graphs representing geospatial-temporal remote sensing data

    Science.gov (United States)

    Brost, Randolph; Perkins, David Nikolaus

    2018-03-06

    Various technologies pertaining to identifying objects of interest in remote sensing images by searching over geospatial-temporal graph representations are described herein. Graphs are constructed by representing objects in remote sensing images as nodes, and connecting nodes with undirected edges representing either distance or adjacency relationships between objects and directed edges representing changes in time. Geospatial-temporal graph searches are made computationally efficient by taking advantage of characteristics of geospatial-temporal data in remote sensing images through the application of various graph search techniques.

  20. Administrative Circular No. 13 (Rev. 3) - Guarantees for representatives of the personnel

    CERN Multimedia

    2014-01-01

    Administrative Circular No. 13 (Rev. 3) entitled “Guarantees for representatives of the personnel”, approved by the Director-General following discussion at the Standing Concertation Committee meeting of 5 December 2013 and entering into force on 1 January 2014, is available on the intranet site of the Human Resources Department (see here).   This circular is applicable to all members of the personnel. It cancels and replaces Administrative Circular No. 13 (Rev. 2) entitled “Guarantees for members of the personnel holding representative office” of November 1992. The circular was revised in order to adapt the time given to the representatives of the personnel to perform their elective mandate and to ensure more transparency in their activities, by indicating, inter alia, the percentage of time worked in the framework of their mandate, as well as the training, activities and ensuing results. Department Head Office HR Department

  1. Representative Model of the Learning Process in Virtual Spaces Supported by ICT

    Science.gov (United States)

    Capacho, José

    2014-01-01

    This paper shows the results of research activities for building the representative model of the learning process in virtual spaces (e-Learning). The formal basis of the model are supported in the analysis of models of learning assessment in virtual spaces and specifically in Dembo´s teaching learning model, the systemic approach to evaluating…

  2. Efeito da variação do ph e da temperatura de síntese no desempenho de adesivos à base de creosoto vegetal desmetilado-formaldeído Effect ph variation and synthesis temperature on the performance of thermosetting adhesive formulations based on demethylated wood creosote-formaldehyde

    Directory of Open Access Journals (Sweden)

    Crístian Bacelar Santos

    2003-08-01

    Full Text Available O objetivo deste trabalho foi a produção de adesivos para madeira a partir de creosoto desmetilado. Para isto, foram sintetizadas diferentes formulações de adesivos para madeira a partir de creosoto desmetilado e paraformaldeído, variando-se o pH inicial da formulação (12,00, 12,25, 12,50, 12,75, 13,00, 13,25 e 13,50 e a temperatura de síntese (60 e 70 °C, para possibilitar a verificação dos melhores pHs e da melhor temperatura para elaboração do adesivo. Foi verificado, por meio da avaliação do gel time, que a melhor temperatura de síntese foi 70 °C. Foram realizadas, então, análises por DSC (calorimetria diferencial exploratória, para obtenção dos parâmetros cinéticos e caracterização das formulações adesivas de creosoto desmetilado sintetizadas a 70 °C. Os adesivos foram utilizados para colagem, a quente (160 °C e sob pressão (12 kgf/cm², de lâminas de Araucaria angustifolia. Após a colagem, foram realizados os ensaios de resistência mecânica ao cisalhamento por tração, para condição seca e úmida. Verificou-se que a resistência da linha de cola e a porcentagem de falha na madeira para os adesivos de creosoto desmetilado sintetizados a 70 °C foram inferiores às do adesivo de fenol-formaldeído sintetizado em laboratório, que foi utilizado como padrão.The objective of this work was the production of adhesives based on demethylated creosote for bonding of wood. Different formulations of demethylated wood bcreosote/formaldehyde were evaluated aiming at improving their bonding properties. The initial pH value and the synthesis temperature were varied in order to obtain the best values for producing the adhesives. Thus, seven pH values (12.00, 12.25, 12.50, 12.75, 13.00, 13.25, and 13.50 and two different temperatures (60 °C and 70 °C were applied. It was observed by gel time evaluation that the best synthesis temperature was 70 °C. The kinetic parameters were obtained through DSC analysis

  3. Life forms of succulent representatives of the family Asclepiadaceae

    Directory of Open Access Journals (Sweden)

    Marina Gaidarzhy

    2013-04-01

    Full Text Available The life forms of succulent’s representatives of the family Asclepiadaceae of the tropical and subtropical plants from the collection of O.V. Fomin Botanical garden according to author classification are characterized.

  4. The value of political parties to representative democracy

    NARCIS (Netherlands)

    Kölln, Ann-Kristin

    2015-01-01

    Political parties play a major role in democratic processes around the world. Recent empirical research suggests that parties are increasingly less important to citizens. Simultaneously, classic and contemporary theories of representative democracy specifically still minimally incorporate accounts

  5. Microalbuminuria represents a feature of advanced renal disease in ...

    African Journals Online (AJOL)

    . The systematic screening for microalbuminuria represents the touchstone to prevent CRF in patients with diabetes mellitus. Microalbuminuria has also been demonstrated in patients with sickle cell disease. Whether this has the same ...

  6. Developing Representative Michigan Truck Configurations for Bridge Load Rating

    Science.gov (United States)

    2018-02-28

    The objective of this study is to recommend a rating process representative of Michigan load effects for legal and extended permit vehicles. For this study, high fidelity WIM data from 20 Michigan sites were analyzed. Using vehicle weight and configu...

  7. UN: new Permanent Representative of Monaco presents credentials

    CERN Multimedia

    2003-01-01

    "Michel Borghini, the new Permanent Representative of Monaco to the United Nations, presented his credentials to Secretary-General Kofi Annan today. He worked as a researcher at CERN from 1965 to 1969" (1/3 page).

  8. On the Representativeness of Norming Samples for Aptitude Test

    National Research Council Canada - National Science Library

    Sims, William

    2003-01-01

    ...). We regressed aptitude test scores on demographics and concluded that: ̂ Norming sample for aptitude tests must be representative of the target population with respect to age, race"ethnicity, gender, respondent's education, and mother's...

  9. Sample representativeness verification of the FADN CZ farm business sample

    Directory of Open Access Journals (Sweden)

    Marie Prášilová

    2011-01-01

    Full Text Available Sample representativeness verification is one of the key stages of statistical work. After having joined the European Union the Czech Republic joined also the Farm Accountancy Data Network system of the Union. This is a sample of bodies and companies doing business in agriculture. Detailed production and economic data on the results of farming business are collected from that sample annually and results for the entire population of the country´s farms are then estimated and assessed. It is important hence, that the sample be representative. Representativeness is to be assessed as to the number of farms included in the survey and also as to the degree of accordance of the measures and indices as related to the population. The paper deals with the special statistical techniques and methods of the FADN CZ sample representativeness verification including the necessary sample size statement procedure. The Czech farm population data have been obtained from the Czech Statistical Office data bank.

  10. Arab Knowledge Society: Who Represents the Arab World Online ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Arab Knowledge Society: Who Represents the Arab World Online? ... Wikipedia's culture of openness, extensive reuse and near ubiquity makes it an ideal place to ... IWRA/IDRC webinar on climate change and adaptive water management.

  11. Elections for staff representatives – Join, commit and vote!

    CERN Multimedia

    Staff Association

    2015-01-01

    The Staff Council is a statutory body representing collectively in the area of employment conditions all CERN staff members (MPE and MPA), as well as the pensioners, former Cernois. The Staff Council is the supreme representative body of the CERN staff and pensioners, which defines the main lines of the policy of the Staff Association. The Staff Council is composed of staff representatives (45 seats to represent staff members, and 5 for representing fellows and associate members), as well as delegates for pensioners (seven positions), designated by GAC-EPA. Every two years, the Council is renewed through elections. Concerning the 45 delegates representing staff members, all departments have a least two seats allocated, one in career paths AA to D and one in career paths E to H. This guarantees a fair distribution of seats among the various organizational units and career paths. The table below, shows the exact number of delegates per department and career paths. Staff members or fellows who want to participa...

  12. Chemical synthesis of high specific-activity [35S]adenosylhomocysteine

    International Nuclear Information System (INIS)

    Stern, P.H.; Hoffman, R.M.

    1986-01-01

    The study of the family of transmethylases, critical to normal cellular function and often altered in cancer, can be facilitated by the availability of a high specific-activity S-adenosylhomocysteine. The authors report the two-step preparation of [ 35 S]adenosylhomocysteine from [ 35 S]methionine at a specific activity of 1420 Ci/mmol in an overall yield of 24% by a procedure involving demethylation of the [ 35 S]methionine to [ 35 S]homocysteine followed by condensation with 5'-chloro-5'-deoxyadenosine. The ease of the reactions, ready availability and low cost of the reagents and high specific-activity and stability of the product make the procedure an attractive one with many uses, and superior to current methodology

  13. A Multi-Agent Framework Manages a Representative Sensor Web

    Science.gov (United States)

    Suri, D.; Schmidt, D.; Biswas, G.; Kinnebrew, J.; Otte, W.; Shankaran, N.

    2008-12-01

    NASA's vision of a Sensor Web (which includes a distributed global observation system) consists of a large number of elements, such as remote spacecraft hosting multiple instruments, in situ terrestrial and oceanic sensor networks, and airborne assets. Researchers and developers of a Sensor web face a number of challenges that arise from (1) the inherent heterogeneous and geographical distributed nature of the Sensor web; (2) the myriad mission goals and objectives that must be satisfied by the Sensor web, ranging from an improved understanding of earth science, weather forecasting, and disaster management to an alleviation of societal problems; and (3) the need to support myriad operational modes, such as long and short-term monitoring and targeted observations. Resolving these challenges requires some form of autonomy - typically embodied in software. Agent technology has emerged both as a salient purveyor of entities that exhibit autonomous behavior and also as a paradigm for constructing complex software systems with a large number of interacting heterogeneous components. This paper describes our experiences integrating the Multi-agent Architecture for Coordinated Responsive Observations (MACRO) into the SouthEast Alaska MOnitoring Network for Science, Telecommunications, Education, and Research (SEAMONSTER). MACRO provides agents at (1) the mission level, where agents interact with users to define science goals and then translate these goals into a set of prioritized tasks that have to be executed to achieve these goals, and (2) the resource level, where agents translate tasks into activities related to data collection, data analysis, and data communication. As a representative small-scale sensor web situated in multiple locations on the Juneau Icefield, SEAMONSTER affords an unparalleled opportunity to develop, mature, and showcase MACRO's multi-level agent capabilities. MACRO is developed by the Lockheed Martin Space System Company's Advanced Technology

  14. Heterogeneous researchers in a two-sector representative consumer economy

    Directory of Open Access Journals (Sweden)

    Orlando Gomes

    2006-06-01

    Full Text Available Research activities have uncertain outcomes. The question asked in this paper is whether or not this uncertainty can be a central piece on the explanation of long run consumption growth paths. More specifically, we inquire how the existence of different research projects, with different degrees of uncertainty, contributes to unpredictable consumption growth paths. The proposed scenario is a two-sector representative consumer model with researchers that invest in different innovation projects. There is heterogeneity in terms of risk associated to research programs (researchers invest in projects with the same expected outcome but different volatility. This difference in volatility, combined with an adaptive learning - bounded rationality rule, implies an aggregate index of technology and a consumption growth rate that do not present a predictable pattern over time.As actividades de investigação produzem resultados incertos. A questão colocada neste artigo é se esta incerteza pode ser uma peça central na explicação das trajectórias de crescimento do consumo no longo prazo. Mais especificamente, pergunta-se como a existência de diferentes projectos de investigação, com diferentes graus de incerteza associados, contribui para trajectórias de crescimento do consumo que não são passíveis de previsão. O cenário proposto é um modelo de consumidor representativo de dois sectores com investigadores que investem em diferentes projectos de inovação. Existe heterogeneidade ao nível do risco associado aos programas de investigação (os investigadores investem em projectos com o mesmo resultado esperado mas diferente volatilidade. A diferença na volatilidade, combinada com uma regra de aprendizagem adaptativa - racionalidade limitada, implica um índice agregado de tecnologia e uma taxa de crescimento do consumo que não apresentam um padrão previsível ao longo do tempo.

  15. Sidestepping questions of legitimacy: how community representatives manoeuvre to effect change in a health service.

    Science.gov (United States)

    Nathan, Sally; Stephenson, Niamh; Braithwaite, Jeffrey

    2014-01-01

    Empirical studies of community participation in health services commonly tie effectiveness to the perceived legitimacy of community representatives among health staff. This article examines the underlying assumption that legitimacy is the major pathway to influence for community representatives. It takes a different vantage point from previous research in its examination of data (primarily through 34 in-depth interviews, observation and recording of 26 meetings and other interactions documented in field notes) from a 3-year study of community representatives' action in a large health region in Australia. The analysis primarily deploys Michel de Certeau's ideas of Strategy and Tactic to understand the action and effects of the generally 'weaker players' in the spaces and places dominated by powerful institutions. Through this lens, we can see the points where community representatives are active participants following their own agenda, tactically capitalising on cracks in the armour of the health service to seize opportunities that present themselves in time to effect change. Being able to see community representatives as active producers of change, not simply passengers following the path of the health service, challenges how we view the success of community participation in health.

  16. Towards Representative Metallurgical Sampling and Gold Recovery Testwork Programmes

    Directory of Open Access Journals (Sweden)

    Simon C. Dominy

    2018-05-01

    Full Text Available When developing a process flowsheet, the risks in achieving positive financial outcomes are minimised by ensuring representative metallurgical samples and high quality testwork. The quality and type of samples used are as important as the testwork itself. The key characteristic required of any set of samples is that they represent a given domain and quantify its variability. There are those who think that stating a sample(s is representative makes it representative without justification. There is a need to consider both (1 in-situ and (2 testwork sub-sample representativity. Early ore/waste characterisation and domain definition are required, so that sampling and testwork protocols can be designed to suit the style of mineralisation in question. The Theory of Sampling (TOS provides an insight into the causes and magnitude of errors that may occur during the sampling of particulate materials (e.g., broken rock and is wholly applicable to metallurgical sampling. Quality assurance/quality control (QAQC is critical throughout all programmes. Metallurgical sampling and testwork should be fully integrated into geometallurgical studies. Traditional metallurgical testwork is critical for plant design and is an inherent part of geometallurgy. In a geometallurgical study, multiple spatially distributed small-scale tests are used as proxies for process parameters. These will be validated against traditional testwork results. This paper focusses on sampling and testwork for gold recovery determination. It aims to provide the reader with the background to move towards the design, implementation and reporting of representative and fit-for-purpose sampling and testwork programmes. While the paper does not intend to provide a definitive commentary, it critically assesses the hard-rock sampling methods used and their optimal collection and preparation. The need for representative sampling and quality testwork to avoid financial and intangible losses is

  17. Associated factors of obesity in Spanish representative samples.

    Science.gov (United States)

    Ortega Anta, Rosa M; López-Solaber, Ana M; Pérez-Farinós, Napoleón

    2013-09-01

    Given the dramatic increase in the prevalence of obesity and the serious health and economic consequences, the scientific community, health professionals and health agencies are looking for the best strategies to prevent/ fight this trend. In order to plan the most appropriate intervention measures the first step is to identify the associated factors of obesity. This paper presents the results of research conducted/coordinated by our research team and promoted by the Spanish Food Safety Agency (AESAN), in the last five years. These studies were focussed on representative samples of the Spanish population, paying attention to the condition of overweight/obesity and their associated factors. The first study, FANPE ("Fuentes alimentarias de nutrientes de la población española") (2009), was centered in 418 adults (18-60 years) from 15 provinces (30 sampling points). Its aim was to analyze the dietary sources of nutrients, paying particular attention to sodium. This research showed that the risk of overweight/obesity increa ses with age, in people who have follow weight control diets, in ex-smokers, married people and those who slept less than 8.5 hours per day, while the risk is lower in women, people who make sport and those with a University degree. It was also found that overweight people had higher sodium intake and urine excretion. Therefore, and having in mind that 88.2% of the subjects took more than 2 g/day of sodium (the maximum recommended), it is advised to lower the sodium intake not only from the health point of view but also as a probably strategy against obesity. The study ALADINO (Estudio de Alimentación, Actividad física, Desarrollo Infantil y Obesidad--Study of the Diet, Physical Activity, Child Development and Obesity) (2010-2011) was focused on 7659 children (6-9 years) from 19 autonomous communities. We founded a higher percentage of overweight/obesity in boys than in girls, and a significant increase in the figures from the age of 7. Being

  18. Selection of Representative Models for Decision Analysis Under Uncertainty

    Science.gov (United States)

    Meira, Luis A. A.; Coelho, Guilherme P.; Santos, Antonio Alberto S.; Schiozer, Denis J.

    2016-03-01

    The decision-making process in oil fields includes a step of risk analysis associated with the uncertainties present in the variables of the problem. Such uncertainties lead to hundreds, even thousands, of possible scenarios that are supposed to be analyzed so an effective production strategy can be selected. Given this high number of scenarios, a technique to reduce this set to a smaller, feasible subset of representative scenarios is imperative. The selected scenarios must be representative of the original set and also free of optimistic and pessimistic bias. This paper is devoted to propose an assisted methodology to identify representative models in oil fields. To do so, first a mathematical function was developed to model the representativeness of a subset of models with respect to the full set that characterizes the problem. Then, an optimization tool was implemented to identify the representative models of any problem, considering not only the cross-plots of the main output variables, but also the risk curves and the probability distribution of the attribute-levels of the problem. The proposed technique was applied to two benchmark cases and the results, evaluated by experts in the field, indicate that the obtained solutions are richer than those identified by previously adopted manual approaches. The program bytecode is available under request.

  19. Effect of Garden Cress Seeds Powder and Its Alcoholic Extract on the Metabolic Activity of CYP2D6 and CYP3A4

    Directory of Open Access Journals (Sweden)

    Fahad I. Al-Jenoobi

    2014-01-01

    Full Text Available The powder and alcoholic extract of dried seeds of garden cress were investigated for their effect on metabolic activity of CYP2D6 and CYP3A4 enzymes. In vitro and clinical studies were conducted on human liver microsomes and healthy human subjects, respectively. Dextromethorphan was used as a common marker for measuring metabolic activity of CYP2D6 and CYP3A4 enzymes. In in vitro studies, microsomes were incubated with NADPH in presence and absence of different concentrations of seeds extract. Clinical investigations were performed in two phases. In phase I, six healthy female volunteers were administered a single dose of dextromethorphan and in phase II volunteers were treated with seeds powder for seven days and dextromethorphan was administered with last dose. The O-demethylated and N-demethylated metabolites of dextromethorphan were measured as dextrorphan (DOR and 3-methoxymorphinan (3-MM, respectively. Observations suggested that garden cress inhibits the formation of DOR and 3-MM metabolites. This inhibition of metabolite level was attributed to the inhibition of CYP2D6 and CYP3A4 activity. Garden cress decreases the level of DOR and 3-MM in urine and significantly increases the urinary metabolic ratio of DEX/DOR and DEX/3-MM. The findings suggested that garden cress seeds powder and ethanolic extract have the potential to interact with CYP2D6 and CYP3A4 substrates.

  20. Assessing the use of cognitive heuristic representativeness in clinical reasoning.

    Science.gov (United States)

    Payne, Velma L; Crowley, Rebecca S; Crowley, Rebecca

    2008-11-06

    We performed a pilot study to investigate use of the cognitive heuristic Representativeness in clinical reasoning. We tested a set of tasks and assessments to determine whether subjects used the heuristics in reasoning, to obtain initial frequencies of heuristic use and related cognitive errors, and to collect cognitive process data using think-aloud techniques. The study investigates two aspects of the Representativeness heuristic - judging by perceived frequency and representativeness as causal beliefs. Results show that subjects apply both aspects of the heuristic during reasoning, and make errors related to misapplication of these heuristics. Subjects in this study rarely used base rates, showed significant variability in their recall of base rates, demonstrated limited ability to use provided base rates, and favored causal data in diagnosis. We conclude that the tasks and assessments we have developed provide a suitable test-bed to study the cognitive processes underlying heuristic errors.

  1. Assessing Use of Cognitive Heuristic Representativeness in Clinical Reasoning

    Science.gov (United States)

    Payne, Velma L.; Crowley, Rebecca S.

    2008-01-01

    We performed a pilot study to investigate use of the cognitive heuristic Representativeness in clinical reasoning. We tested a set of tasks and assessments to determine whether subjects used the heuristics in reasoning, to obtain initial frequencies of heuristic use and related cognitive errors, and to collect cognitive process data using think-aloud techniques. The study investigates two aspects of the Representativeness heuristic - judging by perceived frequency and representativeness as causal beliefs. Results show that subjects apply both aspects of the heuristic during reasoning, and make errors related to misapplication of these heuristics. Subjects in this study rarely used base rates, showed significant variability in their recall of base rates, demonstrated limited ability to use provided base rates, and favored causal data in diagnosis. We conclude that the tasks and assessments we have developed provide a suitable test-bed to study the cognitive processes underlying heuristic errors. PMID:18999140

  2. Knowledge environments representing molecular entities for the virtual physiological human.

    Science.gov (United States)

    Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

    2008-09-13

    In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

  3. Enterprise Systems Implementations: Organizational Influence Processes for Corporate User Representatives

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Nordheim, Stig

    2008-01-01

    -depth, interpretive study from the oil industry, where we analyze a case of innovative integration of an ECM system with collaboration technologies. The data collection has been longitudinal. The data analysis has been performed through the perspective of organizational influence processes. The main finding concerns...... an organizational role as corporate user representative to deal with the scale and complexities of implementation. A single person was particularly influential in the role. At the outset a user representative had to perform upward influence processes from a lower formal position. This is impeding...

  4. Representing and reasoning about program in situation calculus

    Science.gov (United States)

    Yang, Bo; Zhang, Ming-yi; Wu, Mao-nian; Xie, Gang

    2011-12-01

    Situation calculus is an expressive tool for modeling dynamical system in artificial intelligence, changes in a dynamical world is represented naturally by the notions of action, situation and fluent in situation calculus. Program can be viewed as a discrete dynamical system, so it is possible to model program with situation calculus. To model program written in a smaller core programming language CL, notion of fluent is expanded for representing value of expression. Together with some functions returning concerned objects from expressions, a basic action theory of CL programming is constructed. Under such a theory, some properties of program, such as correctness and termination can be reasoned about.

  5. A geometric language for representing structure in polyphonic music

    DEFF Research Database (Denmark)

    Meredith, David

    2012-01-01

    In 1981, Deutsch and Feroe proposed a formal language for representing melodic pitch structure that employed the powerful concept of hierarchically-related pitch alphabets. However, neither rhythmic structure nor pitch structure in polyphonic music can be adequately represented using this language....... A new language is proposed here that incorporates certain features of Deutsch and Feroe’s model but extends and generalises it to allow for the representation of both rhythm and pitch structure in polyphonic music. The new language adopts a geometric approach in which a passage of polyphonic music...

  6. Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients

    DEFF Research Database (Denmark)

    Schmidt, L E; Olsen, A K; Stentoft, K

    2001-01-01

    BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). The erythromycin breath test is an in vivo assay of hepatic CYP3A activity......, but the method has never been directly validated. The aim of the study was to investigate whether an early postoperative erythromycin breath test correlated with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients. METHODS: In 18 liver transplant recipients, the erythromycin...... breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for the CYP3A protein level by Western blotting and for CYP3A activity with erythromycin demethylation and testosterone 6beta- hydroxylation assays. RESULTS: The erythromycin breath...

  7. Representing User Navigation in XML Retrieval with Structural Summaries

    DEFF Research Database (Denmark)

    Ali, M. S.; Consens, Mariano P.; Larsen, Birger

    This poster presents a novel way to represent user navigation in XML retrieval using collection statistics from XML summaries. Currently, developing user navigation models in XML retrieval is costly and the models are specific to collected user assessments. We address this problem by proposing...

  8. Representing nature : Late twentieth century green infrastructures in Paris

    NARCIS (Netherlands)

    Van der Velde, J.R.T.; De Wit, S.I.

    2015-01-01

    The appreciation of green infrastructures as ‘nature’ by urban communities presents a critical challenge for the green infrastructure concept. While many green infrastructures focus on functional considerations, their refinement as places where concepts of nature are represented and where nature can

  9. On the representativeness of behavior observation samples in classrooms.

    Science.gov (United States)

    Tiger, Jeffrey H; Miller, Sarah J; Mevers, Joanna Lomas; Mintz, Joslyn Cynkus; Scheithauer, Mindy C; Alvarez, Jessica

    2013-01-01

    School consultants who rely on direct observation typically conduct observational samples (e.g., 1 30-min observation per day) with the hopes that the sample is representative of performance during the remainder of the day, but the representativeness of these samples is unclear. In the current study, we recorded the problem behavior of 3 referred students for 4 consecutive school days between 9:30 a.m. and 2:30 p.m. using duration recording in consecutive 10-min sessions. We then culled 10-min, 20-min, 30-min, and 60-min observations from the complete record and compared these observations to the true daily mean to assess their accuracy (i.e., how well individual observations represented the daily occurrence of target behaviors). The results indicated that when behavior occurred with low variability, the majority of brief observations were representative of the overall levels; however, when behavior occurred with greater variability, even 60-min observations did not accurately capture the true levels of behavior. © Society for the Experimental Analysis of Behavior.

  10. Representativeness of the European social partner organisations: Hospitals - Netherlands

    NARCIS (Netherlands)

    Grünell, M.

    2009-01-01

    The aim of this representativeness study is to identify the respective national and supranational actors (i.e. trade unions and employer organisations) in the field of industrial relations. This study will, in particular, focus on their representational quality as well as on their role in collective

  11. Representativeness of the European social partner organisations: Catering sector - Netherlands

    NARCIS (Netherlands)

    Grünell, M.

    2010-01-01

    The aim of this representativeness study is to identify the respective national and supranational actors (i.e. trade unions and employer organisations) in the field of industrial relations in the contract catering sector in the Netherlands. In order to determine their relative importance in the

  12. 'To Think Representatively': Arendt on Judgment and the Imagination

    African Journals Online (AJOL)

    ... the standpoint of the spectator, I go on to examine their most distinctive features, in particular, the link between judgment, the imagination, and the ability to think 'representatively'. I also examine the philosophical sources of Arendt's theory of judgment, namely, Kant's theory of aesthetic judgment and its criteria of validity.

  13. Cephalopods represented by beaks in the stomach of a sperm ...

    African Journals Online (AJOL)

    More than 3 000 cephalopod beaks taken from the stomach of a sperm whale stranded at Paekakariki, North Island, New Zealand, were identified to species and measured; estimates were made of the masses and standard lengths of the cephalopods represented. In all, 24 species of cephalopod in 13 families were ...

  14. 26 CFR 31.3211-3 - Employee representative supplemental tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Employee representative supplemental tax. 31... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Railroad Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) Tax on Employee...

  15. Party member recruitment and the representativeness of party membership

    DEFF Research Database (Denmark)

    Kosiara-Pedersen, Karina

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

  16. Re-Presenting Self: Reading Some Van Kalker Studio Photographs ...

    African Journals Online (AJOL)

    The photographic implement, from the earliest days of its invention in Europe, in 1839, has been used to document events considered as real. However, notions of 'reality' could be ambiguous as objects or sceneries intended to be photographed are sometimes constructed to represent an imagined stereotypical reality.

  17. A Balanced and Representative Corpus: The Effects of Strict Corpus ...

    African Journals Online (AJOL)

    Theoretically the Northern Sotho language is made up of almost 30 dialects while practically it is not so, because the standard language was formed from very few of its dialects. As a result, even today the language has no corpus which is balanced or representative owing to the fact that almost all of the available corpora ...

  18. Quantitative radiomic profiling of glioblastoma represents transcriptomic expression.

    Science.gov (United States)

    Kong, Doo-Sik; Kim, Junhyung; Ryu, Gyuha; You, Hye-Jin; Sung, Joon Kyung; Han, Yong Hee; Shin, Hye-Mi; Lee, In-Hee; Kim, Sung-Tae; Park, Chul-Kee; Choi, Seung Hong; Choi, Jeong Won; Seol, Ho Jun; Lee, Jung-Il; Nam, Do-Hyun

    2018-01-19

    Quantitative imaging biomarkers have increasingly emerged in the field of research utilizing available imaging modalities. We aimed to identify good surrogate radiomic features that can represent genetic changes of tumors, thereby establishing noninvasive means for predicting treatment outcome. From May 2012 to June 2014, we retrospectively identified 65 patients with treatment-naïve glioblastoma with available clinical information from the Samsung Medical Center data registry. Preoperative MR imaging data were obtained for all 65 patients with primary glioblastoma. A total of 82 imaging features including first-order statistics, volume, and size features, were semi-automatically extracted from structural and physiologic images such as apparent diffusion coefficient and perfusion images. Using commercially available software, NordicICE, we performed quantitative imaging analysis and collected the dataset composed of radiophenotypic parameters. Unsupervised clustering methods revealed that the radiophenotypic dataset was composed of three clusters. Each cluster represented a distinct molecular classification of glioblastoma; classical type, proneural and neural types, and mesenchymal type. These clusters also reflected differential clinical outcomes. We found that extracted imaging signatures does not represent copy number variation and somatic mutation. Quantitative radiomic features provide a potential evidence to predict molecular phenotype and treatment outcome. Radiomic profiles represents transcriptomic phenotypes more well.

  19. Crime’s face: Imagining and representing kleptomania

    NARCIS (Netherlands)

    de Haan, W.J.M.

    2015-01-01

    Marlene Dumas is regarded as one of the most important international painters of this time. In this article, an analysis is made of what her painting The Kleptomaniac (2005) and, in particular, what its title represents. Drawing upon art history, I begin by looking at the original Portrait of a

  20. The occipital place area represents the local elements of scenes.

    Science.gov (United States)

    Kamps, Frederik S; Julian, Joshua B; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D

    2016-05-15

    Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents is not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found that OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements - both in spatial boundary and scene content representation - while PPA and RSC represent global scene properties. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 78 FR 19400 - Registry for Attorneys and Representatives

    Science.gov (United States)

    2013-04-01

    ... digits of his or her Social Security number. See 68 FR 75162. EOIR notes that online security standards... are only accredited to appear before the Department of Homeland Security. See id. \\3\\ As part of the... accredited representative registers, he or she will create a unique UserID and password for online access to...

  2. Professional Human Service Occupation Biases Represented in General Psychology Textbooks

    Science.gov (United States)

    Firmin, Michael W.; Johnson, Erica J.; Wikler, Jeremiah

    2009-01-01

    We examined the coverage given by General Psychology textbooks, representing 8 major commercial publishers, regarding the professions of psychology, counseling, marriage & family therapy, and social workers. Of the 24 textbooks assessed, we found substantial bias favoring the coverage of psychology. While 25% of the texts mentioned social workers,…

  3. Under-Representation in Nationally Representative Secondary Data

    Science.gov (United States)

    Frederick, Karen; Barnard-Brak, Lucy; Sulak, Tracey

    2012-01-01

    There has been a significant increase in the use of secondary data sets. Many such data sets purport to be nationally representative. Secondary data sets include research commissioned by the National Center for Education Statistics, the Centers for Disease Control, and other public entities. Research increasingly utilizes these secondary data in…

  4. Education and support for representative, direct and stealth democracy

    NARCIS (Netherlands)

    Coffé, Hilde; Michels, Ank

    2014-01-01

    Using data collected within the scope of a Dutch internet panel survey (LISS) in 2011, this study tracks public support for direct, stealth and representative democracy according to educational level. Our findings indicate that, in terms of overall support for each specific type of democracy, lower

  5. Communication received from the Resident Representatives of Argentina and Brazil

    International Nuclear Information System (INIS)

    1993-01-01

    The document reproduces the communication received by the Director General from the Resident Representatives of Argentina and Brazil to the Agency to inform him about the official inauguration on 9 December 1992 of the headquarters of the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) in Rio de Janeiro

  6. 40 CFR 197.31 - What is a representative volume?

    Science.gov (United States)

    2010-07-01

    ... supply a given water demand. The DOE must project the concentration of radionuclides released from the... Public Health and Environmental Standards for Disposal Ground Water Protection Standards § 197.31 What is a representative volume? (a) It is the volume of ground water that would be withdrawn annually from...

  7. 32 CFR 705.14 - Embarkation of media representatives.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Embarkation of media representatives. 705.14 Section 705.14 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES... to avoid any interpretation of such review as “censorship” or interference with freedom of the press...

  8. 40 CFR 73.33 - Authorized account representative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Authorized account representative. 73.33 Section 73.33 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE ALLOWANCE SYSTEM Allowance Tracking System § 73.33 Authorized account...

  9. Depression and Suicidality among Bisexual Youth: A Nationally Representative Sample

    Science.gov (United States)

    Taliaferro, Lindsay A.; Gloppen, Kari M.; Muehlenkamp, Jennifer J.; Eisenberg, Marla E.

    2018-01-01

    To address gaps in the literature on bisexual youth, we used the first nationally representative sample of high school students from the United States to determine profiles of behaviors related to depressive symptoms, a suicide attempt, and a medically-serious attempt. We examined the data from 922 bisexual students in grades 9-12 who completed…

  10. Identifying and representing elements of local contexts in Namibia

    DEFF Research Database (Denmark)

    Rodil, Kasper; Jensen, Kasper Løvborg; Rehm, Matthias

    2013-01-01

    In an attempt to represent local context in a 3D visualisa- tionfor rural elders in Namibia we have foundmajor dierences in thecon- ceptualizationof this context between external and local partners in the co-creation process. Through the evaluation of a mobile context capture tool we found a clea...

  11. Markov LIMID processes for representing and solving renewal problems

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Kristensen, Anders Ringgaard; Nilsson, Dennis

    2014-01-01

    to model a Markov Limid Process, where each TemLimid represents a macro action. Algorithms are presented to find optimal plans for a sequence of such macro actions. Use of algorithms is illustrated based on an extended version of an example from pig production originally used to introduce the Limid concept...

  12. Can Democracy Represent Children? Toward a Politics of Difference

    Science.gov (United States)

    Wall, John

    2012-01-01

    Children and youth under 18 have made significant strides in recent years toward fuller inclusion in democratic processes. These strides, however, rarely rise to the level of direct political representation, whether in changing policies, making laws, or voting. This article argues that democracies will be able to represent children only by…

  13. The role of a representative reinsurer in optimal reinsurance

    NARCIS (Netherlands)

    Boonen, T.J.; Tan, K.S.; Zhuang, S.C.

    2016-01-01

    In this paper, we consider a one-period optimal reinsurance design model with nn reinsurers and an insurer. For very general preferences of the insurer and that all reinsurers use a distortion premium principle, we establish the existence of a representative reinsurer and this in turn facilitates

  14. Representativeness and seasonality of major ion records derived from NEEM firn cores

    Directory of Open Access Journals (Sweden)

    G. Gfeller

    2014-10-01

    Full Text Available The seasonal and annual representativeness of ionic aerosol proxies (among others, calcium, sodium, ammonium and nitrate in various firn cores in the vicinity of the NEEM drill site in northwest Greenland have been assessed. Seasonal representativeness is very high as one core explains more than 60% of the variability within the area. The inter-annual representativeness, however, can be substantially lower (depending on the species making replicate coring indispensable to derive the atmospheric variability of aerosol species. A single core at the NEEM site records only 30% of the inter-annual atmospheric variability in some species, while five replicate cores are already needed to cover approximately 70% of the inter-annual atmospheric variability in all species. The spatial representativeness is very high within 60 cm, rapidly decorrelates within 10 m but does not diminish further within 3 km. We attribute this to wind reworking of the snow pack leading to sastrugi formation. Due to the high resolution and seasonal representativeness of the records we can derive accurate seasonalities of the measured species for modern (AD 1990–2010 times as well as for pre-industrial (AD 1623–1750 times. Sodium and calcium show similar seasonality (peaking in February and March respectively for modern and pre-industrial times, whereas ammonium and nitrate are influenced by anthropogenic activities. Nitrate and ammonium both peak in May during modern times, whereas during pre-industrial times ammonium peaked during July–August and nitrate during June–July.

  15. Twenty-sixth general conference meeting of representatives of RCA member states. Report

    International Nuclear Information System (INIS)

    1997-10-01

    The meeting discussed the following issues: RCA Annual Report 1996; Report of the 19th RCA Working Group Meeting, Yangon Myanmar, 10-14 March 1997; RCA in the next 25 years; Development finance and the RCA; locating a senior RCA representative in the region; RCA guidelines and operating rules; TCDC activities; terminal tripartite review meeting on UNDP/RCA/IAEA project; status of new joint UNDP/RCA/IAEA project; options for the new joint project; RCA activities and budget in 1997 and 1998; reformulation and health care project; RCA proposed programme for 1999-2000; country statements; extension of RCA agreement; RCA 25th anniversary; venue and date of the 20th regular meeting of national RCA representatives

  16. Twenty-sixth general conference meeting of representatives of RCA member states. Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-10-01

    The meeting discussed the following issues: RCA Annual Report 1996; Report of the 19th RCA Working Group Meeting, Yangon Myanmar, 10-14 March 1997; RCA in the next 25 years; Development finance and the RCA; locating a senior RCA representative in the region; RCA guidelines and operating rules; TCDC activities; terminal tripartite review meeting on UNDP/RCA/IAEA project; status of new joint UNDP/RCA/IAEA project; options for the new joint project; RCA activities and budget in 1997 and 1998; reformulation and health care project; RCA proposed programme for 1999-2000; country statements; extension of RCA agreement; RCA 25th anniversary; venue and date of the 20th regular meeting of national RCA representatives.

  17. An affordable proxy of representative national survey on radon concentration in dwellings: Design, organisation and preliminary evaluation of representativeness

    International Nuclear Information System (INIS)

    Antignani, Sara; Carelli, Vinicio; Cordedda, Carlo; Zonno, Fedele; Ampollini, Marco; Carpentieri, Carmela; Venoso, Gennaro; Bochicchio, Francesco

    2013-01-01

    Representative national surveys in dwellings are important to unbiasedly evaluate the exposure of the general population to radon. In Italy, a representative national survey was conducted from 1989 to 1996, which involved about 5600 dwellings in 232 towns. Later on, some Regions carried out more detailed surveys, but a new national survey in dwellings is necessary in order to obtain a more thorough estimate of radon concentration distribution over the Italian territory. The need to make this survey in an affordable way led to implement a new approach based on the collaboration between the Istituto Superiore di Sanità and a national company with workplaces and employees' homes throughout the country. The intent is to carry out a proxy of a population representative survey by measuring radon concentration in the homes of a random sample of the company employees. The realisation of this survey was affordable, thanks to the availability of corporate e-mail for each employee, intranet service, and company internal mail service. A dedicated web procedure and e-questionnaires allowed to automatically manage the contact with employees and to collect their data, which were both cost- and time-saving. Using this e-mail contact approach, 53% of contacted employees consented to participate in the survey. Radon concentration passive measuring devices were distributed to about 7000 dwellings, using about 14000 CR-39 detectors (two measured rooms per dwelling). In order to reduce costs, the devices were exposed for 12 months instead of two consecutive 6-month periods (as with the former national survey). A first checking of the actual representativeness of the sample was done by comparing characteristics of dwellings and occupants in the sample with corresponding data from the latest National Census. This was accomplished thanks to the fact that the questions in the survey questionnaire were tailored to the categories adopted for the Census questionnaire. A preliminary

  18. Chaos control applied to cardiac rhythms represented by ECG signals

    International Nuclear Information System (INIS)

    Borem Ferreira, Bianca; Amorim Savi, Marcelo; Souza de Paula, Aline

    2014-01-01

    The control of irregular or chaotic heartbeats is a key issue in cardiology. In this regard, chaos control techniques represent a good alternative since they suggest treatments different from those traditionally used. This paper deals with the application of the extended time-delayed feedback control method to stabilize pathological chaotic heart rhythms. Electrocardiogram (ECG) signals are employed to represent the cardiovascular behavior. A mathematical model is employed to generate ECG signals using three modified Van der Pol oscillators connected with time delay couplings. This model provides results that qualitatively capture the general behavior of the heart. Controlled ECG signals show the ability of the strategy either to control or to suppress the chaotic heart dynamics generating less-critical behaviors. (paper)

  19. Vulvar Skin Disorders throughout Lifetime: About Some Representative Dermatoses

    Directory of Open Access Journals (Sweden)

    Jean Doyen

    2014-01-01

    Full Text Available The objective of this paper is to present general considerations which should be kept in mind by clinicians in charge of women with vulvar diseases. Four representative vulvar dermatoses are described. Lichen simplex chronicus is a pathological condition related to chemical and mechanical irritant agents. Detrimental effects of these irritants, in the presence of other dermatoses, have to be considered when therapeutic responses are unsatisfactory. Lichen sclerosus is the most common vulvar dermatosis in elderly. However, it should be kept in mind that it may be diagnosed at any age. Lichen planus, in spite of sharing a similar range of etiological factors with lichen sclerosus, is a very distinct entity. Finally, Paget’s disease, although rare, is also described especially because of the challenge it represents both clinically and therapeutically.

  20. Representing the environment 3.0. Maps, models, networks.

    Directory of Open Access Journals (Sweden)

    Letizia Bollini

    2014-05-01

    Full Text Available Web 3.0 is changing the world we live and perceive the environment anthropomorphized, making a stratifation of levels of experience and mediated by the devices. If the urban landscape is designed, shaped and planned space, there is a social landscape that overwrite the territory of values, representations shared images, narratives of personal and collective history. Mobile technology introduces an additional parameter, a kind of non-place, which allows the coexistence of the here and elsewhere in an sort of digital landscape. The maps, mental models, the system of social networks become, then, the way to present, represented and represent themselves in a kind of ideal coring of the co-presence of levels of physical, cognitive and collective space.

  1. Patient representatives' views on patient information in clinical cancer trials

    DEFF Research Database (Denmark)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    of future simplified and more attractive informed consent forms. CONCLUSIONS: The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language......BACKGROUND: Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed...... consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. METHODS: Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I...

  2. Representing climate change on public service television: A case study.

    Science.gov (United States)

    Debrett, Mary

    2017-05-01

    Publicly funded broadcasters with a track record in science programming would appear ideally placed to represent climate change to the lay public. Free from the constraints of vested interests and the economic imperative, public service providers are better equipped to represent the scientific, social and economic aspects of climate change than commercial media, where ownership conglomeration, corporate lobbyists and online competition have driven increasingly tabloid coverage with an emphasis on controversy. This prime-time snapshot of the Australian Broadcasting Corporation's main television channel explores how the structural/rhetorical conventions of three established public service genres - a science programme, a documentary and a live public affairs talk show - impact on the representation of anthropogenic climate change. The study findings note implications for public trust, and discuss possibilities for innovation in the interests of better public understanding of climate change.

  3. Representing Scientific Communities by Data Visualization (1/2)

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    These lectures present a research that investigates the representation of communities, and the way to foster their understanding by different audiences. Communities are complex multidimensional entities intrinsically difficult to represent synthetically. The way to represent them is likely to differ depending on the audience considered: governing entities trying to make decision for the future of the community, general public trying to understand the nature of the community and the members of the community themselves. This work considers two types of communities as example: a scientific organization and an arising domain: the EPFL institutional community composed of faculty members and researchers and, at a world wide level, the emerging community of Digital Humanities researchers. For both cases, the research is organised as a process going from graphical research to actual materialization as physical artefacts (posters, maps, etc.), possibly extended using digital devices (augmented reality applications). T...

  4. Crystallochemical particularities of complexes with lower representatives of dicarboiylic acids

    International Nuclear Information System (INIS)

    Dmitrova, G.I.; Kiosse, G.A.

    1982-01-01

    A review is given of crystallochemical particularities of nonsubstituted dicarboxylic acids, HOOC-(CHsub(2))sub(n)-COOH, complexes with lower representatives of the given series (n=0.1). Besides published data, the studies on the structures obtained by the authors are included herein. From the structure data of salts and complexes with the lower representatives of dicarboxylic acids and oxyacids (among which there are complexes of rare earths and niobium) one can distinguish the formation of two-and polynuclear chelate complexes. Configuration of molecules of oxalic and malonic (and its derivatives) acids does not depend on the type of the compounds formed. The turn of carboxylic groups with respect to the plane of central carbon atoms in oxalate- and malonate-ions depends on their structural environment. The structures of complexes with malonic acid derivatives are not studied well although they are of great theoretical and practical interest

  5. Manikin families representing obese airline passengers in the US.

    Science.gov (United States)

    Park, Hanjun; Park, Woojin; Kim, Yongkang

    2014-01-01

    Aircraft passenger spaces designed without proper anthropometric analyses can create serious problems for obese passengers, including: possible denial of boarding, excessive body pressures and contact stresses, postural fixity and related health hazards, and increased risks of emergency evacuation failure. In order to help address the obese passenger's accommodation issues, this study developed male and female manikin families that represent obese US airline passengers. Anthropometric data of obese individuals obtained from the CAESAR anthropometric database were analyzed through PCA-based factor analyses. For each gender, a 99% enclosure cuboid was constructed, and a small set of manikins was defined on the basis of each enclosure cuboid. Digital human models (articulated human figures) representing the manikins were created using a human CAD software program. The manikin families were utilized to develop design recommendations for selected aircraft seat dimensions. The manikin families presented in this study would greatly facilitate anthropometrically accommodating large airline passengers.

  6. Processes, data structures, and apparatuses for representing knowledge

    Science.gov (United States)

    Hohimer, Ryan E [West Richland, WA; Thomson, Judi R [Guelph, CA; Harvey, William J [Richland, WA; Paulson, Patrick R [Pasco, WA; Whiting, Mark A [Richland, WA; Tratz, Stephen C [Richland, WA; Chappell, Alan R [Seattle, WA; Butner, R Scott [Richland, WA

    2011-09-20

    Processes, data structures, and apparatuses to represent knowledge are disclosed. The processes can comprise labeling elements in a knowledge signature according to concepts in an ontology and populating the elements with confidence values. The data structures can comprise knowledge signatures stored on computer-readable media. The knowledge signatures comprise a matrix structure having elements labeled according to concepts in an ontology, wherein the value of the element represents a confidence that the concept is present in an information space. The apparatus can comprise a knowledge representation unit having at least one ontology stored on a computer-readable medium, at least one data-receiving device, and a processor configured to generate knowledge signatures by comparing datasets obtained by the data-receiving devices to the ontologies.

  7. Representing electrons a biographical approach to theoretical entities

    CERN Document Server

    Arabatzis, Theodore

    2006-01-01

    Both a history and a metahistory, Representing Electrons focuses on the development of various theoretical representations of electrons from the late 1890s to 1925 and the methodological problems associated with writing about unobservable scientific entities. Using the electron-or rather its representation-as a historical actor, Theodore Arabatzis illustrates the emergence and gradual consolidation of its representation in physics, its career throughout old quantum theory, and its appropriation and reinterpretation by chemists. As Arabatzis develops this novel biographical

  8. Obtaining Samples Representative of Contaminant Distribution in an Aquifer

    International Nuclear Information System (INIS)

    Schalla, Ronald; Spane, Frank A.; Narbutovskih, Susan M.; Conley, Scott F.; Webber, William D.

    2002-01-01

    Historically, groundwater samples collected from monitoring wells have been assumed to provide average indications of contaminant concentrations within the aquifer over the well-screen interval. In-well flow circulation, heterogeneity in the surrounding aquifer, and the sampling method utilized, however, can significantly impact the representativeness of samples as contaminant indicators of actual conditions within the surrounding aquifer. This paper identifies the need and approaches essential for providing cost-effective and technically meaningful groundwater-monitoring results. Proper design of the well screen interval is critical. An accurate understanding of ambient (non-pumping) flow conditions within the monitoring well is essential for determining the contaminant distribution within the aquifer. The ambient in-well flow velocity, flow direction and volumetric flux rate are key to this understanding. Not only do the ambient flow conditions need to be identified for preferential flow zones, but also the probable changes that will be imposed under dynamic conditions that occur during groundwater sampling. Once the in-well flow conditions are understood, effective sampling can be conducted to obtain representative samples for specific depth zones or zones of interest. The question of sample representativeness has become an important issue as waste minimization techniques such as low flow purging and sampling are implemented to combat the increasing cost of well purging and sampling at many hazardous waste sites. Several technical approaches (e.g., well tracer techniques and flowmeter surveys) can be used to determine in-well flow conditions, and these are discussed with respect to both their usefulness and limitations. Proper fluid extraction methods using minimal, (low) volume and no purge sampling methods that are used to obtain representative samples of aquifer conditions are presented

  9. DOES FAIR VALUE REPRESENT A CONCERN FOR ROMANIAN RESEARCHERS?

    Directory of Open Access Journals (Sweden)

    Jurcau Anca-Sabina

    2010-07-01

    Full Text Available In the actual economic context, the fair value concept is of high interest .We tried to see if the concept is only talk about, or if research in Romania has been actually done on this theme. We have analyzed the Romanian Journals recognized by CNCSIS in order to see if this concept represents a concern for Romanian researchers. This article is a literature review of the economic Romanian journals recognize by CNCSIS in the field of “fair value”.

  10. Patient representatives? views on patient information in clinical cancer trials

    OpenAIRE

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    Background Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives? views and perceptions on the written trial information used in clinical cancer trials. Methods Written patient information leaflet...

  11. The Parliament of Catalonia, representing a millenary people

    OpenAIRE

    Mateu Vilaseca, Marcel

    2017-01-01

    Catalonia is a millenary nation, which the current Spanish constitutional order frames as an “autonomous community”. However, Catalonia as a nation was not born with the Spanish Constitution in 1978, nor has any possibility for the future been democratically barred. The most important contribution to Catalonia made by the 1978 Constitution was to make it possible for the Catalan Statute to create the Catalan Parliament, an institution that democratically represents the people of Catalonia and...

  12. Representing value judgements in the evaluation options for nuclear waste

    International Nuclear Information System (INIS)

    Watson, S.R.

    1985-08-01

    In this report we show how the concept of Best Practical Environmental Option for nuclear waste management may be articulated using the methods of Multi-attribute Value Analysis. The concept of characteristic weights is introduced to represent differences of opinion on the relative importance of different factors that may reasonably be held, and show how these may be used to summarise information for decision-makers in a concise way. (author)

  13. Early menarche and childhood adversities in a nationally representative sample

    OpenAIRE

    Henrichs, Kimberly L; McCauley, Heather L; Miller, Elizabeth; Styne, Dennis M; Saito, Naomi; Breslau, Joshua

    2014-01-01

    Background Epidemiological evidence suggests that early menarche, defined as onset of menses at age 11 or earlier, has increased in prevalence in recent birth cohorts and is associated with multiple poor medical and mental health outcomes in adulthood. There is evidence that childhood adversities occurring prior to menarche contribute to early menarche. Methods Data collected in face-to-face interviews with a nationally representative sample of women age 18 and over (N = 3288), as part of the...

  14. Representing health and illness: thoughts for the 21st century.

    Science.gov (United States)

    Gilman, Sander L

    2011-06-01

    The on-going discussion about a new empiricism in the study of the medical humanities has lead to a misapprehension about the problems attendant to representing health and illness. The difficulty in understanding the politics of health and illness as well as the concomitant new aestheticism that has arisen concerning its representation demands a rethinking of these categories in the 21st century. Obesity can provide a model for the importance of this problem today.

  15. The Netherlands: The representativeness of trade unions and employer associations in the cleaning activities sector

    OpenAIRE

    Grünell, M.

    2012-01-01

    The cleaning sector is a small but important sector of the Dutch service economy, employing around 2% of the work force. Employers are organised in one association, the Employer Organisation Cleaning and Business Services, de Ondernemersorganisatie Schoonmaak- en Bedrijfsdiensten, OSB. Employees in the sector are organised, either by the unions of FNV or CNV, the two main employee organisations. These three parties conclude the collective labour agreement on behalf of the 750 members of OSB (...

  16. Psychical conflict and representative activity as central core of psychopedagogical treatment

    OpenAIRE

    Rego, María Victoria

    2007-01-01

    El propósito de este artículo es presentar un modo de análisis de las transformaciones en la producción simbólica de niños con problemas de aprendizaje que asisten a tratamiento psicopedagógico grupal en el marco del Servicio de Asistencia Psicopedagógica de la Cátedra de Psicopedagogía Clínica de la Facultad de Psicología. Se plantean dos categorías para dicho análisis: conflicto psíquico y actividad representativa. A partir de las mismas se busca dar cuenta de un particular modo de interpre...

  17. The incorporation of technetium into a representative low-activity waste glass

    International Nuclear Information System (INIS)

    Ebert, W.L.; Bakel, A.J.; Bowers, D.L.; Buck, E.C.; Emery, J.W.

    1997-01-01

    A glass that has been tested to understand the corrosion behavior of waste glasses with high soda contents for immobilizing Hanford incidental wastes has been made by melting crushed glass with either TcO 2 or NaTcO 4 at 1,100--1,300 C. Incorporation of technetium in the glass was affected by solubility or kinetic effects. Metallic technetium inclusions formed in all the TcO 2 -doped glasses. Inclusions also formed in glasses with added NaTcO 4 that were melted at 1,100 C, but a glass melted at 1,200 C did not contain detectable inclusions. The presence of Tc-bearing inclusions complicates the interpretation of results from dissolution tests because of the simultaneous release of technetium from more than one phase, the unknown surface areas of each phase, and the possible incorporation of technetium that is released from one phase into another phase. A glass containing about 0.15 mass % Tc dissolved in the glass is being used in dissolution tests to study the release behavior of technetium

  18. The Netherlands: The representativeness of trade unions and employer associations in the cleaning activities sector

    NARCIS (Netherlands)

    Grünell, M.

    2012-01-01

    The cleaning sector is a small but important sector of the Dutch service economy, employing around 2% of the work force. Employers are organised in one association, the Employer Organisation Cleaning and Business Services, de Ondernemersorganisatie Schoonmaak- en Bedrijfsdiensten, OSB. Employees in

  19. Representing Sikhism: essays in memory of the Irish scholar Max Arthur Macauliffe

    OpenAIRE

    Shackle, Christopher; Bocking, Brian

    2017-01-01

    This is an introduction, by the guest editors, to the special issue of JISASR (Vol 4, 2017) entitled 'Representing Sikhism: Essays in Memory of the Irish Scholar Max Arthur Macauliffe'. The genesis of this special issue lies in pioneering work on Macauliffe's Irish identity and personal and scholarly life undertaken by Professor Tadhg Foley (Galway). The active interest and support of members of the Sikh community in Ireland led to a conference, hosted by the Study of Religions Department at ...

  20. Risk Gambling and Personality: Results from a Representative Swedish Sample.

    Science.gov (United States)

    Sundqvist, Kristina; Wennberg, Peter

    2015-12-01

    The association between personality and gambling has been explored previously. However, few studies are based on representative populations. This study aimed at examining the association between risk gambling and personality in a representative Swedish population. A random Swedish sample (N = 19,530) was screened for risk gambling using the Lie/Bet questionnaire. The study sample (N = 257) consisted of those screening positive on Lie/Bet and completing a postal questionnaire about gambling and personality (measured with the NODS-PERC and the HP5i respectively). Risk gambling was positively correlated with Negative Affectivity (a facet of Neuroticism) and Impulsivity (an inversely related facet of Conscientiousness), but all associations were weak. When taking age and gender into account, there were no differences in personality across game preference groups, though preferred game correlated with level of risk gambling. Risk gamblers scored lower than the population norm data with respect to Negative Affectivity, but risk gambling men scored higher on Impulsivity. The association between risk gambling and personality found in previous studies was corroborated in this study using a representative sample. We conclude that risk and problem gamblers should not be treated as a homogeneous group, and prevention and treatment interventions should be adapted according to differences in personality, preferred type of game and the risk potential of the games.

  1. Representing Spatial Layout According to Intrinsic Frames of Reference.

    Science.gov (United States)

    Xie, Chaoxiang; Li, Shiyi; Tao, Weidong; Wei, Yiping; Sun, Hong-Jin

    2017-01-01

    Mou and McNamara have suggested that object locations are represented according to intrinsic reference frames. In three experiments, we investigated the limitations of intrinsic reference frames as a mean to represent object locations in spatial memory. Participants learned the locations of seven or eight common objects in a rectangular room and then made judgments of relative direction based on their memory of the layout. The results of all experiments showed that when all objects were positioned regularly, judgments of relative direction were faster or more accurate for novel headings that were aligned with the primary intrinsic structure than for other novel headings; however, when one irregularly positioned object was added to the layout, this advantage was eliminated. The experiments further indicated that with a single view at study, participants could represent the layout from either an egocentric orientation or a different orientation, according to experimental instructions. Together, these results suggest that environmental reference frames and intrinsic axes can influence performance for novel headings, but their role in spatial memory depends on egocentric experience, layout regularity, and instructions.

  2. Patch-based visual tracking with online representative sample selection

    Science.gov (United States)

    Ou, Weihua; Yuan, Di; Li, Donghao; Liu, Bin; Xia, Daoxun; Zeng, Wu

    2017-05-01

    Occlusion is one of the most challenging problems in visual object tracking. Recently, a lot of discriminative methods have been proposed to deal with this problem. For the discriminative methods, it is difficult to select the representative samples for the target template updating. In general, the holistic bounding boxes that contain tracked results are selected as the positive samples. However, when the objects are occluded, this simple strategy easily introduces the noises into the training data set and the target template and then leads the tracker to drift away from the target seriously. To address this problem, we propose a robust patch-based visual tracker with online representative sample selection. Different from previous works, we divide the object and the candidates into several patches uniformly and propose a score function to calculate the score of each patch independently. Then, the average score is adopted to determine the optimal candidate. Finally, we utilize the non-negative least square method to find the representative samples, which are used to update the target template. The experimental results on the object tracking benchmark 2013 and on the 13 challenging sequences show that the proposed method is robust to the occlusion and achieves promising results.

  3. Using SNOMED CT to Represent Two Interface Terminologies

    Science.gov (United States)

    Rosenbloom, S. Trent; Brown, Steven H.; Froehling, David; Bauer, Brent A.; Wahner-Roedler, Dietlind L.; Gregg, William M.; Elkin, Peter L.

    2009-01-01

    Objective Interface terminologies are designed to support interactions between humans and structured medical information. In particular, many interface terminologies have been developed for structured computer based documentation systems. Experts and policy-makers have recommended that interface terminologies be mapped to reference terminologies. The goal of the current study was to evaluate how well the reference terminology SNOMED CT could map to and represent two interface terminologies, MEDCIN and the Categorical Health Information Structured Lexicon (CHISL). Design Automated mappings between SNOMED CT and 500 terms from each of the two interface terminologies were evaluated by human reviewers, who also searched SNOMED CT to identify better mappings when this was judged to be necessary. Reviewers judged whether they believed the interface terms to be clinically appropriate, whether the terms were covered by SNOMED CT concepts and whether the terms' implied semantic structure could be represented by SNOMED CT. Measurements Outcomes included concept coverage by SNOMED CT for study terms and their implied semantics. Agreement statistics and compositionality measures were calculated. Results The SNOMED CT terminology contained concepts to represent 92.4% of MEDCIN and 95.9% of CHISL terms. Semantic structures implied by study terms were less well covered, with some complex compositional expressions requiring semantics not present in SNOMED CT. Among sampled terms, those from MEDCIN were more complex than those from CHISL, containing an average 3.8 versus 1.8 atomic concepts respectively, pterms. PMID:18952944

  4. Using SNOMED CT to represent two interface terminologies.

    Science.gov (United States)

    Rosenbloom, S Trent; Brown, Steven H; Froehling, David; Bauer, Brent A; Wahner-Roedler, Dietlind L; Gregg, William M; Elkin, Peter L

    2009-01-01

    Interface terminologies are designed to support interactions between humans and structured medical information. In particular, many interface terminologies have been developed for structured computer based documentation systems. Experts and policy-makers have recommended that interface terminologies be mapped to reference terminologies. The goal of the current study was to evaluate how well the reference terminology SNOMED CT could map to and represent two interface terminologies, MEDCIN and the Categorical Health Information Structured Lexicon (CHISL). Automated mappings between SNOMED CT and 500 terms from each of the two interface terminologies were evaluated by human reviewers, who also searched SNOMED CT to identify better mappings when this was judged to be necessary. Reviewers judged whether they believed the interface terms to be clinically appropriate, whether the terms were covered by SNOMED CT concepts and whether the terms' implied semantic structure could be represented by SNOMED CT. Outcomes included concept coverage by SNOMED CT for study terms and their implied semantics. Agreement statistics and compositionality measures were calculated. The SNOMED CT terminology contained concepts to represent 92.4% of MEDCIN and 95.9% of CHISL terms. Semantic structures implied by study terms were less well covered, with some complex compositional expressions requiring semantics not present in SNOMED CT. Among sampled terms, those from MEDCIN were more complex than those from CHISL, containing an average 3.8 versus 1.8 atomic concepts respectively, pterms.

  5. Patient representatives' views on patient information in clinical cancer trials.

    Science.gov (United States)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-02-01

    Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

  6. Reference materials and representative test materials: the nanotechnology case

    International Nuclear Information System (INIS)

    Roebben, G.; Rasmussen, K.; Kestens, V.; Linsinger, T. P. J.; Rauscher, H.; Emons, H.; Stamm, H.

    2013-01-01

    An increasing number of chemical, physical and biological tests are performed on manufactured nanomaterials for scientific and regulatory purposes. Existing test guidelines and measurement methods are not always directly applicable to or relevant for nanomaterials. Therefore, it is necessary to verify the use of the existing methods with nanomaterials, thereby identifying where modifications are needed, and where new methods need to be developed and validated. Efforts for verification, development and validation of methods as well as quality assurance of (routine) test results significantly benefit from the availability of suitable test and reference materials. This paper provides an overview of the existing types of reference materials and introduces a new class of test materials for which the term ‘representative test material’ is proposed. The three generic concepts of certified reference material, reference material(non-certified) and representative test material constitute a comprehensive system of benchmarks that can be used by all measurement and testing communities, regardless of their specific discipline. This paper illustrates this system with examples from the field of nanomaterials, including reference materials and representative test materials developed at the European Commission’s Joint Research Centre, in particular at the Institute for Reference Materials and Measurements (IRMM), and at the Institute for Health and Consumer Protection (IHCP).

  7. Representing metarepresentations: is there theory of mind-specific cognition?

    Science.gov (United States)

    Egeth, Marc; Kurzban, Robert

    2009-03-01

    What cognitive mechanisms underlie Theory of Mind? Some infer domain-specific Theory of Mind cognition based the pattern of children diagnosed with autism failing the False Belief test but passing the False Photograph test. However, we argue that the False Belief test entails various task demands the False Photograph task does not, including the necessity to represent a higher-order representation (a metarepresentation), thus confounding the inference of domain-specificity. Instead, a general difficulty that affects representations of metarepresentations might account for the seeming domain-specific failure. Here we find that False-Belief failing False-Photograph passing children fail the Meta Photograph test, a new photograph-domain test that requires subjects to represent a metarepresentation. We conclude that people who fail the False Belief test but pass the False Photograph test do not necessarily have a content-specific Theory of Mind deficit. Instead, the general ability to represent representations and metarepresentations might underlie Theory of Mind.

  8. Representativeness of wind measurements in moderately complex terrain

    Science.gov (United States)

    van den Bossche, Michael; De Wekker, Stephan F. J.

    2018-02-01

    We investigated the representativeness of 10-m wind measurements in a 4 km × 2 km area of modest relief by comparing observations at a central site with those at four satellite sites located in the same area. Using a combination of established and new methods to quantify and visualize representativeness, we found significant differences in wind speed and direction between the four satellite sites and the central site. The representativeness of the central site wind measurements depended strongly on surface wind speed and direction, and atmospheric stability. Through closer inspection of the observations at one of the satellite sites, we concluded that terrain-forced flows combined with thermally driven downslope winds caused large biases in wind direction and speed. We used these biases to generate a basic model, showing that terrain-related differences in wind observations can to a large extent be predicted. Such a model is a cost-effective way to enhance an area's wind field determination and to improve the outcome of pollutant dispersion and weather forecasting models.

  9. Incidence of invasive macrophytes on methylmercury budget in temperate lakes: Central role of bacterial periphytic communities

    International Nuclear Information System (INIS)

    Gentès, Sophie; Monperrus, Mathilde; Legeay, Alexia; Maury-Brachet, Régine; Davail, Stephane; André, Jean-Marc; Guyoneaud, Rémy

    2013-01-01

    Several studies demonstrated high mercury (Hg) methylation and demethylation in the periphyton associated with floating roots in tropical ecosystems. The importance of aquatic plants on methylmercury production in three temperate ecosystems from south-western France was evaluated through Hg species concentrations, and Hg methylation/demethylation activities by using stable isotopic tracers ( 199 Hg(II), Me 201 Hg). Hg accumulation and high methylation and demethylation yields were detected in plant roots and periphyton, whereas results for sediment and water were low to insignificant. The presence of sulfate reducing prokaryotes was detected in all compartments (T-RFLP based on dsrAB amplified through nested PCR) and their main role in Hg methylation could be demonstrated. In turn, sulfate reduction inhibition did not affect demethylation activities. The estimation of net MeHg budgets in these ecosystems suggested that aquatic rhizosphere is the principal location for methylmercury production and may represent an important source for the contamination of the aquatic food chain. - Highlights: ► Both Hg methylation and demethylation occur in the periphyton of temperate ecosystems. ► Aquatic rhizosphere is the main compartment for net methylmercury production. ► Sulfate reducers are detected in all ecosystem compartments (water, sediment, periphyton). ► Sulfate reducers are responsible for methylmercury production in aquatic roots. - The incidence of periphytic microbial communities on net methylmercury production is highlighted in temperate aquatic ecosystems.

  10. Model parameters for representative wetland plant functional groups

    Science.gov (United States)

    Williams, Amber S.; Kiniry, James R.; Mushet, David M.; Smith, Loren M.; McMurry, Scott T.; Attebury, Kelly; Lang, Megan; McCarty, Gregory W.; Shaffer, Jill A.; Effland, William R.; Johnson, Mari-Vaughn V.

    2017-01-01

    Wetlands provide a wide variety of ecosystem services including water quality remediation, biodiversity refugia, groundwater recharge, and floodwater storage. Realistic estimation of ecosystem service benefits associated with wetlands requires reasonable simulation of the hydrology of each site and realistic simulation of the upland and wetland plant growth cycles. Objectives of this study were to quantify leaf area index (LAI), light extinction coefficient (k), and plant nitrogen (N), phosphorus (P), and potassium (K) concentrations in natural stands of representative plant species for some major plant functional groups in the United States. Functional groups in this study were based on these parameters and plant growth types to enable process-based modeling. We collected data at four locations representing some of the main wetland regions of the United States. At each site, we collected on-the-ground measurements of fraction of light intercepted, LAI, and dry matter within the 2013–2015 growing seasons. Maximum LAI and k variables showed noticeable variations among sites and years, while overall averages and functional group averages give useful estimates for multisite simulation modeling. Variation within each species gives an indication of what can be expected in such natural ecosystems. For P and K, the concentrations from highest to lowest were spikerush (Eleocharis macrostachya), reed canary grass (Phalaris arundinacea), smartweed (Polygonum spp.), cattail (Typha spp.), and hardstem bulrush (Schoenoplectus acutus). Spikerush had the highest N concentration, followed by smartweed, bulrush, reed canary grass, and then cattail. These parameters will be useful for the actual wetland species measured and for the wetland plant functional groups they represent. These parameters and the associated process-based models offer promise as valuable tools for evaluating environmental benefits of wetlands and for evaluating impacts of various agronomic practices in

  11. Representativeness of the LifeLines Cohort Study.

    Directory of Open Access Journals (Sweden)

    Bart Klijs

    Full Text Available LifeLines is a large prospective population-based three generation cohort study in the north of the Netherlands. Different recruitment strategies were adopted: recruitment of an index population via general practitioners, subsequent inclusion of their family members, and online self-registration. Our aim was to investigate the representativeness of the adult study population at baseline and to evaluate differences in the study population according to recruitment strategy.Demographic characteristics of the LifeLines study population, recruited between 2006-2013, were compared with the total adult population in the north of the Netherlands as registered in the Dutch population register. Socioeconomic characteristics, lifestyle, chronic diseases, and general health were further compared with participants of the Permanent Survey of Living Conditions within the region (2005-2011, N = 6,093. Differences according to recruitment strategy were assessed.Compared with the population of the north of the Netherlands, LifeLines participants were more often female, middle aged, married, living in a semi-urban place and Dutch native. Adjusted for differences in demographic composition, in LifeLines a smaller proportion had a low educational attainment (5% versus 14% or had ever smoked (54% versus 66%. Differences in the prevalence of various chronic diseases and low general health scores were mostly smaller than 3%. The age profiles of the three recruitment groups differed due to age related inclusion criteria of the recruitment groups. Other differences according to recruitment strategy were small.Our results suggest that, adjusted for differences in demographic composition, the LifeLines adult study population is broadly representative for the adult population of the north of the Netherlands. The recruitment strategy had a minor effect on the level of representativeness. These findings indicate that the risk of selection bias is low and that risk estimates

  12. Out-of-Autoclave Manufacturing of Aerospace Representative Parts

    Science.gov (United States)

    Cauberghs, Julien

    The use of carbon fibre reinforced composites for aerospace structures has seen a high increase in recent years, and is still growing. The high stiffness-to-weight ratio of these materials makes them ideal for primary structures on airplanes, satellites, and spacecrafts. Nevertheless, the manufacturing of composites remains very costly since it requires equipment investment such as an autoclave, and very qualified workers. Out-of-autoclave manufacturing technology is very promising since it only requires a traditional oven, while still aiming at similar part quality. However, the absence of positive pressure compared with an autoclave makes it more difficult to achieve low porosity parts. This research investigates the manufacturing of complex features with out-of autoclave prepreg technology. The features studied are tight-radius corners with a curvature change, and ply drop-offs. Ply drop-offs tests were conducted to identify if porosity is higher at ply terminations. In corners, the bagging arrangement was modified to achieve the most uniform thickness in areas of curvature change, even with small radii. The conclusions from these studies provided us with guidelines to manufacture larger representative parts, which included these features. The representative parts were tested for porosity, thickness uniformity, mechanical performance, and glass transition temperature (Tg). A total of four representative parts were manufactured with out-of-autoclave technology, and one more was manufactured with an autoclave to allow for a proper comparison between the two processes. The materials used were MTM45-1 5 harness satin and CYCOM5320 plain weave for the out-of-autoclave parts, and CYCOM5276-1 plain weave for the autoclave part. The effect of ply drop-offs on porosity was found to be negligible. Thickness deviation in corners was attributed to a combination of consumable bridging, prepreg's bulk factor and inter-ply shear. Overall, out-of-autoclave prepregs showed

  13. Representative Vector Machines: A Unified Framework for Classical Classifiers.

    Science.gov (United States)

    Gui, Jie; Liu, Tongliang; Tao, Dacheng; Sun, Zhenan; Tan, Tieniu

    2016-08-01

    Classifier design is a fundamental problem in pattern recognition. A variety of pattern classification methods such as the nearest neighbor (NN) classifier, support vector machine (SVM), and sparse representation-based classification (SRC) have been proposed in the literature. These typical and widely used classifiers were originally developed from different theory or application motivations and they are conventionally treated as independent and specific solutions for pattern classification. This paper proposes a novel pattern classification framework, namely, representative vector machines (or RVMs for short). The basic idea of RVMs is to assign the class label of a test example according to its nearest representative vector. The contributions of RVMs are twofold. On one hand, the proposed RVMs establish a unified framework of classical classifiers because NN, SVM, and SRC can be interpreted as the special cases of RVMs with different definitions of representative vectors. Thus, the underlying relationship among a number of classical classifiers is revealed for better understanding of pattern classification. On the other hand, novel and advanced classifiers are inspired in the framework of RVMs. For example, a robust pattern classification method called discriminant vector machine (DVM) is motivated from RVMs. Given a test example, DVM first finds its k -NNs and then performs classification based on the robust M-estimator and manifold regularization. Extensive experimental evaluations on a variety of visual recognition tasks such as face recognition (Yale and face recognition grand challenge databases), object categorization (Caltech-101 dataset), and action recognition (Action Similarity LAbeliNg) demonstrate the advantages of DVM over other classifiers.

  14. The live album or many ways of representing performance

    Directory of Open Access Journals (Sweden)

    Mazzanti Sergio

    2014-01-01

    Full Text Available The analysis of live albums can clarify the dialectic between studio recordings and live performances. After discussing key concepts such as authenticity, space, time and place, and documentation, the author gives a preliminary definition of live albums, combining available descriptions and comparing them with different typologies and functions of these recordings. The article aims to give a new definition of the concept of live albums, gathering their primary elements: “A live album is an officially released extended recording of popular music representing one or more actually occurred public performances”.

  15. Direct and Representative Democracy - Supplementing, not Excluding Each Other

    DEFF Research Database (Denmark)

    Svensson, Palle

    2007-01-01

    : and (4) more transparency and enlightened understanding versus less confidentiality. The arguments are discussed in relation to general political goals of good government such as legitimacy, efficiency and stability. The basic thesis of the paper is that direct and representative forms of democracy...... are not exclusive. Much of the disagreement among those in favour of and in opposition to the introduction of more elements of direct democracy is caused by arguments that could be tested empirically and on more or less implicit assumptions about an either-or rather than a more-or-less of these forms of government...

  16. OKBL: A language for representing object oriented knowledge

    International Nuclear Information System (INIS)

    Matsumoto, Y.; Sugiyai, I.; Ishikawa, K.

    1984-01-01

    Industrial system is operated by using numerous ''operator's knowledge'' about the system. Each knowledge can be regarded as an object and is represented and maintained as an 'ACTOR' and written in a language based on the actor concept. OKBL (Object Oriented Operational KnowledgeBase Management Language) is the language proposed here for this purpose and used in OKBS (a system based on OKBL). The OKBS inference mechanism on the knowledgebase written in OKBL is implemented by message passings among ACTORs. OKBS has been applied to the guidance system for the operators of electric power dispatch control stations

  17. Retention performance of green roofs in representative climates worldwide

    Science.gov (United States)

    Viola, F.; Hellies, M.; Deidda, R.

    2017-10-01

    The ongoing process of global urbanization contributes to an increase in stormwater runoff from impervious surfaces, threatening also water quality. Green roofs have been proved to be innovative stormwater management measures to partially restore natural states, enhancing interception, infiltration and evapotranspiration fluxes. The amount of water that is retained within green roofs depends not only on their depth, but also on the climate, which drives the stochastic soil moisture dynamic. In this context, a simple tool for assessing performance of green roofs worldwide in terms of retained water is still missing and highly desirable for practical assessments. The aim of this work is to explore retention performance of green roofs as a function of their depth and in different climate regimes. Two soil depths are investigated, one representing the intensive configuration and another representing the extensive one. The role of the climate in driving water retention has been represented by rainfall and potential evapotranspiration dynamics. A simple conceptual weather generator has been implemented and used for stochastic simulation of daily rainfall and potential evapotranspiration. Stochastic forcing is used as an input of a simple conceptual hydrological model for estimating long-term water partitioning between rainfall, runoff and actual evapotranspiration. Coupling the stochastic weather generator with the conceptual hydrological model, we assessed the amount of rainfall diverted into evapotranspiration for different combinations of annual rainfall and potential evapotranspiration in five representative climatic regimes. Results quantified the capabilities of green roofs in retaining rainfall and consequently in reducing discharges into sewer systems at an annual time scale. The role of substrate depth has been recognized to be crucial in determining green roofs retention performance, which in general increase from extensive to intensive settings. Looking at the

  18. Analysis of Mental Processes Represented in Models of Artificial Consciousness

    Directory of Open Access Journals (Sweden)

    Luana Folchini da Costa

    2013-12-01

    Full Text Available The Artificial Consciousness concept has been used in the engineering area as being an evolution of the Artificial Intelligence. However, consciousness is a complex subject and often used without formalism. As a main contribution, in this work one proposes an analysis of four recent models of artificial consciousness published in the engineering area. The mental processes represented by these models are highlighted and correlations with the theoretical perspective of cognitive psychology are made. Finally, considerations about consciousness in such models are discussed.

  19. Object-Relational Management of Multiply Represented Geographic Entities

    DEFF Research Database (Denmark)

    Friis-Christensen, Anders; Jensen, Christian Søndergaard

    2003-01-01

    Multiple representation occurs when information about the same geographic entity is represented electronically more than once. This occurs frequently in practice, and it invariably results in the occurrence of inconsistencies among the different representations. We propose to resolve this situation...... by introducing a multiple representation management system (MRMS), the schema of which includes rules that specify how to identify representations of the same entity, rules that specify consistency requirements, and rules used to restore consistency when necessary. In this paper, we demonstrate by means...

  20. Shortest triplet clustering: reconstructing large phylogenies using representative sets

    Directory of Open Access Journals (Sweden)

    Sy Vinh Le

    2005-04-01

    Full Text Available Abstract Background Understanding the evolutionary relationships among species based on their genetic information is one of the primary objectives in phylogenetic analysis. Reconstructing phylogenies for large data sets is still a challenging task in Bioinformatics. Results We propose a new distance-based clustering method, the shortest triplet clustering algorithm (STC, to reconstruct phylogenies. The main idea is the introduction of a natural definition of so-called k-representative sets. Based on k-representative sets, shortest triplets are reconstructed and serve as building blocks for the STC algorithm to agglomerate sequences for tree reconstruction in O(n2 time for n sequences. Simulations show that STC gives better topological accuracy than other tested methods that also build a first starting tree. STC appears as a very good method to start the tree reconstruction. However, all tested methods give similar results if balanced nearest neighbor interchange (BNNI is applied as a post-processing step. BNNI leads to an improvement in all instances. The program is available at http://www.bi.uni-duesseldorf.de/software/stc/. Conclusion The results demonstrate that the new approach efficiently reconstructs phylogenies for large data sets. We found that BNNI boosts the topological accuracy of all methods including STC, therefore, one should use BNNI as a post-processing step to get better topological accuracy.

  1. The Representatives of Amelanchier Medik. Genus in Ukraine

    Directory of Open Access Journals (Sweden)

    Opalko Anatoliy Ivanovich

    2015-04-01

    Full Text Available The information on fruit and decorative value, honey and medicinal properties of the genus Amelanchier Medik. is generalized. Their biological characteristics, chemical composition and palatability traits of the fruit, the ways of consumption and processing, including drying, preparing juices, syrups, jams, candied fruit jellies, confiture, and fruit wine are specified. The environmental adaptability and effectiveness of using juneberry for phytomelioration are mentioned. Several versions of the origin of the genus Amelanchier name and interpretation of its specific epithets are described. The controversial issues of the genus Amelanchier system were discussed from the classical and molecular genetic approaches. The attention is focused on two main aspects of views on the place of the genus Amelanchier representatives of the family Rosaceae Juss. within the particular subfamily, namely the subfamily Pyroideae Burnett (Maloideae S. Weber or the subfamily Amygdaloideae Arn., which indicates the necessity for further comparative morphological and molecular genetic studies of the family Rosaceae. The directions of evolution, habitat and invasive ability of some species of the genus Amelanchier are characterised. The list of the genus Amelanchier representatives cultivated in Ukraine is given.

  2. Foot Complications in a Representative Australian Inpatient Population

    Directory of Open Access Journals (Sweden)

    Peter A. Lazzarini

    2017-01-01

    Full Text Available We investigated the prevalence and factors independently associated with foot complications in a representative inpatient population (adults admitted for any reason with and without diabetes. We analysed data from the Foot disease in inpatients study, a sample of 733 representative inpatients. Previous amputation, previous foot ulceration, peripheral arterial disease (PAD, peripheral neuropathy (PN, and foot deformity were the foot complications assessed. Sociodemographic, medical, and foot treatment history were collected. Overall, 46.0% had a foot complication with 23.9% having multiple; those with diabetes had higher prevalence of foot complications than those without diabetes (p<0.01. Previous amputation (4.1% was independently associated with previous foot ulceration, foot deformity, cerebrovascular accident, and past surgeon treatment (p<0.01. Previous foot ulceration (9.8% was associated with PN, PAD, past podiatry, and past nurse treatment (p<0.02. PAD (21.0% was associated with older age, males, indigenous people, cancer, PN, and past surgeon treatment (p<0.02. PN (22.0% was associated with older age, diabetes, mobility impairment, and PAD (p<0.05. Foot deformity (22.4% was associated with older age, mobility impairment, past podiatry treatment, and PN (p<0.01. Nearly half of all inpatients had a foot complication. Those with foot complications were older, male, indigenous, had diabetes, cerebrovascular accident, mobility impairment, and other foot complications or past foot treatment.

  3. An analysis of spatial representativeness of air temperature monitoring stations

    Science.gov (United States)

    Liu, Suhua; Su, Hongbo; Tian, Jing; Wang, Weizhen

    2018-05-01

    Surface air temperature is an essential variable for monitoring the atmosphere, and it is generally acquired at meteorological stations that can provide information about only a small area within an r m radius ( r-neighborhood) of the station, which is called the representable radius. In studies on a local scale, ground-based observations of surface air temperatures obtained from scattered stations are usually interpolated using a variety of methods without ascertaining their effectiveness. Thus, it is necessary to evaluate the spatial representativeness of ground-based observations of surface air temperature before conducting studies on a local scale. The present study used remote sensing data to estimate the spatial distribution of surface air temperature using the advection-energy balance for air temperature (ADEBAT) model. Two target stations in the study area were selected to conduct an analysis of spatial representativeness. The results showed that one station (AWS 7) had a representable radius of about 400 m with a possible error of less than 1 K, while the other station (AWS 16) had the radius of about 250 m. The representable radius was large when the heterogeneity of land cover around the station was small.

  4. Human visual system automatically represents large-scale sequential regularities.

    Science.gov (United States)

    Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

    2010-03-04

    Our brain recordings reveal that large-scale sequential regularities defined across non-adjacent stimuli can be automatically represented in visual sensory memory. To show that, we adopted an auditory paradigm developed by Sussman, E., Ritter, W., and Vaughan, H. G. Jr. (1998). Predictability of stimulus deviance and the mismatch negativity. NeuroReport, 9, 4167-4170, Sussman, E., and Gumenyuk, V. (2005). Organization of sequential sounds in auditory memory. NeuroReport, 16, 1519-1523 to the visual domain by presenting task-irrelevant infrequent luminance-deviant stimuli (D, 20%) inserted among task-irrelevant frequent stimuli being of standard luminance (S, 80%) in randomized (randomized condition, SSSDSSSSSDSSSSD...) and fixed manners (fixed condition, SSSSDSSSSDSSSSD...). Comparing the visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in human visual sensory system, revealed that visual MMN elicited by deviant stimuli was reduced in the fixed compared to the randomized condition. Thus, the large-scale sequential regularity being present in the fixed condition (SSSSD) must have been represented in visual sensory memory. Interestingly, this effect did not occur in conditions with stimulus-onset asynchronies (SOAs) of 480 and 800 ms but was confined to the 160-ms SOA condition supporting the hypothesis that large-scale regularity extraction was based on perceptual grouping of the five successive stimuli defining the regularity. 2010 Elsevier B.V. All rights reserved.

  5. In search of a representative sample of residential building work.

    Science.gov (United States)

    Lobb, Brenda; Woods, Gregory R

    2012-09-01

    Most research investigating injuries in construction work is limited by reliance on work samples unrepresentative of the multiple, variable-cycle tasks involved, resulting in incomplete characterisation of ergonomic exposures. In this case study, a participatory approach was used including hierarchical task analysis and site observations of a typical team of house builders in New Zealand, over several working days, to obtain a representative work sample. The builders' work consisted of 14 goal-defined jobs using varying subsets of 15 task types, each taking from less than 1 s to more than 1 h and performed in a variety of postures. Task type and duration varied within and between participants and days, although all participants spent at least 25% of the time moving from place to place, mostly carrying materials, and more than half the time either reaching up or bending down to work. This research has provided a description of residential building work based on a work sample more nearly representative than those previously published and has demonstrated a simple, low-cost but robust field observation method that can provide a valid basis for further study of hazard exposures. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  6. Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Verbeek, Jef; Jacobs, Ans; Spincemaille, Pieter; Cassiman, David

    2016-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  7. Engaging workplace representatives in research: what recruitment strategies work best?

    Science.gov (United States)

    Coole, C; Nouri, F; Narayanasamy, M; Baker, P; Khan, S; Drummond, A

    2018-05-23

    Workplaces are key stakeholders in work and health but little is known about the methods used to recruit workplace representatives (WRs), including managers, occupational health advisers and colleagues, to externally funded healthcare research studies. To detail the strategies used in recruiting WRs from three areas of the UK to a qualitative study concerning their experience of employees undergoing hip or knee replacement, to compare the strategies and inform recruitment methods for future studies. Six strategies were used to recruit WRs from organizations of different sizes and sectors. Data on numbers approached and responses received were analysed descriptively. Twenty-five WRs were recruited. Recruitment had to be extended outside the main three study areas, and took several months. It proved more difficult to recruit from non-service sectors and small- and medium-sized enterprises. The most successful strategies were approaching organizations that had participated in previous research studies, or known professionally or personally to team members. Recruiting a diverse sample of WRs to healthcare research requires considerable resources and persistence, and a range of strategies. Recruitment is easier where local relationships already exist; the importance of building and maintaining these relationships cannot be underestimated. However, the potential risks of bias and participant fatigue need to be acknowledged and managed. Further studies are needed to explore how WRs can be recruited to health research, and to identify the researcher effort and costs involved in achieving unbiased and representative samples.

  8. Challenges to Issues of Balance and Representativeness in African Lexicography

    Directory of Open Access Journals (Sweden)

    Thapelo Joseph Otlogetswe

    2011-10-01

    Full Text Available

    Abstract: Modern dictionaries depend on corpora of different sizes and types for frequency listings, concordances and collocations, illustrative sentences and grammatical information. With the help of computer software, retrieving such information has increasingly become relatively easy. However, the quality of retrieved information for lexicographic purposes depends on the information input at the stage of corpus construction. If corpora are not representative of the different language usages of a speech community, they may prove to be unreliable sources of lexicographic information. There are, however, issues in African languages which make many African corpora questionable. These issues include a lack of texts of different genres, the unavailability of balanced and representative written texts, a complete absence of spoken texts as well as literacy problems in African societies. This article therefore explores the different challenges to the construction of reliable corpora in African languages. It argues that African languages face peculiar challenges and corpus research may require a different treatment compared to European and American corpus research. It finally concludes that issues of balance and representativeness appear theoretically impossible when looking at the results of sociolinguistic research on the different existing language varieties which are difficult to represent accurately in a corpus.

    Keywords: AFRICAN LANGUAGES, BALANCE, BANK OF ENGLISH, BORROWING,BRITISH NATIONAL CORPUS, COBUILD, CODE-SWITCHING, COMPUTERS, CORPORA,DIALECT, DICTIONARIES, FREQUENCY, LANGUAGE VARIETY, REPRESENTATIVENESS,SETSWANA, SOCIOLINGUISTICS, SPEECH, TEXT

    Opsomming: Uitdagings betreffende kwessies van balans en verteenwoordigendheidin Afrikaleksikografie. Moderne woordeboeke steun op korpusse vanverskillende groottes en soorte vir frekwensielyste, konkordansies en kollokasies, voorbeeldsinneen taalkundige inligting. Met die hulp van

  9. Using Common Graphics Paradigms Implemented in a Java Applet to Represent Complex Scheduling Requirements

    Science.gov (United States)

    Jaap, John; Meyer, Patrick; Davis, Elizabeth

    1997-01-01

    The experiments planned for the International Space Station promise to be complex, lengthy and diverse. The scarcity of the space station resources will cause significant competition for resources between experiments. The scheduling job facing the Space Station mission planning software requires a concise and comprehensive description of the experiments' requirements (to ensure a valid schedule) and a good description of the experiments' flexibility (to effectively utilize available resources). In addition, the continuous operation of the station, the wide geographic dispersion of station users, and the budgetary pressure to reduce operations manpower make a low-cost solution mandatory. A graphical representation of the scheduling requirements for station payloads implemented via an Internet-based application promises to be an elegant solution that addresses all of these issues. The graphical representation of experiment requirements permits a station user to describe his experiment by defining "activities" and "sequences of activities". Activities define the resource requirements (with alternatives) and other quantitative constraints of tasks to be performed. Activities definitions use an "outline" graphics paradigm. Sequences define the time relationships between activities. Sequences may also define time relationships with activities of other payloads or space station systems. Sequences of activities are described by a "network" graphics paradigm. The bulk of this paper will describe the graphical approach to representing requirements and provide examples that show the ease and clarity with which complex requirements can be represented. A Java applet, to run in a web browser, is being developed to support the graphical representation of payload scheduling requirements. Implementing the entry and editing of requirements via the web solves the problems introduced by the geographic dispersion of users. Reducing manpower is accomplished by developing a concise

  10. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    International Nuclear Information System (INIS)

    Shine, E. P.; Poirier, M. R.

    2013-01-01

    Representative sampling is important throughout the Defense Waste Processing Facility (DWPF) process, and the demonstrated success of the DWPF process to achieve glass product quality over the past two decades is a direct result of the quality of information obtained from the process. The objective of this report was to present sampling methods that the Savannah River Site (SRS) used to qualify waste being dispositioned at the DWPF. The goal was to emphasize the methodology, not a list of outcomes from those studies. This methodology includes proven methods for taking representative samples, the use of controlled analytical methods, and data interpretation and reporting that considers the uncertainty of all error sources. Numerous sampling studies were conducted during the development of the DWPF process and still continue to be performed in order to evaluate options for process improvement. Study designs were based on use of statistical tools applicable to the determination of uncertainties associated with the data needs. Successful designs are apt to be repeated, so this report chose only to include prototypic case studies that typify the characteristics of frequently used designs. Case studies have been presented for studying in-tank homogeneity, evaluating the suitability of sampler systems, determining factors that affect mixing and sampling, comparing the final waste glass product chemical composition and durability to that of the glass pour stream sample and other samples from process vessels, and assessing the uniformity of the chemical composition in the waste glass product. Many of these studies efficiently addressed more than one of these areas of concern associated with demonstrating sample representativeness and provide examples of statistical tools in use for DWPF. The time when many of these designs were implemented was in an age when the sampling ideas of Pierre Gy were not as widespread as they are today. Nonetheless, the engineers and

  11. Defining And Characterizing Sample Representativeness For DWPF Melter Feed Samples

    Energy Technology Data Exchange (ETDEWEB)

    Shine, E. P.; Poirier, M. R.

    2013-10-29

    Representative sampling is important throughout the Defense Waste Processing Facility (DWPF) process, and the demonstrated success of the DWPF process to achieve glass product quality over the past two decades is a direct result of the quality of information obtained from the process. The objective of this report was to present sampling methods that the Savannah River Site (SRS) used to qualify waste being dispositioned at the DWPF. The goal was to emphasize the methodology, not a list of outcomes from those studies. This methodology includes proven methods for taking representative samples, the use of controlled analytical methods, and data interpretation and reporting that considers the uncertainty of all error sources. Numerous sampling studies were conducted during the development of the DWPF process and still continue to be performed in order to evaluate options for process improvement. Study designs were based on use of statistical tools applicable to the determination of uncertainties associated with the data needs. Successful designs are apt to be repeated, so this report chose only to include prototypic case studies that typify the characteristics of frequently used designs. Case studies have been presented for studying in-tank homogeneity, evaluating the suitability of sampler systems, determining factors that affect mixing and sampling, comparing the final waste glass product chemical composition and durability to that of the glass pour stream sample and other samples from process vessels, and assessing the uniformity of the chemical composition in the waste glass product. Many of these studies efficiently addressed more than one of these areas of concern associated with demonstrating sample representativeness and provide examples of statistical tools in use for DWPF. The time when many of these designs were implemented was in an age when the sampling ideas of Pierre Gy were not as widespread as they are today. Nonetheless, the engineers and

  12. Psychosocial workload and stress in the workers’ representative

    Directory of Open Access Journals (Sweden)

    Rabe Martin

    2012-10-01

    Full Text Available Abstract Background Using a data set of works councils of trade union IG Metal, this paper investigates psychosocial stress and strain on this specific group in comparison to employees working in administration in general (leadership and non-leadership-role and a national reference value. Methods For assessing psychosocial work factors on works councils within the sector represented by the trade union IG Metal in Germany, a research by using the German standard version of COPSOQ (Copenhagen Psychosocial Questionnaire was performed. The instrument includes 87 single items forming 25 aspects of strain and stress. Results from the study group of works councils were compared to those from employees working in administration and to the general population mean (COPSOQ database. Statistical analysis included t-tests, analysis of variance and multiple comparisons of means. To be significant in terms of statistics, p Results All in all, 309 works councils from a national survey of the German chemical and metalworking industries took part in the study. 113 were full-time works council members (exempted from the duty to perform their regular work, 196 were voluntary members (acting as employee representatives on an honorary basis alongside their normal duties. Comparison between works councils and employees working in administration (leadership roles (N=1810 and non-leadership roles (N=2970 and for employees in general (N=35.000 showed unfavourable values for works councils for most scales. Significantly higher values indicating higher strain and stress were found for the scales: emotional demands, work-privacy conflict, role conflicts, mobbing, cognitive stress symptoms and burnout. Unfavourable results were obtained for the aspects: quality of leadership, social support, sense of community and general health. Favourable findings were found on the scales: influence at work, quantity of social relations and the partly positive values for quantitative

  13. Health behaviour in children and adolescents with type 1 diabetes compared to a representative reference population.

    Directory of Open Access Journals (Sweden)

    Sebastian Kummer

    Full Text Available We provide a population-based overview of health behaviours of children and adolescents with type 1 diabetes in comparison to the general population, and analyse their relevance for glycaemic control and self-rated health status.Data from questionnaires of 11- to 17-year-old children and adolescents with diabetes (n = 629 were compared to a representative sample (n = 6,813.Children and adolescents with type 1 diabetes had a significantly increased odds of infrequent physical activity (adjusted OR 1.56, short overall duration of physical activity per week (OR 1.55, difference -1.3 hours/week, and high daily computer use (OR 2.51. They had a lower odds of active and passive smoking (OR 0.31 and OR 0.29, and high daily television time (OR 0.68. The odds of an at least good and excellent self-rated health status was increased with intense physical activity, and decreased with active smoking and prolonged daily use of computer and television. Active smoking and prolonged daily use of computer were associated with higher HbA1c.Children and adolescents with type 1 diabetes showed a different profile of health behaviour. Their overall health may improve if their education stresses specifically frequent physical activity with longer overall duration and less frequent television or computer use.

  14. Effects of Conazole Fungicides on Spontaneous Activity in Neural Networks

    Science.gov (United States)

    Hexaconazole (HEX), Tetraconazole (TET), Fluconazole (FLU), and Triadimefon (TRI) are conazole fungicides, used to control powdery mildews on crops, and as veterinary and clinical treatments. TRI, a demethylation inhibitor, is neurotoxic in vivo, and previous in vitro experiments...

  15. Coping with traumatic brain injury: representative case studies.

    Science.gov (United States)

    Kwasnica, C M; Heinemann, A

    1994-04-01

    This case report compares the use of social supports and vulnerability to substance abuse for two rehabilitation clients after traumatic brain injury (TBI). Using a psychosocial assessment, the Motivational Structure Questionnaire, Adaptive Skills Battery, and Ways of Coping Checklist within a representative case method, we studied two individuals in depth to understand differences in postinjury drinking behaviors. We also examined differences in availability and use of social supports and how support was related to coping efforts. Finally, we illustrated goal-setting and the relationship between long-term planning and follow-through on goals. Social supports, adaptive problem-solving behaviors, and positive reappraisal of situations seem to be important elements in postinjury abstinence. Clinically, this research supports the need for fostering use of both social supports and substance use prevention and treatment services when working with both inpatient and outpatient TBI clients.

  16. Linear elastic properties derivation from microstructures representative of transport parameters.

    Science.gov (United States)

    Hoang, Minh Tan; Bonnet, Guy; Tuan Luu, Hoang; Perrot, Camille

    2014-06-01

    It is shown that three-dimensional periodic unit cells (3D PUC) representative of transport parameters involved in the description of long wavelength acoustic wave propagation and dissipation through real foam samples may also be used as a standpoint to estimate their macroscopic linear elastic properties. Application of the model yields quantitative agreement between numerical homogenization results, available literature data, and experiments. Key contributions of this work include recognizing the importance of membranes and properties of the base material for the physics of elasticity. The results of this paper demonstrate that a 3D PUC may be used to understand and predict not only the sound absorbing properties of porous materials but also their transmission loss, which is critical for sound insulation problems.

  17. [Involvement of medical representatives in team medical care].

    Science.gov (United States)

    Hirotsu, Misaki; Sohma, Michiro; Takagi, Hidehiko

    2009-04-01

    In recent years, chemotherapies have been further advanced because of successive launch of new drugs, introduction of molecular targeting, etc., and the concept of so-called Team Medical Care ,the idea of sharing interdisciplinary expertise for collaborative treatment, has steadily penetrated in the Japanese medical society. Dr. Naoto Ueno is a medical oncologist at US MD Anderson Cancer Center, the birthplace of the Team Medical Care. He has advocated the concept of ABC of Team Oncology by positioning pharmaceutical companies as Team C. Under such team practice, we believe that medical representatives of a pharmaceutical company should also play a role as a member of the Team Medical Care by providing appropriate drug use information to healthcare professionals, supporting post-marketing surveillance of treated patients, facilitating drug information sharing among healthcare professionals at medical institutions, etc.

  18. [Attitudes of general practitioners to pharmaceutical sales representatives in Sousse].

    Science.gov (United States)

    Ben Abdelaziz, A; Harrabi, I; Rahmani, S; Ghedira, A; Gaha, K; Ghannem, H

    2003-01-01

    The therapeutic knowledge of physicians is the corner stone to the rational use of medicines; however information about medicines is generally obtained from the pharmaceutical industry via their sales representatives (reps). We aimed to identify general practitioners' (GPs) attitudes to pharmaceutical reps and the information they provide. We surveyed 140 GPs using a self-administered questionnaire. The response rate was 78% (72 GPs from the public sector and 68 from the private sector). About 10% of the GPs said they received daily visits from pharmaceutical reps; 84% of GPs considered them an efficient source of information and 31% said they might change their therapeutic prescribing following visits from these reps. Because of their positive perception of pharmaceutical reps, GPs are susceptible to the information they provide. Controlling the validity of the therapeutic information imparted by the pharmaceutical industry is thus a fundamental component of the programme for the rational use of medicines.

  19. On the Alignment of Shapes Represented by Fourier Descriptors

    DEFF Research Database (Denmark)

    Sjöstrand, Karl; Ericsson, Anders; Larsen, Rasmus

    2006-01-01

    The representation of shapes by Fourier descriptors is a time-honored technique that has received relatively little attention lately. Nevertheless, it has many benefits and is applicable for describing a range of medical structures in two dimensions. Delineations in medical applications often...... consist of continuous outlines of structures, where no information of correspondence between samples exist. In this article, we discuss an alignment method that works directly with the functional representation of Fourier descriptors, and that is optimal in a least-squares sense. With corresponding...... represented by common landmarks can be constructed in an automatic fashion. If the aligned Fourier descriptors are inverse transformed from the frequency domain to the spatial domain, a set of roughly aligned landmarks are obtained. The positions of these are then adjusted along the contour of the objects...

  20. Use of S-α diagram for representing tokamak equilibrium

    International Nuclear Information System (INIS)

    Takahashi, H.; Chance, M.; Kessel, C.; LeBlanc, B.; Manickam, J.; Okabayashi, M.

    1991-05-01

    A use of the S-α diagram is proposed as a tool for representing the plasma equilibrium with a qualitative characterization of its stability through pattern recognition. The diagram is an effective tool for visually presenting the relationship between the shear and dimensionless pressure gradient of an equilibrium. In the PBX-M tokamak, an H-mode operating regime with high poloidal β and L-mode regime with high toroidal β, obtained using different profile modification techniques, are found to have distinct S-α trajectory patterns. Pellet injection into a plasma in the H-mode regime with high toroidal β, obtained using different profile modification techniques, are found to have distinct S-α trajectory patterns. Pellet injection into a plasma in the H-mode regime results in favorable qualities of both regimes. The β collapse process and ELM event also manifest themselves as characteristic changes in the S-α pattern