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Sample records for cpg site autonomy

  1. Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

    Science.gov (United States)

    Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

    2017-03-09

    It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

  2. Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas

    International Nuclear Information System (INIS)

    Xiang, Shengyan; Liu, Zhaojun; Zhang, Baozhen; Zhou, Jing; Zhu, Bu-Dong; Ji, Jiafu; Deng, Dajun

    2010-01-01

    Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively

  3. Detection of Turner syndrome using X-chromosome inactivation specific differentially methylated CpG sites: A pilot study.

    Science.gov (United States)

    Zhang, Qiang; Guo, Xiaohong; Tian, Tian; Wang, Teng; Li, Qiaoli; Wang, Lei; Liu, Yun; Xing, Qinghe; He, Lin; Zhao, Xinzhi

    2017-05-01

    Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs. Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS. XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. DNA Methylation at a Bovine Alpha Satellite I Repeat CpG Site during Development following Fertilization and Somatic Cell Nuclear Transfer

    OpenAIRE

    Couldrey, Christine; Wells, David N.

    2013-01-01

    Incomplete epigenetic reprogramming is postulated to contribute to the low developmental success following somatic cell nuclear transfer (SCNT). Here, we describe the epigenetic reprogramming of DNA methylation at an alpha satellite I CpG site (αsatI-5) during development of cattle generated either by artificial insemination (AI) or in vitro fertilization (IVF) and SCNT. Quantitative methylation analysis identified that SCNT donor cells were highly methylated at αsatI-5 and resulting SCNT bla...

  5. Assessment of clusters of transcription factor binding sites in relationship to human promoter, CpG islands and gene expression

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    Sakaki Yoshiyuki

    2004-02-01

    Full Text Available Abstract Background Gene expression is regulated mainly by transcription factors (TFs that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS using position weight matrices (PWMs that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. Results We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster, we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. Conclusion Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1 those that show TFBS clustered in promoters associated with CGI, and (2 those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in

  6. Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation

    International Nuclear Information System (INIS)

    Wu, Yanyuan; Alvarez, Monica; Slamon, Dennis J; Koeffler, Phillip; Vadgama, Jaydutt V

    2010-01-01

    Epigenetic changes associated with promoter DNA methylation results in silencing of several tumor suppressor genes that lead to increased risk for tumor formation and for progression of the cancer. Methylation specific PCR (MSP) and bisulfite sequencing were used for determination of proapoptotic gene Caspase 8 (CASP8) and the tumor suppressor gene maspin promoter methylation in four breast cancer and two non-tumorigenic breast cell lines. Involvement of histone H3 methylation in those cell lines were examined by CHIP assay. The CpG sites in the promoter region of CASP8 and maspin were methylated in all four breast cancer cell lines but not in two non-tumorigenic breast cell lines. Demethylation agent 5-aza-2'-deoxycytidine (5-aza-dc) selectively inhibits DNA methyltransferases, DNMT3a and DNMT3b, and restored CASP8 and maspin gene expression in breast cancer cells. 5-aza-dc also reduced histone H3k9me2 occupancy on CASP8 promoter in SKBR3cells, but not in MCF-7 cells. Combination of histone deacetylase inhibitor Trichostatin A (TSA) and 5-aza-dc significant decrease in nuclear expression of Di-methyl histone H3-Lys27 and slight increase in acetyl histone H3-Lys9 in MCF-7 cells. CASP8 mRNA and protein level in MCF-7 cells were increased by the 5-aza-dc in combination with TSA. Data from our study also demonstrated that treatment with 5-FU caused a significant increase in unmethylated CASP8 and in CASP8 mRNA in all 3 cancer lines. CASP8 and maspin expression were reduced in breast cancer cells due to promoter methylation. Selective application of demethylating agents could offer novel therapeutic opportunities in breast cancer

  7. Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia

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    Nancy D Merner

    2015-10-01

    Full Text Available Many encoded gene products responsible for neurodevelopmental disorders (NDs like autism spectrum disorders (ASD, schizophrenia (SCZ, intellectual disability (ID, and idiopathic generalized epilepsy (IGE converge on networks controlling synaptic function. An increase in KCC2 (SLC12A5 Cl- transporter activity drives the developmental GABA excitatory-inhibitory sequence, but the role of KCC2 in human NDs is essentially unknown. Here, we report two rare, non-synonymous (NS, functionally-impairing variants in the KCC2 C-terminal regulatory domain (CTRD in human ASD (R952H and R1049C and SCZ (R952H previously linked with IGE and familial febrile seizures, and another novel NS KCC2 variant in ASD (R1048W with highly-predicted pathogenicity. Exome data from 2517 simplex families in the ASD Simon Simplex Collection revealed significantly more KCC2 CTRD variants in ASD cases than controls, and interestingly, these were more often synonymous and predicted to disrupt or introduce a CpG site. Furthermore, full gene analysis showed ASD cases are more likely to contain rare KCC2 variants affecting CpG sites than controls. These data suggest genetically-encoded dysregulation of KCC2-dependent GABA signaling may contribute to multiple human NDs.

  8. The CpG island searcher: a new WWW resource.

    Science.gov (United States)

    Takai, Daiya; Jones, Peter A

    2003-01-01

    Clusters of CpG dinucleotides in GC rich regions of the genome called "CpG islands" frequently occur in the 5' ends of genes. Methylation of CpG islands plays a role in transcriptional silencing in higher organisms in certain situations. We have established a CpG-island-extraction algorithm, which we previously developed [Takai and Jones, 2002], on a web site which has a simple user interface to identify CpG islands from submitted sequences of up to 50kb. The web site determines the locations of CpG islands using parameters (lower limit of %GC, ObsCpG/ExpCpG, length) set by the user, to display the value of parameters on each CpG island, and provides a graphical map of CpG dinucleotide distribution and borders of CpG islands. A command-line version of the CpG islands searcher has also been developed for larger sequences. The CpG Island Searcher was applied to the latest sequence and mapping information of human chromosomes 20, 21 and 22, and a total of 2345 CpG islands were extracted and 534 (23%) of them contained first coding exons and 650 (28%) contained other exons. The CpG Island Searcher is available on the World Wide Web at http://www.cpgislands.com or http://www.uscnorris.com/cpgislands/cpg.cgi.

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

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    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.

  10. DNA methylation at a bovine alpha satellite I repeat CpG site during development following fertilization and somatic cell nuclear transfer.

    Directory of Open Access Journals (Sweden)

    Christine Couldrey

    Full Text Available Incomplete epigenetic reprogramming is postulated to contribute to the low developmental success following somatic cell nuclear transfer (SCNT. Here, we describe the epigenetic reprogramming of DNA methylation at an alpha satellite I CpG site (αsatI-5 during development of cattle generated either by artificial insemination (AI or in vitro fertilization (IVF and SCNT. Quantitative methylation analysis identified that SCNT donor cells were highly methylated at αsatI-5 and resulting SCNT blastocysts showed significantly more methylation than IVF blastocysts. At implantation, no difference in methylation was observed between SCNT and AI in trophoblast tissue at αsatI-5, however, SCNT embryos were significantly hyper-methylated compared to AI controls at this time point. Following implantation, DNA methylation at αsatI-5 decreased in AI but not SCNT placental tissues. In contrast to placenta, the proportion of methylation at αsatI-5 remained high in adrenal, kidney and muscle tissues during development. Differences in the average proportion of methylation were smaller in somatic tissues than placental tissues but, on average, SCNT somatic tissues were hyper-methylated at αsatI-5. Although sperm from all bulls was less methylated than somatic tissues at αsatI-5, on average this site remained hyper-methylated in sperm from cloned bulls compared with control bulls. This developmental time course confirms that epigenetic reprogramming does occur, at least to some extent, following SCNT. However, the elevated methylation levels observed in SCNT blastocysts and cellular derivatives implies that there is either insufficient time or abundance of appropriate reprogramming factors in oocytes to ensure complete reprogramming. Incomplete reprogramming at this CpG site may be a contributing factor to low SCNT success rates, but more likely represents the tip of the iceberg in terms of incompletely reprogramming. Until protocols ensure the epigenetic

  11. DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.

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    Shimrat Mamrut

    Full Text Available Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.

  12. Instrumentalizing Szeklerland Autonomy Through Szekler Memory Sites and Rites in post-1989 Romania

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    Petru Szedlacsek

    2015-08-01

    Full Text Available In post-communist Romania, Szekler political and intellectual elites have taken advantage of a long discursive tradition on Szekler autonomy, which developed throughout the nineteenth and twentieth centuries within the nationalizing states (Brubaker 1996 of Hungary and Romania. As part of the interwar ideology of Transylvanianism, a particular Szekler identity-construction mechanism was developed, buttressed by a rhetoric on geographical remoteness in relation to the centers of power of Budapest and Bucharest. More precisely, the Szekler-ization of geography was enabled by imagining and cultivating sites and rites of memory in the Szeklerland – from pilgrimages to the funerary monuments of Szekler cultural elites and the sanctifying of Hungarian and Szekler flags in public squares. Drawing on this context, my paper explores the post-1989 revival of Szekler commemoration narratives that have attempted to construct a Szekler life-world within Romania by linking memory to territory. Since minority rituals of memory, parallel to the official state ones, are no longer silenced in Szekler public spaces after the fall of communism, interwar realms of memory have been reframed and popularized. On the line suggested by Katherine Verdery in The Political Lives of Dead Bodies (1999, this analysis also looks at how funeral ceremonies shape the relationship between the Szekler community and “its” territory with the Romanian Other. In this respect, this study focuses on the attempt to rebury the Szekler pro-Nazi writer József Nyirő on Szekler (yet Romanian soil. Apart from triggering a huge diplomatic incident between Hungary and Romania in the summer of 2012, it also pinpoints the reformulation of Szekler identity discourse within the Romanian post-communist context. In short, I will address questions regarding the practices of memory production permitted in present, the aims of Szekler elites in popularizing such practices and the way  these aims

  13. Revised genomic consensus for the hypermethylated CpG island region of the human L1 transposon and integration sites of full length L1 elements from recombinant clones made using methylation-tolerant host strains

    DEFF Research Database (Denmark)

    Crowther, P J; Doherty, J P; Linsenmeyer, M E

    1991-01-01

    preferentially from L1 members which have accumulated mutations that have removed sites of methylation. We present a revised consensus from the 5' presumptive control region of these elements. This revised consensus contains a consensus RNA polymerase III promoter which would permit the synthesis of transcripts......Efficient recovery of clones from the 5' end of the human L1 dispersed repetitive elements necessitates the use of deletion mcr- host strains since this region contains a CpG island which is hypermethylated in vivo. Clones recovered with conventional mcr+ hosts seem to have been derived...... from the 5' end of full length L1 elements. Such potential transcripts are likely to exhibit a high degree of secondary structure. In addition, we have determined the flanking sequences for 6 full length L1 elements. The majority of full length L1 clones show no convincing evidence for target site...

  14. CpG traffic lights are markers of regulatory regions in humans

    KAUST Repository

    Khamis, Abdullah M.; Lioznova, Anna V.; Artemov, Artem V.; Ramensky, Vasily; Bajic, Vladimir B.; Medvedeva, Yulia A.

    2016-01-01

    DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.

  15. CpG traffic lights are markers of regulatory regions in humans

    KAUST Repository

    Khamis, Abdullah M.

    2016-12-29

    DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.

  16. Relatively high rates of G:C → A:T transitions at CpG sites were observed in certain epithelial tissues including pancreas and submaxillary gland of adult big blue® mice.

    Science.gov (United States)

    Prtenjaca, Anita; Tarnowski, Heather E; Marr, Alison M; Heney, Melanie A; Creamer, Laura; Sathiamoorthy, Sarmitha; Hill, Kathleen A

    2014-01-01

    With few exceptions, spontaneous mutation frequency and pattern are similar across tissue types and relatively constant in young to middle adulthood in wild type mice. Underrepresented in surveys of spontaneous mutations across murine tissues is the diversity of epithelial tissues. For the first time, spontaneous mutations were detected in pancreas and submaxillary gland and compared with kidney, lung, and male germ cells from five adult male Big Blue® mice. Mutation load was assessed quantitatively through measurement of mutant and mutation frequency and qualitatively through identification of mutations and characterization of recurrent mutations, multiple mutations, mutation pattern, and mutation spectrum. A total of 9.6 million plaque forming units were screened, 226 mutants were collected, and 196 independent mutations were identified. Four novel mutations were discovered. Spontaneous mutation frequency was low in pancreas and high in the submaxillary gland. The submaxillary gland had multiple recurrent mutations in each of the mice and one mutant had two independent mutations. Mutation patterns for epithelial tissues differed from that observed in male germ cells with a striking bias for G:C to A:T transitions at CpG sites. A comprehensive review of lacI spontaneous mutation patterns in young adult mice and rats identified additional examples of this mutational bias. An overarching observation about spontaneous mutation frequency in adult tissues of the mouse remains one of stability. A repeated observation in certain epithelial tissues is a higher rate of G:C to A:T transitions at CpG sites and the underlying mechanisms for this bias are not known. Copyright © 2013 Wiley Periodicals, Inc.

  17. Reproducibility of methylated CpG typing with the Illumina MiSeq

    DEFF Research Database (Denmark)

    Kampmann, Marie-Louise; Meyer, Olivia Strunge; Greby Schmidt, Suzanne

    2017-01-01

    DNA methylation patterns may be used for identification of body fluids and for age estimation of human individuals. We evaluated some of the challenges and pitfalls of studying methylated CpG sites. We compared the methylated CpG analysis of two different methods 1) massively parallel sequencing...

  18. Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals

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    Keightley Peter D

    2008-09-01

    Full Text Available Abstract Background Molecular evolutionary studies in mammals often estimate nucleotide substitution rates within and outside CpG dinucleotides separately. Frequently, in alignments of two sequences, the division of sites into CpG and non-CpG classes is based simply on the presence or absence of a CpG dinucleotide in either sequence, a procedure that we refer to as CpG/non-CpG assignment. Although it likely that this procedure is biased, it is generally assumed that the bias is negligible if species are very closely related. Results Using simulations of DNA sequence evolution we show that assignment of the ancestral CpG state based on the simple presence/absence of the CpG dinucleotide can seriously bias estimates of the substitution rate, because many true non-CpG changes are misassigned as CpG. Paradoxically, this bias is most severe between closely related species, because a minimum of two substitutions are required to misassign a true ancestral CpG site as non-CpG whereas only a single substitution is required to misassign a true ancestral non-CpG site as CpG in a two branch tree. We also show that CpG misassignment bias differentially affects fourfold degenerate and noncoding sites due to differences in base composition such that fourfold degenerate sites can appear to be evolving more slowly than noncoding sites. We demonstrate that the effects predicted by our simulations occur in a real evolutionary setting by comparing substitution rates estimated from human-chimp coding and intronic sequence using CpG/non-CpG assignment with estimates derived from a method that is largely free from bias. Conclusion Our study demonstrates that a common method of assigning sites into CpG and non CpG classes in pairwise alignments is seriously biased and recommends against the adoption of ad hoc methods of ancestral state assignment.

  19. Autonomy @ Ames

    Science.gov (United States)

    Van Dalsem, William; Krishnakumar, Kalmanje Srinivas

    2016-01-01

    This is a powerpoint presentation that highlights autonomy across the 15 NASA technology roadmaps, including specific examples of projects (past and present) at NASA Ames Research Center. The NASA technology roadmaps are located here: http:www.nasa.govofficesocthomeroadmapsindex.html

  20. Syntactic autonomy

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, L.M.

    1998-12-01

    The study of adapting and evolving autonomous agents should be based on a complex systems-theoretic framework which requires both self-organizing and symbolic dimensions. An inclusive framework based on the notions of semiotics and situated action is advanced to build models capable of representing, as well as evolving in their environments.Such undertaking is pursued by discussing the ways in which symbol and self-organization are irreducibly intertwined in evolutionary systems. With this semiotic view of self-organization and symbols, the authors re-think the notion of autonomy of evolving systems, and show that evolutionary systems are characterized by a particular type of syntactic autonomy. Recent developments in emergent computation in cellular automata are discussed as examples of the emergence of syntactic autonomy in computational environments. New experiments emphasizing this syntactic autonomy in cellular automata are presented.

  1. Professional autonomy.

    Science.gov (United States)

    Aprile, A E

    1998-02-01

    Professional autonomy may represent the first step to implementing measures that will allow CRNAs to attain a level of independent practice consistent with their clinical and educational training. Autonomy is regarded as an essential ingredient of professionalism and confers independent function at the individual practitioner level. The principle of autonomy refers to the individual's capacity to make independent decisions based on the assumption that he or she possesses the cognitive, psychological, and emotional faculties to make rational decisions. Nursing practice meets the first two criteria of professionalism--competence and dedication to an important social good. The third criterion of professionalism, autonomy, has been a focal point for controversy since the late nineteenth century, in which obedience to supervisors and physicians remained a central focus of nursing ethics teaching until the advent of feminism in the 1970s. This article presents a thorough analysis of these concepts with some thoughts on how understanding the fundamental precepts and further research may not only help maintain the current level of CRNA professional autonomy but serve to guide us to become more autonomous in the future.

  2. Autonomy as Aesthetic Practice

    NARCIS (Netherlands)

    Lütticken, S.

    2014-01-01

    This essay examines various conceptions of autonomy in relation to recent artistic practices. Starting from the apparent opposition between modernist notions of the autonomy of art and theorizations of political autonomy, the text problematizes the notion of the autonomy of art by using Jacques

  3. University autonomy as sensemaking

    DEFF Research Database (Denmark)

    Lind, Jonas Krog

    The formal autonomy of universities in Europe has generally increased over recent decades. However, new forms of accountability measures and more indirect state steering have accompanied this development, making it difficult to assess the actual autonomy. The article addresses this problem...... by applying the sensemaking approach to the study of organizational autonomy. Enacted autonomy is suggested as a new conceptualization that challenges the basic assumption in studies on formal autonomy that autonomy is only about external constraints on action. It does so by insisting on the active subjects...... in the enactment of the environment, thereby questioning the validity of a clear distinction between what is internal and what is external to an organization. By acknowledging the subjective dimension of autonomy, a set of stylized identities is developed as a tool for understanding the enactment of autonomy...

  4. Respect for rational autonomy.

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    Walker, Rebecca L

    2009-12-01

    The standard notion of autonomy in medical ethics does not require that autonomous choices not be irrational. The paper gives three examples of seemingly irrational patient choices and discusses how a rational autonomy analysis differs from the standard view. It then considers whether a switch to the rational autonomy view would lead to overriding more patient decisions but concludes that this should not be the case. Rather, a determination of whether individual patient decisions are autonomous is much less relevant than usually considered in determining whether health care providers must abide by these decisions. Furthermore, respect for rational autonomy entails strong positive requirements of respect for the autonomy of the person as a rational decision maker. The rationality view of autonomy is conceptually stronger than the standard view, allows for a more nuanced understanding of the practical moral calculus involved in respecting patient autonomy, and promotes positive respect for patient autonomy.

  5. GaussianCpG: a Gaussian model for detection of CpG island in human genome sequences.

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    Yu, Ning; Guo, Xuan; Zelikovsky, Alexander; Pan, Yi

    2017-05-24

    As crucial markers in identifying biological elements and processes in mammalian genomes, CpG islands (CGI) play important roles in DNA methylation, gene regulation, epigenetic inheritance, gene mutation, chromosome inactivation and nuclesome retention. The generally accepted criteria of CGI rely on: (a) %G+C content is ≥ 50%, (b) the ratio of the observed CpG content and the expected CpG content is ≥ 0.6, and (c) the general length of CGI is greater than 200 nucleotides. Most existing computational methods for the prediction of CpG island are programmed on these rules. However, many experimentally verified CpG islands deviate from these artificial criteria. Experiments indicate that in many cases %G+C is human genome. We analyze the energy distribution over genomic primary structure for each CpG site and adopt the parameters from statistics of Human genome. The evaluation results show that the new model can predict CpG islands efficiently by balancing both sensitivity and specificity over known human CGI data sets. Compared with other models, GaussianCpG can achieve better performance in CGI detection. Our Gaussian model aims to simplify the complex interaction between nucleotides. The model is computed not by the linear statistical method but by the Gaussian energy distribution and accumulation. The parameters of Gaussian function are not arbitrarily designated but deliberately chosen by optimizing the biological statistics. By using the pseudopotential analysis on CpG islands, the novel model is validated on both the real and artificial data sets.

  6. Regimes of Autonomy

    NARCIS (Netherlands)

    Anderson, Joel

    2014-01-01

    Like being able to drive a car, being autonomous is a socially attributed, claimed, and contested status. Normative debates about criteria for autonomy (and what autonomy entitles one to) are best understood, not as debates about what autonomy, at core, really is, but rather as debates about the

  7. Controlled Autonomy: Novice Principals' Schema for District Control and School Autonomy

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    Weiner, Jennie M.; Woulfin, Sarah L.

    2017-01-01

    Purpose: The purpose of this paper is to gain insights into how a group of novice principals, all in schools that deployed principles of autonomy as mechanisms for improvement, conceptualized what the authors label "controlled autonomy"--a condition in which school leaders are expected to both make site-based decisions and be accountable…

  8. Autonomy: Life and Being

    Science.gov (United States)

    Williams, Mary-Anne

    This paper uses robot experience to explore key concepts of autonomy, life and being. Unfortunately, there are no widely accepted definitions of autonomy, life or being. Using a new cognitive agent architecture we argue that autonomy is a key ingredient for both life and being, and set about exploring autonomy as a concept and a capability. Some schools of thought regard autonomy as the key characteristic that distinguishes a system from an agent; agents are systems with autonomy, but rarely is a definition of autonomy provided. Living entities are autonomous systems, and autonomy is vital to life. Intelligence presupposes autonomy too; what would it mean for a system to be intelligent but not exhibit any form of genuine autonomy. Our philosophical, scientific and legal understanding of autonomy and its implications is immature and as a result progress towards designing, building, managing, exploiting and regulating autonomous systems is retarded. In response we put forward a framework for exploring autonomy as a concept and capability based on a new cognitive architecture. Using this architecture tools and benchmarks can be developed to analyze and study autonomy in its own right as a means to further our understanding of autonomous systems, life and being. This endeavor would lead to important practical benefits for autonomous systems design and help determine the legal status of autonomous systems. It is only with a new enabling understanding of autonomy that the dream of Artificial Intelligence and Artificial Life can be realized. We argue that designing systems with genuine autonomy capabilities can be achieved by focusing on agent experiences of being rather than attempting to encode human experiences as symbolic knowledge and know-how in the artificial agents we build.

  9. CpG island mapping by epigenome prediction.

    Directory of Open Access Journals (Sweden)

    Christoph Bock

    2007-06-01

    Full Text Available CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1 reliance on arbitrary threshold parameters that bear little biological justification, (2 failure to account for widespread heterogeneity among CpG islands, and (3 apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of "CpG island strength" that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted "bona fide" CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to

  10. CpG island mapping by epigenome prediction.

    Science.gov (United States)

    Bock, Christoph; Walter, Jörn; Paulsen, Martina; Lengauer, Thomas

    2007-06-01

    CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1) reliance on arbitrary threshold parameters that bear little biological justification, (2) failure to account for widespread heterogeneity among CpG islands, and (3) apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of "CpG island strength" that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted "bona fide" CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to their characteristic

  11. The Evolution of Autonomy.

    Science.gov (United States)

    Stammers, Trevor

    2015-01-01

    There can be little doubt, at least in the Western world, that autonomy is theruling principle in contemporary bioethics. In spite of its 'triumph' however,the dominance of the utilitarian concept of autonomy is being increasinglyquestioned. In this paper, I explore the nature of autonomy, how it came todisplace the Hippocratic tradition in medicine and how different conceptsof autonomy have evolved. I argue that the reduction of autonomy to'the exercise of personal choice' in medicine has led to a 'tyranny of autonomy' which can be inimical to ethical medical practice rather than conducive to it.I take the case of Kerrie Wooltorton as an illustration of how misplacedadherence to respect for patient autonomy can lead to tragic consequences.An analysis of autonomy based on the work of Rachel Haliburton isdescribed and applied to the role of autonomy in a recent bioethicaldebate--that arising from Savulescu's proposal that conscientious objection by health-care professionals should not be permitted in the NHS. Inconclusion, I suggest Kukla's concept of conscientious autonomy as onepromising pathway to circumvent both the limitations and adverse effectsof the dominance of current (mis)understandings of autonomy in biomedical ethics.

  12. Unique DNA methylome profiles in CpG island methylator phenotype colon cancers

    Science.gov (United States)

    Xu, Yaomin; Hu, Bo; Choi, Ae-Jin; Gopalan, Banu; Lee, Byron H.; Kalady, Matthew F.; Church, James M.; Ting, Angela H.

    2012-01-01

    A subset of colorectal cancers was postulated to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylation. The validity of CIMP, its molecular basis, and its prognostic value remain highly controversial. Using MBD-isolated genome sequencing, we mapped and compared genome-wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens. Multidimensional scaling analysis revealed that each specimen could be clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups have distinctly different global methylation patterns. We discovered 3780 sites in various genomic contexts that were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal colon. An additional 2026 sites were found to be hypermethylated in CIMP tumors only; and importantly, 80% of these sites were located in CpG islands. These data demonstrate on a genome-wide level that the additional hypermethylation seen in CIMP tumors occurs almost exclusively at CpG islands and support definitively that these tumors were appropriately named. When these sites were examined more closely, we found that 25% were adjacent to sites that were also hypermethylated in non-CIMP tumors. Thus, CIMP is also characterized by more extensive methylation of sites that are already prone to be hypermethylated in colon cancer. These observations indicate that CIMP tumors have specific defects in controlling both DNA methylation seeding and spreading and serve as an important first step in delineating molecular mechanisms that control these processes. PMID:21990380

  13. Restoration of CpG Methylation in The Egf Promoter Region during Rat Liver Regeneration

    Science.gov (United States)

    Deming, Li; Ziwei, Li; Xueqiang, Guo; Cunshuan, Xu

    2015-01-01

    Epidermal growth factor (EGF) is an important factor for healing after tissue damage in diverse experimental models. It plays an important role in liver regeneration (LR). The objective of this experiment is to investigate the methylation variation of 10 CpG sites in the Egf promoter region and their relevance to Egf expression during rat liver regenera- tion. As a follow up of our previous study, rat liver tissue was collected after rat 2/3 partial hepatectomy (PH) during the re-organization phase (from days 14 to days 28). Liver DNA was extracted and modified by sodium bisulfate. The methylation status of 10 CpG sites in Egf promoter region was determined using bisulfite sequencing polymerase chain reaction (PCR), as BSP method. The results showed that 3 (sites 3, 4 and 9) out of 10 CpG sites have strikingly methylation changes during the re-organization phase compared to the regeneration phase (from 2 hours to 168 hours, P=0.002, 0.048 and 0.018, respectively). Our results showed that methylation modification of CpGs in the Egf promoter region could be restored to the status before PH operation and changes of methylation didn’t affect Egf mRNA expression during the re-organization phase. PMID:26464832

  14. Polycomb-like proteins link the PRC2 complex to CpG islands

    Energy Technology Data Exchange (ETDEWEB)

    Li, Haojie; Liefke, Robert; Jiang, Junyi; Kurland, Jesse Vigoda; Tian, Wei; Deng, Pujuan; Zhang, Weidi; He, Qian; Patel, Dinshaw J.; Bulyk, Martha L.; Shi, Yang; Wang, Zhanxin

    2017-09-06

    The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression1,2 and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components3, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci4,5,6,7,8,9,10,11,12,13. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation14. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.

  15. Marine Robot Autonomy

    CERN Document Server

    2013-01-01

    Autonomy for Marine Robots provides a timely and insightful overview of intelligent autonomy in marine robots. A brief history of this emerging field is provided, along with a discussion of the challenges unique to the underwater environment and their impact on the level of intelligent autonomy required.  Topics covered at length examine advanced frameworks, path-planning, fault tolerance, machine learning, and cooperation as relevant to marine robots that need intelligent autonomy.  This book also: Discusses and offers solutions for the unique challenges presented by more complex missions and the dynamic underwater environment when operating autonomous marine robots Includes case studies that demonstrate intelligent autonomy in marine robots to perform underwater simultaneous localization and mapping  Autonomy for Marine Robots is an ideal book for researchers and engineers interested in the field of marine robots.      

  16. Autonomy of State Agencies

    DEFF Research Database (Denmark)

    Hansen, Morten Balle; Niklasson, Birgitta; Roness, Paul

    agencies in four Nordic countries: Denmark, Finland, Norway and Sweden. By using survey data from more than 500 state agencies in the four countries, the article analyses whether there is indeed a Scandinavian style of autonomy and result control and assesses which structural, cultural, and environmental......NPM-doctrines states that ideal-type agencies should have a high level of managerial autonomy, while being controlled through result-based control instruments, like performance contracts. In this article, the authors present a first preliminary attempt to comparatively analyze the autonomy of state...... variables might explain similarities and differences in the autonomy of agencies....

  17. Standby-battery autonomy versus power quality

    Science.gov (United States)

    Bitterlin, Ian F.

    Batteries are used in a wide variety of applications as an energy store to bridge gaps in the primary source of supplied power for a given period of time. In some cases this bridging time, the battery's "autonomy", is fixed by local legislation but it is also often set by historically common practices. However, even if common practice dictates a long autonomy time, we are entering a new era of "cost and benefit realism" underpinned by environmentally friendly policies and we should challenge these historical practices at every opportunity if it can lead to resource and cost savings. In some cases the application engineer has no choice in the design autonomy; either follow a piece of local legislation (e.g. 4 h autonomy for a "life safety" application), or actually work out what is needed! An example of the latter would be for a remote site, off-grid, using integrated wind/solar power (without emergency generator back-up) where you may have to design-in several days' battery autonomy. This short paper proposes that a battery's autonomy should be related to the time expected for the system to be without the primary power source, balanced by the capital costs and commercial risk of power failure. To discuss this we shall consider the factors in selecting the autonomy time and other related aspects for high voltage battery systems used in facility-wide uninterruptible power supply (UPS) systems.

  18. Fine mapping of the EDA gene: A translocation breakpoint is associated with a CpG island that is transcribed

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, A.K.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); Montonen, O. [Univ. of Helsinki (Finland)] [and others

    1996-01-01

    In order to identify the gene for human X-linked anhidrotic ectodermal dysplasia (EDA), a translocation breakpoint in a female with t(X;1)(q13.1;p36.3) and EDA (patient AK) was finely mapped. The EDA region contains five groups of rare-cutter restriction sites that define CpG islands. The two more centromeric of these islands are associated with transcripts of 3.5 kb and 1.8 kb. The third CpG island maps within <1 kb of the translocation breakpoint in patient AK, as indicated by a genomic rearrangement, and {approximately}100 kb centromeric from another previously mapped translocation breakpoint (patient AnLy). Northern analysis with a probe from this CpG island detected an {approximately}6-kb mRNA in several fetal tissues tested. An extended YAC contig of 1,200 kb with an average of fivefold coverage was constructed. The two most telomeric CpG islands map 350 kb telomeric of the two translocations. Taken together, the results suggest that the CpG island just proximal of the AK translocation breakpoint lies at the 5{prime} end of a candidate gene for EDA. 26 refs., 4 figs., 1 tab.

  19. Markets & Myths: Autonomy in Public & Private Schools

    Directory of Open Access Journals (Sweden)

    Sandra Rubin Glass

    1997-01-01

    Full Text Available

    School choice is the most controversial education policy issue of the 1990s. John Chubb and Terry Moe's Politics, Markets and America's Schools stimulated this investigation. They concluded that teacher and administrator autonomy was the most important influence on student achievement. They assumed that the organization of private schools offered greater autonomy resulting in higher student achievement and that the bureaucracy of public schools stifles autonomy limiting student achievement. The research undertaken here elaborates, elucidates, and fills in the framework of teacher and principal autonomy in public and private secondary schools. Interviews of more than thirty teachers and administrators in six high schools, observations, field notes, and analysis of documents collected in the field form the empirical base of this work. The sites included three private, independent, nondenominational secondary schools which are college preparatory and three public secondary schools noted for high graduation rates and offering numerous advanced placement courses.

    The feelings expressed by both public and private school participants in this study testify to equally high degrees of autonomy. Issues that emerged from data analysis in this study which mitigate and shape autonomy include the following: conflicting and contradictory demands, shared beliefs, layers of protection, a system of laws, funding constraints and matters of size of the institution. These issues challenge oversimplified assertions that differences of any importance exist between the autonomy experienced by professionals in public and private high schools. This study reveals the complexity of the concept of autonomy and challenges the myth that teachers and principals in private schools enjoy autonomy and freedom from democratic bureaucracy that their public school counterparts do not.

  20. Autonomy and minority rights

    DEFF Research Database (Denmark)

    Barten, Ulrike

    2008-01-01

    on the content of the syllabus. When autonomy is understood in the literal sense, of giving oneself one's own laws, then there is a clear connection. Autonomy is usually connected to politics and a geographically limited territory. Special political rights of minorities - e.g. is the Danish minority party SSW...

  1. Dualism of gene GC content and CpG pattern in regard to expression in the human genome: magnitude versus breadth.

    Science.gov (United States)

    Vinogradov, Alexander E

    2005-12-01

    In this article, I show that, in the human genome, the GC content in genes (but not the CpG island in the promoter) is related to the maximum level of gene expression among tissues, whereas the promoter CpG island and gene CpG level are more strongly related to the breadth of expression among tissues. The relevance of gene GC content to expression cannot be a consequence (i.e. a byproduct) of transcription because it does not correlate with expression in the germline. The variation of GC content and CpG level can determine the characteristics of gene expression in a synergistic interplay with transcription-factor-binding sites (mediated by chromatin condensation).

  2. Entrepreneurial autonomy and its dynamics

    NARCIS (Netherlands)

    van Gelderen, M.W.

    2016-01-01

    Founding and owning an independent business does not automatically provide the owner/founder with autonomy. Autonomy-motivated entrepreneurs must often make an effort to achieve and maintain autonomy. The aim of this research is to investigate the experience of autonomy, its variations over time,

  3. A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

    Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

  4. CpG island methylator phenotype (CIMP) in cancer: causes and implications.

    Science.gov (United States)

    Teodoridis, Jens M; Hardie, Catriona; Brown, Robert

    2008-09-18

    Strong evidence exists for a subgroup of tumours, from a variety of tissue types, exhibiting concordant tumour specific DNA methylation: the "CpG island methylator phenotype" (CIMP). Occurrence of CIMP is associated with a range of genetic and environmental factors, although the molecular causes are not well-understood. Both increased expression and aberrant targeting of DNA methyltransferases (DNMTs) could contribute to the occurrence of CIMP. One under-explored area is the possibility that DNA damage may induce or select for CIMP during carcinogenesis or treatment of tumours with chemotherapy. DNA damaging agents can induce DNA damage at guanine rich regions throughout the genome, including CpG islands. This DNA damage can result in stalled DNA synthesis, which will lead to localised increased DNMT1 concentration and therefore potentially increased DNA methylation at these sites. Chemotherapy can select for cells which have increased tolerance to DNA damage due to increased lesion bypass, in some cases by mechanisms which involve inactivation of genes by CpG island methylation. CIMP has been associated with worse patient prognosis, probably due to increased epigenetic plasticity. Therefore, further clinical testing of the diagnostic and prognostic value of the current CIMP markers, as well as increasing our understanding of the molecular causes underlying CIMP are required.

  5. Changing professional autonomy?

    DEFF Research Database (Denmark)

    Jespersen, Peter Kragh

    The paper presents a typology for the analysis for professional autonomy and an application of the typology in realation to discourses of quality development in the 'Health Care sector in Denmark and Norway......The paper presents a typology for the analysis for professional autonomy and an application of the typology in realation to discourses of quality development in the 'Health Care sector in Denmark and Norway...

  6. Anagogy of autonomy.

    Science.gov (United States)

    Boyd, A L

    2000-07-01

    The philosophical and ethical concept of autonomy is herein examined, ex post facto, using an existential lens to examine the process of a personal friend's dying. Anagogy, defined as interpretation of a word, passage, or text that finds beyond the literal, allegorical, and moral senses a fourth and ultimate spiritual or mystical sense, is intended to enlarge the understanding of the use of autonomy in this case. The idea of personhood linked inextricably to reason is, therefore, understood as empowering an individual to choose among various actions, to define and redefine life goals, and to give priority to selected values and moral tenants, which reveal a moral hermeneutic. Conditions and circumstances, existentially exposed, limit choice in unexpected ways, such that the predicted value of autonomy is vulnerable to misuse or misunderstanding. The intent to respect the dignity of every person is central to the philosophy of Respect for Persons ethics, and assumes that autonomy, as freedom of the moral agent, is a moral duty. Implicit reality of freedom is, in a practical sense, essential to being rational agents who can thereby exercise informed choice. The moral law, law of freedom, involves the autonomy of the will and an ultimate end to which all action is directed. Defined as the highest good, morality unites virtue and happiness by ascribing the ultimate end sought as God. The freedom to use rational will finds principles within its own rational nature. The ability to create maxims is autonomy of the will, which equates with the dignity of persons. My recent experience as a companion to a personal friend with a terminal illness inspired me to re-evaluate the concept of autonomy as it is too often interpreted in modern ethical discourse as a individualistic right of choice as opposed to the hermeneutic of dignity of person. This paper describes a shift of position in understanding the paradox of autonomy in this existential context.

  7. Autonomy and hyperthyroidism

    International Nuclear Information System (INIS)

    Emrich, D.; Schicha, H.; Baehre, M.

    1986-01-01

    The significance of autonomy in iodine-deficiency goiter for the development of hyperthyroidism was investigated. (1) In 171 of 426 consecutive patients high-resolution quantitative scintiscans showed signs suggestive of autonomy. With increasing 99mTc uptake by the thyroid their TT3 levels were found to rise progressively during suppression, while their pre-suppression TSH levels dropped progressively. This suggests global sup(99m)Tc uptake by the thyroid during suppression to be a useful indicator of the functional significance of autonomy. (2) Based on 326 patients with hyperthyroidism a system for differentiating between autonomy-related and immunogenic disease was developed and validated prospectively in another 162 patients with hyperthyroidism by assaying for thyroid stimulating antibodies (TSAb). TSAb was found to be present in 82% of the 77 patients diagnosed as having immunogenic hyperthyroidism and in only 8% of the 85 patients with autonomy-related hyperthyroidism. Our results support the assumption that autonomy in iodine-deficiency goiter plays a major role in the development of hyperthyroidism, while autoimmune processes appear to be of secondary importance. (Author)

  8. Understanding nurse practitioner autonomy.

    Science.gov (United States)

    Weiland, Sandra A

    2015-02-01

    This Gadamerian hermeneutic study was undertaken to understand the meaning of autonomy as interpreted by nurse practitioners (NPs) through their lived experiences of everyday practice in primary health care. A purposive sample of nine NPs practicing in primary health care was used. Network sampling achieved a broad swath of primary care NPs and practice settings. Data were collected by face-to-face interviews. Because NP autonomy is concerned with gender and marginalization, Gilligan's feminist perspective was utilized during interpretive analysis. Having Genuine NP Practice was the major theme, reflecting the participants' overall meaning of their autonomy. Practicing alone with the patient provided the context within which participants shaped the meaning of Having Genuine NP Practice. Having Genuine NP Practice had four subthemes: relationships, self-reliance, self-empowerment, and defending the NP role. The understanding of Having Genuine NP Practice will enable NPs to articulate their autonomy clearly and better influence healthcare reform. Implications for advanced practice nursing education include integrating findings into classroom discussion to prompt self-reflection of what autonomy means and socialization to the NP role. ©2014 American Association of Nurse Practitioners.

  9. Autonomy in chimpanzees.

    Science.gov (United States)

    Beauchamp, Tom L; Wobber, Victoria

    2014-04-01

    Literature on the mental capacities and cognitive mechanisms of the great apes has been silent about whether they can act autonomously. This paper provides a philosophical theory of autonomy supported by psychological studies of the cognitive mechanisms that underlie chimpanzee behavior to argue that chimpanzees can act autonomously even though their psychological mechanisms differ from those of humans. Chimpanzees satisfy the two basic conditions of autonomy: (1) liberty (the absence of controlling influences) and (2) agency (self-initiated intentional action), each of which is specified here in terms of conditions of understanding, intention, and self-control. In this account, chimpanzees make knowledge-based choices reflecting a richly information-based and socially sophisticated understanding of the world. Finally, two major theories of autonomy (Kantian theory and two-level theory) are rejected as too narrow to adequately address these issues, necessitating the modifications made in the present approach.

  10. A cross-study analysis of prenatal exposures to environmental contaminants and the epigenome: support for stress-responsive transcription factor occupancy as a mediator of gene-specific CpG methylation patterning

    Science.gov (United States)

    Martin, Elizabeth M.; Fry, Rebecca C.

    2016-01-01

    Abstract A biological mechanism by which exposure to environmental contaminants results in gene-specific CpG methylation patterning is currently unknown. We hypothesize that gene-specific CpG methylation is related to environmentally perturbed transcription factor occupancy. To test this hypothesis, a database of 396 genes with altered CpG methylation either in cord blood leukocytes or placental tissue was compiled from 14 studies representing assessments of six environmental contaminants. Subsequently, an in silico approach was used to identify transcription factor binding sites enriched among the genes with altered CpG methylation in relationship to the suite of environmental contaminants. For each study, the sequences of the promoter regions (representing −1000 to +500 bp from the transcription start site) of all genes with altered CpG methylation were analyzed for enrichment of transcription factor binding sites. Binding sites for a total of 56 unique transcription factors were identified to be enriched within the promoter regions of the genes. Binding sites for the Kidney-Enriched Krupple-like Factor 15, a known responder to endogenous stress, were enriched ( P  contaminants. These data support the transcription factor occupancy theory as a potential mechanism underlying environmentally-induced gene-specific CpG methylation. PMID:27066266

  11. [What is patient autonomy?

    Science.gov (United States)

    Durand, Guillaume

    What does patient autonomy mean? If an autonomous choice is defined as an objective and rational choice, is the doctor's prescription not always the best route? Our contemporary democracies are marked by moral and religious pluralism which obliges society to respect a multiplicity of choices of existence. Three levels are important in terms of autonomy: a range of intellectual capacities, freedom with regard to constraints (external and internal), the capacity to be in control of one's existence. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. De novo CpG methylation on an artificial chromosome-like vector maintained for a long-term in mammalian cells.

    Science.gov (United States)

    Nishioka, Keisuke; Kishida, Tsunao; Masui, Shinji; Mazda, Osam

    2016-04-01

    To examine whether an autonomously replicating, artificial chromosome-like vector containing a long genomic DNA sequence (namely, Epigenosome-Nanog) undergoes de novo CpG methylation after maintenance in cultured cells for more than a half year. Epigenosome-Nanog efficiently replicated in iPS cells after transfection. In HeLa and C2C12 cells Epigenosome-Nanog was stably maintained for more than eight months. The CpG methylation occurred de novo at the Nanog gene promoter region on the epigenosome in C2C12 cells but the degrees of methylation were much lower than those at the same CpG sites on the chromosomes. Among the four CpG sites at the region, the upstream two CpGs underwent methylation in a correlated manner while methylation at the downstream two CpGs was also correlated to each other, and these correlations were commonly shared between the epigenosome and the chromosome. CpG methylation thus was not solely dependent on the nucleotide sequence at the DNA locus. The epigenosome may become a useful tool to study the mechanisms of epigenetic regulation of a genetic region of interest in mammalian cells.

  13. CpG Island Methylator Phenotype in Primary Gastric Carcinoma

    OpenAIRE

    TOJO Masayuki:筆頭著者; KONISHI Kazuo; YANO Yuichiro; KATAGIRI Atsushi; NOZAWA Hisako; KUBOTA Yutaro; MURAMOTO Takashi; KONDA Kenichi; SHINMURA Kensuke; TAKIMOTO Masafumi; IMAWARI Michio; YOSHIDA Hitoshi

    2013-01-01

    Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L...

  14. (Re)Discovering University Autonomy

    DEFF Research Database (Denmark)

    Reilly, John; Turcan, Romeo V.; Bugaian, Larisa

    2016-01-01

    discussion of challenges. The other outcome is the extent to which academic colleagues in a wide-range of disciplines and not directly engaged with research on university autonomy may not perceive or engage with the wider autonomy outcomes of their work and as a result their own case studies may not fully...... identify the autonomy impact real or potential. Many academic staff take for granted university autonomy without questioning its sometimes contradictory assumptions and impacts....

  15. Finding Autonomy in Birth*

    Science.gov (United States)

    Kukla, Rebecca; Kuppermann, Miriam; Little, Margaret; Lyerly, Anne Drapkin; Mitchell, Lisa M; Armstrong, Elizabeth M.; Harris, Lisa

    2009-01-01

    Over the last several years, as cesarean deliveries have grown increasingly common, there has been a great deal of public and professional interest in the phenomenon of women ‘choosing’ to deliver by cesarean section in the absence of any specific medical indication. The issue has sparked intense conversation, as it raises questions about the nature of autonomy in birth. Whereas mainstream bioethical discourse is used to associating autonomy with having a large array of choices, this conception of autonomy does not seem adequate to capture concerns and intuitions that have a strong grip outside of this discourse. An empirical and conceptual exploration of how delivery decisions ought to be negotiated must be guided by a rich understanding of women’s agency and its placement within a complicated set of cultural meanings and pressures surrounding birth. It is too early to be ‘for’ or ‘against’ women’s access to cesarean delivery in the absence of traditional medical indications - and indeed, a simple pro- or con- position is never going to do justice to the subtlety of the issue. The right question is not whether women ought to be allowed to choose their delivery approach, but rather, taking the value of women’s autonomy in decision-making around birth as a given, what sorts of guidelines, practices, and social conditions will best promote and protect women’s full inclusion in a safe and positive birth process. PMID:19076937

  16. Om evalueringsforskningens relative autonomi

    DEFF Research Database (Denmark)

    Nørholm, Morten

    2008-01-01

    Det empiriske udgangspunkt for artiklen "Om evalueringsforskningens relative autonomi - dansk normal evalueringsforskning som et ikke-autonomt (sub)felt i magtens felt" er en række tekster af fire dominerende danske evalueringsforskere. Det teoretiske udgangspunkt er især Pierre Bourdieus teori om...

  17. The economic value of autonomy

    NARCIS (Netherlands)

    Boot, A.W.A.; Thakor, A.V.

    2003-01-01

    We develop an economic theory of "autonomy", which we interpret as the discretion or ability to make a decision that others disagree with. We show that autonomy is essentially an option for the decisionmaker, and can be valued as such. The value of the autonomy option is decreasing in the extent to

  18. Senegal : School Autonomy and Accountability

    OpenAIRE

    World Bank

    2012-01-01

    Senegal has accelerated the decentralization of education since 1996. Budgetary autonomy is latent. Autonomy over the management of operational budgets has been delegated to the communes, but salaries for teachers are managed at the central level. Autonomy in personnel management is latent. Both school directors and teachers are appointed at the central level. The role of the school counci...

  19. Compulsory Autonomy-Promoting Education

    Science.gov (United States)

    Schinkel, Anders

    2010-01-01

    Today, many liberal philosophers of education worry that certain kinds of education may frustrate the development of personal autonomy, with negative consequences for the individuals concerned, the liberal state, or both. Autonomy liberals hold not only that we should promote the development of autonomy in children, but also that this aim should…

  20. Phosphoinositide 3-kinaseγ controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages.

    Directory of Open Access Journals (Sweden)

    Kaoru Hazeki

    Full Text Available Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG stimulate innate immune responses. Phosphoinositide 3-kinase (PI3K has been implicated in CpG-induced immune activation; however, its precise role has not yet been clarified. CpG-induced production of IL-10 was dramatically increased in macrophages deficient in PI3Kγ (p110γ(-/-. By contrast, LPS-induced production of IL-10 was unchanged in the cells. CpG-induced, but not LPS-induced, IL-10 production was almost completely abolished in SCID mice having mutations in DNA-dependent protein kinase catalytic subunit (DNA-PKcs. Furthermore, wortmannin, an inhibitor of DNA-PKcs, completely inhibited CpG-induced IL-10 production, both in wild type and p110γ(-/- cells. Microscopic analyses revealed that CpG preferentially localized with DNA-PKcs in p110γ(-/- cells than in wild type cells. In addition, CpG was preferentially co-localized with the acidic lysosomal marker, LysoTracker, in p110γ(-/- cells, and with an early endosome marker, EEA1, in wild type cells. Over-expression of p110γ in Cos7 cells resulted in decreased acidification of CpG containing endosome. A similar effect was reproduced using kinase-dead mutants, but not with a ras-binding site mutant, of p110γ. Thus, it is likely that p110γ, in a manner independent of its kinase activity, inhibits the acidification of CpG-containing endosomes. It is considered that increased acidification of CpG-containing endosomes in p110γ(-/- cells enforces endosomal escape of CpG, which results in increased association of CpG with DNA-PKcs to up-regulate IL-10 production in macrophages.

  1. Autonomy and the principle of respect for autonomy.

    Science.gov (United States)

    Gillon, R

    1985-06-15

    Autonomy is defined as the capacity to think, decide, and act freely and independently on the basis of such thought and decisions. Three types of autonomy are distinguished: autonomy of thought, which embraces the wide range of human intellectual activities called "thinking for oneself"; autonomy of will, or the capacity to decide to do things on the basis of one's deliberations; and autonomy of action, the absence of which is illustrated by the situation of a patient whose voluntary muscles are paralyzed by curariform drugs and who thus cannot tell the surgeon that the anesthetist has forgotten the nitrous oxide. Autonomy is viewed as a prerequisite for all the virtues, rather than as a virtue in its own right. The arguments of Immanuel Kant and John Stuart Mill concerning the principle of respect for autonomy are summarized as exemplars respectively of the deontological and utilitarian philosophical approaches.

  2. A novel method to quantify local CpG methylation density by regional methylation elongation assay on microarray

    Directory of Open Access Journals (Sweden)

    Qiao Yingjuan

    2008-01-01

    Full Text Available Abstract Background DNA methylation based techniques are important tools in both clinical diagnostics and therapeutics. But most of these methods only analyze a few CpG sites in a target region. Indeed, difference of site-specific methylation may also lead to a change of methylation density in many cases, and it has been found that the density of methylation is more important than methylation of single CpG site for gene silencing. Results We have developed a novel approach for quantitative analysis of CpG methylation density on the basis of microarray-based hybridization and incorporation of Cy5-dCTP into the Cy3 labeled target DNA by using Taq DNA Polymerase on microarray. The quantification is achieved by measuring Cy5/Cy3 signal ratio which is proportional to methylation density. This methylation-sensitive technique, termed RMEAM (regional methylation elongation assay on microarray, provides several advantages over existing methods used for methylation analysis. It can determine an exact methylation density of the given region, and has potential of high throughput. We demonstrate a use of this method in determining the methylation density of the promoter region of the tumor-related gene MLH1, TERT and MGMT in colorectal carcinoma patients. Conclusion This technique allows for quantitative analysis of regional methylation density, which is the representative of all allelic methylation patterns in the sample. The results show that this technique has the characteristics of simplicity, rapidness, specificity and high-throughput.

  3. Law, autonomy and advance directives.

    Science.gov (United States)

    Willmott, Lindy; White, Ben; Mathews, Ben

    2010-12-01

    The principle of autonomy underpins legal regulation of advance directives that refuse life-sustaining medical treatment. The primacy of autonomy in this domain is recognised expressly in the case law, through judicial pronouncement, and implicitly in most Australian jurisdictions, through enactment into statute of the right to make an advance directive. This article seeks to justify autonomy as an appropriate principle for regulating advance directives and relies on three arguments: the necessity of autonomy in a liberal democracy; the primacy of autonomy in medical ethics discourse; and the uncontested importance of autonomy in the law on contemporaneous refusal of medical treatment. This article also responds to key criticisms that autonomy is not an appropriate organising principle to underpin legal regulation of advance directives.

  4. Autonomy and Automation

    Science.gov (United States)

    Shively, Jay

    2017-01-01

    A significant level of debate and confusion has surrounded the meaning of the terms autonomy and automation. Automation is a multi-dimensional concept, and we propose that Remotely Piloted Aircraft Systems (RPAS) automation should be described with reference to the specific system and task that has been automated, the context in which the automation functions, and other relevant dimensions. In this paper, we present definitions of automation, pilot in the loop, pilot on the loop and pilot out of the loop. We further propose that in future, the International Civil Aviation Organization (ICAO) RPAS Panel avoids the use of the terms autonomy and autonomous when referring to automated systems on board RPA. Work Group 7 proposes to develop, in consultation with other workgroups, a taxonomy of Levels of Automation for RPAS.

  5. Autonomy and the emotions

    OpenAIRE

    Tappolet, Christine

    2006-01-01

    Can actions caused by emotions be free and autonomous? The rationalist conception of autonomy denies this. Only actions done in the light of reflective choices can be autonomous and hence free. I argue that the rationalist conception does not make room for akratic actions, that is, free and intentional actions performed against the agent’s best judgement. I then develop an account inspired by Harry Frankfurt and David Shoemaker, according to which an action is autonomous when it is determined...

  6. The Autonomy of Deportation

    Directory of Open Access Journals (Sweden)

    Nicholas de Genova

    2017-06-01

    Full Text Available As ostensibly unwanted or undesirable non-citizens, the utter disposability of deportees appears to be finally and conclusively verified by deportation as a sovereign state power’s perfunctory and mundane act of 'taking out the trash.' Hence, it is no accident that, etymologically, the origins of the very word 'deportation' would indicate a carrying away, a removal, a disposal. The eradication of deportees’ individual lives — their personal identities and life trajectories — emerges as a frightfully routine and prosaic fact of deportation. In spite of the sheer violence of the ruptures inflicted though deportation, however, those who have been rendered the objects of this power persistently reassert their own subjectivity. Ethnographic insights into the lived struggles of the deported (as well as their loved ones and communities elucidates the enduring subjectivity of those who have been made the objects of such sovereign acts of state power and subjected to deportation's techniques of eradication, and illustrates the stubborn incorrigibility of human life against the myriad forces that would seek to enforce its precarity and disposability. In the post-deportation condition, we confront anew the elementary and elemental human freedom of movement, and the incorrigibility of the autonomy and subjectivity of migration. Much as the autonomy of migration instigates a contest in which state power never has the first word, what we may now conceive as the autonomy of deportation — an autonomy and subjectivity of the deported within and against their predicaments of deportation — similarly ensures that state power never has the last word, either.

  7. Perspectives on autonomy.

    Science.gov (United States)

    Keys, Yolanda

    2009-09-01

    This department, sponsored by the AONE, presents information to assist nurse leaders in shaping the future of healthcare through creative and innovative leadership. The strategic priorities of AONE anchor the editorial content. They reflect contemporary healthcare and nursing practice issues that challenge nurse executives as they strive to meet the needs of patients. This article describes how 9 Magnet-hospital, chief nursing officers perceive their autonomy and its importance in accomplishing their work.

  8. Autonomy, Trust, and Respect.

    Science.gov (United States)

    Nys, Thomas

    2016-02-01

    This article seeks to explore and analyze the relationship between autonomy and trust, and to show how these findings could be relevant to medical ethics. First, I will argue that the way in which so-called "relational autonomy theories" tie the notions of autonomy and trust together is not entirely satisfying Then, I will introduce the so-called Encapsulated Interest Account as developed by Russell Hardin. This will bring out the importance of the reasons for trust. What good reasons do we have for trusting someone? I will criticize Hardin's business model as insufficiently robust, especially in the context of health care, and then turn to another source of trust, namely, love. It may seem that trust-through-love is much better suited for the vulnerability that is often involved in health care, but I will also show that it has its own deficiencies. Good health care should therefore pay attention to both models of trust, and I will offer some tentative remarks on how to do this. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Autonomy, recognition and education

    Directory of Open Access Journals (Sweden)

    Angelo Vitório Cenci

    2015-01-01

    Full Text Available This paper addresses Honneth’s concept of autonomy from two dimensions of his work, distinct, though inseparable. The first one is suggested through the subject’s positive practical self-relation linked to the patterns of reciprocal recognition of love, right and social esteem; the second is formulated as non-centered autonomy opposed to the present-day criticism of the modern autonomous subject encompassing three levels, namely: the capacity of linguistic articulation, the narrative coherence of life and the complementation of being guided by principles with some criteria of moral sensitivity to the context. We defend the position that, by metaphysically anchoring the concept of autonomy onto the intersubjective assumptions of his/her theory of the subject, and exploring it linked to the subject’s positive practical self-relation and to a non-centered meaning, Honneth has managed to renew it, which allows drawing important consequences of such effort to the field of education.

  10. Ignorance, information and autonomy.

    Science.gov (United States)

    Harris, J; Keywood, K

    2001-09-01

    People have a powerful interest in genetic privacy and its associated claim to ignorance, and some equally powerful desires to be shielded from disturbing information are often voiced. We argue, however, that there is no such thing as a right to remain in ignorance, where a fight is understood as an entitlement that trumps competing claims. This does not of course mean that information must always be forced upon unwilling recipients, only that there is no prima facie entitlement to be protected from true or honest information about oneself. Any claims to be shielded from information about the self must compete on equal terms with claims based in the rights and interests of others. In balancing the weight and importance of rival considerations about giving or withholding information, if rights claims have any place, rights are more likely to be defensible on the side of honest communication of information rather than in defence of ignorance. The right to free speech and the right to decline to accept responsibility to take decisions for others imposed by those others seem to us more plausible candidates for fully fledged rights in this field than any purported right to ignorance. Finally, and most importantly, if the right to autonomy is invoked, a proper understanding of the distinction between claims to liberty and claims to autonomy show that the principle of autonomy, as it is understood in contemporary social ethics and English law, supports the giving rather than the withholding of information in most circumstances.

  11. Autonomy and autonomy competencies: a practical and relational approach.

    Science.gov (United States)

    Atkins, Kim

    2006-10-01

    This essay will address a general philosophical concern about autonomy, namely, that a conception of autonomy focused on freedom of the will alone is inadequate, once we consider the effects of oppressive forms of socialization on individuals' formation of choices. In response to this problem, I will present a brief overview of Diana Meyers's account of autonomy as relational and practical. On this view, autonomy consists in a set of socially acquired practical competencies in self-discovery, self-definition, self-knowledge, and self-direction. This account provides a distinction between choices that express unreflectively internalized social norms and those that are the result of a critical 'self-reading'. I conclude that this practical conception of autonomy makes much higher demands upon nurses (and patients) than has previously been thought. In fact, if nurses are to be expected to genuinely promote autonomy, they are going to need specific training in counselling-type communication skills.

  12. Patient autonomy: a view from the kitchen.

    Science.gov (United States)

    Struhkamp, Rita M

    2005-01-01

    In contemporary liberal ethics patient autonomy is often interpreted as the right to self-determination: when it comes to treatment decisions, the patient is given the right to give or withhold informed consent. This paper joins in the philosophical and ethical criticism of the liberal interpretation as it does not regard patient autonomy as a right, rule or principle, but rather as a practice. Patient autonomy, or so I will argue, is realised in the concrete activities of day-to-day health care, in the material and technological context of care, in arrangements of health care institutions, in the physical training of people with disabilities, as well as in the concrete activities of care-giving. This move from conversations in the consultation room to other sites and situations in the practice of care takes seriously the empirical reality of medical care and intends to show that patient autonomy is practically realised in a much richer and more creative way than most ethical theory seems to assume.

  13. University Internationalization and University Autonomy

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Gulieva, Valeria

    2016-01-01

    Turcan and Gulieva deepen our theoretical understanding of the process of university internationalisation by exploring the relationship between university internationalisation and university autonomy. They conjecture that the process of university internationalisation and its sustainability are d......, dissimilar, and sometimes conflicting dimensions of the financial, legal, organisational, staffing, and academic autonomy of the host country, are compromising key aspects of their own autonomy and core mission?......Turcan and Gulieva deepen our theoretical understanding of the process of university internationalisation by exploring the relationship between university internationalisation and university autonomy. They conjecture that the process of university internationalisation and its sustainability...... are determined by the structure and exercise of university autonomy settings at home and in the host countries, and that the process itself cannot be successfully achieved and maintained without changes in the autonomy settings. The key question the authors ask is to what degree universities, in embracing new...

  14. Autonomy, Social Interactions and Culture

    OpenAIRE

    Marini, Annalisa; Navarra, Pietro

    2016-01-01

    The present paper, using a social interactions model, studies the impact of culture on autonomy of immigrants. The results suggest that: (i) immigrants' autonomy is largely influenced by the autonomy of individuals living in a host country; (ii) some immigrants are better off in countries and regions with better institutional environments. The results are robust to sensitivity checks. The contributions of the paper are as follows. First, we estimate a social interactions model that models bot...

  15. CpG methylation controls reactivation of HIV from latency

    Czech Academy of Sciences Publication Activity Database

    Blažková, Jana; Trejbalová, Kateřina; Gondois-Rey, F.; Halfon, P.; Philibert, P.; Guiguen, A.; Verdin, E.; Olive, D.; Van Lint, C.; Hejnar, Jiří; Hirsch, I.

    2009-01-01

    Roč. 5, č. 8 (2009), e1000554-e1000554 E-ISSN 1553-7374 R&D Projects: GA ČR GA204/05/0939; GA ČR GP204/08/P616 Institutional research plan: CEZ:AV0Z50520514 Keywords : HIV-1 * proviral latency * CpG methylation * histone modifications * HAART * epigenetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.978, year: 2009

  16. Architecture for autonomy

    Science.gov (United States)

    Broten, Gregory S.; Monckton, Simon P.; Collier, Jack; Giesbrecht, Jared

    2006-05-01

    In 2002 Defence R&D Canada changed research direction from pure tele-operated land vehicles to general autonomy for land, air, and sea craft. The unique constraints of the military environment coupled with the complexity of autonomous systems drove DRDC to carefully plan a research and development infrastructure that would provide state of the art tools without restricting research scope. DRDC's long term objectives for its autonomy program address disparate unmanned ground vehicle (UGV), unattended ground sensor (UGS), air (UAV), and subsea and surface (UUV and USV) vehicles operating together with minimal human oversight. Individually, these systems will range in complexity from simple reconnaissance mini-UAVs streaming video to sophisticated autonomous combat UGVs exploiting embedded and remote sensing. Together, these systems can provide low risk, long endurance, battlefield services assuming they can communicate and cooperate with manned and unmanned systems. A key enabling technology for this new research is a software architecture capable of meeting both DRDC's current and future requirements. DRDC built upon recent advances in the computing science field while developing its software architecture know as the Architecture for Autonomy (AFA). Although a well established practice in computing science, frameworks have only recently entered common use by unmanned vehicles. For industry and government, the complexity, cost, and time to re-implement stable systems often exceeds the perceived benefits of adopting a modern software infrastructure. Thus, most persevere with legacy software, adapting and modifying software when and wherever possible or necessary -- adopting strategic software frameworks only when no justifiable legacy exists. Conversely, academic programs with short one or two year projects frequently exploit strategic software frameworks but with little enduring impact. The open-source movement radically changes this picture. Academic frameworks

  17. Autonomy, Automation, and Systems

    Science.gov (United States)

    Turner, Philip R.

    1987-02-01

    Aerospace industry interest in autonomy and automation, given fresh impetus by the national goal of establishing a Space Station, is becoming a major item of research and technology development. The promise of new technology arising from research in Artificial Intelligence (AI) has focused much attention on its potential in autonomy and automation. These technologies can improve performance in autonomous control functions that involve planning, scheduling, and fault diagnosis of complex systems. There are, however, many aspects of system and subsystem design in an autonomous system that impact AI applications, but do not directly involve AI technology. Development of a system control architecture, establishment of an operating system within the design, providing command and sensory data collection features appropriate to automated operation, and the use of design analysis tools to support system engineering are specific examples of major design issues. Aspects such as these must also receive attention and technology development support if we are to implement complex autonomous systems within the realistic limitations of mass, power, cost, and available flight-qualified technology that are all-important to a flight project.

  18. Compulsory autonomy-promoting education

    NARCIS (Netherlands)

    A. Schinkel (Anders)

    2010-01-01

    textabstractToday, many liberal philosophers of education worry that certain kinds of education may frustrate the development of personal autonomy, with negative consequences for the individuals concerned, the liberal state, or both. Autonomy liberals hold not only that we should promote the

  19. Autonomy, Vulnerability, Recognition, and Justice

    NARCIS (Netherlands)

    Anderson, J.H.; Honneth, A.

    2005-01-01

    One of liberalism’s core commitments is to safeguarding individuals’ autonomy. And a central aspect of liberal social justice is the commitment to protecting the vulnerable. Taken together, and combined with an understanding of autonomy as an acquired set of capacities to lead one’s own life,

  20. Personal Autonomy and Rational Suicide.

    Science.gov (United States)

    Webber, May A.; Shulman, Ernest

    That certain suicides (which can be designated as rational) ought not to be interfered with is closely tied to the notion of the "right to autonomy." Specifically it is because the individual in question has this right that interference is prohibited. A proper understanding of the right to autonomy, while essential to understanding why…

  1. (Re)Discovering University Autonomy

    DEFF Research Database (Denmark)

    This book challenges traditional approach to university autonomy which is based on four pillars: organisational, financial, human resource, and academic. The main thesis is that a fuller understanding of university autonomy can only be obtained through a more holistic view of the complex inter-re...

  2. The Principalship, Autonomy, and After

    Science.gov (United States)

    Eacott, Scott

    2015-01-01

    Contemporary discourses in educational administration have exponentially grown the number of adjectival leaderships, challenged traditional organisational structures, and offered autonomy as a solution to performance issues. In this theoretical paper, I ask "what does the principalship look like after autonomy?" Despite the range of…

  3. Teacher Autonomy: Power or Control?

    Science.gov (United States)

    Lawson, Tony

    2004-01-01

    The article explores the issue of teacher autonomy in relation to its potential for freedom or control. It examines the concept of empowerment as applied to education, arguing that, although it is traditionally cast as a means of achieving autonomy, an alternative approach sees empowerment as part of the disciplinary apparatus of late modern…

  4. Intention, autonomy, and brain events.

    Science.gov (United States)

    Gillett, Grant

    2009-07-01

    Informed consent is the practical expression of the doctrine of autonomy. But the very idea of autonomy and conscious free choice is undercut by the view that human beings react as their unconscious brain centres dictate, depending on factors that may or may not be under rational control and reflection. This worry is, however, based on a faulty model of human autonomy and consciousness and needs close neurophilosophical scrutiny. A critique of the ethics implied by the model takes us towards a 'care of the self' view of autonomy and the subject's attunement to the truth as the crux of reasoning rather than the inner mental/neural state views of autonomy and human choice on offer at present.

  5. The Challenge of University Autonomy

    DEFF Research Database (Denmark)

    Reilly, John; Turcan, Romeo V.; Bugaian, Larisa

    2016-01-01

    The authors introduce the reader to the book, providing a historical perspective and a current understanding of university autonomy. While appreciating the central role of the four dimensions of university autonomy – organisational, financial, human resource, and academic – the authors conjecture...... that a fuller understanding of university autonomy can only be obtained through a holistic view of the complex inter-relationships between stakeholders and policies which can reinforce and, equally, pull in opposite directions. This holistic view is represented in a model of institutional university autonomy......, which is discussed at length in the chapter. The authors conclude by presenting international case studies that give new insights and reinforce our understanding that the issues relating to institutional university autonomy are genuinely global....

  6. (Re)Discovering University Autonomy

    DEFF Research Database (Denmark)

    This book challenges traditional approach to university autonomy which is based on four pillars: organisational, financial, human resource, and academic. The main thesis is that a fuller understanding of university autonomy can only be obtained through a more holistic view of the complex inter......-relationships between stakeholders and policies which can reinforce and equally pull in opposite directions. The holistic view is expressed in a model of institutional university autonomy that brings together the traditional basic four pillars of autonomy, and five interfaces: government–university; university......–university staff; academic staff–students; university–business; and university–internationalisation. This model is explored through international case studies that give new insights and reinforce our understanding that the issues relating to institutional university autonomy are complex, interactive and genuinely...

  7. Neuromodulation, agency and autonomy.

    Science.gov (United States)

    Glannon, Walter

    2014-01-01

    Neuromodulation consists in altering brain activity to restore mental and physical functions in individuals with neuropsychiatric disorders and brain and spinal cord injuries. This can be achieved by delivering electrical stimulation that excites or inhibits neural tissue, by using electrical signals in the brain to move computer cursors or robotic arms, or by displaying brain activity to subjects who regulate that activity by their own responses to it. As enabling prostheses, deep-brain stimulation and brain-computer interfaces (BCIs) are forms of extended embodiment that become integrated into the individual's conception of himself as an autonomous agent. In BCIs and neurofeedback, the success or failure of the techniques depends on the interaction between the learner and the trainer. The restoration of agency and autonomy through neuromodulation thus involves neurophysiological, psychological and social factors.

  8. Autonomy, Independence, Inclusion

    Directory of Open Access Journals (Sweden)

    Filippo Angelucci

    2015-04-01

    Full Text Available The living environment must not only meet the primary needs of living, but also the expectations of improvement of life and social relations and people’s work. The need for a living environment that responds to the needs of users with their different abilities, outside of standardizations, is increasingly felt as autonomy, independence and well-being are the result of real usability and adaptability of the spaces. The project to improve the inclusivity of living space and to promote the rehabilitation of fragile users need to be characterized as an interdisciplinary process in which the integration of specialized contributions leads to adaptive customization of space solutions and technological that evolve with the changing needs, functional capacities and abilities of individuals.

  9. Depletion of CpG Dinucleotides in Papillomaviruses and Polyomaviruses: A Role for Divergent Evolutionary Pressures.

    Science.gov (United States)

    Upadhyay, Mohita; Vivekanandan, Perumal

    2015-01-01

    Papillomaviruses and polyomaviruses are small ds-DNA viruses infecting a wide-range of vertebrate hosts. Evidence supporting co-evolution of the virus with the host does not fully explain the evolutionary path of papillomaviruses and polyomaviruses. Studies analyzing CpG dinucleotide frequencies in virus genomes have provided interesting insights on virus evolution. CpG dinucleotide depletion has not been extensively studied among papillomaviruses and polyomaviruses. We sought to analyze the relative abundance of dinucleotides and the relative roles of evolutionary pressures in papillomaviruses and polyomaviruses. We studied 127 full-length sequences from papillomaviruses and 56 full-length sequences from polyomaviruses. We analyzed the relative abundance of dinucleotides, effective codon number (ENC), differences in synonymous codon usage. We examined the association, if any, between the extent of CpG dinucleotide depletion and the evolutionary lineage of the infected host. We also investigated the contribution of mutational pressure and translational selection to the evolution of papillomaviruses and polyomaviruses. All papillomaviruses and polyomaviruses are CpG depleted. Interestingly, the evolutionary lineage of the infected host determines the extent of CpG depletion among papillomaviruses and polyomaviruses. CpG dinucleotide depletion was more pronounced among papillomaviruses and polyomaviruses infecting human and other mammals as compared to those infecting birds. Our findings demonstrate that CpG depletion among papillomaviruses is linked to mutational pressure; while CpG depletion among polyomaviruses is linked to translational selection. We also present evidence that suggests methylation of CpG dinucleotides may explain, at least in part, the depletion of CpG dinucleotides among papillomaviruses but not polyomaviruses. The extent of CpG depletion among papillomaviruses and polyomaviruses is linked to the evolutionary lineage of the infected host. Our

  10. CpG + CpNpG Analysis of Protein-Coding Sequences from Tomato

    DEFF Research Database (Denmark)

    Hobolth, Asger; Nielsen, Rasmus; Wang, Ying

    2006-01-01

    We develop codon-based models for simultaneously inferring the mutational effects of CpG and CpNpG methylation in coding regions. In a data set of 369 tomato genes, we show that there is very little effect of CpNpG methylation but a strong effect of CpG methylation affecting almost all genes. We...... further show that the CpNpG and CpG effects are largely uncorrelated. Our results suggest different roles of CpG and CpNpG methylation, with CpNpG methylation possibly playing a specialized role in defense against transposons and RNA viruses....

  11. Consolidated Recovered Materials Advisory Notice (RMAN) for the Comprehensive Procurement Guideline (CPG)

    Data.gov (United States)

    U.S. Environmental Protection Agency — EPA's Comprehensive Procurement Guideline (CPG) designates recycled content products that government agencies should buy. EPA publishes purchasing guidance and...

  12. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    International Nuclear Information System (INIS)

    Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

    2011-01-01

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: ► Nicotine-induced StAR inhibition in two human adrenal cell models. ► Nicotine-induced single CpG site methylation in StAR promoter. ► Persistent StAR inhibition and single CpG methylation after nicotine termination. ► Single CpG methylation located at Pax6 binding motif regulates St

  13. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Chen, Man; Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Cheng, Huaiyan [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Yan, You-E [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Feng, Ying-Hong, E-mail: yhfeng@usuhs.edu [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2011-12-15

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: Black-Right-Pointing-Pointer Nicotine-induced StAR inhibition in two human adrenal cell models. Black-Right-Pointing-Pointer Nicotine-induced single CpG site methylation in StAR promoter. Black-Right-Pointing-Pointer Persistent StAR inhibition and single CpG methylation after nicotine termination

  14. CpG methylation controls reactivation of HIV from latency.

    Directory of Open Access Journals (Sweden)

    Jana Blazkova

    2009-08-01

    Full Text Available DNA methylation of retroviral promoters and enhancers localized in the provirus 5' long terminal repeat (LTR is considered to be a mechanism of transcriptional suppression that allows retroviruses to evade host immune responses and antiretroviral drugs. However, the role of DNA methylation in the control of HIV-1 latency has never been unambiguously demonstrated, in contrast to the apparent importance of transcriptional interference and chromatin structure, and has never been studied in HIV-1-infected patients. Here, we show in an in vitro model of reactivable latency and in a latent reservoir of HIV-1-infected patients that CpG methylation of the HIV-1 5' LTR is an additional epigenetic restriction mechanism, which controls resistance of latent HIV-1 to reactivation signals and thus determines the stability of the HIV-1 latency. CpG methylation acts as a late event during establishment of HIV-1 latency and is not required for the initial provirus silencing. Indeed, the latent reservoir of some aviremic patients contained high proportions of the non-methylated 5' LTR. The latency controlled solely by transcriptional interference and by chromatin-dependent mechanisms in the absence of significant promoter DNA methylation tends to be leaky and easily reactivable. In the latent reservoir of HIV-1-infected individuals without detectable plasma viremia, we found HIV-1 promoters and enhancers to be hypermethylated and resistant to reactivation, as opposed to the hypomethylated 5' LTR in viremic patients. However, even dense methylation of the HIV-1 5'LTR did not confer complete resistance to reactivation of latent HIV-1 with some histone deacetylase inhibitors, protein kinase C agonists, TNF-alpha, and their combinations with 5-aza-2deoxycytidine: the densely methylated HIV-1 promoter was most efficiently reactivated in virtual absence of T cell activation by suberoylanilide hydroxamic acid. Tight but incomplete control of HIV-1 latency by CpG

  15. Distribution of CpG Motifs in Upstream Gene Domains in a Reef Coral and Sea Anemone: Implications for Epigenetics in Cnidarians.

    Directory of Open Access Journals (Sweden)

    Adam G Marsh

    Full Text Available Coral reefs are under assault from stressors including global warming, ocean acidification, and urbanization. Knowing how these factors impact the future fate of reefs requires delineating stress responses across ecological, organismal and cellular scales. Recent advances in coral reef biology have integrated molecular processes with ecological fitness and have identified putative suites of temperature acclimation genes in a Scleractinian coral Acropora hyacinthus. We wondered what unique characteristics of these genes determined their coordinate expression in response to temperature acclimation, and whether or not other corals and cnidarians would likewise possess these features. Here, we focus on cytosine methylation as an epigenetic DNA modification that is responsive to environmental stressors. We identify common conserved patterns of cytosine-guanosine dinucleotide (CpG motif frequencies in upstream promoter domains of different functional gene groups in two cnidarian genomes: a coral (Acropora digitifera and an anemone (Nematostella vectensis. Our analyses show that CpG motif frequencies are prominent in the promoter domains of functional genes associated with environmental adaptation, particularly those identified in A. hyacinthus. Densities of CpG sites in upstream promoter domains near the transcriptional start site (TSS are 1.38x higher than genomic background levels upstream of -2000 bp from the TSS. The increase in CpG usage suggests selection to allow for DNA methylation events to occur more frequently within 1 kb of the TSS. In addition, observed shifts in CpG densities among functional groups of genes suggests a potential role for epigenetic DNA methylation within promoter domains to impact functional gene expression responses in A. digitifera and N. vectensis. Identifying promoter epigenetic sequence motifs among genes within specific functional groups establishes an approach to describe integrated cellular responses to

  16. Distribution of CpG Motifs in Upstream Gene Domains in a Reef Coral and Sea Anemone: Implications for Epigenetics in Cnidarians.

    Science.gov (United States)

    Marsh, Adam G; Hoadley, Kenneth D; Warner, Mark E

    2016-01-01

    Coral reefs are under assault from stressors including global warming, ocean acidification, and urbanization. Knowing how these factors impact the future fate of reefs requires delineating stress responses across ecological, organismal and cellular scales. Recent advances in coral reef biology have integrated molecular processes with ecological fitness and have identified putative suites of temperature acclimation genes in a Scleractinian coral Acropora hyacinthus. We wondered what unique characteristics of these genes determined their coordinate expression in response to temperature acclimation, and whether or not other corals and cnidarians would likewise possess these features. Here, we focus on cytosine methylation as an epigenetic DNA modification that is responsive to environmental stressors. We identify common conserved patterns of cytosine-guanosine dinucleotide (CpG) motif frequencies in upstream promoter domains of different functional gene groups in two cnidarian genomes: a coral (Acropora digitifera) and an anemone (Nematostella vectensis). Our analyses show that CpG motif frequencies are prominent in the promoter domains of functional genes associated with environmental adaptation, particularly those identified in A. hyacinthus. Densities of CpG sites in upstream promoter domains near the transcriptional start site (TSS) are 1.38x higher than genomic background levels upstream of -2000 bp from the TSS. The increase in CpG usage suggests selection to allow for DNA methylation events to occur more frequently within 1 kb of the TSS. In addition, observed shifts in CpG densities among functional groups of genes suggests a potential role for epigenetic DNA methylation within promoter domains to impact functional gene expression responses in A. digitifera and N. vectensis. Identifying promoter epigenetic sequence motifs among genes within specific functional groups establishes an approach to describe integrated cellular responses to environmental stress in

  17. Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

    Science.gov (United States)

    Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

    2014-10-20

    The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

  18. Radioiodine therapy of thyroid autonomy

    Energy Technology Data Exchange (ETDEWEB)

    Reiners, Christoph; Schneider, Peter [Clinic and Policlinic for Nuclear Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg (Germany)

    2002-08-01

    Over half a century, treatment of thyroid autonomy with an oral dose of iodine-131 has proven to be effective. The optimum management strategy for the patient is, however, still a matter of debate. The article provides an overview of the pathogenesis of functional autonomy and its clinical relevance. According to the guidelines on both sides of the Atlantic, radioiodine treatment is considered the most comfortable and economical approach to the treatment of the toxic nodular goitre. Some differences in the preparation procedures in the guidelines of the American and the German Society of Nuclear Medicine are discussed with respect to therapy results and the subtypes of thyroid autonomy. The results of studies are summarised concerning changes in thyroid function and thyroid volume after a course of radioiodine treatment. Therapy-related risks, such as immunogenic hypothyroidism or thyroid cancer, are discussed. {sup 131}I treatment of functional autonomy and hyperthyroidism is considered an effective and safe procedure. (orig.)

  19. Subsidiary Autonomy and Knowledge Transfer

    DEFF Research Database (Denmark)

    Søberg, Peder Veng; Wæhrens, Brian Vejrum

    2015-01-01

    Purpose: This paper explores the effect of subsidiary autonomy on knowledge transfers during captive R&D offshoring to emerging markets. Design/methodology/approach: A framework to this end is developed and illustrated in relation to four cases of captive R&D offshoring to emerging markets....... Findings: Subsidiary autonomy has a mainly negative effect on primary knowledge transfer and a mainly positive effect on reverse knowledge transfer. Newly established R&D subsidiaries in emerging markets need primary knowledge transfer in order to build up their competence before they can add...... to the knowledge level of the MNE. Originality: A dual role of subsidiary autonomy is identified. Gradual increase in R&D subsidiary autonomy is beneficial for subsidiary innovation performance....

  20. Radioiodine therapy of thyroid autonomy

    International Nuclear Information System (INIS)

    Reiners, Christoph; Schneider, Peter

    2002-01-01

    Over half a century, treatment of thyroid autonomy with an oral dose of iodine-131 has proven to be effective. The optimum management strategy for the patient is, however, still a matter of debate. The article provides an overview of the pathogenesis of functional autonomy and its clinical relevance. According to the guidelines on both sides of the Atlantic, radioiodine treatment is considered the most comfortable and economical approach to the treatment of the toxic nodular goitre. Some differences in the preparation procedures in the guidelines of the American and the German Society of Nuclear Medicine are discussed with respect to therapy results and the subtypes of thyroid autonomy. The results of studies are summarised concerning changes in thyroid function and thyroid volume after a course of radioiodine treatment. Therapy-related risks, such as immunogenic hypothyroidism or thyroid cancer, are discussed. 131 I treatment of functional autonomy and hyperthyroidism is considered an effective and safe procedure. (orig.)

  1. Intramitochondrial autonomy in rat tissues

    International Nuclear Information System (INIS)

    Subramanian, M.; Rajwade, M.S.; Satav, J.G.; Katyare, S.S.; Fatterpaker, P.; Sreenivasan, A.

    1974-01-01

    The biogenesis of mitochondria in rat liver and their protein turnover has been investigated using 1- 14 C leucine. The results indicate that intramitochondrial autonomy exists both with respect to their genesis and turnover. (M.G.B.)

  2. Institutional Financial Autonomy in Practice

    DEFF Research Database (Denmark)

    Szwebs, Witold

    2016-01-01

    The article reveals how university autonomy may in practice prove to be restrictive for units within the university. The need to implement and interpret external regulations and protect the institution may, argued in the paper, lead to a risk averse, conservative approach which is experienced...... by departments as bureaucratic and hampering effective research. Thus autonomy has produced new internal tensions between the central management/administration and the departments which it is argued is counter-productive and not beneficial for research and could be seen as a perverse aspect of greater autonomy....... Indeed because university policy and ‘interference’ is much closer to the researcher than in former less autonomous times and the university may now exercise other direct incentives through resource allocation, promotion and salary enhancement, the department and the individual may view autonomy...

  3. Learning for autonomy

    Science.gov (United States)

    Rivero, Jose

    1989-12-01

    There is a need for a new concept of post-literacy which goes beyond the learning of codes. The target population is defined on the basis of their need to be given the capacity to take decisions on essential economic, civic, political and day-to-day aspects of their lives. The main arena of post-literacy lies in the countries of the Third World, where the economic crisis has serious effects on the quality of life and impairs the motivation to learn. Particular reference is made to the concept of participation and to the ability to determine four types of basic educational need: fundamental needs, productivity needs, social service needs and community organization needs. Four Latin American programmes linked to these four types of need are presented and discussed in terms of their particular features: popular participation in decision making; the search for methods and techniques which give the population a certain degree of autonomy; and respect for the cultures and world visions of the communities in the conduct of post-literacy, educational innovation and other activities. The programmes are: post-literacy in Nicaragua (fundamental education needs); research on post-literacy and employment in 13 countries (productivity needs); the CIPCA project for peasants in Piura, on the northern coast of Peru (social service needs); and the `Talking Maps' project developed with the Paez community in Cauca, Colombia (community organization needs).

  4. Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias

    Directory of Open Access Journals (Sweden)

    Sofie Degerman

    2014-07-01

    Full Text Available We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs, islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

  5. Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias.

    Science.gov (United States)

    Degerman, Sofie; Landfors, Mattias; Siwicki, Jan Konrad; Revie, John; Borssén, Magnus; Evelönn, Emma; Forestier, Erik; Chrzanowska, Krystyna H; Rydén, Patrik; Keith, W Nicol; Roos, Göran

    2014-07-01

    We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  6. Detection and discrimination of maintenance and de novo CpG methylation events using MethylBreak.

    Science.gov (United States)

    Hsu, William; Mercado, Augustus T; Hsiao, George; Yeh, Jui-Ming; Chen, Chung-Yung

    2017-05-15

    Understanding the principles governing the establishment and maintenance activities of DNA methyltransferases (DNMTs) can help in the development of predictive biomarkers associated with genetic disorders and diseases. A detection system was developed that distinguishes and quantifies methylation events using methylation-sensitive endonucleases and molecular beacon technology. MethylBreak (MB) is a 22-mer oligonucleotide with one hemimethylated and two unmethylated CpG sites, which are also recognition sites for Sau96I and SacII, and is attached to a fluorophore and a quencher. Maintenance methylation was quantified by fluorescence emission due to the digestion of SacII when the hemimethylated CpG site is methylated, which inhibits Sau96I cleavage. The signal difference between SacII digestion of both MB substrate and maintenance methylated MB corresponds to de novo methylation event. Our technology successfully discriminated and measured both methylation activities at different concentrations of MB and achieved a high correlation coefficient of R 2 =0.997. Additionally, MB was effectively applied to normal and cancer cell lines and in the analysis of enzymatic kinetics and RNA inhibition of recombinant human DNMT1. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. CpG dinucleotide frequencies reveal the role of host methylation capabilities in parvovirus evolution.

    Science.gov (United States)

    Upadhyay, Mohita; Samal, Jasmine; Kandpal, Manish; Vasaikar, Suhas; Biswas, Banhi; Gomes, James; Vivekanandan, Perumal

    2013-12-01

    Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to "fractional" methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.

  8. The CpG island methylator phenotype: What's in a name?

    NARCIS (Netherlands)

    L.A.E. Hughes (Laura A.); V. Melotte (Veerle); J.D. Schrijver (Joachim De); M.P.M. de Maat (Moniek); V.T.H.B.M. Smit (Vincent); J.V.M.G. Bovée (Judith); P.J. French (Pim); P.A. van den Brandt (Piet); L. Schouten (Leo); T. Meyer (Thorsten); W. van Criekinge (Wim); N. Ahuja (Nita); J.G. Herman (James); M.P. Weijenberg (Matty); M. van Engeland (Manon)

    2013-01-01

    textabstractAlthough the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast,

  9. Endogenous sunk costs and the geographic differences in the market structures of CPG Categories

    NARCIS (Netherlands)

    Bronnenberg, B.J.; Dhar, S.; Dube, J.P.

    2011-01-01

    We describe the industrial market structure of CPG categories. The analysis uses a unique database spanning 31 consumer package goods (CPG) categories, 39 months, and the 50 largest US metropolitan markets. We organize our description of market structure around the notion that firms can improve

  10. THE CHALLENGE OF AUTONOMY: AN EMPIRICAL STUDY OF THE VARIOUS DIMENSIONS OF AUTONOMY

    OpenAIRE

    Cristi IFTENE

    2009-01-01

    There are various dimensions of autonomy (policy, financial, structural, personnel, legal, institutional) as different scholars demonstrated (Christensen 2001, Verhoest et. al. 2004). In the present paper we will focus only on political and financial autonomy. As Yesilkagit and van Thiel demonstrated there is a difference between formal and de facto autonomy. They found that formal autonomy does not reinforce de facto autonomy and that organizations with less autonomy report higher levels of ...

  11. Designing Autonomy: Opportunities for New Wildness in the Anthropocene.

    Science.gov (United States)

    Cantrell, Bradley; Martin, Laura J; Ellis, Erle C

    2017-03-01

    Maintaining wild places increasingly involves intensive human interventions. Several recent projects use semi-automated mediating technologies to enact conservation and restoration actions, including re-seeding and invasive species eradication. Could a deep-learning system sustain the autonomy of nonhuman ecological processes at designated sites without direct human interventions? We explore here the prospects for automated curation of wild places, as well as the technical and ethical questions that such co-creation poses for ecologists, conservationists, and designers. Our goal is to foster innovative approaches to creating and maintaining the autonomy of evolving ecological systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Models, controls, and levels of semiotic autonomy

    Energy Technology Data Exchange (ETDEWEB)

    Joslyn, C.

    1998-12-01

    In this paper the authors consider forms of autonomy, forms of semiotic systems, and any necessary relations among them. Levels of autonomy are identified as levels of system identity, from adiabatic closure to disintegration. Forms of autonomy or closure in systems are also recognized, including physical, dynamical, functional, and semiotic. Models and controls are canonical linear and circular (closed) semiotic relations respectively. They conclude that only at higher levels of autonomy do semiotic properties become necessary. In particular, all control systems display at least a minimal degree of semiotic autonomy; and all systems with sufficiently interesting functional autonomy are semiotically related to their environments.

  13. The Ideal of Moral Autonomy

    Directory of Open Access Journals (Sweden)

    Ricardo Marquisio Aguirre

    2017-10-01

    Full Text Available Some elements of the ideal of moral autonomy are discussed in this paper. Such ideal is a key assumption in social practices focused on normative imputation, particularly morality and law. First, a constructivist conception of normativity is introduced, taking reasons as an essential and non-reducible element, and focused on the conceptual features of moral reasons within the normative domain. Then, an idea of moral autonomy based on the self-constitution is developed including three key features: the possibility of responding to reasons based on shared social expectations; the responsibility for certain scope of actions, according to a set of reasons available to the individual and to their maximum extent of expansion; and the need to preserve autonomy as a purpose unifying the set of autonomous actions of moral agents.

  14. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies.

    Science.gov (United States)

    Hanagata, Nobutaka

    2017-01-01

    Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.

  15. CpG Oligodeoxynucleotides as a Future Vaccine for Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Kunio Sano

    2005-01-01

    Full Text Available An astounding feature of the DNA sequences termed CpG motifs is the induction of immune and inflammatory responses in a senseless manner. CpG motifs exist abundantly in microbes and evoke innate immunity that constitutes the first line of defense against microbial infections in vertebrates. CpG motifs that essentially work in an antigen-nonspecific fashion, however, turn into novel immunomodulators that can manipulate acquired immunity in an antigen-specific manner if oligodeoxynucleotides containing CpG motifs (CpG ODNs are directly conjugated to the antigen. CpG ODNs with potent polyclonal Th1-inducing ability show promise for application in immunotherapy whereby neutralization of dominant allergy-prone Th2 cells is achieved by inducing allergen-specific Th1 cells. The underlying mechanisms include an unexpected enhancement of dendritic cell function as a linker between innate and acquired immunity. In the foreseeable future the mainstream therapeutic role of corticosteroids in anti-inflammatory therapy for allergic diseases could possibly be replaced by immunotherapy using CpG ODN-conjugated antigens.

  16. CpG islands undermethylation in human genomic regions under selective pressure.

    Directory of Open Access Journals (Sweden)

    Sergio Cocozza

    Full Text Available DNA methylation at CpG islands (CGIs is one of the most intensively studied epigenetic mechanisms. It is fundamental for cellular differentiation and control of transcriptional potential. DNA methylation is involved also in several processes that are central to evolutionary biology, including phenotypic plasticity and evolvability. In this study, we explored the relationship between CpG islands methylation and signatures of selective pressure in Homo Sapiens, using a computational biology approach. By analyzing methylation data of 25 cell lines from the Encyclopedia of DNA Elements (ENCODE Consortium, we compared the DNA methylation of CpG islands in genomic regions under selective pressure with the methylation of CpG islands in the remaining part of the genome. To define genomic regions under selective pressure, we used three different methods, each oriented to provide distinct information about selective events. Independently of the method and of the cell type used, we found evidences of undermethylation of CGIs in human genomic regions under selective pressure. Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure show lower genetic variation. Our findings suggest that the CpG islands in regions under selective pressure seem to be somehow more "protected" from methylation when compared with other regions of the genome.

  17. Autonomy and dignity: a discussion on contingency and dominance.

    Science.gov (United States)

    Van Brussel, Leen

    2014-06-01

    With dying increasingly becoming a medicalised experience in old age, we are witnessing a shift from concern over death itself to an interest in dying 'well'. Fierce discussions about end-of-life decision making and the permissibility of medical intervention in dying, discursively structured around the notion of a 'good' death, are evidence of this shift. This article focuses on 'autonomy' and 'dignity' as key signifiers in these discussions. Rather than being fully fixed and stable, both signifiers are contingent and carry a variety of meanings within different discursive projects. The article aims to distinguish the varieties of these signifiers by elaborating existing theoretical perspectives on autonomy and dignity, and also, starting from a perspective on mass media as sites of meaning production and contestation, to study the contingency of autonomy and dignity in Belgian newspaper coverage of four prominent euthanasia cases. By means of a discourse-theoretical textual analysis, this study exposes a dominant--yet contested--articulation of rational-personal autonomy and of dignity in external terms as something that can be obtained, retained or lost, rather than in terms of intrinsic human integrity. These logics of representation reflect a more general late modern dominance of liberal autonomy and of dignity as being closely connected to self-identity, but at the same time result in limited visibility of alternative ways of experiencing an autonomous and dignified death.

  18. Mental health as rational autonomy.

    Science.gov (United States)

    Edwards, R B

    1981-08-01

    Rather than eliminate the terms "mental health and illness" because of the grave moral consequences of psychiatric labeling, conservative definitions are proposed and defended. Mental health is rational autonomy, and mental illness is the sustained loss of such. Key terms are explained, advantages are explored, and alternative concepts are criticized. The value and descriptive components of all such definitions are consciously acknowledged. Where rational autonomy is intact, mental hospitals and psychotherapists should not think of themselves as treating an illness. Instead, they are functioning as applied axiologists, moral educators, spiritual mentors, etc. They deal with what Szasz has called "personal, social, and ethical problems in living." But mental illness is real.

  19. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.

    Directory of Open Access Journals (Sweden)

    Ruth D Ellis

    2010-01-01

    Full Text Available Merozoite surface protein 1(42 (MSP1(42 is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42 were mixed (MSP1(42-C1. To improve the level of antibody response, MSP1(42-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909.A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months.Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42 antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42-C1/Alhydrogel alone (p<0.0001. After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10% in the non CPG groups versus 14% (3 to 32% in the CPG groups.The favorable safety profile and high antibody responses induced with MSP1(42-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909.ClinicalTrials.gov Identifier: NCT00320658.

  20. Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord

    DEFF Research Database (Denmark)

    Kiehn, Ole; Butt, Simon J.B.

    2003-01-01

    . These latter experiments have defined EphA4 as a molecular marker for mammalian excitatory hindlimb CPG neurons. We also review genetic approaches that can be applied to the mouse spinal cord. These include methods for identifying sub-populations of neurons by genetically encoded reporters, techniques to trace...... network connectivity with cell-specific genetically encoded tracers, and ways to selectively ablate or eliminate neuron populations from the CPG. We propose that by applying a multidisciplinary approach it will be possible to understand the network structure of the mammalian locomotor CPG...

  1. The ADEPT Framework for Intelligent Autonomy

    National Research Council Canada - National Science Library

    Ricard, Michael; Kolitz, Stephan

    2003-01-01

    ...) architecture for intelligent autonomy. Intelligent autonomy is the ability to plan and execute complex activities in a manner that provides rapid, effective response to stochastic and dynamic mission events...

  2. Full autonomy; Autarkie im Komplettpaket

    Energy Technology Data Exchange (ETDEWEB)

    Augsten, Eva

    2011-05-31

    Normally, those who talk of full solar autonomy refer to the annual balance of a house. Now, architect Timo Leukefeld and Helma Eigenheimbau AG presented a really autonomous solar house which is available on a turnkey basis for 363,000 Euros.

  3. Privatization, convergence, and institutional autonomy

    NARCIS (Netherlands)

    Rooijen, van M.

    2011-01-01

    Some of the trends incoming for 2011 – greater institutional autonomy, public/private convergence, entrepreneurial management, civic engagement – suggest innovation for hard times, with socio-economic and political rationales increasingly driving borderless developments. Others – open learning and

  4. Student Perceptions of Their Autonomy at University

    Science.gov (United States)

    Henri, D. C.; Morrell, L. J.; Scott, G. W.

    2018-01-01

    Learner autonomy is a primary learning outcome of Higher Education in many countries. However, empirical evaluation of how student autonomy progresses during undergraduate degrees is limited. We surveyed a total of 636 students' self-perceived autonomy during a period of two academic years using the Autonomous Learning Scale. Our analysis suggests…

  5. School Autonomy, Leadership and Learning: A Reconceptualisation

    Science.gov (United States)

    Cheng, Yin Cheong; Ko, James; Lee, Theodore Tai Hoi

    2016-01-01

    Purpose: The purpose of this paper is to develop a framework for reconceptualising research on school autonomy to redress the limitations of traditional research, strengthen the conceptual links between school autonomy and learning outcomes and offer a range of new strategies for studying the interplay of school autonomy, leadership and learning.…

  6. Respect for autonomy and technological risks

    NARCIS (Netherlands)

    Asveld, L.

    2008-01-01

    Technological developments can undermine the autonomy of the individual. Autonomy is one's ability to make and act upon decisions according to one's own moral framework. Respect for autonomy dictates that risks should not be imposed on the individual without her consent. Technological developments

  7. Rawls: The Problem of Autonomy and Coherentism

    Directory of Open Access Journals (Sweden)

    Elnora Gondim

    2010-12-01

    Full Text Available The transformation of the idea of autonomy into that of justice as equality modifies the work of Rawls taken as a whole. Thus, while in the Theory of Justice, a Kantian- type of autonomy is adopted, in Political Liberalism, autonomy is extended to the sphere of the political.

  8. The Connotations of Language Teacher Autonomy

    Science.gov (United States)

    Han, Ligang

    2017-01-01

    With the research on the development of learner autonomy in foreign language education, teacher autonomy has become a hot topic in the research of foreign language teacher education. However, it is the most difficult question to define language teacher autonomy and any answer to it is likely to be subjective. On the basis of expounding upon the…

  9. The Use of Chlorhexidine/n-Propyl Gallate (CPG) as an Ambient-Temperature Urine Preservative

    Science.gov (United States)

    Nillen, Jeannie L.; Smith, Scott M.

    2003-01-01

    A safe, effective ambient temperature urine preservative, chlorhexidine/n-propyl gallate (CPG), has been formulated for use during spacefli ght that reduces the effects of oxidation and bacterial contamination on sample integrity while maintaining urine pH. The ability of this preservative to maintain stability of nine key analytes was evaluated for a period of one year. CPG effectively maintained stability of a mmonia, total nitrogen, 3-methylhistidine, chloride, sodium, potassiu m, and urea; however, creatinine and osmolality were not preserved by CPG. These data indicate that CPG offers prolonged room-temperature storage for multiple urine analytes, reducing the requirements for f rozen urine storage on future spaceflights. Iii medical applications on Earth, this technology can allow urine samples to be collected in remote settings and eliminate the need to ship frozen samples.

  10. Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oglionucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennise

    2001-01-01

    .... Additional studies examining the ability of these CpG ODN to act as adjuvants when co-administered with vaccines being developed to prevent infection by biowarfare pathogens are also being pursued...

  11. Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oglionucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennise

    2001-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  12. Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oligonucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennis

    2003-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory "CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  13. Rapid Induction of Protective Immunity Against Biothreat Agens Using CPG-Based Oglionucleotides

    National Research Council Canada - National Science Library

    Klinman, Dennis

    1999-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG' motifs to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  14. Reinforcement learning for a biped robot based on a CPG-actor-critic method.

    Science.gov (United States)

    Nakamura, Yutaka; Mori, Takeshi; Sato, Masa-aki; Ishii, Shin

    2007-08-01

    Animals' rhythmic movements, such as locomotion, are considered to be controlled by neural circuits called central pattern generators (CPGs), which generate oscillatory signals. Motivated by this biological mechanism, studies have been conducted on the rhythmic movements controlled by CPG. As an autonomous learning framework for a CPG controller, we propose in this article a reinforcement learning method we call the "CPG-actor-critic" method. This method introduces a new architecture to the actor, and its training is roughly based on a stochastic policy gradient algorithm presented recently. We apply this method to an automatic acquisition problem of control for a biped robot. Computer simulations show that training of the CPG can be successfully performed by our method, thus allowing the biped robot to not only walk stably but also adapt to environmental changes.

  15. CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of murine tumors

    International Nuclear Information System (INIS)

    Mason, Kathryn A.; Neal, Robert; Hunter, Nancy; Ariga, Hisanori; Ang, Kian; Milas, Luka

    2006-01-01

    Background and purpose: Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs bind to Toll-like receptor 9 (TLR9) and stimulate both innate and adaptive immune reactions and possess anti-tumor activity. We recently reported that CpG ODN 1826 strongly enhances radioresponse of both immunogenic [Milas L, Mason K, Ariga H, et al. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res 2004;64:5074-7] and non-immunogenic [Mason KA, Ariga H, Neal R, et al. Targeting toll-like receptor-9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy. Clin Cancer Res 2005;11:361-9] murine tumors. Using two immunogenic murine tumors, a fibrosarcoma (FSa) and a mammary carcinoma (MCa-K), the present study explored whether CpG ODN 1826 also improves the response of murine tumors to the chemotherapeutic agent docetaxel (DOC). Materials and methods: CpG ODN 1826 (100 μg) was given sc three times: when leg tumors were 6 mm, when they grew to 8 mm and again 1 week later. DOC (33 mg/kg iv) and local tumor radiation (10 Gy) were given when tumors were 8 mm. Effects of the treatments were assayed by tumor growth delay, defined as days for tumors to grow from 8 to 12 mm in diameter. Results: Treatment with CpG ODN 1826 resulted in strongly enhanced response of FSa tumors to radiation and MCa-K tumors to the chemotherapeutic agent DOC. Enhancement of tumor treatment response was demonstrated by a strong prolongation in the primary tumor treatment endpoint, tumor growth delay. Coincidentally, this treatment also resulted in a higher rate of tumor cure than that observed after tumor radiotherapy or chemotherapy alone. When all three agents were combined the effect was comparable to that of the combination of CpG ODN 1826 with radiation in the case of FSa or of the combination of CpG ODN 1826 with DOC in the case of MCa-K. Conclusion: Overall results show that CpG ODN 1826 can markedly improve tumor response

  16. Human Vav1 expression in hematopoietic and cancer cell lines is regulated by c-Myb and by CpG methylation.

    Directory of Open Access Journals (Sweden)

    Lena Ilan

    Full Text Available Vav1 is a signal transducer protein that functions as a guanine nucleotide exchange factor for the Rho/Rac GTPases in the hematopoietic system where it is exclusively expressed. Recently, Vav1 was shown to be involved in several human malignancies including neuroblastoma, lung cancer, and pancreatic ductal adenocarcinoma (PDA. Although some factors that affect vav1 expression are known, neither the physiological nor pathological regulation of vav1 expression is completely understood. We demonstrate herein that mutations in putative transcription factor binding sites at the vav1 promoter affect its transcription in cells of different histological origin. Among these sites is a consensus site for c-Myb, a hematopoietic-specific transcription factor that is also found in Vav1-expressing lung cancer cell lines. Depletion of c-Myb using siRNA led to a dramatic reduction in vav1 expression in these cells. Consistent with this, co-transfection of c-Myb activated transcription of a vav1 promoter-luciferase reporter gene construct in lung cancer cells devoid of Vav1 expression. Together, these results indicate that c-Myb is involved in vav1 expression in lung cancer cells. We also explored the methylation status of the vav1 promoter. Bisulfite sequencing revealed that the vav1 promoter was completely unmethylated in human lymphocytes, but methylated to various degrees in tissues that do not normally express vav1. The vav1 promoter does not contain CpG islands in proximity to the transcription start site; however, we demonstrated that methylation of a CpG dinucleotide at a consensus Sp1 binding site in the vav1 promoter interferes with protein binding in vitro. Our data identify two regulatory mechanisms for vav1 expression: binding of c-Myb and CpG methylation of 5' regulatory sequences. Mutation of other putative transcription factor binding sites suggests that additional factors regulate vav1 expression as well.

  17. Public Health Autonomy: A Critical Reappraisal.

    Science.gov (United States)

    Zimmerman, Frederick J

    2017-11-01

    The ethical principle of autonomy is among the most fundamental in ethics, and it is particularly salient for those in public health, who must constantly balance the desire to improve health outcomes by changing behavior with respect for individual freedom. Although there are some areas in which there is a genuine tension between public health and autonomy-childhood vaccine mandates, for example-there are many more areas where not only is there no tension, but public health and autonomy come down to the same thing. These areas of overlap are often rendered invisible by a thin understanding of autonomy. Better integrating newer theoretical insights about autonomy into applied ethics can make discussions of public health ethics more rigorous, incisive, and effective. Even more importantly, bringing modern concepts of autonomy into public health ethics can showcase the many areas in which public health and autonomy have the same goals, face the same threats, and can be mutually advanced by the same kinds of solutions. This article provides a schema for relational autonomy in a public health context and gives concrete examples of how autonomy can be served through public-health interventions. It marshals insights from sociology, psychology, and philosophy to advance a theory of autonomy and coercion that recognizes three potential threats to autonomy: threats to choice sets, threats to knowledge, and threats to preferences. © 2017 The Hastings Center.

  18. Identification of a boron nitride nanosphere-binding peptide for the intracellular delivery of CpG oligodeoxynucleotides

    Science.gov (United States)

    Zhang, Huijie; Yamazaki, Tomohiko; Zhi, Chunyi; Hanagata, Nobutaka

    2012-09-01

    CpG oligonucleotides (CpG ODNs) interact with Toll-like receptor 9 (TLR9), which results in the induction of immunostimulatory cytokines. We delivered CpG ODNs intracellularly using boron nitride nanospheres (BNNS). To enhance the loading capacity of CpG ODNs on BNNS, we used a phage display technique to identify a 12-amino acid peptide designated as BP7, with specific affinity for BNNS, and used it as a linker to load CpG ODNs on BNNS. The tyrosine residue (Y) at the eighth position from the N-terminus played a crucial role in the affinity of BP7 to BNNS. BNNS that bound BP7 (BNNS-BP7) were taken up by cells and showed no cytotoxicity, and CpG ODNs were successfully crosslinked with BP7 to create BP7-CpG ODN conjugates. Using BP7 as a linker, the loading efficiency of CpG ODNs on BNNS increased 5-fold compared to the direct binding of CpG ODNs to BNNS. Furthermore, the BP7-CpG ODN conjugate-loaded BNNS had a greater capacity to induce interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) than that of CpG ODNs directly loaded on BNNS. The higher amount of cytokine induction by BP7-CpG ODN conjugate-loaded BNNS may be attributed to a higher loading capacity and stronger binding to BNNS of the linker BP7. The greater functionality of BP7-conjugated CpG ODNs on BNNS expands the potential of BNNS for drug delivery applications.CpG oligonucleotides (CpG ODNs) interact with Toll-like receptor 9 (TLR9), which results in the induction of immunostimulatory cytokines. We delivered CpG ODNs intracellularly using boron nitride nanospheres (BNNS). To enhance the loading capacity of CpG ODNs on BNNS, we used a phage display technique to identify a 12-amino acid peptide designated as BP7, with specific affinity for BNNS, and used it as a linker to load CpG ODNs on BNNS. The tyrosine residue (Y) at the eighth position from the N-terminus played a crucial role in the affinity of BP7 to BNNS. BNNS that bound BP7

  19. Enhancing autonomy in paid surrogacy.

    Science.gov (United States)

    Damelio, Jennifer; Sorensen, Kelly

    2008-06-01

    The gestational surrogate--and her economic and educational vulnerability in particular--is the focus of many of the most persistent worries about paid surrogacy. Those who employ her, and those who broker and organize her services, usually have an advantage over her in resources and information. That asymmetry exposes her to the possibility of exploitation and abuse. Accordingly, some argue for banning paid surrogacy. Others defend legal permission on grounds of surrogate autonomy, but often retain concerns about the surrogate. In response to the dilemma of a ban versus bald permission, we propose a 'soft law' approach: states should require several hours of education of surrogates--education aimed at informing and enhancing surrogate autonomy.

  20. Epistemic merit, autonomy, and testimony

    Directory of Open Access Journals (Sweden)

    Jesús VEGA ENCABO

    2008-01-01

    Full Text Available In this paper, it is argued that both the informer and the hearer in a testimonial situation deserve epistemic merit insofar as they contribute to the collaborative achievement of sharing knowledge. The paper introduces a distinction between the ideals of self-sufficiency and epistemic autonomy. The autonomous exercise of our epistemic agency is very often carried out under strong conditions of epistemic dependence. Testimony exhibits a kind of social dependence that does not threaten the autonomy of the subjects that need to consider their own epistemic capacities. When involved in a testimonial situation, both speaker and hearer declare, at least implicitly, the standings they occupy in an epistemic space and are obliged to recognise certain epistemic requirements.

  1. Autonomy and the akratic patient.

    Science.gov (United States)

    McKnight, C J

    1993-01-01

    I argue that the distinction which is current in much writing on medical ethics between autonomous and non-autonomous patients cannot cope comfortably with weak-willed (incontinent) patients. I describe a case involving a patient who refuses a blood transfusion even though he or she agrees that it would be in his or her best interests. The case is discussed in the light of the treatment of autonomy by B Brody and R Gillon. These writers appear to force us to treat an incontinent patient either as autonomous, just like a rational agent whose decisions are in accordance with his beliefs or as non-autonomous, like comatose patients or children. Though neither is entirely satisfactory I opt for describing such patients as autonomous but point out that in cases like this the principle of respect for autonomy does not give a determinate answer about how the patient ought to be treated. PMID:8308874

  2. Reproductive autonomy: A case study

    Directory of Open Access Journals (Sweden)

    David R Hall

    2016-11-01

    Full Text Available Reproductive autonomy (RA has been challenged by the availability of genetic information, disability and the ethics of selective reproduction. Utilitarian and rights-based approaches, as well as procreative beneficence (PB fail to provide compelling reasons for infringing RA, and may even be likened to dangerous eugenics. Parents are not morally obliged to prevent the birth of a disabled child. Society should rather adopt inclusivity, recognising and providing persons with disabilities opportunities for capability and worthwhile lives.

  3. The many faces of autonomy.

    Science.gov (United States)

    Gracia, Diego

    2012-02-01

    What does autonomy mean from a moral point of view? Throughout Western history, autonomy has had no less than four different meanings. The first is political: the capacity of old cities and modern states to give themselves their own laws. The second is metaphysical, and was introduced by Kant in the second half of the 18th century. In this meaning, autonomy is understood as an intrinsic characteristic of all rational beings. Opposed to this is the legal meaning, in which actions are called autonomous when performed with due information and competency and without coercion. This last meaning, the most frequently used in bioethics, is primarily legal instead of moral. Is there a proper moral meaning of the word autonomy? If so, this would be a fourth meaning. Acts can only be called moral when they are postconventional (using the terminology coined by Lawrence Kohlberg), inner-directed (as expressed by David Riesman), and responsible (according to Hannah Arendt). Such acts are autonomous in this new, fourth, and to my mind, the only one proper, moral meaning. The goal of ethics cannot be other than forming human beings capable of making autonomous and responsible decisions, and doing so because they think this is their duty and not because of any other nonmoral motivation, like comfort, convenience, or satisfaction. The goal of ethics is to promote postconventional and mature human beings. This was what Socrates tried to do with the young people of Athens. And it is also the objective of every course of ethics and of any process of training.

  4. Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Zhe-Ming Lu

    Full Text Available BACKGROUND: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding" sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC samples (36/40 was significantly higher than that observed in gastritis (19/45 or normal samples (7/13 (P<0.01. Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5'UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P<0.01. In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens. CONCLUSIONS/SIGNIFICANCE: It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 5'UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo.

  5. CPG-based Locomotion Controller Design for a Boxfish-like Robot

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-06-01

    Full Text Available This paper focuses on a Central Pattern Generator (CPG-based locomotion controller design for a boxfish-like robot. The bio-inspired controller is aimed at flexible switching in multiple 3D swimming patterns and exact attitude control of yaw and roll such that the robot will swim more like a real boxfish. The CPG network comprises two layers, the lower layer is the network of coupled linear oscillators and the upper is the transition layer where the lower-dimensional locomotion stimuli are transformed into the higher-dimensional control parameters serving for all the oscillators. Based on such a two-layer framework, flexible switching between multiple three-dimensional swimming patterns, such as swimming forwards/backwards, turning left/right, swimming upwards/downwards and rolling clockwise/counter-clockwise, can be simply realized by inputting different stimuli. Moreover, the stability of the CPG network is strictly proved to guarantee the intrinsic stability of the swimming patterns. As to exact attitude control, based on this open-loop CPG network and the sensory feedback from the Inertial Measurement Unit (IMU, a closed-loop CPG controller is advanced for yaw and roll control of the robotic fish for the first time. This CPG-based online attitude control for a robotic fish will greatly facilitate high-level practical underwater applications. A series of relevant experiments with the robotic fish are conducted systematically to validate the effectiveness and stability of the open-loop and closed-loop CPG controllers.

  6. Parvovirus b19 DNA CpG dinucleotide methylation and epigenetic regulation of viral expression.

    Directory of Open Access Journals (Sweden)

    Francesca Bonvicini

    Full Text Available CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression.The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections.The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19.

  7. Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

    Science.gov (United States)

    Bonvicini, Francesca; Manaresi, Elisabetta; Di Furio, Francesca; De Falco, Luisa; Gallinella, Giorgio

    2012-01-01

    CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression. The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections. The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19. PMID:22413013

  8. Integrative DNA methylation and gene expression analysis to assess the universality of the CpG island methylator phenotype.

    Science.gov (United States)

    Moarii, Matahi; Reyal, Fabien; Vert, Jean-Philippe

    2015-10-13

    The CpG island methylator phenotype (CIMP) was first characterized in colorectal cancer but since has been extensively studied in several other tumor types such as breast, bladder, lung, and gastric. CIMP is of clinical importance as it has been reported to be associated with prognosis or response to treatment. However, the identification of a universal molecular basis to define CIMP across tumors has remained elusive. We perform a genome-wide methylation analysis of over 2000 tumor samples from 5 cancer sites to assess the existence of a CIMP with common molecular basis across cancers. We then show that the CIMP phenotype is associated with specific gene expression variations. However, we do not find a common genetic signature in all tissues associated with CIMP. Our results suggest the existence of a universal epigenetic and transcriptomic signature that defines the CIMP across several tumor types but does not indicate the existence of a common genetic signature of CIMP.

  9. A CpG oligonucleotide can protect mice from a low aerosol challenge dose of Burkholderia mallei.

    Science.gov (United States)

    Waag, David M; McCluskie, Michael J; Zhang, Ningli; Krieg, Arthur M

    2006-03-01

    Treatment with an oligodeoxynucleotide (ODN) containing CPG motifs (CpG ODN 7909) was found to protect BALB/c mice from lung infection or death after aerosol challenge with Burkholderia mallei. Protection was associated with enhanced levels of gamma interferon (IFN-gamma)-inducible protein 10, interleukin-12 (IL-12), IFN-gamma, and IL-6. Preexposure therapy with CpG ODNs may protect victims of a biological attack from glanders.

  10. Autonomy and Firefighting: Perceived Competence and Stress.

    Science.gov (United States)

    Chiang, Evelyn S; Baley, John; Ponder, Joy; Padilla, Miguel A

    2016-12-01

    In workplace settings, autonomy is implicated in employee motivation as well as supervisor autonomy support. As a profession of risk, firefighters may experience greater levels of stress. A self-determination paradigm was applied to the firefighter workplace. Of particular interest were perceived competence (to perform job duties) and the experience of stress. Firefighters' levels of autonomous and controlled regulation were surveyed, along with their perceptions of the autonomy support of their immediate supervisor. Autonomous regulation was positively related to perceived competence, whereas controlled regulation was negatively related. Higher levels of controlled regulation were also connected with greater stress. In contrast, greater perceived autonomy support was associated with decreased stress. Both perceived competence and stress are related to firefighter motivation and autonomy support. Recommendations are offered to increase autonomy support by chief officers.

  11. Autonomy and the Sources of Political Normativity

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    Contemporary political liberals argue for extending the scope of reasonable disagreement to include also the principle of autonomy that was central in classical liberal theory. I take outset in Charles Larmore, The Autonomy of Morality (2008), which argues that liberal theory can dispense...... with the commitment to autonomy that one finds in Locke, Kant, and Mill, because "the essential convictions of liberal thought lie at a more fundamental level," namely in the principle of respect for persons. The main question I address is whether we can see the commitment to respect for persons as separable from...... the commitment to autonomy. My focus is the Kantian conception of autonomy, and I argue for understanding this conception practically and politically, rather than metaphysically and theoretically. In this way we can separate the principle of respect for persons from the metaphysical idea of autonomy as self...

  12. The impact of intragenic CpG content on gene expression.

    Science.gov (United States)

    Bauer, Asli Petra; Leikam, Doris; Krinner, Simone; Notka, Frank; Ludwig, Christine; Längst, Gernot; Wagner, Ralf

    2010-07-01

    The development of vaccine components or recombinant therapeutics critically depends on sustained expression of the corresponding transgene. This study aimed to determine the contribution of intragenic CpG content to expression efficiency in transiently and stably transfected mammalian cells. Based upon a humanized version of green fluorescent protein (GFP) containing 60 CpGs within its coding sequence, a CpG-depleted variant of the GFP reporter was established by carefully modulating the codon usage. Interestingly, GFP reporter activity and detectable protein amounts in stably transfected CHO and 293 cells were significantly decreased upon CpG depletion and independent from promoter usage (CMV, EF1 alpha). The reduction in protein expression associated with CpG depletion was likewise observed for other unrelated reporter genes and was clearly reflected by a decline in mRNA copy numbers rather than translational efficiency. Moreover, decreased mRNA levels were neither due to nuclear export restrictions nor alternative splicing or mRNA instability. Rather, the intragenic CpG content influenced de novo transcriptional activity thus implying a common transcription-based mechanism of gene regulation via CpGs. Increased high CpG transcription correlated with changed nucleosomal positions in vitro albeit histone density at the two genes did not change in vivo as monitored by ChIP.

  13. Freedom of Expression, Deliberation, Autonomy and Respect

    OpenAIRE

    Rostbøll, Christian F.

    2011-01-01

    This paper elaborates on the deliberative democracy argument for freedom of expression in terms of its relationship to different dimensions of autonomy. It engages the objection that Enlightenment theories pose a threat to cultures that reject autonomy and argues that autonomy-based democracy is not only compatible with but necessary for respect for cultural diversity. On the basis of an intersubjective epistemology, it argues that people cannot know how to live on mutually respectful terms w...

  14. A Reconfigurable Testbed Environment for Spacecraft Autonomy

    Science.gov (United States)

    Biesiadecki, Jeffrey; Jain, Abhinandan

    1996-01-01

    A key goal of NASA's New Millennium Program is the development of technology for increased spacecraft on-board autonomy. Achievement of this objective requires the development of a new class of ground-based automony testbeds that can enable the low-cost and rapid design, test, and integration of the spacecraft autonomy software. This paper describes the development of an Autonomy Testbed Environment (ATBE) for the NMP Deep Space I comet/asteroid rendezvous mission.

  15. From solidarity to autonomy: towards a redefinition of the parameters of the notion of autonomy.

    Science.gov (United States)

    Fainzang, Sylvie

    2016-12-01

    Starting from examples of concrete situations in France, I show that autonomy and solidarity can coexist only if the parameters of autonomy are redefined. I show on the one hand that in situations where autonomy is encouraged, solidarity nevertheless remains at the foundation of their practices. On the other hand, in situations largely infused with family solidarity, the individual autonomy may be put in danger. Yet, based on my ethnographic observations regarding clinical encounters and medical secrecy, I show that while solidarity may endanger individual autonomy, it does not necessarily endanger autonomy itself. The social practices observable in France reflect the reality of an autonomy that goes beyond the individual, a reality that involves a collective subject and includes solidarity. The opposition between these two values can then be resolved if the content of the notion of autonomy is understood to be dependent on its cultural context of application and on its social use.

  16. The Future of Reproductive Autonomy.

    Science.gov (United States)

    Johnston, Josephine; Zacharias, Rachel L

    2017-12-01

    In a project The Hastings Center is now running on the future of prenatal testing, we are encountering clear examples, both in established law and in the practices of individual providers, of failures to respect women's reproductive autonomy: when testing is not offered to certain demographics of women, for instance, or when the choices of women to terminate or continue pregnancies are prohibited or otherwise not supported. But this project also raises puzzles for reproductive autonomy. We have learned that some clinicians and patients do not discuss the fact that prenatal testing can lead to a decision about whether to terminate a pregnancy-they just don't talk about it. And while the decision whether to agree to prenatal screening and diagnostic testing is to be made with women's free and informed consent, many screening tests have been routinized in such a way that some women do not even recall agreeing to testing, while others feel that agreeing to testing is what their clinicians expect of them or that the testing is necessary to protect themselves and their families from the significant financial hardship of raising a child with a disability. In the face of these pressures, can one really say that women are freely choosing to undergo testing or are freely choosing to continue or terminate a pregnancy following receipt of test results? The reality of these pressures is requiring us to consider expanding the scope of our investigation beyond the clinical encounter to the broader context-to think harder about what reproductive autonomy means and how best to enhance it. © 2017 The Hastings Center.

  17. Adolescents, Graduated Autonomy, and Genetic Testing

    Directory of Open Access Journals (Sweden)

    Susan Fox

    2012-01-01

    Full Text Available Autonomy takes many shapes. The concept of “graduated autonomy” is conceived as comprising several unique features: (1 it is incremental, (2 it is proportional, and (3 it is related to the telos of the life stage during which it occurs. This paper focuses on graduated autonomy in the context of genetic testing during adolescence. Questions can be raised about other life stages as well, and some of these questions will be addressed by discussing a possible fourth characteristic of graduated autonomy, that is, its elasticity. Further scholarship and analysis is needed to refine the concept of graduated autonomy and examine its applications.

  18. Characteristics of Law-Autonomy Foreign Subsidiaries

    DEFF Research Database (Denmark)

    Gammelgaard, Jens; McDonald, Frank; Stephan, Andreas

    2012-01-01

    This paper examines several characteristics of foreign subsidiaries with low autonomy. Data derived from a survey of 381 MNC subsidiaries located in Denmark, Germany and the UK demonstrate that low-autonomy subsidiaries are highly embedded in their respective MNC networks and that they establish ...... relationship between lower autonomy and the production activities carried out by the subsidiary. In fact, low-autonomy subsidiaries appear to be specialized in that they focus on a few value-chain activities and they typically serve as marketing outlets....

  19. An intercultural nursing perspective on autonomy.

    Science.gov (United States)

    Hanssen, Ingrid

    2004-01-01

    This article is based on an empirical study regarding ethical challenges in intercultural nursing. The focus is on autonomy and disclosure. Autonomy is a human capacity that has become an important ethical principle in nursing. Although the relationship between autonomy and patients' possibly harmful choices is discussed, the focus is on 'forced' autonomy. Nurses seem to equate respect with autonomy; it seems to be hard to cope with the fact that there are patients who voluntarily undergo treatment but who actively participate neither in the treatment offered nor in making choices regarding that treatment. Nurses' demand for patients to be autonomous may in some cases jeopardize the respect, integrity and human worth that the ethical principle of autonomy is meant to ensure. Even though respect for a person's autonomy is also respect for the person, one's respect for the person in question should not depend on his or her capacity or aptitude to act autonomously. Is autonomy necessarily a universal ethical principle? This article negates this question and, through the issues of culture, individualism versus collectivism, first- and second-order autonomy, communication and the use of family interpreters, and respect, an attempt is made to explain why.

  20. Professional Autonomy versus Corporate Control

    Directory of Open Access Journals (Sweden)

    Pål Nygaard

    2012-06-01

    Full Text Available Professionalism and bureaucracy tend to be understood as incompatible systems of work organization, represented by the ideals of collegiality and auton-omy versus control and supervision. I present a historical case study from early 20th century Norway examining the potential clash between efforts made toward professionalization and bureaucratization in industry. Based on my findings, I argue that there is neither an inherent conflict between professionalism and bureaucracy nor static national trajectories at the level of professional versus bureaucratic work organization.

  1. Autonomy and Acceptance of Long-Term Care

    Science.gov (United States)

    Hsu, Hui-Chuan; Ting, Yu-Shan; Jiang, Ting-Wen; Chien, Ming-Chih; Chien, Chih-Hsin

    2009-01-01

    This study explored the relationship between four types of autonomy (health autonomy, informational autonomy, living autonomy, and financial autonomy) and the acceptance of five types of long-term care (adult day care, respite care, assisted living, unit care, and group home) for the elderly in Taiwan. Data were collected from 167 middle-aged and…

  2. Motivating Proteges' Personal Learning in Teams: A Multilevel Investigation of Autonomy Support and Autonomy Orientation

    Science.gov (United States)

    Liu, Dong; Fu, Ping-ping

    2011-01-01

    This study examined the roles of 3 multilevel motivational predictors in proteges' personal learning in teams: an autonomy-supportive team climate, mentors' autonomy support, and proteges' autonomy orientation. The authors followed 305 proteges in 58 teams for 12 weeks and found that all 3 predictors were positively related to the proteges'…

  3. Individual autonomy in work teams : the role of team autonomy, self-efficacy, and social support

    NARCIS (Netherlands)

    Mierlo, van H.; Rutte, C.G.; Vermunt, J.K.; Kompier, M.A.J.; Doorewaard, J.A.C.M.

    2006-01-01

    Task autonomy is long recognized as a means to improve functioning of individuals and teams. Taking a multilevel approach, we unravelled the constructs of team and individual autonomy and studied the interplay between team autonomy, self-efficacy, and social support in determining individual

  4. University Reform and Institutional Autonomy: A Framework for Analysing the Living Autonomy

    Science.gov (United States)

    Maassen, Peter; Gornitzka, Åse; Fumasoli, Tatiana

    2017-01-01

    In this article we discuss recent university reforms aimed at enhancing university autonomy, highlighting various tensions in the underlying reform ideologies. We examine how the traditional interpretation of university autonomy has been expanded in the reform rationales. An analytical framework for studying how autonomy is interpreted and used…

  5. Transcription of hepatitis B virus covalently closed circular DNA is regulated by CpG methylation during chronic infection.

    Directory of Open Access Journals (Sweden)

    Yongmei Zhang

    Full Text Available The persistence of hepatitis B virus (HBV infection is maintained by the nuclear viral covalently closed circular DNA (cccDNA, which serves as transcription template for viral mRNAs. Previous studies suggested that cccDNA contains methylation-prone CpG islands, and that the minichromosome structure of cccDNA is epigenetically regulated by DNA methylation. However, the regulatory effect of each CpG island methylation on cccDNA activity remains elusive. In the present study, we analyzed the distribution of CpG methylation within cccDNA in patient samples and investigated the impact of CpG island methylation on cccDNA-driven virus replication. Our study revealed the following observations: 1 Bisulfite sequencing of cccDNA from chronic hepatitis B patients indicated that CpG island I was seldom methylated, 2 CpG island II methylation was correlated to the low level of serum HBV DNA in patients, and in vitro methylation studies confirmed that CpG island II methylation markedly reduced cccDNA transcription and subsequent viral core DNA replication, 3 CpG island III methylation was associated with low serum HBsAg titers, and 4 Furthermore, we found that HBV genotype, HBeAg positivity, and patient age and liver fibrosis stage were also relevant to cccDNA CpG methylation status. Therefore, we clearly demonstrated that the status of cccDNA methylation is connected to the biological behavior of HBV. Taken together, our study provides a complete profile of CpG island methylation within HBV cccDNA and new insights for the function of CpG methylation in regulating HBV cccDNA transcription.

  6. Synergy of anti-CD40, CpG and MPL in activation of mouse macrophages.

    Science.gov (United States)

    Shi, Yongyu; Felder, Mildred A R; Sondel, Paul M; Rakhmilevich, Alexander L

    2015-08-01

    Activation of macrophages is a prerequisite for their antitumor effects. Several reagents, including agonistic anti-CD40 monoclonal antibody (anti-CD40), CpG oligodeoxynucleotides (CpG) and monophosphoryl lipid A (MPL), can stimulate activation of macrophages. Our previous studies showed synergy between anti-CD40 and CpG and between anti-CD40 and MPL in macrophage activation and antitumor efficacy in mice. In the present study, we asked whether there was synergy among these three reagents. The activation of adherent peritoneal exudate cells (PEC) obtained from mice injected with anti-CD40 and then treated with CpG and/or MPL in vitro was determined by their ability to suppress proliferation of tumor cells and to produce various cytokines and chemokines in vitro. Cell sorting and histology followed by functional testing showed that macrophages were the main cell population in PEC activated by CD40 ligation in vivo. A combination of anti-CD40, CpG or MPL activated PEC to suppress proliferation of B16 cells and produce nitric oxide far greater than the single reagents or any of the double combinations of these reagents. In addition, the combination of all three reagents activated PEC to secrete IL-12, IFN-γ and MCP-1 to a greater degree than any single reagent or any two combined reagents. These results demonstrate that macrophages can be synergistically activated by anti-CD40, CpG and MPL, suggesting that this novel combined approach might be further investigated as potential cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Synergy of anti-CD40, CpG and MPL in activation of mouse macrophages

    Science.gov (United States)

    Shi, Yongyu; Felder, Mildred A.R.; Sondel, Paul M.; Rakhmilevich, Alexander L.

    2015-01-01

    Activation of macrophages is a prerequisite for their antitumor effects. Several reagents, including agonistic anti-CD40 monoclonal antibody (anti-CD40), CpG oligodeoxynucleotides (CpG) and monophosphoryl lipid A (MPL), can stimulate activation of macrophages. Our previous studies showed synergy between anti-CD40 and CpG and between anti-CD40 and MPL in macrophage activation and antitumor efficacy in mice. In the present study, we asked whether there was synergy among these three reagents. The activation of adherent peritoneal exudate cells (PEC) obtained from mice injected with anti-CD40 and then treated with CpG and/or MPL in vitro was determined by their ability to suppress proliferation of tumor cells and to produce various cytokines and chemokines in vitro. Cell sorting and histology followed by functional testing showed that macrophages were the main cell population in PEC activated by CD40 ligation in vivo. A combination of anti-CD40, CpG or MPL activated PEC to suppress proliferation of B16 cells and produce nitric oxide far greater than the single reagents or any of the double combinations of these reagents. In addition, the combination of all three reagents activated PEC to secrete IL-12, IFN-γ and MCP-1 to a greater degree than any single reagent or any two combined reagents. These results demonstrate that macrophages can be synergistically activated by anti-CD40, CpG and MPL, suggesting that this novel combined approach might be further investigated as potential cancer therapy. PMID:25829245

  8. Agency is Distinct from Autonomy

    Directory of Open Access Journals (Sweden)

    Fred Cummins

    2014-11-01

    Full Text Available Both autonomy and agency play central roles in the emerging enactive vocabulary. Although some treat these concepts as practically synonymous, others have sought to be more explicit about the conditions required for agency over and above autonomy. I attempt to be self-conscious about the role of the observer (or scientist in such discussions, and emphasise that the concept of agency, in particular, is deeply entwined with the nature of the observer and the framing of the observation. This is probably well known to enactivists, but runs the risk of being badly misunderstood if it is not made explicit. A heightened awareness of the role of the observer in the attribution of agency may allow us to make advances in questions in which progress is hindered by assuming a single split between subject and object. I argue that human experience is characterized by our embedding in webs of meaning arising from our participation in systems of many sorts, and that this richness demands a corresponding lightness of touch with respect to the identification of agentive subjects.

  9. Autopoiesis: Autology, Autotranscendence and Autonomy

    DEFF Research Database (Denmark)

    and 1990s – particularly in a French context. While his work has remained (to date) at distance from the rising number of suggestions, especi- ally regarding social and cultural theory, that have come out of these debates on self-organization, Castoriadis made a speci¿c and original contribution to them...... ‘reality-modeling’ (John Casti) – whether via cognitive frameworks or models of society and culture. Secondly, attempts to adapt debates within the humanities, e.g. in philosophy, social theory and cultural studies, have tended to end in anti-humanism, ranging from Deleuze and Guattari’s ‘abstract machine......’s philosophy. She argues that a focus on the self-organization of the living being implies not only a distinct move towards an ontology of radical physis in Castoriadis’s later work, but also, along with it, a revised version of his project of autonomy. Autonomy, like autology and the other theme of this issue...

  10. Protective immunity against Megalocytivirus infection in rock bream (Oplegnathus fasciatus) following CpG ODN administration.

    Science.gov (United States)

    Jung, Myung-Hwa; Lee, Jehee; Ortega-Villaizan, M; Perez, Luis; Jung, Sung-Ju

    2017-06-27

    Rock bream iridovirus (RBIV) disease in rock bream (Oplegnathus fasciatus) remains an unsolved problem in Korea aquaculture farms. CpG ODNs are known as immunostimulant, can improve the innate immune system of fish providing resistance to diseases. In this study, we evaluated the potential of CpG ODNs to induce anti-viral status protecting rock bream from different RBIV infection conditions. We found that, when administered into rock bream, CpG ODN 1668 induces better antiviral immune responses compared to other 5 CpG ODNs (2216, 1826, 2133, 2395 and 1720). All CpG ODN 1668 administered fish (1/5µg) at 2days before infection (1.1×10 7 ) held at 26°C died even though mortality was delayed from 8days (1µg) and 4days (5µg). Similarly, CpG ODN 1668 administered (5µg) at 2days before infection (1.2×10 6 ) held at 23/20°C had 100% mortality; the mortality was delayed from 9days (23°C) and 11days (20°C). Moreover, when CpG ODN 1668 administered (1/5/10µg) at 2/4/7days before infection or virus concentration was decreased to 1.1×10 4 and held at 20°C had mortality rates of 20/60/30% (2days), 30/40/60% (4days) and 60/60/20% (7days), respectively, for the respective administration dose, through 100 dpi. To investigate the development of a protective immune response, survivors were re-infected with RBIV (1.1×10 7 ) at 100 and 400 dpi, respectively. While 100% of the previously unexposed fish died, 100% of the previously infected fish survived. The high survival rate of fish following re-challenge with RBIV indicates that protective immunity was established in the surviving rock bream. Our results showed the possibility of developing preventive measures against RBIV using CpG ODN 1668 by reducing RBIV replication speed (i.e. water temperature of 20°C and infection dose of 1.1×10 4 ). Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.

    Science.gov (United States)

    Weisenberger, Daniel J; Levine, A Joan; Long, Tiffany I; Buchanan, Daniel D; Walters, Rhiannon; Clendenning, Mark; Rosty, Christophe; Joshi, Amit D; Stern, Mariana C; LeMarchand, Loic; Lindor, Noralane M; Daftary, Darshana; Gallinger, Steven; Selander, Teresa; Bapat, Bharati; Newcomb, Polly A; Campbell, Peter T; Casey, Graham; Ahnen, Dennis J; Baron, John A; Haile, Robert W; Hopper, John L; Young, Joanne P; Laird, Peter W; Siegmund, Kimberly D

    2015-03-01

    The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known. We measured the CIMP status of 3,119 primary population-based colorectal cancer tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case-case study comparing risk factor frequency of colorectal cancer cases with CIMP and non-CIMP tumors using logistic regression to estimate the case-case odds ratio (ccOR). We found associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P CIMP status for both males and females (P = 0.0001 and P = 0.02, respectively), use of multivitamin or calcium supplements did not. Only for female colorectal cancer was CIMP status associated with increased pack-years of smoking (Ptrend CIMP status, and the associations of smoking and obesity with tumor subtype were evident only for females. Differences in the associations of a unique DNA methylation-based subgroup of colorectal cancer with important lifestyle and environmental exposures increase understanding of the molecular pathologic epidemiology of this heavily methylated subset of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 512-9. ©2015 AACR. ©2015 American Association for Cancer Research.

  12. Netherlands: Steady decline in job autonomy

    NARCIS (Netherlands)

    Muller, J.; Hooftmann, W.; Houtman, I.L.D.

    2015-01-01

    Research shows that job autonomy has predominantly positive effects, such as the prevention of stress, burnout and cardiovascular disease. Employees with a good deal of autonomy generally report better well-being, are more productive, more creative, have more self-esteem and have higher work

  13. Epistemic Autonomy: A Criterion for Virtue?

    Science.gov (United States)

    Mudd, Sasha

    2013-01-01

    Catherine Elgin proposes a novel principle for identifying epistemic virtue. Based loosely on Kant's Categorical Imperative, it identifies autonomy as our fundamental epistemic responsibility, and defines the epistemic virtues as those traits of character needed to exercise epistemic autonomy. I argue that Elgin's principle fails as a…

  14. Scaffolding Learner Autonomy in Online University Courses

    Science.gov (United States)

    Ribbe, Elisa; Bezanilla, María José

    2013-01-01

    This paper deals with the question in what ways teachers and course designers can support the development and exertion of learner autonomy among online university students. It advocates that a greater attention to learner autonomy could help more students to complete their course successfully and thus contribute the decrease of the high dropout…

  15. Becoming Autonomous: Nonideal Theory and Educational Autonomy

    Science.gov (United States)

    Wilson, Terri S.; Ryg, Matthew A.

    2015-01-01

    Autonomy operates as a key term in debates about the rights of families to choose distinct approaches to education. Yet, what autonomy means is often complicated by the actual circumstances and contexts of schools, families, and children. In this essay, Terri S. Wilson and Matthew A. Ryg focus on the challenges involved in translating an ideal of…

  16. On the Compatibility of Autonomy and Relatedness.

    Science.gov (United States)

    Hodgins, Holley S.; And Others

    1996-01-01

    Investigates the relation of autonomy to naturally occurring social interactions in two studies: the first investigated college students' interactions with parents, and the second examined interactions across all relationships. Autonomy was significantly related to more positive and naturally occurring interaction, whereas control related more to…

  17. Stories of Human Autonomy, Law, and Technology

    Science.gov (United States)

    Tranter, Kieran

    2010-01-01

    Considering the relationship between human autonomy, law and technology has deep origins. Both technology studies and legal theory tell origin stories about human autonomy as the prize from either a foundational technological or jurisprudential event. In these narratives either law is considered a second order consequence of technology or…

  18. Changing Light Bulbs: Practice, Motivation, and Autonomy

    Science.gov (United States)

    Carter, Jean A.

    2011-01-01

    The comment on the Ryan, Lynch, Vansteenkiste, and Deci (2011) article on motivation and autonomy in psychotherapy considers motivation and its role as prerequisite, process variable, or appropriate outcome, speculating that all are appropriate ways to conceptualize motivation in the behavior change process. Autonomy, as a useful addition, refers…

  19. Progress in medicine: autonomy, oughtonomy and nudging.

    Science.gov (United States)

    Devisch, Ignaas

    2011-10-01

    In this article, I argue that we need a new perspective in the debate on autonomy in medicine, to understand many of the problems we face today - dilemmas that are situated at the intersection of autonomy and heteronomy, such as why well informed and autonomous people make unhealthy lifestyle choices. If people do not choose what they want, this is not simply caused by their lack of character or capability, but also by the fact that absolute autonomy is impossible; autonomous individuals are 'contaminated' by heteronymous aspects, by influences from 'outside'. Consequently, there are many good reasons to question the widely accepted hierarchical opposition of autonomy (progress) versus heteronomy (paternalism) in medicine. In an earlier article an analysis is made of the neologism 'oughtonomy' to support the thesis that when it comes down to human existence, autonomy and heteronomy are intertwined, rather than being merely opposites. In this article, I reflect upon how social conditions might improve our 'choice architecture', what Thaler & Sunstein have called 'nudging': how to change individual health choices without being paternalistic? I explore the extent to which both oughtonomy and nudging are able to challenge the question of autonomy in today's medicine. Autonomy may and should be a shared target in today's medicine, but we should never forget that it is always intertwined with heteronomy. Starting from this perspective, progress in medicine demands far more than the increase of autonomy. © 2011 Blackwell Publishing Ltd.

  20. Buddhism and Autonomy-Facilitating Education

    Science.gov (United States)

    Morgan, Jeffrey

    2013-01-01

    This article argues that Buddhists can consistently support autonomy as an educational ideal. The article defines autonomy as a matter of thinking and acting according to principles that one has oneself endorsed, showing the relationship between this ideal and the possession of an enduring self. Three central Buddhist doctrines of conditioned…

  1. Protecting autonomy as authenticity using Ulysses contracts.

    Science.gov (United States)

    van Willigenburg, Theo; Delaere, Patrick

    2005-08-01

    Pre-commitment directives or Ulysses contracts are often defended as instruments that may strengthen the autonomous self-control of episodically disordered psychiatric patients. Autonomy is understood in this context in terms of sovereignty ("governing" or "managing" oneself). After critically analyzing this idea of autonomy in the context of various forms of self-commitment and pre-commitment, we argue that what is at stake in using Ulysses contracts in psychiatry is not autonomy as sovereignty, but autonomy as authenticity. Pre-commitment directives do not function to protect autonomous self-control. They serve in upholding the guidance that is provided by one's deepest identity conferring concerns. We elucidate this concept of autonomy as authenticity, by showing how Ulysses contracts protect the possibility of being "a self."

  2. Autonomy and independence in language learning

    CERN Document Server

    Benson, Phil

    2014-01-01

    The topics of autonomy and independence play an increasingly important role in language education. They raise issues such as learners' responsibility for their own learning, and their right to determine the direction of their own learning, the skills which can be learned and applied in self-directed learning and capacity for independent learning and the extents to which this can be suppressed by institutional education. This volume offers new insights into the principles of autonomy and independence and the practices associated with them focusing on the area of EFL teaching. The editors' introduction provides the context and outlines the main issues involved in autonomy and independence. Later chapters discuss the social and political implications of autonomy and independence and their effects on educational structures. The consequences for the design of learner-centred materials and methods is discussed, together with an exploration of the practical ways of implementing autonomy and independence in language ...

  3. Indications for treatment of thyroid autonomy

    International Nuclear Information System (INIS)

    Emrich, D.

    1989-01-01

    Based on pathophysiological findings and considerations it is attempted to review critically the present state of indications and therapeutic modalities in cases of thyroid autonomy. If hyperthyroidism occurs or has occurred in autonomy, definitive treatment with radioiodine or surgery is indicated. In cases of autonomy with euthyroidism, treatment planning and indication of definite therapy are difficult still today, because the risk to develop hyperthyroidism cannot as yet be sufficiently estimated. A useful indicator in such cases seems to be the percentage of global thyreoidal uptake of 99m-technetium under supression. If autonomy is severe surgical treatment today is superior to radio-iodine therapy, but is associated with a higher rate of manifest hypothyroidism. Further research into both the risk of hyperthyroidism in thyroid autonomy and the optimization of radio-iodine therapy are needed. (orig./MG) [de

  4. Integrated System Health Management (ISHM) and Autonomy

    Science.gov (United States)

    Figueroa, Fernando; Walker, Mark G.

    2018-01-01

    Systems capabilities on ISHM (Integrated System Health Management) and autonomy have traditionally been addressed separately. This means that ISHM functions, such as anomaly detection, diagnostics, prognostics, and comprehensive system awareness have not been considered traditionally in the context of autonomy functions such as planning, scheduling, and mission execution. One key reason is that although they address systems capabilities, both ISHM and autonomy have traditionally individually been approached as independent strategies and models for analysis. Additionally, to some degree, a unified paradigm for ISHM and autonomy has been difficult to implement due to limitations of hardware and software. This paper explores a unified treatment of ISHM and autonomy in the context of distributed hierarchical autonomous operations.

  5. The Autonomy Activity Status of Multinational Subsidiaries

    DEFF Research Database (Denmark)

    Dzikowska, Marlena; Gammelgaard, Jens; Jindra, Björn

    Research concerning the autonomy of subsidiaries has been concentrated on the possession of decision-making rights. Building on the definitional and empirical argumentation, we claim that so understood autonomy has a prospective character, is not equal to the implementation of actual actions (or...... lack of thereof) and neglects the issue of the scope of potential actions. This paper aims to fill in the current literature gap by offering a holistic stance in which we assert that subsidiaries can be meaningfully differentiated according to their levels of autonomy and corresponding actions. We base...... this argumentation on the findings of real option theory and competitive dynamics perspective, develop a typology specific to a subsidiary’s autonomy activity status (the position of a subsidiary in terms of its autonomy level confronted with the extent of actions taken in a corresponding area). We evaluate...

  6. Freedom of Expression, Deliberation, Autonomy, and Respect

    DEFF Research Database (Denmark)

    Rostbøll, Christian Fogh

    for freedom of expression in terms of its relationship to different dimensions of autonomy. In response to the objection that Enlightenment theories pose a threat to cultures that reject autonomy, it is argued that autonomy-based democracy is not only compatible with but necessary for respect for cultural......The strongest versions of the democracy argument for freedom of expression rely on the deliberative conception of democracy. Deliberative democracy entails both an ideal of political autonomy and of autonomous preference formation. This paper elaborates the deliberative democracy argument...... diversity. On the basis of an intersubjective epistemology, I argue that citizens cannot know how to live on mutually respectful terms without engaging in public deliberation. Moreover, to be successful deliberation must foster some degree of personal autonomy, at least the ability to distinguish what...

  7. Freedom of Expression, Deliberation, Autonomy and Respect

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    2011-01-01

    This paper elaborates on the deliberative democracy argument for freedom of expression in terms of its relationship to different dimensions of autonomy. It engages the objection that Enlightenment theories pose a threat to cultures that reject autonomy and argues that autonomy-based democracy...... is not only compatible with but necessary for respect for cultural diversity. On the basis of an intersubjective epistemology, it argues that people cannot know how to live on mutually respectful terms without engaging in public deliberation and develop some degree of personal autonomy. While freedom...... of expression is indispensable for deliberation and autonomy, this does not mean that people have no obligations regarding how they speak to each other. The moral insights provided by deliberation depend on the participants in the process treating one another with respect. The argument is related to the Danish...

  8. [Is autonomy ground of human dignity?].

    Science.gov (United States)

    Gordillo Alvarez-Valdés, Lourdes

    2008-01-01

    This paper considers the conditions of autonomy if this is to be the foundation of human dignity. Since Kant Modernity has dissociated nature from morality and has tried to support autonomy in its purely formal aspect. To forget nature has voluntarist consequences that affect the way in which autonomy is understand. But autonomy does not consist of not having links, but of knowing how to assume one's own links freely and to be conscious of one's own limits. Autonomy and liberty are the very thing of the rational being, capable of discerning good and bad, and this must direct our actions. Reason directs as and distances us from reality to recognize the advisable thing in the human being.

  9. Effective means of planning for and implementing autonomy

    DEFF Research Database (Denmark)

    Rehof, Lars Adam

    1991-01-01

    Autonomy, self-government, indigenous people, human rights, minority protection, minority rights......Autonomy, self-government, indigenous people, human rights, minority protection, minority rights...

  10. Are the benefits of autonomy satisfaction and the costs of autonomy frustration dependent on individuals' autonomy strength?

    Science.gov (United States)

    Van Assche, Jasper; van der Kaap-Deeder, Jolene; Audenaert, Elien; De Schryver, Maarten; Vansteenkiste, Maarten

    2018-01-29

    From a self-determination theory perspective, individuals are assumed to benefit and suffer from, respectively, the satisfaction and frustration of the psychological need for autonomy, even if they score low on autonomy strength. Yet, previous studies on need strength are scarce, operationalized need strength differently, and produced inconsistent findings. In two studies among 224 South African adults (M age  = 24.13, SD = 4.25; 54.0% male) and 156 Belgian prisoners (M age  = 38.60, SD = 11.68; 88.5% male), we investigated the moderating role of autonomy valuation and desire in the relations of autonomy satisfaction and frustration with a variety of well-being and ill-being indicators. Study 1 provided some evidence for the moderating role of mostly explicit autonomy desire (rather than explicit autonomy valuation). In Study 2, neither explicit nor implicit autonomy desire played a consistent moderating role. Overall, these findings are congruent with a moderate (albeit not with a strong) interpretation of the universality claim made within self-determination theory, provide initial evidence for a differentiation between deficit-based and growth-oriented interpersonal differences in need strength, and indicate that the potential moderating role of need strength deserves continued attention before any firm conclusions can be drawn. © 2018 Wiley Periodicals, Inc.

  11. Mission Level Autonomy for USSV

    Science.gov (United States)

    Huntsberger, Terry; Stirb, Robert C.; Brizzolara, Robert

    2011-01-01

    On-water demonstration of a wide range of mission-proven, advanced technologies at TRL 5+ that provide a total integrated, modular approach to effectively address the majority of the key needs for full mission-level autonomous, cross-platform control of USV s. Wide baseline stereo system mounted on the ONR USSV was shown to be an effective sensing modality for tracking of dynamic contacts as a first step to automated retrieval operations. CASPER onboard planner/replanner successfully demonstrated realtime, on-water resource-based analysis for mission-level goal achievement and on-the-fly opportunistic replanning. Full mixed mode autonomy was demonstrated on-water with a seamless transition between operator over-ride and return to current mission plan. Autonomous cooperative operations for fixed asset protection and High Value Unit escort using 2 USVs (AMN1 & 14m RHIB) were demonstrated during Trident Warrior 2010 in JUN 2010

  12. University Institutional Autonomy in Moldova

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Bugaian, Larisa

    This book introduces four evaluation studies in which the current status of university institutional autonomy in Moldova is evaluated. For the purpose of these evaluation studies, a research methodology was developed by the EUniAM project team and used by the Task Force teams to collect and analy...... in Moldova. Preliminary findings of the evaluation studies were presented at the International Conference on “A Quest to (Re)define University Autonomy” organized by the EUniAM project. At the same time, these findings had an impact on the context of the new Code of Education....... the data. Unobtrusive data in the form of laws regulating directly or indirectly the higher education system in Moldova, governmental and ministerial decrees, university chapters and organizational structures, and education records were collected and analysed. A total number of 144 documents have been...

  13. High CpG island methylation ofp16 gene and loss of p16 protein ...

    Indian Academy of Sciences (India)

    Navya

    employed to detect CpG island methylation in p16 promoter region and ... of Fallot;p16 gene;p16 protein;CpG islands;Methylation;Promoter regions ..... Our findings that p16 has a role in heart development is ... Asian Pac J Cancer Prev 15, 75-84. .... phenotype in colorectal cancer using a large population-based sample.

  14. High CpG island methylation of p16 gene and loss of p16 protein ...

    Indian Academy of Sciences (India)

    SI-JU GAO

    The study subjects consisted of 75 healthy controls and 63 ToF ... Additionally, our analysis suggested that CpG island methylation in p16 promoters in ToF ..... reduced p16 protein expression in lung cancer (Kondo et al. 2006). In this context ..... promoter methylation in gastric carcinogenesis: a meta-analysis. Mol. Biol. Rep.

  15. AtMBD6, a methyl CpG binding domain protein, maintains gene ...

    Indian Academy of Sciences (India)

    DNA methylation, mediated by double-stranded RNA, is a conserved epigenetic phenomenon that protects a genome fromtransposons, silences unwanted genes and has a paramount function in plant or animal development. Methyl CpG bindingdomain proteins are members of a class of proteins that bind tomethylated ...

  16. Compositional searching of CpG islands in the human genome

    Science.gov (United States)

    Luque-Escamilla, Pedro Luis; Martínez-Aroza, José; Oliver, José L.; Gómez-Lopera, Juan Francisco; Román-Roldán, Ramón

    2005-06-01

    We report on an entropic edge detector based on the local calculation of the Jensen-Shannon divergence with application to the search for CpG islands. CpG islands are pieces of the genome related to gene expression and cell differentiation, and thus to cancer formation. Searching for these CpG islands is a major task in genetics and bioinformatics. Some algorithms have been proposed in the literature, based on moving statistics in a sliding window, but its size may greatly influence the results. The local use of Jensen-Shannon divergence is a completely different strategy: the nucleotide composition inside the islands is different from that in their environment, so a statistical distance—the Jensen-Shannon divergence—between the composition of two adjacent windows may be used as a measure of their dissimilarity. Sliding this double window over the entire sequence allows us to segment it compositionally. The fusion of those segments into greater ones that satisfy certain identification criteria must be achieved in order to obtain the definitive results. We find that the local use of Jensen-Shannon divergence is very suitable in processing DNA sequences for searching for compositionally different structures such as CpG islands, as compared to other algorithms in literature.

  17. 78 FR 28904 - CPG Carlyle Private Equity Fund, LLC, et al.; Notice of Application

    Science.gov (United States)

    2013-05-16

    ... as Delaware limited liability companies. The Feeder Fund operates as a feeder fund in a master-feeder..., and mezzanine). 2. The Adviser, a Delaware limited liability company and wholly- owned subsidiary of... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30512; 812-14089] CPG...

  18. AtMBD6, a methyl CpG binding domain protein, maintains gene ...

    Indian Academy of Sciences (India)

    2017-01-13

    Jan 13, 2017 ... 13 methyl CpG binding domain (MBD) proteins, but the molecular/biological functions of most of these ... AtMBD5, AtMBD6 and AtMBD7 are more similar to those .... prey were able to grow on -AHLW (-Ade, -His, -Leu, -Trp).

  19. Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

    DEFF Research Database (Denmark)

    Riising, Eva Madi; Vacher-Comet, Itys; Leblanc, Benjamin Olivier

    2014-01-01

    -wide ectopic PRC2 recruitment to endogenous PcG target genes found in other tissues. PRC2 binding analysis shows that it is restricted to nucleosome-free CpG islands (CGIs) of untranscribed genes. Our results show that it is the transcriptional state that governs PRC2 binding, and we propose that it binds...

  20. High CpG island methylation of p16 gene and loss of p16 protein

    Indian Academy of Sciences (India)

    Methylation-specific polymerase chain reaction (MSP) was employed to detect CpG island methylation in p16 promoter region andWestern blotting was used to detect p16 expression of all subjects. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was performed to test p16 mRNA expression.

  1. 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

  2. Shared decision-making and patient autonomy.

    Science.gov (United States)

    Sandman, Lars; Munthe, Christian

    2009-01-01

    In patient-centred care, shared decision-making is advocated as the preferred form of medical decision-making. Shared decision-making is supported with reference to patient autonomy without abandoning the patient or giving up the possibility of influencing how the patient is benefited. It is, however, not transparent how shared decision-making is related to autonomy and, in effect, what support autonomy can give shared decision-making. In the article, different forms of shared decision-making are analysed in relation to five different aspects of autonomy: (1) self-realisation; (2) preference satisfaction; (3) self-direction; (4) binary autonomy of the person; (5) gradual autonomy of the person. It is argued that both individually and jointly these aspects will support the models called shared rational deliberative patient choice and joint decision as the preferred versions from an autonomy perspective. Acknowledging that both of these models may fail, the professionally driven best interest compromise model is held out as a satisfactory second-best choice.

  3. [Adult learning, professional autonomy and individual commitment].

    Science.gov (United States)

    Pardell-Alentá, H

    The concept of 'andragogy' is the basis of the adult education which is different from pedagogy in several aspects, particularly in the autonomy of the adult learner in choosing the educational programmes and the methodologies and sites in where learning occurs. This happens very often in the worksite. The professionals have to learn permanently during their active lives in order to maintain their competence updated. In this sense, continuing education correlates with continuing professional development, which is an attempt to enlarge the traditional domains of continuing education. Continuing education must be clearly differentiated from formal education, which is a requirement for granting professional degrees or titles. Very often it arises from the changing health needs and for this reason is necessary to avoid the institutionalization of continuing education programmes. Professional associations should be actively involved in providing and accrediting continuing education-continuing professional development programmes, because this involvement is an essential component of the professionals' self-regulation in the context of the current medical professionalism ideology.

  4. CpG methylation differences between neurons and glia are highly conserved from mouse to human.

    Science.gov (United States)

    Kessler, Noah J; Van Baak, Timothy E; Baker, Maria S; Laritsky, Eleonora; Coarfa, Cristian; Waterland, Robert A

    2016-01-15

    Understanding epigenetic differences that distinguish neurons and glia is of fundamental importance to the nascent field of neuroepigenetics. A recent study used genome-wide bisulfite sequencing to survey differences in DNA methylation between these two cell types, in both humans and mice. That study minimized the importance of cell type-specific differences in CpG methylation, claiming these are restricted to localized genomic regions, and instead emphasized that widespread and highly conserved differences in non-CpG methylation distinguish neurons and glia. We reanalyzed the data from that study and came to markedly different conclusions. In particular, we found widespread cell type-specific differences in CpG methylation, with a genome-wide tendency for neuronal CpG-hypermethylation punctuated by regions of glia-specific hypermethylation. Alarmingly, our analysis indicated that the majority of genes identified by the primary study as exhibiting cell type-specific CpG methylation differences were misclassified. To verify the accuracy of our analysis, we isolated neuronal and glial DNA from mouse cortex and performed quantitative bisulfite pyrosequencing at nine loci. The pyrosequencing results corroborated our analysis, without exception. Most interestingly, we found that gene-associated neuron vs. glia CpG methylation differences are highly conserved across human and mouse, and are very likely to be functional. In addition to underscoring the importance of independent verification to confirm the conclusions of genome-wide epigenetic analyses, our data indicate that CpG methylation plays a major role in neuroepigenetics, and that the mouse is likely an excellent model in which to study the role of DNA methylation in human neurodevelopment and disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Accurate CpG and non-CpG cytosine methylation analysis by high-throughput locus-specific pyrosequencing in plants.

    Science.gov (United States)

    How-Kit, Alexandre; Daunay, Antoine; Mazaleyrat, Nicolas; Busato, Florence; Daviaud, Christian; Teyssier, Emeline; Deleuze, Jean-François; Gallusci, Philippe; Tost, Jörg

    2015-07-01

    Pyrosequencing permits accurate quantification of DNA methylation of specific regions where the proportions of the C/T polymorphism induced by sodium bisulfite treatment of DNA reflects the DNA methylation level. The commercially available high-throughput locus-specific pyrosequencing instruments allow for the simultaneous analysis of 96 samples, but restrict the DNA methylation analysis to CpG dinucleotide sites, which can be limiting in many biological systems. In contrast to mammals where DNA methylation occurs nearly exclusively on CpG dinucleotides, plants genomes harbor DNA methylation also in other sequence contexts including CHG and CHH motives, which cannot be evaluated by these pyrosequencing instruments due to software limitations. Here, we present a complete pipeline for accurate CpG and non-CpG cytosine methylation analysis at single base-resolution using high-throughput locus-specific pyrosequencing. The devised approach includes the design and validation of PCR amplification on bisulfite-treated DNA and pyrosequencing assays as well as the quantification of the methylation level at every cytosine from the raw peak intensities of the Pyrograms by two newly developed Visual Basic Applications. Our method presents accurate and reproducible results as exemplified by the cytosine methylation analysis of the promoter regions of two Tomato genes (NOR and CNR) encoding transcription regulators of fruit ripening during different stages of fruit development. Our results confirmed a significant and temporally coordinated loss of DNA methylation on specific cytosines during the early stages of fruit development in both promoters as previously shown by WGBS. The manuscript describes thus the first high-throughput locus-specific DNA methylation analysis in plants using pyrosequencing.

  6. Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

    Science.gov (United States)

    Khan, Faraz A; Squires, Robert H; Litman, Heather J; Balint, Jane; Carter, Beth A; Fisher, Jeremy G; Horslen, Simon P; Jaksic, Tom; Kocoshis, Samuel; Martinez, J Andres; Mercer, David; Rhee, Susan; Rudolph, Jeffrey A; Soden, Jason; Sudan, Debra; Superina, Riccardo A; Teitelbaum, Daniel H; Venick, Robert; Wales, Paul W; Duggan, Christopher

    2015-07-01

    In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Oppression, Autonomy and the Impossibility of the Inner Citadel

    Science.gov (United States)

    Nelsen, Peter

    2010-01-01

    This paper argues for a conception of autonomy that takes social oppression seriously without sapping autonomy of its valuable focus on individual self-direction. Building on recent work in relational accounts of autonomy, the paper argues that current conceptions of autonomy from liberal, feminist and critical theorists do not adequately account…

  8. Heteronomous Citizenship: Civic Virtue and the Chains of Autonomy

    Science.gov (United States)

    Swaine, Lucas

    2010-01-01

    In this article, I distinguish personal autonomy from heteronomy, and consider whether autonomy provides a suitable basis for liberalism. I argue that liberal government should not promote autonomy in all its citizens, on the grounds that not all members of liberal democracies require autonomy for a good life. I then outline an alternative option…

  9. Hypermutability of CpG dinucleotides in the propeptide-encoding sequence of the human albumin gene

    International Nuclear Information System (INIS)

    Brennan, S.O.; Peach, R.; Myles, T.; George, P.; Arai, Kunio; Madison, J.; Watkins, S.; Putnam, F.W.; Laurell, C.B.; Galliano, M.

    1990-01-01

    An electrophoretically slow albumin variant was detected with a phenotype frequency of about 1:1,000 in Sweden and was also found in a family of Scottish descent from Kaikoura, New Zealand, and in five families in Tradate, Italy. Structural study established that the major variant component was arginyl-albumin, in which arginine at the -1 position of the propeptide is still attached to the processed albumin. A minor component with the amino-terminal sequence of proalbumin was also present as 3-6% of the total albumin. After amplification of the gene segment encoding the prepro sequence of albumin, specific hybridization of DNA to an oligonucleotide probe encoding cysteine at position -2 indicated the mutation of arginine at the -2 position to cysteine (-2 Arg → Cys). This produced the propeptide sequence Arg-Gly-Val-Phe-Cys-Arg. This was confirmed by sequence analysis after pyridylethylation of the cysteine. This mutation produces an alternate signal peptidase cleavage site in the variant proalbumin precursor of arginyl-albumin giving rise to two possible products, arginyl-albumin and the variant proalbumin. Another plasma from Bremen had an alloalbumin with a previously described substitution (1 Asp → Val), which also affects propeptide cleavage. Hypermutability of two CpG dinucleotides in the codons for the diarginyl sequence may account for the frequency of mutations in the propeptide. Mutation at these two sites results in a series of recurrent proalbumin variants that have arisen independently in diverse populations

  10. How important is Autonomy to Professional Workers?

    Directory of Open Access Journals (Sweden)

    Arne Mastekaasa

    2011-11-01

    Full Text Available A common assumption is that autonomy is crucial to professional workers. I examine this using survey data on a sample of public sector welfare professionals, viz. medical doctors, nurses, teachers, social workers. Comparisons are made with general population data from the International Social Survey Programme. Two methods of assessing the importance of work autonomy are employed; respondents’ direct ratings and statistical associations between work autonomy (and other job characteristics on the one hand and job satisfaction and organizational commitment on the other. Findings: Autonomy is not rated as more important among the professionals than in the general population, and neither is it more strongly related to job satisfaction. Interesting work and workplace social support appear to be more central.

  11. Autonomy, nudging and post-truth politics.

    Science.gov (United States)

    Keeling, Geoff

    2017-11-16

    In his excellent essay, 'Nudges in a post-truth world', Neil Levy argues that 'nudges to reason', or nudges which aim to make us more receptive to evidence, are morally permissible. A strong argument against the moral permissibility of nudging is that nudges fail to respect the autonomy of the individuals affected by them. Levy argues that nudges to reason do respect individual autonomy, such that the standard autonomy objection fails against nudges to reason. In this paper, I argue that Levy fails to show that nudges to reason respect individual autonomy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Emotional autonomy and depression among Chinese adolescents.

    Science.gov (United States)

    Chou, K L

    2000-06-01

    Depression is quite common among young people in Hong Kong Chinese society. This study examined the association between emotional autonomy and depressive symptomatology among Chinese young people in Hong Kong. The respondents were 512 young people between 16 and 18 years of age from a cross-sectional study in Hong Kong. Significant bivariate relationships were found between depressive symptomatology and three dimensions of emotional autonomy (individuation, nondependency on parents, and deidealization of parents). Using multiple regression models, the author found that depressive symptomatology was associated with two aspects of emotional autonomy: individuation and deidealization of parents. Results indicate that the relationships between depressive symptomatology and these three aspects of emotional autonomy are similar in both individualistic and collectivistic societies.

  13. [The medical autonomy of elderly in Taiwan].

    Science.gov (United States)

    Chen, Kai-Li; Chen, Ching-Huey

    2014-10-01

    The elderly population is increasing rapidly in Taiwan. With the average life expectancy on the rise, the elderly have become major consumers of healthcare products and services. Factors that influence respect for autonomy, a core value of medical ethics, may be related to family, society, and the medical culture. Especially in patients who are already elderly, aging causes declines in physical, mental and societal capacities. Practicing a respect for patient autonomy is particularly challenging for healthcare professionals in Taiwan due the unique culture background of elderly Taiwanese patients. This article reviews and integrates the literature related to the issue of patient autonomy and elaborates on medical decision-making among elderly patients in Taiwan in the contexts of: the disadvantages faced by the elderly, the background of Chinese culture, and the current medical decision-making environment. A few suggestions are proposed to help preserve the medical-decision-making autonomy of elderly patients in Taiwan.

  14. Decision-Making Autonomy and Subsidiary Innovation

    DEFF Research Database (Denmark)

    Van Vo, Dut; Beugelsdijk, Sjoerd; de Jong, Gjalt

    2013-01-01

    This paper investigates how decision-making autonomy affects the possibility and intensity of innovation in subsidiaries of multinational enterprises (MNEs). Subsidiaries are increasingly identified as sources of innovation and as vehicles for cross-border transfer of new competences. The question...... of how much decision-making autonomy subsidiaries should have is a core issue in the management of headquarters-subsidiary relationships. Using two complementary theoretical perspectives, we hypothesize a non-linear relationship between subsidiary’s decision-making autonomy and innovation. We test our...... hypothesis in a multi-country and multiindustry database based on survey evidence of 134 subsidiaries located in five Central and Eastern European countries from 23 home countries. The empirical results provide support for a non-linear U shaped relationship between subsidiary decision-making autonomy...

  15. Fiscal autonomy of urban councils in Zimbabwe

    African Journals Online (AJOL)

    LAW

    current system of decentralisation entrenches the financial autonomy of urban ..... of the UCA to deploy auditors to inspect the accounts of urban councils ..... Act; the payment of compensation; the liquidation of the principal monies owing on.

  16. Epigenetic Loss of MLH1 Expression in Normal Human Hematopoietic Stem Cell Clones is Defined by the Promoter CpG Methylation Pattern Observed by High-Throughput Methylation Specific Sequencing.

    Science.gov (United States)

    Kenyon, Jonathan; Nickel-Meester, Gabrielle; Qing, Yulan; Santos-Guasch, Gabriela; Drake, Ellen; PingfuFu; Sun, Shuying; Bai, Xiaodong; Wald, David; Arts, Eric; Gerson, Stanton L

    Normal human hematopoietic stem and progenitor cells (HPC) lose expression of MLH1 , an important mismatch repair (MMR) pathway gene, with age. Loss of MMR leads to replication dependent mutational events and microsatellite instability observed in secondary acute myelogenous leukemia and other hematologic malignancies. Epigenetic CpG methylation upstream of the MLH1 promoter is a contributing factor to acquired loss of MLH1 expression in tumors of the epithelia and proximal mucosa. Using single molecule high-throughput bisulfite sequencing we have characterized the CpG methylation landscape from -938 to -337 bp upstream of the MLH1 transcriptional start site (position +0), from 30 hematopoietic colony forming cell clones (CFC) either expressing or not expressing MLH1 . We identify a correlation between MLH1 promoter methylation and loss of MLH1 expression. Additionally, using the CpG site methylation frequencies obtained in this study we were able to generate a classification algorithm capable of sorting the expressing and non-expressing CFC. Thus, as has been previously described for many tumor cell types, we report for the first time a correlation between the loss of MLH1 expression and increased MLH1 promoter methylation in CFC derived from CD34 + selected hematopoietic stem and progenitor cells.

  17. Futility, autonomy, and informed consent.

    Science.gov (United States)

    Trau, J M

    1994-03-01

    If clinicians deem a treatment medically futile, is it appropriate to mention such a treatment to patients? Do healthcare professionals violate informed consent if they do not offer patients an opportunity to decline futile treatments? The notion of futility involves an assessment of patient best interest--both short-term and long-term therapeutic benefit for a patient and the community in which he or she intends to survive and flourish. Although survival interests may be construed as long term, a treatment that offers survival without any promise of flourishing is not the goal of medicine and is futile. Flourishing requires some cognitive and affective function. The goal of informed consent practices is to ensure that patients accept the benefits of treatment with cognizance of the burdens and risks. Given the impact of illness on the emotional and psychological states of patients and their families and their resultant vulnerability, the omission of futile options from treatment plans is logical and exemplifies the best of paternalistic behavior. The claim that requests for futile treatment must be honored is based on a perverse understanding of patient autonomy. Rational medicine demands that patients' requests be reasonable from a clinical perspective, as well as from a subjective one. The practice of informed consent can be implemented as a balance between these two interests.

  18. Protection of Balb/c mice against infection with FMDV by immunostimulation with CpG oligonucleotides

    DEFF Research Database (Denmark)

    Kamstrup, Søren; Frimann, Tine; Barfoed, Annette Malene

    2006-01-01

    disease virus (FMDV). Susceptibility of Balb/c mice to infection with isolates from the different serotypes of FMDV was investigated, and, at the same time, the capacity of CpG ODN to modulate the infection was evaluated. Treatment with CpG significantly reduced viremia, disease and death in five of six...... serotypes, when compared to no treatment or treatment with a control ODN. The effect was observed when ODN was administered simultaneously with, or up to 12 h after, infection with FMDV, and lasted for 14 days post treatment. The potential application of CpG ODN for control of FMDV during an outbreak...

  19. Job autonomy and job satisfaction: new evidence

    OpenAIRE

    Taylor, J; Bradley, S; Nguyen, A N

    2003-01-01

    This paper investigates the impact of perceived job autonomy on job satisfaction. We use the fifth sweep of the National Educational Longitudinal Study (1988-2000), which contains personally reported job satisfaction data for a sample of individuals eight years after the end of compulsory education. After controlling for a wide range of personal and job-related variables, perceived job autonomy is found to be a highly significant determinant of five separate domains of job satisfaction (pay, ...

  20. Autonomy, Competence and Non-interference

    OpenAIRE

    Roberts, Joseph T.F.

    2017-01-01

    In light of the variety of uses of the term autonomy in recent bioethics literature, in this paper, I suggest that competence, not being as contested, is better placed to play the anti-paternalistic role currently assigned to autonomy. The demonstration of competence, I will argue, can provide individuals with robust spheres of non-interference in which they can pursue their lives in accordance with their own values. This protection from paternalism is achieved by granting individuals rights ...

  1. The Changing Scope of Professional Autonomy

    DEFF Research Database (Denmark)

    Jespersen, Peter Kragh; Wrede, Sirpa

    2009-01-01

    Kapitlet undersøger hvordan lægeprofessionens autonomi ændres i relation til ledelse i sygehuse i Danmark, Norge, Sverige og Finland i tiden fra 1970 og fremefter.......Kapitlet undersøger hvordan lægeprofessionens autonomi ændres i relation til ledelse i sygehuse i Danmark, Norge, Sverige og Finland i tiden fra 1970 og fremefter....

  2. SOCIOTROPY AND AUTONOMY IN EATING DISORDERS

    OpenAIRE

    Radziwiłłowicz, Wioletta; Czarniak, Katarzyna

    2014-01-01

    Objectives: Studies of development psychopathology and psychia try have shown that personality variables are greatly associated with eating disorders. Sociotropy and autonomy may be features that facilitate the occurrence and persistence of the eating disturbances. Theoretical framework for own research was mainly the A. Beck’s concept of autonomy and sociotropy. The aim of the study was to answer the research question whether a person suffering from an eating disorder is characterized by ...

  3. Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

    International Nuclear Information System (INIS)

    Ivanova, Tatiana A; Golovina, Daria A; Zavalishina, Larisa E; Volgareva, Galina M; Katargin, Alexey N; Andreeva, Yulia Y; Frank, Georgy A; Kisseljov, Fjodor L; Kisseljova, Natalia P

    2007-01-01

    High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16 ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16 ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16 ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16 ink4a was analyzed by RT-PCR and by immunohistochemical technique. The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16 ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective

  4. CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer.

    Science.gov (United States)

    Stefansson, Olafur Andri; Hermanowicz, Stefan; van der Horst, Jasper; Hilmarsdottir, Holmfridur; Staszczak, Zuzanna; Jonasson, Jon Gunnlaugur; Tryggvadottir, Laufey; Gudjonsson, Thorkell; Sigurdsson, Stefan

    2017-07-05

    DNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E. coli AlkB homologs ALKBH2 and ALKBH3 have also been linked to direct reversal of alkylation damage. However, it is currently unknown whether ALKBH2 or ALKBH3 are found inactivated in cancer. Methylome datasets (GSE52865, GSE20713, GSE69914), available through Omnibus, were used to determine whether ALKBH2 or ALKBH3 are found inactivated by CpG promoter methylation. TCGA dataset enabled us to then assess the impact of CpG promoter methylation on mRNA expression for both ALKBH2 and ALKBH3. DNA methylation analysis for the ALKBH3 promoter region was carried out by pyrosequencing (PyroMark Q24) in 265 primary breast tumours and 30 proximal normal breast tissue samples along with 8 breast-derived cell lines. ALKBH3 mRNA and protein expression were analysed in cell lines using RT-PCR and Western blotting, respectively. DNA alkylation damage assay was carried out in cell lines based on immunofluorescence and confocal imaging. Data on clinical parameters and survival outcomes in patients were obtained and assessed in relation to ALKBH3 promoter methylation. The ALKBH3 gene, but not ALKBH2, undergoes CpG promoter methylation and transcriptional silencing in breast cancer. We developed a quantitative alkylation DNA damage assay based on immunofluorescence and confocal imaging revealing higher levels of alkylation damage in association with epigenetic inactivation of the ALKBH3 gene (P = 0.029). In our cohort of 265 primary breast cancer, we found 72 cases showing aberrantly high CpG promoter methylation over the ALKBH3 promoter (27%; 72 out of 265). We further show that increasingly higher degree of ALKBH3 promoter methylation is associated with reduced breast-cancer specific survival times in patients. In this analysis, ALKBH3 promoter methylation at >20

  5. Understanding critical care nurses' autonomy in Jordan.

    Science.gov (United States)

    Maharmeh, Mahmoud

    2017-10-02

    Purpose The aim of this study was to describe Jordanian critical care nurses' experiences of autonomy in their clinical practice. Design/methodology/approach A descriptive correlational design was applied using a self-reported cross-sectional survey. A total of 110 registered nurses who met the eligibility criteria participated in this study. The data were collected by a structured questionnaire. Findings A majority of critical care nurses were autonomous in their decision-making and participation in decisions to take action in their clinical settings. Also, they were independent to develop their own knowledge. The study identified that their autonomy in action and acquired knowledge were influenced by a number of factors such as gender and area of practice. Practical implications Nurse's autonomy could be increased if nurses are made aware of the current level of autonomy and explore new ways to increase empowerment. This could be offered through classroom lectures that concentrate on the concept of autonomy and its implication in practice. Nurses should demonstrate autonomous nursing care at the same time in the clinical practice. This could be done through collaboration between educators and clinical practice to help merge theory to practice. Originality/value Critical care nurses were more autonomous in action and knowledge base. This may negatively affect the quality of patient care and nurses' job satisfaction. Therefore, improving nurses' clinical decision-making autonomy could be done by the support of both hospital administrators and nurses themselves.

  6. Autonomy and informed consent: a mistaken association?

    Science.gov (United States)

    Kristinsson, Sigurdur

    2007-09-01

    For decades, the greater part of efforts to improve regulatory frameworks for research ethics has focused on informed consent procedures; their design, codification and regulation. Why is informed consent thought to be so important? Since the publication of the Belmont Report in 1979, the standard response has been that obtaining informed consent is a way of treating individuals as autonomous agents. Despite its political success, the philosophical validity of this Belmont view cannot be taken for granted. If the Belmont view is to be based on a conception of autonomy that generates moral justification, it will either have to be reinterpreted along Kantian lines or coupled with a something like Mill's conception of individuality. The Kantian interpretation would be a radical reinterpretation of the Belmont view, while the Millian justification is incompatible with the liberal requirement that justification for public policy should be neutral between controversial conceptions of the good. This consequence might be avoided by replacing Mill's conception of individuality with a procedural conception of autonomy, but I argue that the resulting view would in fact fail to support a non-Kantian, autonomy-based justification of informed consent. These difficulties suggest that insofar as informed consent is justified by respect for persons and considerations of autonomy, as the Belmont report maintained, the justification should be along the lines of Kantian autonomy and not individual autonomy.

  7. Perceived autonomy in the first semester of mathematics studies

    OpenAIRE

    Liebendörfer, Michael; Hochmuth, Reinhard

    2015-01-01

    International audience; We focus on the perceived autonomy of mathematics students in their first semester at university. According to self-determination theory by Deci and Ryan (1985), students have to satisfy their need for autonomy in order to develop intrinsic motivation. Using two facets of autonomy, we analyse interview data to explore which situations foster or hinder the students' perceived autonomy. The main factors affecting students' autonomy are briefly discussed.

  8. Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement

    International Nuclear Information System (INIS)

    Broderick, T.P.; Schaff, D.A.; Bertino, A.M.; Dush, M.K.; Tischfield, J.A.; Stambrook, P.J.

    1987-01-01

    The functional human adenine phosphoribosyltransferase (APRT) gene is <2.6 kilobases in length and contains five exons. The amino acid sequences of APRTs have been highly conserved throughout evolution. The human enzyme is 82%, 90%, and 40% identical to the mouse, hamster, and Escherichia coli enzymes, respectively. The promoter region of the human APRT gene, like that of several other housekeeping genes, lacks TATA and CCAAT boxes but contains five GC boxes that are potential binding sites for the Sp1 transcription factor. The distal three, however, are dispensable for gene expression. Comparison between human and mouse APRT gene nucleotide sequences reveals a high degree of homology within protein coding regions but an absence of significant homology in 5' flanking, 3' untranslated, and intron sequences, except for similarly positioned GC boxes in the promoter region and a 26-base-pair region in intron 3. This 26-base-pair sequence is 92% identical with a similarly positioned sequence in the mouse gene and is also found in intron 3 of the hamster gene, suggesting that its retention may be a consequence of stringent selection. The positions of all introns have been precisely retained in the human and both rodent genes. Retention of an elevated CpG dinucleotide content, despite loss of sequence homology, suggests that there may be selection for CpG dinucleotides in these regions and that their maintenance may be important for APRT gene function

  9. DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

  10. Deletion and aberrant CpG island methylation of Caspase 8 gene in medulloblastoma.

    Science.gov (United States)

    Gonzalez-Gomez, Pilar; Bello, M Josefa; Inda, M Mar; Alonso, M Eva; Arjona, Dolores; Amiñoso, Cinthia; Lopez-Marin, Isabel; de Campos, Jose M; Sarasa, Jose L; Castresana, Javier S; Rey, Juan A

    2004-09-01

    Aberrant methylation of promoter CpG islands in human genes is an alternative genetic inactivation mechanism that contributes to the development of human tumors. Nevertheless, few studies have analyzed methylation in medulloblastomas. We determined the frequency of aberrant CpG island methylation for Caspase 8 (CASP8) in a group of 24 medulloblastomas arising in 8 adult and 16 pediatric patients. Complete methylation of CASP8 was found in 15 tumors (62%) and one case displayed hemimethylation. Three samples amplified neither of the two primer sets for methylated or unmethylated alleles, suggesting that genomic deletion occurred in the 5' flanking region of CASP8. Our findings suggest that methylation commonly contributes to CASP8 silencing in medulloblastomas and that homozygous deletion or severe sequence changes involving the promoter region may be another mechanism leading to CASP8 inactivation in this neoplasm.

  11. CpG oligodeoxyribonucleotides protect mice from Burkholderia pseudomallei but not Francisella tularensis Schu S4 aerosols.

    Science.gov (United States)

    Rozak, David A; Gelhaus, Herbert C; Smith, Mark; Zadeh, Mojgan; Huzella, Louis; Waag, David; Adamovicz, Jeffrey J

    2010-02-05

    Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species.

  12. Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

    Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

  13. The effect of TLR9 agonist CpG oligodeoxynucleotides on the intestinal immune response of cobia (Rachycentron canadum).

    Science.gov (United States)

    Byadgi, Omkar; Puteri, Dinda; Lee, Jai-Wei; Chang, Tsung-Chou; Lee, Yan-Horn; Chu, Chun-Yen; Cheng, Ta-Chih

    2014-01-01

    Cytosine-guanine oligodeoxynucleotide (CpG ODN) motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9) and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B) was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA consists of 3113bp encoding 1009 amino acids containing three regions, leucine rich repeats, transmembrane domain, and toll/interleukin-1 receptor (TIR) domain. Intraperitoneal injection of CpG ODN 2395 upregulated RCTLR9 A and B and MyD88 and also induced the expressions of Mx, chemokine CC, and interleukin IL-1 β . Cobia intraperitoneally injected with CpG ODN 1668 and 2395 had increased survival rates after challenge with Photobacterium damselae subsp. piscicida. In addition, formulation of CpG ODN with formalin-killed bacteria (FKB) and aluminum hydroxide gel significantly increased expressions of RCTLR9 A (50 folds) and B (30 folds) isoforms at 10 dpi (CpG ODN 1668) and MyD88 (21 folds) at 6 dpv (CpG ODN 2395). Subsequently, IL-1 β increased at 6 dpv in 1668 group. No histopathological damage and inflammatory responses were observed in the injected cobia. Altogether, these results facilitate CpG ODNs as an adjuvant to increase bacterial disease resistance and efficacy of vaccines in cobia.

  14. The Effect of TLR9 Agonist CpG Oligodeoxynucleotides on the Intestinal Immune Response of Cobia (Rachycentron canadum

    Directory of Open Access Journals (Sweden)

    Omkar Byadgi

    2014-01-01

    Full Text Available Cytosine-guanine oligodeoxynucleotide (CpG ODN motifs of bacterial DNA are recognized through toll-like receptor 9 (TLR9 and are potent activators of innate immunity. However, the interaction between TLR9 and CpG ODN in aquatic species has not been well characterized. Hence, cobia TLR9 isoform B (RCTLR9B was cloned and its expression and induction in intestine were investigated. RCTLR9B cDNA consists of 3113bp encoding 1009 amino acids containing three regions, leucine rich repeats, transmembrane domain, and toll/interleukin-1 receptor (TIR domain. Intraperitoneal injection of CpG ODN 2395 upregulated RCTLR9 A and B and MyD88 and also induced the expressions of Mx, chemokine CC, and interleukin IL-1β. Cobia intraperitoneally injected with CpG ODN 1668 and 2395 had increased survival rates after challenge with Photobacterium damselae subsp. piscicida. In addition, formulation of CpG ODN with formalin-killed bacteria (FKB and aluminum hydroxide gel significantly increased expressions of RCTLR9 A (50 folds and B (30 folds isoforms at 10 dpi (CpG ODN 1668 and MyD88 (21 folds at 6 dpv (CpG ODN 2395. Subsequently, IL-1β increased at 6 dpv in 1668 group. No histopathological damage and inflammatory responses were observed in the injected cobia. Altogether, these results facilitate CpG ODNs as an adjuvant to increase bacterial disease resistance and efficacy of vaccines in cobia.

  15. Autonomy and School Improvement: What Do We Know and Where Do We Go from Here?

    Science.gov (United States)

    Honig, Meredith I.; Rainey, Lydia R.

    2012-01-01

    New "autonomy initiatives" aim to increase schools' decision-making authority as a strategy to leverage school improvement. These policies build on lessons of previous reforms such as site-based management in ways that bode well for their success. However, how are these policies actually faring in implementation? The authors addressed that…

  16. Dynamic Modelling of a CPG-Controlled Amphibious Biomimetic Swimming Robot

    Directory of Open Access Journals (Sweden)

    Rui Ding

    2013-04-01

    Full Text Available This paper focuses on the modelling and control problems of a self-propelled, multimodal amphibious robot. Inspired by the undulatory body motions of fish and dolphins, the amphibious robot propels itself underwater by oscillations of several modular fish-like propelling units coupled with a pair of pectoral fins capable of non-continuous 360 degree rotation. In order to mimic fish-like undulating propulsion, a control architecture based on Central Pattern Generator (CPG is applied to the amphibious robot for robust swimming gaits, including forward and backward swimming and turning, etc. With the simplification of the robot as a multi-link serial mechanism, a Lagrangian function is employed to establish the hydrodynamic model for steady swimming. The CPG motion control law is then imported into the Lagrangian-based dynamic model, where an associated system of kinematics and dynamics is formed to solve real-time movements and, further, to guide the exploration of the CPG parameters and steady locomotion gaits. Finally, comparative results between the simulations and experiments are provided to show the effectiveness of the built control models.

  17. CpG plus radiotherapy: a review of preclinical works leading to clinical trial

    International Nuclear Information System (INIS)

    Mason, Kathy A.; Hunter, Nancy R.

    2012-01-01

    Studies performed three decades ago in our laboratory supported the hypothesis that radiation efficacy may be augmented by bacterial extracts that stimulate non-specific systemic antitumor immune responses. Application to the clinic was halted by unacceptable side effects and toxicities resulting from exposure to whole bacterial pathogens. Later scientific advances demonstrated that DNA isolated from bacteria was immunostimulatory and could be reproduced with synthetic oligodeoxynucleotides (ODNs), thus fueling the transition from bugs to drugs. Unmethylated CpG motifs within bacterial DNA induce activation of Toll-like receptor 9 and subsequently activate antigen-specific cellular immune responses. CpG ODNs have demonstrated favorable toxicity profiles in phase I clinical trials. We showed that this potent immunoadjuvant can be used in combination with radiation therapy to enhance local and systemic responses of several murine tumors. Studies demonstrated that enhanced tumor response is mediated in part by the host immune system. Antitumor efficacy was diminished in immunocompromised mice. Animals cured by combination of radiation and CpG ODN were resistant to subsequent tumor rechallenge. This body of work contributes to our understanding of the dynamic interplay between tumor irradiation and the host immune system and may facilitate translation to clinical trials.

  18. CpG plus radiotherapy: a review of preclinical works leading to clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Mason, Kathy A.; Hunter, Nancy R., E-mail: kmason@mdanderson.org [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-08-14

    Studies performed three decades ago in our laboratory supported the hypothesis that radiation efficacy may be augmented by bacterial extracts that stimulate non-specific systemic antitumor immune responses. Application to the clinic was halted by unacceptable side effects and toxicities resulting from exposure to whole bacterial pathogens. Later scientific advances demonstrated that DNA isolated from bacteria was immunostimulatory and could be reproduced with synthetic oligodeoxynucleotides (ODNs), thus fueling the transition from bugs to drugs. Unmethylated CpG motifs within bacterial DNA induce activation of Toll-like receptor 9 and subsequently activate antigen-specific cellular immune responses. CpG ODNs have demonstrated favorable toxicity profiles in phase I clinical trials. We showed that this potent immunoadjuvant can be used in combination with radiation therapy to enhance local and systemic responses of several murine tumors. Studies demonstrated that enhanced tumor response is mediated in part by the host immune system. Antitumor efficacy was diminished in immunocompromised mice. Animals cured by combination of radiation and CpG ODN were resistant to subsequent tumor rechallenge. This body of work contributes to our understanding of the dynamic interplay between tumor irradiation and the host immune system and may facilitate translation to clinical trials.

  19. Smooth transition for CPG-based body shape control of a snake-like robot

    International Nuclear Information System (INIS)

    Nor, Norzalilah Mohamad; Ma, Shugen

    2014-01-01

    This paper presents a locomotion control based on central pattern generator (CPG) of a snake-like robot. The main point addressed in this paper is a method that produces a smooth transition of the body shape of a snake-like robot. Body shape transition is important for snake-like robot locomotion to adapt to different space widths and also for obstacle avoidance. By manipulating the phase difference of the CPG outputs instantly, it will results in a sharp point or discontinuity which lead to an unstable movement of the snake-like robot. To tackle the problem, we propose a way of controlling the body shape: by incorporating activation function in the phase oscillator CPG model. The simplicity of the method promises an easy implementation and simple control. Simulation results and torque analysis confirm the effectiveness of the proposed control method and thus, can be used as a locomotion control in various potential applications of a snake-like robot. (paper)

  20. Humanoids Learning to Walk: A Natural CPG-Actor-Critic Architecture.

    Science.gov (United States)

    Li, Cai; Lowe, Robert; Ziemke, Tom

    2013-01-01

    The identification of learning mechanisms for locomotion has been the subject of much research for some time but many challenges remain. Dynamic systems theory (DST) offers a novel approach to humanoid learning through environmental interaction. Reinforcement learning (RL) has offered a promising method to adaptively link the dynamic system to the environment it interacts with via a reward-based value system. In this paper, we propose a model that integrates the above perspectives and applies it to the case of a humanoid (NAO) robot learning to walk the ability of which emerges from its value-based interaction with the environment. In the model, a simplified central pattern generator (CPG) architecture inspired by neuroscientific research and DST is integrated with an actor-critic approach to RL (cpg-actor-critic). In the cpg-actor-critic architecture, least-square-temporal-difference based learning converges to the optimal solution quickly by using natural gradient learning and balancing exploration and exploitation. Futhermore, rather than using a traditional (designer-specified) reward it uses a dynamic value function as a stability indicator that adapts to the environment. The results obtained are analyzed using a novel DST-based embodied cognition approach. Learning to walk, from this perspective, is a process of integrating levels of sensorimotor activity and value.

  1. Humanoids Learning to Walk: a Natural CPG-Actor-Critic Architecture

    Directory of Open Access Journals (Sweden)

    CAI eLI

    2013-04-01

    Full Text Available The identification of learning mechanisms for locomotion has been the subject of much researchfor some time but many challenges remain. Dynamic systems theory (DST offers a novel approach to humanoid learning through environmental interaction. Reinforcement learning (RL has offered a promising method to adaptively link the dynamic system to the environment it interacts with via a reward-based value system.In this paper, we propose a model that integrates the above perspectives and applies it to the case of a humanoid (NAO robot learning to walk the ability of which emerges from its value-based interaction with the environment. In the model,a simplified central pattern generator (CPG architecture inspired by neuroscientific research and DST is integrated with an actor-critic approach to RL (cpg-actor-critic. In the cpg-actor-critic architecture, least-square-temporal-difference (LSTD based learning converges to the optimal solution quickly by using natural gradient and balancing exploration and exploitation. Futhermore, rather than using a traditional (designer-specified reward it uses a dynamic value function as a stability indicator (SI that adapts to the environment.The results obtained are analyzed and explained by using a novel DST embodied cognition approach. Learning to walk, from this perspective, is a process of integrating sensorimotor levels and value.

  2. The development of autonomy in children's education.

    Directory of Open Access Journals (Sweden)

    Laura Cavana

    2011-12-01

    Full Text Available This work deals with the development of autonomy in the education of the child and focuses on the analysis of empirical data collected in some services for children in North and South of Italy (Trento, Bologna, Caltagirone, through the administration of semi-structured interviews with educators of the nursery and kindergarten teachers. The returned responses were read in the light of the phenomenological paradigm that permitted to highlight two major kinds of considerations: the one refers to as "parents support and encourage the development of the autonomy of their child more in words than deeds"; the other to as the educators and teachers interviewed showed an explicit difficulty to attribute a clear meaning to the concept of adult autonomy. The incoming in this set of considerations first of all emphasize the important role of adult education and its path of reflexivity and growth.

  3. The autonomy of grammar and semantic internalism

    Directory of Open Access Journals (Sweden)

    Dobler Tamara

    2014-01-01

    Full Text Available In his post-Tractatus work on natural language use, Wittgenstein defended the notion of what he dubbed the autonomy of grammar. According to this thought, grammar - or semantics, in a more recent idiom - is essentially autonomous from metaphysical considerations, and is not answerable to the nature of things. The argument has several related incarnations in Wittgenstein’s post-Tractatus writings, and has given rise to a number of important insights, both critical and constructive. In this paper I will argue for a potential connection between Wittgenstein’s autonomy argument and some more recent internalist arguments for the autonomy of semantics. My main motivation for establishing this connection comes from the fact that the later Wittgenstein’s comments on grammar and meaning stand in opposition to some of the core assumptions of semantic externalism.

  4. School nurses' perceptions of empowerment and autonomy.

    Science.gov (United States)

    DeSisto, Marie C; DeSisto, Thomas Patrick

    2004-08-01

    The purpose of this study was to explore Kanter's Theory of Structural Power in Organizations, using school nurses and to answer the research question of whether there is a relationship between empowerment and autonomy in school nurses. This study found a positive relationship between the nurses' perceptions of empowerment and autonomy. The school nurses surveyed perceived themselves to have a high degree of autonomy and a moderate degree of empowerment, and they reported that their access to informal power structures was higher than their access to formal power structures in their school systems. School nurses can benefit by understanding factors that can increase their empowerment in the workplace. They need to understand the organizational structure of their workplace to increase their effectiveness and job satisfaction.

  5. Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

    Directory of Open Access Journals (Sweden)

    Frank Georgy A

    2007-03-01

    Full Text Available Abstract Background High risk type human papilloma viruses (HR-HPV induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas Methods Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16ink4a was analyzed by RT-PCR and by immunohistochemical technique. Results The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands. The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16ink4a cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. Conclusion Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical

  6. Characterization of Immune Responses to an Inactivated Avian Influenza Virus Vaccine Adjuvanted with Nanoparticles Containing CpG ODN.

    Science.gov (United States)

    Singh, Shirene M; Alkie, Tamiru N; Abdelaziz, Khaled Taha; Hodgins, Douglas C; Novy, Anastasia; Nagy, Éva; Sharif, Shayan

    2016-06-01

    Avian influenza virus (AIV), a mucosal pathogen, gains entry into host chickens through respiratory and gastrointestinal routes. Most commercial AIV vaccines for poultry consist of inactivated, whole virus with adjuvant, delivered by parenteral administration. Recent advances in vaccine development have led to the application of nanoparticle emulsion delivery systems, such as poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to enhance antigen-specific immune responses. In chickens, the Toll-like receptor 21 ligand, CpG oligodeoxynucleotides (ODNs), have been demonstrated to be immunostimulatory. The objective of this study was to compare the adjuvant potential of CpG ODN 2007 encapsulated in PLGA nanoparticles with nonencapsulated CpG ODN 2007 when combined with a formalin-inactivated H9N2 virus, through intramuscular and aerosol delivery routes. Chickens were vaccinated at days 7 and 21 posthatch for the intramuscular route and at days 7, 21, and 35 for the aerosol route. Antibody-mediated responses were evaluated weekly in sera and lacrimal secretions in specific pathogen-free chickens. The results indicate that nonencapsulated CpG ODN 2007 in inactivated AIV vaccines administered by the intramuscular route generated higher antibody responses compared to the encapsulated CpG ODN 2007 formulation by the same route. Additionally, encapsulated CpG ODN 2007 in AIV vaccines administered by the aerosol route elicited higher mucosal responses compared to nonencapsulated CpG ODN 2007. Future studies may be aimed at evaluating protective immune responses induced with PLGA encapsulation of AIV and adjuvants.

  7. Changing Professional autonomy in the Context of Institutional Change

    DEFF Research Database (Denmark)

    Jespersen, Peter Kragh; Houlberg Salomonsen, Heidi

    The Changing autonomy of doctors and civil servants  in Denmark in different institutional contexts......The Changing autonomy of doctors and civil servants  in Denmark in different institutional contexts...

  8. Autonomy, Respect, and Arrogance in the Danish Cartoon Controversy

    OpenAIRE

    Rostbøll, Christian F.

    2009-01-01

    Udgivelsesdato: 2009 Autonomy is increasingly rejected as a fundamental principle by liberal political theorists, because it is regarded as incompatible with respect for diversity. This article seeks, via an analysis of the Danish cartoon controversy, to show that the relationship between autonomy and diversity is more complex than often posited. Particularly, it asks whether the autonomy defense of freedom of expression encourages disrespect for religious feelings. Autonomy leads to disre...

  9. The application of methylation specific electrophoresis (MSE to DNA methylation analysis of the 5' CpG island of mucin in cancer cells

    Directory of Open Access Journals (Sweden)

    Yokoyama Seiya

    2012-02-01

    Full Text Available Abstract Background Methylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. Methods Here, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE. The MSE method is comprised of the following steps: (a bisulfite treatment of genomic DNA, (b amplification of the target DNA by a nested PCR approach and (c applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices. Result The MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is Conclusions The MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical samples, and this may facilitate identification of new risk markers.

  10. CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology.

    Science.gov (United States)

    Shaw, Richard J; Hall, Gillian L; Lowe, Derek; Bowers, Naomi L; Liloglou, Triantafillos; Field, John K; Woolgar, Julia A; Risk, Janet M

    2007-10-01

    Studies in several tumour sites highlight the significance of the CpG island methylation phenotype (CIMP), with distinct features of histology, biological aggression and outcome. We utilise pyrosequencing techniques of quantitative methylation analysis to investigate the presence of CIMP in oral squamous cell carcinoma (OSCC) for the first time, and evaluate its correlation with allelic imbalance, pathology and clinical behaviour. Tumour tissue, control tissue and PBLs were obtained from 74 patients with oral squamous cell carcinoma. Pyrosequencing was used to analyse methylation patterns in 75-200 bp regions of the CpG rich gene promoters of 10 genes with a broad range of cellular functions. Allelic imbalance was investigated using a multiplexed panel of 11 microsatellite markers. Corresponding variables, histopathological staging and grading were correlated with these genetic and epigenetic aberrations. A cluster of tumours with a greater degree of promoter methylation than would be predicted by chance alone (P=0.001) were designated CIMP+ve. This group had less aggressive tumour biology in terms of tumour thickness (p=0.015) and nodal metastasis (P=0.012), this being apparently independent of tumour diameter. Further, it seems that these CIMP+ve tumours excited a greater host inflammatory response (P=0.019). The exact mechanisms underlying CIMP remain obscure but the association with a greater inflammatory host response supports existing theories relating these features in other tumour sites. As CIMP has significant associations with other well documented prognostic indicators, it may prove beneficial to include methylation analyses in molecular risk modelling of tumours.

  11. The autonomy: A challenge in shared spaces

    Directory of Open Access Journals (Sweden)

    María Elena NITRI

    2009-11-01

    Full Text Available This paper has as a goal, to study a few up- dated alternatives on the field of Teaching Coaching toe the focus of reflection. From the concept to autonomy we built and implement teaching strategies focussing on the development of autonomous working projects and tutorial systems, whose aim is placed in the creation of shared spaces which allow decision-taking.

  12. A Dynamic Coordination Mechanism Using Adjustable Autonomy

    NARCIS (Netherlands)

    Neef, R.M.; Vecht, B. van der; Dignum, F.; Meyer, J.J.C.

    2008-01-01

    Agents in an organization need to coordinate their actions in order to reach the organizational goals. This research describes the relation between types of coordination and the autonomy of actors. In an experimental setting we show that there is not one best way to coordinate in all situations. The

  13. A Dynamic Coordination Mechanism Using Adjustable Autonomy

    NARCIS (Netherlands)

    Vecht, B. van der; Dignum, F.; Meyer, J.J.C.; Neef, R.M.

    2007-01-01

    Agents in an organization need to coordinate their actions in order to reach the organizational goals. This research describes the relation between types of coordination and the autonomy of actors. In an experimental setting we show that there is not one best way to coordinate in all situations. The

  14. The Development of Personal Autonomy throughout Cultures

    Science.gov (United States)

    Helwig, Charles C.

    2006-01-01

    It is argued here that autonomy entails universal psychological needs pertaining to agency and identity formation, expressed in different ways over different developmental periods. As children develop skills and abilities related to psychological needs for self-expression and competence, they will claim areas related to the exercise of these…

  15. Identity, Motivation and Autonomy in Language Learning

    Science.gov (United States)

    Lamb, Terry; Murray, Garold; Gao, Xuesong

    2011-01-01

    In this volume researchers from Asia, Europe, the Middle East and North and South America employ a variety of theoretical perspectives and methodological approaches in their exploration of the links between identity, motivation, and autonomy in language learning. On a conceptual level the authors explore issues related to agency, metacognition,…

  16. The Charter School Experience: Autonomy in Practice

    Science.gov (United States)

    McDonald, Tonya Senne

    2013-01-01

    While traditional public school and charter school systems continue to undergo dramatic reforms in response to the educational crisis, charter schools are praised as possessing the distinguishing characteristic of maintaining autonomy in exchange for increased accountability (Buckley & Schneider, 2009). The expectations for charter schools are…

  17. Autonomy in the case of enthyreotic goiter

    International Nuclear Information System (INIS)

    Mahlstedt, J.

    1981-01-01

    To identify, quantify, and exclude thyroidal autonomy, under enthyreotic conditions (positive TRH-test), the in-vivo diagnosing with radionuclides is the only method available to assess the thyroidal trap in connection with the suppression test. Its application is urgently necessary for any goiter patient in the iodine lacking region, the methodical proceeding depends on the individual circumstances. (orig.) [de

  18. On autonomy and participation in rehabilitation.

    NARCIS (Netherlands)

    Cardol, M.; Jong, B.A. de; Ward, C.D.

    2002-01-01

    To explore the concept of autonomy as a basis for social participation, with particular reference to rehabilitation. Method: A study of relevant literature from the field of rehabilitation, building on theory developed in other fields (ethics, social sciences), and deriving important concepts and

  19. How Sex Selection Undermines Reproductive Autonomy.

    Science.gov (United States)

    Browne, Tamara Kayali

    2017-06-01

    Non-medical sex selection is premised on the notion that the sexes are not interchangeable. Studies of individuals who undergo sex selection for non-medical reasons, or who have a preference for a son or daughter, show that they assume their child will conform to the stereotypical roles and norms associated with their sex. However, the evidence currently available has not succeeded in showing that the gender traits and inclinations sought are caused by a "male brain" or a "female brain". Therefore, as far as we know, there is no biological reason why parents cannot have the kind of parenting experience they seek with a child of any sex. Yet gender essentialism, a set of unfounded assumptions about the sexes which pervade society and underpin sexism, prevents parents from realising this freedom. In other words, unfounded assumptions about gender constrain not only a child's autonomy, but also the parent's. To date, reproductive autonomy in relation to sex selection has predominantly been regarded merely as the freedom to choose the sex of one's child. This paper points to at least two interpretations of reproductive autonomy and argues that sex selection, by being premised on gender essentialism and/or the social pressure on parents to ensure their children conform to gender norms, undermines reproductive autonomy on both accounts.

  20. Critical Thinking, Autonomy and Practical Reason

    Science.gov (United States)

    Cuypers, Stefaan E.

    2004-01-01

    This article points out an internal tension, or even conflict, in the conceptual foundations of Harvey Siegel's conception of critical thinking. Siegel justifies critical thinking, or critically rational autonomy, as an educational ideal first and foremost by an appeal to the Kantian principle of respect for persons. It is made explicit that this…

  1. Codes of Ethics and Teachers' Professional Autonomy

    Science.gov (United States)

    Schwimmer, Marina; Maxwell, Bruce

    2017-01-01

    This article considers the value of adopting a code of professional ethics for teachers. After having underlined how a code of ethics stands to benefits a community of educators--namely, by providing a mechanism for regulating autonomy and promoting a shared professional ethic--the article examines the principal arguments against codes of ethics.…

  2. Educating for Well-Being and Autonomy

    Science.gov (United States)

    Cuypers, Stefaan E.; Haji, Ishtiyaque

    2008-01-01

    Liberals champion the view that promoting autonomy--seeing to it that our children develop into individuals who are self-governing in the conduct of their lives--is a vital aim of education, though one generally accredited as being subsidiary to well-being. Our prime goal in this article is to provide a partial validation of this liberal ideal…

  3. Agility and adaptive autonomy in networked organizations

    NARCIS (Netherlands)

    Neef, R.M.; Vecht, B. van der

    2010-01-01

    In any multi-actor environment, there is an inevitable trade-off between achieving global coordination of activities and respecting the autonomy of the actors involved. Agile and resilient behavior demands dynamic coordination capabilities, but task and resource allocation quickly becomes

  4. Adjustable Autonomy: Controling Influences on Decision Making

    NARCIS (Netherlands)

    Vecht, B. van der

    2009-01-01

    Due to technological developments we foresee future systems where groups of actors coordinate their actions in a dynamic manner to reach their goals. Our aim is to develop a reasoning model for artificial actors in such systems. Starting point is the relation between autonomy of individuals and

  5. Autonomy and the Working-Class Freelance

    Science.gov (United States)

    Medway, Peter

    2015-01-01

    In taking into account the realities of the writing process in the ways teachers organize their classrooms, they inescapably find themselves involved with the notion of student autonomy. Some guidelines for supporting independent-minded adolescents in the classroom suggest themselves, and this article provides other suggestions for planning…

  6. Autonomy Level Specification for Intelligent Autonomous Vehicles

    Science.gov (United States)

    2003-09-01

    Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  7. Autonomy under threat: a revised Frankfurtian account

    NARCIS (Netherlands)

    Nys, T.

    2009-01-01

    In the early 1970s Harry Frankfurt argued that so-called ‘coercive threats’ cause a violation of their victim's autonomy, thereby excluding him from moral responsibility. A person is therefore not responsible for doing what he is forced to do. Although this seems correct on an intuitive level, I

  8. University Autonomy: Two Fault-Lines

    Science.gov (United States)

    Evans, G. R.

    2010-01-01

    The doctrine of university autonomy in the UK contains a least two major "fault-lines" where the structure is inherently weak and there is danger of functional breakdown. The first occurs at the junction between the institution and the state, the second within the institution, where the unity in policy-making between academic and…

  9. Supporting Student Autonomy in Physical Education

    Science.gov (United States)

    Perlman, Dana; Webster, Collin A.

    2011-01-01

    The lack of motivation among students is a common challenge in physical education. Studies drawing on the self-determination theory consistently show that perceived autonomy facilitates adaptive motivation in students, which can lead to a wide range of desired educational outcomes. However, instructional strategies designed to support student…

  10. Autonomi og informeret samtykke i sygeplejepraksis

    DEFF Research Database (Denmark)

    Mathar, Helle; Morville, Annette

    2006-01-01

    is described as freedom from compulsion and other forms of regulatory influence. In relation to autonomy and informed consent, information is a defined nursing responsibility in connection with self-managed nursing duties, nursing research and duties where nurses have had been entrusted with responsibility...

  11. Introducing, Defining and Balancing 'Autonomy vs. Paternalism'

    NARCIS (Netherlands)

    W.H. van Boom (Willem); A.I. Ogus (Anthony)

    2010-01-01

    textabstractAutonomy is generally regarded as the fundamental right of individuals to shape their own future through voluntary action. In private law, it is associated with freedom of contract and the concept of casum sentit dominus (the loss lies where it falls). As such, it is opposed to legal

  12. Construction of a Personal Autonomy Inventory.

    Science.gov (United States)

    Strumpfer, D. J. W.

    The inventory contains three factural scales: independence of judgement, moral relativism, and adventurousness. The item pool was based upon descriptions of the need for autonomy (positive) and for independence (negative). The preliminary English form included the Crowne-Marlowe Social Desirability Scale, and was completed by 233 English-speaking…

  13. Autonomy and Complexity at Sandia Executive Summary of Academic Alliance Workshop on Autonomy and Complex Systems.

    Energy Technology Data Exchange (ETDEWEB)

    Hayden, Nancy Kay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kleban, Stephen D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-05-01

    Sandia has identified autonomy as a strategic initiative and an important area for providing national leadership. A key question is, “How might autonomy change how we think about the national security challenges we address and the kinds of solutions we deliver?” Three workshops at Sandia early in 2017 brought together internal stakeholders and potential academic partners in autonomy to address this question. The first focused on programmatic applications and needs. The second explored existing internal capabilities and research and development needs. This report summarizes the outcome of the third workshop, held March 3, 2017 in Albuquerque, NM, which engaged Academic Alliance partners in autonomy efforts at Sandia by discussing research needs and synergistic areas of interest within the complex systems and system modeling domains, and identifying opportunities for partnering on laboratory directed and other joint research opportunities.

  14. Autonomy and Interests: The Social Life of a Curriculum.

    Science.gov (United States)

    Reddiford, Gordon

    1993-01-01

    Examines the arguments that students should determine their own curriculum. Reviews the case for student autonomy based on philosophical anarchism and Immanuel Kant's views on autonomy. Argues that curriculum should be a result of the shared autonomy of students and teachers. (CFR)

  15. Fathers' Autonomy Support and Social Competence of Sons and Daughters

    Science.gov (United States)

    Corwyn, Robert F.; Bradley, Robert H.

    2016-01-01

    Relations between paternal autonomy support and four aspects of adolescent social competence and responsibility at age 16 were examined using data from the NICHD Study of Early Child Care and Youth Development. With controls on maternal autonomy support, significant relations were observed between paternal autonomy support and three of the four…

  16. "It's My Life": Autonomy and People with Intellectual Disabilities

    Science.gov (United States)

    Björnsdóttir, Kristín; Stefánsdóttir, Guðrún V; Stefánsdóttir, Ástríður

    2015-01-01

    This article discusses autonomy in the lives of adults with intellectual disabilities. The article draws on inclusive research in Iceland with 25 women and 16 men and employs ideas of relational autonomy from the perspectives of the Nordic relational approach to disability. In this article, we examine autonomy in relation to private life, that is,…

  17. Lessons for Hospital Autonomy : Implementation in Vietnam from International Experience

    OpenAIRE

    Vietnam Ministry of Health; Health Strategy and Policy Institute; World Bank; World Health Organization

    2011-01-01

    The Government of Vietnam sees hospital autonomy policy as important and consistent with current development trends in Vietnam. It is based on government policies as laid out in government Decree on financial autonomy of revenue-generating public service entities; and to 2006, it is replaced by decree on professional, organizational, human resource management and financial autonomy of reve...

  18. Advancing Learner Autonomy in TEFL via Collaborative Learning

    Science.gov (United States)

    Jacobs, George M.; Shan, Tan Hui

    2015-01-01

    The present paper begins by situating learner autonomy and collaborative learning as part of a larger paradigm shift towards student-centred learning. Next are brief discussions of learner autonomy and how learner autonomy links with collaborative learning. In the main part of the paper, four central principles of collaborative learning are…

  19. Charter School Autonomy: The Mismatch between Theory and Practice

    Science.gov (United States)

    Finnigan, Kara S.

    2007-01-01

    In theory, the charter school concept is based on a trade-off or exchange: greater autonomy for increased accountability. Although charter schools have been operating for more than 10 years, little is known about charter school autonomy in practice. This mixed-methods study used survey and case study data to examine the degree of autonomy of…

  20. Physicians’ Perceptions of Autonomy across Practice Types: Is Autonomy in Solo Practice a Myth?

    Science.gov (United States)

    Lin, Katherine Y.

    2013-01-01

    Physicians in the United States are now less likely to practice in smaller, more traditional, solo practices, and more likely to practice in larger group practices. Though older theory predicts conflict between bureaucracy and professional autonomy, studies have shown that professions in general, and physicians in particular, have adapted to organizational constraints. However, much work remains in clarifying the nature of this relationship and how exactly physicians have adapted to various organizational settings. To this end, the present study examines physicians’ autonomy experiences in different decision types between organization sizes. Specifically, I ask: In what kinds of decisions do doctors perceive autonomous control? How does this vary by organizational size? Using stacked “spell” data constructed from the Community Tracking Study (CTS) Physician Survey (1996–2005) (n=16,519) I examine how physicians’ perceptions of autonomy vary between solo/two physician practices, small group practices with three to ten physicians, and large practices with ten or more physicians, in two kinds of decisions: logistic-based and knowledge-based decisions. Capitalizing on the longitudinal nature of the data I estimate how changes in practice size are associated with perceptions of autonomy, accounting for previous reports of autonomy. I also test whether managed care involvement, practice ownership, and salaried employment help explain part of this relationship. I find that while physicians practicing in larger group practices reported lower levels of autonomy in logistic-based decisions, physicians in solo/two physician practices reported lower levels of autonomy in knowledge-based decisions. Managed care involvement and ownership explain some, but not all, of the associations. These findings suggest that professional adaptation to various organizational settings can lead to varying levels of perceived autonomy across different kinds of decisions. PMID:24444835

  1. Physicians' perceptions of autonomy across practice types: Is autonomy in solo practice a myth?

    Science.gov (United States)

    Lin, Katherine Y

    2014-01-01

    Physicians in the United States are now less likely to practice in smaller, more traditional, solo practices, and more likely to practice in larger group practices. Though older theory predicts conflict between bureaucracy and professional autonomy, studies have shown that professions in general, and physicians in particular, have adapted to organizational constraints. However, much work remains in clarifying the nature of this relationship and how exactly physicians have adapted to various organizational settings. To this end, the present study examines physicians' autonomy experiences in different decision types between organization sizes. Specifically, I ask: In what kinds of decisions do doctors perceive autonomous control? How does this vary by organizational size? Using stacked "spell" data constructed from the Community Tracking Study (CTS) Physician Survey (1996-2005) (n = 16,519) I examine how physicians' perceptions of autonomy vary between solo/two physician practices, small group practices with three to ten physicians, and large practices with ten or more physicians, in two kinds of decisions: logistic-based and knowledge-based decisions. Capitalizing on the longitudinal nature of the data I estimate how changes in practice size are associated with perceptions of autonomy, accounting for previous reports of autonomy. I also test whether managed care involvement, practice ownership, and salaried employment help explain part of this relationship. I find that while physicians practicing in larger group practices reported lower levels of autonomy in logistic-based decisions, physicians in solo/two physician practices reported lower levels of autonomy in knowledge-based decisions. Managed care involvement and ownership explain some, but not all, of the associations. These findings suggest that professional adaptation to various organizational settings can lead to varying levels of perceived autonomy across different kinds of decisions. Copyright © 2013

  2. Glutamatergic mechanisms for speed control and network operation in the rodent locomotor CPG

    DEFF Research Database (Denmark)

    Talpalar, Adolfo E.; Kiehn, Ole

    2010-01-01

    in mammals have produced conflicting results regarding the necessity and role of the different ionotropic glutamate receptors (GluRs) in the CPG function. Here, we use electrophysiological and pharmacological techniques in the in vitro neonatal mouse lumbar spinal cord to investigate the role of a broad...... mechanisms acting at various network levels. AMPA and kainate receptors are necessary for generating the highest locomotor frequencies. For coordination, NMDARs are more important than non-NMDARs for conveying the rhythmic signal from the network to the motor neurons during long-lasting and steady locomotor...

  3. LEARNER AUTONOMY IN THE INDONESIAN EFL SETTINGS

    Directory of Open Access Journals (Sweden)

    Nenden Sri Lengkanawati

    2017-01-01

    Full Text Available Learner autonomy in Indonesian educational institutions has not commonly been listed as a teaching-learning objective, and most teachers seem to be hardly acquainted with learner autonomy (LA.  Therefore, it is very essential  to conduct a study of LA as perceived and experienced by school teachers and to find out the importance of LA training for professional development. A questionnaire was used to collect the data about English teachers’ perceptions regarding LA and LA-based practices. In addition, an LA training was conducted to see its significance for professional development.  After the data were qualitatively and quantitatively analyzed, it was found that the participating teachers tended to maintain that autonomy should be inculcated among learners, and that the LA concept should not be misinterpreted as learning without a teacher. Concerning choices and decisions by  the learners, it was believed that learners’ making choices about how they learned and what activities they did, and involving them to decide what and how to learn could promote autonomy among learners. As regards LA-based teaching-learning practices, it was revealed that most teachers desired to implement LA principles in their teaching-learning contexts, although they identified that many of the LA principles were not that feasible to apply in their situation. It was also found that LA training could improve the teachers’ perceptions regarding LA concepts and principles. There were some constraints which could make learner autonomy difficult to develop among Indonesian learners in general: limited time allotted for the implementation of the curriculum, learners’ lack of autonomous learning experience, too much focus on national examinations, and insufficient proficiency of English.  LA-based teaching-learning practices were most desired; however, many were considered as having insufficient feasibility. In this respect, commitment is certainly the key to

  4. CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

    Science.gov (United States)

    Vartanian, Keri B; Mitchell, Hugh D; Stevens, Susan L; Conrad, Valerie K; McDermott, Jason E; Stenzel-Poore, Mary P

    2015-01-01

    Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage. PMID:25388675

  5. [Autonomy and dementia Part II: autonomy and representation: a possible combination?].

    Science.gov (United States)

    Rigaux, Natalie

    2011-06-01

    This paper, based on a critical review of the medico-social literature, questions the representation of patients with dementia in relation to the autonomy perspectives presented in a previous article. In the canonical perspective of autonomy (defined as a rational decision-making by a stand alone self), the surrogate is the spokeperson of the subject's wills when he was competent because he knows these wills through advance directives or assuming them via substituted judgment. Best patient's interest is then depreciated because it is focused on the present incompetent self. In the relational perspective, where autonomy is constructed through a dialogue with others, the surrogate is the present interlocutor, making the decisions with the patient and care-givers in a way varying with the disease process. He represents the subject with dementia as he was before the disease but also as he has become. Therefore, there is a continuum between autonomy and representation. Autonomy and well being are both the surrogate aims. The relational perspective allows care continuity of patients with dementia even when considered as incompetent. It offers a more balanced perspective on the patient autonomy since it is embedded in all others, and opens a richer view on what good life is, untill the end of dementia.

  6. School Autonomy and District Support: How Principals Respond to a Tiered Autonomy Initiative in Philadelphia Public Schools

    Science.gov (United States)

    Steinberg, Matthew P.; Cox, Amanda Barrett

    2017-01-01

    A tiered autonomy policy was recently implemented in Philadelphia, where select principals were granted autonomy to manage school operations while others were promised greater district support to improve school functioning. This article provides evidence on how principals used their autonomy and the extent of district support for non-autonomous…

  7. Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.

    Science.gov (United States)

    Emeny, Rebecca T; Baumert, Jens; Zannas, Anthony S; Kunze, Sonja; Wahl, Simone; Iurato, Stella; Arloth, Janine; Erhardt, Angelika; Balsevich, Georgia; Schmidt, Mathias V; Weber, Peter; Kretschmer, Anja; Pfeiffer, Liliane; Kruse, Johannes; Strauch, Konstantin; Roden, Michael; Herder, Christian; Koenig, Wolfgang; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Binder, Elisabeth B; Ladwig, Karl-Heinz

    2018-01-01

    Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress

  8. CpG oligodeoxynucleotides containing GACGTT motifs enhance the immune responses elicited by a goose parvovirus vaccine in ducks.

    Science.gov (United States)

    Lee, Jai-Wei; Lin, Yu-Ming; Yen, Ting-Ying; Yang, Wen-Jen; Chu, Chun-Yen

    2010-11-23

    Recombinant parvovirus VP2 (rVP2) was formulated with different types of adjuvant, including aluminum adjuvant and CpG oligodeoxynucleotides (ODNs), and the immunological responses after vaccination in ducks were examined. In comparison with the control group, production of rVP2-specific antibodies, expression of cytokines in peripheral blood mononuclear cells (PBMC) stimulated by rVP2, and percentage of CD4(+)/CD8(+) cells in PBMC were significantly increased in ducks immunized with rVP2 formulated with CpG ODNs containing 3 copies of GACGTT motif. CpG ODNs with GACGTT motifs might be used to improve the efficacy of vaccines for ducks. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. MPT-51/CpG DNA vaccine protects mice against Mycobacterium tuberculosis.

    Science.gov (United States)

    Silva, Bruna Daniella de Souza; da Silva, Ediane Batista; do Nascimento, Ivan Pereira; Dos Reis, Michelle Cristina Guerreiro; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2009-07-16

    Tuberculosis (TB) is a severe infectious disease that kills approximately two million people worldwide every year. Because BCG protection is variable and does not protects adults, there is a great need for a new vaccine against TB that does not represent a risk for immunocompromised patients and that is also capable of protecting adult individuals. MPT-51 is a protein found in the genome of mycobacteria and binds to the fibronectin of the extracellular matrix, which may have a role in host tissue attachment and virulence. In order to test the usefulness of MPT-51 as a subunit vaccine, BALB/c were vaccinated and challenged with Mycobacterium tuberculosis. The infection of BALB/c with M. tuberculosis increased the number of IFN-gamma(+) T lymphocytes specific to MPT-51 in the spleen and lungs. Inoculation with rMPT-51/FIA and with rMPT-51/CpG DNA in non-infected BALB/c increased the amounts of IFN-gamma(+) T lymphocytes. Inoculation with rMPT-51/FIA also induced a humoral response specific to MPT-51. CFU counts of lung tissues done 60 days after infection showed a reduction of about 2 log in the bacteria load in the group of animals inoculated with rMPT-51/CpG DNA. These results make MPT-51 a valuable component to be further evaluated in the development of other subunit vaccines.

  10. FPGA implementation of a configurable neuromorphic CPG-based locomotion controller.

    Science.gov (United States)

    Barron-Zambrano, Jose Hugo; Torres-Huitzil, Cesar

    2013-09-01

    Neuromorphic engineering is a discipline devoted to the design and development of computational hardware that mimics the characteristics and capabilities of neuro-biological systems. In recent years, neuromorphic hardware systems have been implemented using a hybrid approach incorporating digital hardware so as to provide flexibility and scalability at the cost of power efficiency and some biological realism. This paper proposes an FPGA-based neuromorphic-like embedded system on a chip to generate locomotion patterns of periodic rhythmic movements inspired by Central Pattern Generators (CPGs). The proposed implementation follows a top-down approach where modularity and hierarchy are two desirable features. The locomotion controller is based on CPG models to produce rhythmic locomotion patterns or gaits for legged robots such as quadrupeds and hexapods. The architecture is configurable and scalable for robots with either different morphologies or different degrees of freedom (DOFs). Experiments performed on a real robot are presented and discussed. The obtained results demonstrate that the CPG-based controller provides the necessary flexibility to generate different rhythmic patterns at run-time suitable for adaptable locomotion. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Frequency Modulation and Spatiotemporal Stability of the sCPG in Preterm Infants with RDS

    Directory of Open Access Journals (Sweden)

    Steven M. Barlow

    2012-01-01

    Full Text Available The nonnutritive suck (NNS is an observable and accessible motor behavior which is often used to make inference about brain development and pre-feeding skill in preterm and term infants. The purpose of this study was to model NNS burst compression pressure dynamics in the frequency and time domain among two groups of preterm infants, including those with respiratory distress syndrome (RDS, N=15 and 17 healthy controls. Digitized samples of NNS compression pressure waveforms recorded at a 1-week interval were collected 15 minutes prior to a scheduled feed. Regression analysis and ANOVA revealed that healthy preterm infants produced longer NNS bursts and the mean burst initiation cycle frequencies were higher when compared to the RDS group. Moreover, the initial 5 cycles of the NNS burst manifest a frequency modulated (FM segment which is a significant feature of the suck central pattern generator (sCPG, and differentially expressed in healthy and RDS infants. The NNS burst structure revealed significantly lower spatiotemporal index values for control versus RDS preterm infants during FM, and provides additional information on the microstructure of the sCPG which may be used to gauge the developmental status and progression of oromotor control systems among these fragile infants.

  12. Determining coding CpG islands by identifying regions significant for pattern statistics on Markov chains.

    Science.gov (United States)

    Singer, Meromit; Engström, Alexander; Schönhuth, Alexander; Pachter, Lior

    2011-09-23

    Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.

  13. CpG island methylator phenotype in adenocarcinomas from the digestive tract: Methods, conclusions, and controversies

    Science.gov (United States)

    Sánchez-Vega, Francisco; Gotea, Valer; Chen, Yun-Ching; Elnitski, Laura

    2017-01-01

    Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype (CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using cross-platform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600E mutation, CDKN2A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials. PMID:28344746

  14. A balanced intervention ladder: promoting autonomy through public health action.

    Science.gov (United States)

    Griffiths, P E; West, C

    2015-08-01

    The widely cited Nuffield Council on Bioethics 'Intervention Ladder' structurally embodies the assumption that personal autonomy is maximized by non-intervention. Consequently, the Intervention Ladder encourages an extreme 'negative liberty' view of autonomy. Yet there are several alternative accounts of autonomy that are both arguably superior as accounts of autonomy and better suited to the issues facing public health ethics. We propose to replace the one-sided ladder, which has any intervention coming at a cost to autonomy, with a two-sided 'Balanced Intervention Ladder,' where intervention can either enhance or diminish autonomy. We show that not only the alternative, richer accounts of autonomy but even Mill's classic version of negative liberty puts some interventions on the positive side of the ladder. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  15. Teacher Autonomy Perceptions of Iranian and Turkish EFL Teachers

    Directory of Open Access Journals (Sweden)

    Ebrahim KHEZERLOU

    2013-07-01

    Full Text Available The study aimed at examining Iranian (N= 218 and Turkish (N=142 high school EFL teachers’ opinions about teacher autonomy over (a the choice of appropriate teaching methods, strategies and techniques and implementation of the established curriculum (b teacher involvement in decision making processes and (c teachers’ use of personal initiative in solving their work problems. An 11-item questionnaire (α= .758 was used to measure autonomy perceptions of the participants. The results revealed that Turkish teachers’ autonomy perceptions were greater than that of Iranian teachers in the three teacher autonomy dimensions. Moreover, it was observed that male and master- holder teachers perceive less autonomy than female and bachelor-holder ones; whereas, no significant relationship were observed for the age and marital status variables with any teacher autonomy dimensions. Lastly, decision making dimension was the strongest predictor of teacher autonomy among both Iranian and Turkish teachers.

  16. BALB/c Mice Vaccinated with Leishmania major Ribosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

    Directory of Open Access Journals (Sweden)

    Laura Ramírez

    2010-01-01

    Full Text Available Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γ in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity.

  17. Epigenetic silencing of BTB and CNC homology 2 and concerted promoter CpG methylation in gastric cancer.

    Science.gov (United States)

    Haam, Keeok; Kim, Hee-Jin; Lee, Kyung-Tae; Kim, Jeong-Hwan; Kim, Mirang; Kim, Seon-Young; Noh, Seung-Moo; Song, Kyu-Sang; Kim, Yong Sung

    2014-09-01

    BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a prominent role in B-cell development. Genetic polymorphisms within a single locus encoding BACH2 are associated with various autoimmune diseases and allergies. In this study, restriction landmark genomic scanning revealed methylation at a NotI site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and primary gastric tumors. Increased methylation of the BACH2 promoter was observed in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was significantly associated with decreased gene expression. Treatment with 5-aza-2'-deoxycytidine and/or trichostatin. A restored BACH2 expression in BACH2-silenced gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e. RNA interference) increased cell proliferation in gastric cancer cells. Clinicopathologic data showed that decreased BACH2 expression occurred significantly more frequently in intestinal-type (27/44, 61%) compared with diffuse-type (13/50, 26%) gastric cancers (P<0.001). Furthermore, BACH2 promoter methylation paralleled that of previously identified targets, such as LRRC3B, LIMS2, PRKD1 and POPDC3, in a given set of gastric tumors. We propose that concerted methylation in many promoters plays a role in accelerating gastric tumor formation and that methylated promoter loci may be targets for therapeutic treatment, such as the recently introduced technique of epigenetic editing. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Comparison of CpG island methylator phenotype (CIMP frequency in colon cancer using different probe- and gene-specific scoring alternatives on recommended multi-gene panels.

    Directory of Open Access Journals (Sweden)

    Marianne Berg

    Full Text Available BACKGROUND: In colorectal cancer a distinct subgroup of tumours demonstrate the CpG island methylator phenotype (CIMP. However, a consensus of how to score CIMP is not reached, and variation in definition may influence the reported CIMP prevalence in tumours. Thus, we sought to compare currently suggested definitions and cut-offs for methylation markers and how they influence CIMP classification in colon cancer. METHODS: Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, with subsequent fragment analysis, was used to investigate methylation of tumour samples. In total, 31 CpG sites, located in 8 different genes (RUNX3, MLH1, NEUROG1, CDKN2A, IGF2, CRABP1, SOCS1 and CACNA1G were investigated in 64 distinct colon cancers and 2 colon cancer cell lines. The Ogino gene panel includes all 8 genes, in addition to the Weisenberger panel of which only 5 of the 8 genes included were investigated. In total, 18 alternative combinations of scoring of CIMP positivity on probe-, gene-, and panel-level were analysed and compared. RESULTS: For 47 samples (71%, the CIMP status was constant and independent of criteria used for scoring; 34 samples were constantly scored as CIMP negative, and 13 (20% consistently scored as CIMP positive. Only four of 31 probes (13% investigated showed no difference in the numbers of positive samples using the different cut-offs. Within the panels a trend was observed that increasing the gene-level stringency resulted in a larger difference in CIMP positive samples than increasing the probe-level stringency. A significant difference between positive samples using 'the most stringent' as compared to 'the least stringent' criteria (20% vs 46%, respectively; p<0.005 was demonstrated. CONCLUSIONS: A statistical significant variation in the frequency of CIMP depending on the cut-offs and genes included in a panel was found, with twice as many positives samples by least compared to most stringent definition

  19. Comparison of CpG island methylator phenotype (CIMP) frequency in colon cancer using different probe- and gene-specific scoring alternatives on recommended multi-gene panels.

    Science.gov (United States)

    Berg, Marianne; Hagland, Hanne R; Søreide, Kjetil

    2014-01-01

    In colorectal cancer a distinct subgroup of tumours demonstrate the CpG island methylator phenotype (CIMP). However, a consensus of how to score CIMP is not reached, and variation in definition may influence the reported CIMP prevalence in tumours. Thus, we sought to compare currently suggested definitions and cut-offs for methylation markers and how they influence CIMP classification in colon cancer. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), with subsequent fragment analysis, was used to investigate methylation of tumour samples. In total, 31 CpG sites, located in 8 different genes (RUNX3, MLH1, NEUROG1, CDKN2A, IGF2, CRABP1, SOCS1 and CACNA1G) were investigated in 64 distinct colon cancers and 2 colon cancer cell lines. The Ogino gene panel includes all 8 genes, in addition to the Weisenberger panel of which only 5 of the 8 genes included were investigated. In total, 18 alternative combinations of scoring of CIMP positivity on probe-, gene-, and panel-level were analysed and compared. For 47 samples (71%), the CIMP status was constant and independent of criteria used for scoring; 34 samples were constantly scored as CIMP negative, and 13 (20%) consistently scored as CIMP positive. Only four of 31 probes (13%) investigated showed no difference in the numbers of positive samples using the different cut-offs. Within the panels a trend was observed that increasing the gene-level stringency resulted in a larger difference in CIMP positive samples than increasing the probe-level stringency. A significant difference between positive samples using 'the most stringent' as compared to 'the least stringent' criteria (20% vs 46%, respectively; pCIMP depending on the cut-offs and genes included in a panel was found, with twice as many positives samples by least compared to most stringent definition used.

  20. Autonomy, Competence and Non-interference.

    Science.gov (United States)

    Roberts, Joseph T F

    2017-12-30

    In light of the variety of uses of the term autonomy in recent bioethics literature, in this paper, I suggest that competence, not being as contested, is better placed to play the anti-paternalistic role currently assigned to autonomy. The demonstration of competence, I will argue, can provide individuals with robust spheres of non-interference in which they can pursue their lives in accordance with their own values. This protection from paternalism is achieved by granting individuals rights to non-interference upon demonstration of competence. In this paper, I present a risk-sensitive account of competence as a means of grounding rights to non-interference. On a risk-sensitive account of competence individuals demonstrate their competence by exercising three capacities to the extent necessary to meet a threshold determined by the riskiness of the decision. These three capacities are the capacity to (i) acquire knowledge, (ii) use instrumental rationality, and (iii) form and revise a life plan.

  1. Focus on energy autonomy in overseas districts

    International Nuclear Information System (INIS)

    Billerey, Jerome

    2016-01-01

    As French overseas territories have also had a role of leader in the development of renewable energies, and as the French law on energy transition states that energy autonomy is an objective by 2030 for these territories, with 50 per cent of renewable energies by 2020, this publication proposes an overview of the situation in these territories which still strongly depend on imported energies, notably for transports. The publication outlines the specificities of these islands with respect to the metropolitan territory in terms of electric power system: small territories, high production costs, strong consumption increase. It describes how the new energy policy plans evolutions to reach this autonomy: development of renewable energies and of smart grids, development of vehicles fuelled with electricity, biofuels or hydrogen, management of energy consumption in housing and through the use of renewable energies

  2. [Euthanasia and the paradoxes of autonomy].

    Science.gov (United States)

    Siqueira-Batista, Rodrigo; Schramm, Fermin Roland

    2008-01-01

    The principle of respect for autonomy has proved very useful for bioethical arguments in favor of euthanasia. However unquestionable its theoretical efficacy, countless aporiae can be raised when conducting a detailed analysis of this concept, probably checkmating it. Based on such considerations, this paper investigates the principle of autonomy, starting with its origins in Greek and Christian traditions, and then charting some of its developments in Western cultures through to its modern formulation, a legacy of Immanuel Kant. The main paradoxes of this concept are then presented in the fields of philosophy, biology, psychoanalysis and politics, expounding several of the theoretical difficulties to be faced in order to make its applicability possible within the scope of decisions relating to the termination of life.

  3. Autonomy, rationality and the wish to die.

    Science.gov (United States)

    Clarke, D M

    1999-12-01

    Although suicide has traditionally carried a negative sanction in Western societies, this is now being challenged, and while there remains substantial public concern surrounding youth and elder suicide, there is a paradoxical push to relax the prohibition under certain circumstances. Central to the arguments behind this are the principles of respect for autonomy and the importance of rationality. It is argued here that the concepts of rationality and autonomy, while valuable, are not strong enough to substantiate a categorical "right to suicide" and that the concepts of "understandability" and "respect" are more useful and able to provide the foundation for responding to a person expressing a wish to die. Roman suicide, sometimes held as an example of "rational suicide", illustrates the effects of culture, tradition and values on the attitudes to, and the practice of, suicide.

  4. Building up Autonomy Through Reading Strategies

    Directory of Open Access Journals (Sweden)

    Alexander Izquierdo Castillo

    2014-10-01

    Full Text Available This article reports on an action research project conducted with six ninth grade students in a rural public school in Colombia. The purpose of the study was to determine how the implementation of three reading strategies (skimming, scanning, and making predictions, when reading topics selected by learners, helps them to improve their reading comprehension and promotes their autonomy in the learning process. The results show that these learners developed some autonomous features such as making decisions for learning and doing assigned homework, increasing reading awareness and motivation. Additionally, the training on reading strategies allowed them to succeed in their reading comprehension. We conclude that these reading strategies are tools that take learners along the path of autonomy.

  5. [School nutrition and autonomy - challenges and opportunities].

    Science.gov (United States)

    Barbosa, Najla Veloso Sampaio; Machado, Neila Maria Viçosa; Soares, Maria Cláudia Veiga; Pinto, Anelise Regina Royer

    2013-04-01

    This study seeks to emphasize school food as an important policy to promote student autonomy by means of food and nutrition education included in the curriculum, integrated with different actors and based on the standpoint of citizenship. It seeks to return to fundamental concepts in the context of school food reflecting on them through theoretical assumptions to identify possible strategies to promote citizenship and autonomy in school. The strategies involved food and nutrition education with the daily presence of quality and suitability in school meals, discussions on the various dimensions of food in the curriculum and integrating food in the pedagogical project extended to various areas of the education system. School food fosters the need for integration of actions, actors and the various social spaces interested in the food issue, such as ministries, education systems, departments and schools, so that they may tackle the demands of contemporary reality in an integrated, systematic, consistent and efficient manner.

  6. Autonomy-Supportive Parenting and Autonomy-Supportive Sibling Interactions: The Role of Mothers' and Siblings' Psychological Need Satisfaction.

    Science.gov (United States)

    van der Kaap-Deeder, Jolene; Vansteenkiste, Maarten; Soenens, Bart; Loeys, Tom; Mabbe, Elien; Gargurevich, Rafael

    2015-11-01

    Autonomy-supportive parenting yields manifold benefits. To gain more insight into the family-level dynamics involved in autonomy-supportive parenting, the present study addressed three issues. First, on the basis of self-determination theory, we examined whether mothers' satisfaction of the psychological needs for autonomy, competence, and relatedness related to autonomy-supportive parenting. Second, we investigated maternal autonomy support as an intervening variable in the mother-child similarity in psychological need satisfaction. Third, we examined associations between autonomy-supportive parenting and autonomy-supportive sibling interactions. Participants were 154 mothers (M age = 39.45, SD = 3.96) and their two elementary school-age children (M age = 8.54, SD = 0.89 and M age = 10.38, SD = 0.87). Although mothers' psychological need satisfaction related only to maternal autonomy support in the younger siblings, autonomy-supportive parenting related to psychological need satisfaction in both siblings and to an autonomy-supportive interaction style between siblings. We discuss the importance of maternal autonomy support for family-level dynamics. © 2015 by the Society for Personality and Social Psychology, Inc.

  7. Demonstration of Human-Autonomy Teaming Principles

    Science.gov (United States)

    Shively, Robert Jay

    2016-01-01

    Known problems with automation include lack of mode awareness, automation brittleness, and risk of miscalibrated trust. Human-Autonomy Teaming (HAT) is essential for improving these problems. We have identified some critical components of HAT and ran a part-task study to introduce these components to a ground station that supports flight following of multiple aircraft. Our goal was to demonstrate, evaluate, and refine HAT principles. This presentation provides a brief summary of the study and initial findings.

  8. On autonomy and participation in rehabilitation.

    OpenAIRE

    Cardol, M.; Jong, B.A. de; Ward, C.D.

    2002-01-01

    To explore the concept of autonomy as a basis for social participation, with particular reference to rehabilitation. Method: A study of relevant literature from the field of rehabilitation, building on theory developed in other fields (ethics, social sciences), and deriving important concepts and strategies for rehabilitation practice. Results: The focus of rehabilitation for people with a chronic disabling condition is shifting from a biomedical to a client-centred perspective. Conceptions o...

  9. [Carers and the policy for autonomy].

    Science.gov (United States)

    Naiditch, Michel

    2016-03-01

    Long-time invisible, the role of informal carers in providing assistance to elderly patients losing their autonomy is gaining recognition. A policy in favour of carers coordinated with that aimed at the people being cared for is necessary, but it is struggling to establish itself in France. Some progress can however be seen with the French bill on adapting society to the ageing of the population. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Autonomy-How much is too much

    Science.gov (United States)

    2007-06-22

    Autonomous Robots Automatically Operated Car (1977) The first demonstration of a driverless car occurred in 1977 in Tsukuba, Japan[19][20] The car ...is autonomy? Brief history of autonomous robots Current field use of robots Current state-of-the-art for autonomous robots Barriers to the use of... autonomous robots Considering the human factor Outlook for the future 19 June 2007 Systems & Software Technology

  11. Autonomy and purity in Kant's moral theory

    OpenAIRE

    Benson, Carolyn Jane

    2010-01-01

    Kant believed that the moral law is a law that the rational will legislates. This thesis examines this claim and its broader implications for Kant’s moral theory. Many are drawn to Kantian ethics because of its emphasis on the dignity and legislative authority of the rational being. The attractiveness of this emphasis on the special standing and capacities of the self grounds a recent tendency to interpret Kantian autonomy as a doctrine according to which individual agents create binding ...

  12. [From dependency to autonomy, a geriatric pathway].

    Science.gov (United States)

    Iglesias, Antoine; Da Costa Ribeiro, Florence; Pedra, Maryse; Chassaigne, Marie-Christine; Berbon, Caroline

    Preventing dependency is essential in our ageing society. One of its components is the avoidable dependency which develops during a period of hospitalisation. Caregivers play an important role in helping the elderly person regain their autonomy. Various actions have been undertaken on this theme within the gerontology unit of Toulouse university hospital, including the creation of a multi-disciplinary group of experts among the caregivers working in the unit. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. DMPD: Signal transduction pathways mediated by the interaction of CpG DNA withToll-like receptor 9. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14751759 Signal transduction pathways mediated by the interaction of CpG DNA withTo...;16(1):17-22. (.png) (.svg) (.html) (.csml) Show Signal transduction pathways mediated by the interaction of... CpG DNA withToll-like receptor 9. PubmedID 14751759 Title Signal transduction pathways media

  14. Maximing Learning Strategies to Promote Learner Autonomy

    Directory of Open Access Journals (Sweden)

    Junaidi Mistar

    2001-01-01

    Full Text Available Learning a new language is ultimately to be able to communicate with it. Encouraging a sense of responsibility on the part of the learners is crucial for training them to be proficient communicators. As such, understanding the strategies that they employ in acquiring the language skill is important to come to ideas of how to promote learner autonomy. Research recently conducted with three different groups of learners of English at the tertiary education level in Malang indicated that they used metacognitive and social startegies at a high frequency, while memory, cognitive, conpensation, and affective strategies were exercised at a medium frewuency. This finding implies that the learners have acquired some degrees of autonomy because metacognive strategies requires them to independently make plans for their learning activities as well as evaluate the progress, and social strategies requires them to independently enhance communicative interactions with other people. Further actions are then to be taken increase their learning autonomy, that is by intensifying the practice of use of the other four strategy categories, which are not yet applied intensively.

  15. Cognitive Architectures and Autonomy: A Comparative Review

    Science.gov (United States)

    Thórisson, Kristinn; Helgasson, Helgi

    2012-05-01

    One of the original goals of artificial intelligence (AI) research was to create machines with very general cognitive capabilities and a relatively high level of autonomy. It has taken the field longer than many had expected to achieve even a fraction of this goal; the community has focused on building specific, targeted cognitive processes in isolation, and as of yet no system exists that integrates a broad range of capabilities or presents a general solution to autonomous acquisition of a large set of skills. Among the reasons for this are the highly limited machine learning and adaptation techniques available, and the inherent complexity of integrating numerous cognitive and learning capabilities in a coherent architecture. In this paper we review selected systems and architectures built expressly to address integrated skills. We highlight principles and features of these systems that seem promising for creating generally intelligent systems with some level of autonomy, and discuss them in the context of the development of future cognitive architectures. Autonomy is a key property for any system to be considered generally intelligent, in our view; we use this concept as an organizing principle for comparing the reviewed systems. Features that remain largely unaddressed in present research, but seem nevertheless necessary for such efforts to succeed, are also discussed.

  16. Multiculturalism and legal autonomy for cultural minorities

    Directory of Open Access Journals (Sweden)

    Morten Ebbe Juul Nielsen

    2013-11-01

    Full Text Available Does multiculturalism imply that certain cultural minorities – nomos groups, whose cultural conceptions extend in important ways into views about the law – should have forms of legal autonomy that go beyond normal multicultural accommodations such as exemptions and special protection? In other words: should we allow «minority jurisdictions» for multicultural reasons and give certain minorities powers of legislation and adjudication on certain issues? The paper sketches how one might arrive at such a conclusion given some standard multicultural reasoning, and then proceeds by examining eight key rejoinders to such a proposal. None of these rejoinders provide by themselves knockdown arguments against extending multicultural rights to forms of legal autonomy, but together they do provide a basis for some skepticism about the cogency and desirability of at least more ambitious forms of legal autonomy for cultural minorities within a liberal framework.http://dx.doi.org/10.5324/eip.v7i2.1798

  17. Understanding gendered influences on women's reproductive health in Pakistan: moving beyond the autonomy paradigm.

    Science.gov (United States)

    Mumtaz, Zubia; Salway, Sarah

    2009-04-01

    Recent research and policy discourse commonly view the limited autonomy of women in developing countries as a key barrier to improvements in their reproductive health. Rarely, however, is the notion of women's autonomy interrogated for its conceptual adequacy or usefulness for understanding the determinants of women's reproductive health, effective policy formulation or program design. Using ethnographic data from 2001, including social mapping exercises, observation of daily life, interviews, case studies and focus group discussions, this paper draws attention to the incongruities between the concept of women's autonomy and the gendered social, cultural, economic and political realities of women's lives in rural Punjab, Pakistan. These inadequacies include: the concept's undue emphasis on women's independent, autonomous action; a lack of attention to men and masculinities; a disregard for the multi-sited constitution of gender relations and gender inequality; an erroneous assumption that uptake of reproductive health services is an indicator of autonomy; and a failure to explore the interplay of other axes of disadvantage such as caste, class or socio-economic position. This paper calls for alternative, more nuanced, theoretical approaches for conceptualizing gender inequalities in order to enhance our understanding of women's reproductive wellbeing in Pakistan. The extent to which our arguments may be relevant to the wider South Asian context, and women's lives in other parts of the world, is also discussed.

  18. Protection of CpG ODN 1826 against radiation pulmonary fibrosis in rats

    International Nuclear Information System (INIS)

    Li Xuan; Qiao Tiankui; Zhuang Xibing; Zhang Jihong

    2014-01-01

    Objective: To explore the protectional function of CpG ODN 1826 against radiation pulmonary fibrosis in rats. Methods: The rat left lung was exposed to 20 Gy of 6 MV X-rays for establishing a radiation pulmonary fibrosis model. SD rats were randomly divided into control group, irradiated group and intervention group, with 30 rats in each group. CpG ODN 1826 was intraperitoneally injected into rats at 0, 1, 2, 5 and 7 d post-irradiation. The rats were terminated at 5, 15, 30 and 90 d post-irradiation, and the lung indexes were recorded. Paraffin sections of the radiated lung were conducted with HE staining and Masson staining, the pulmonary fibrosis scores were recorded. The serum concentrations of TGF-β1 and hydroxyproline (Hyp) were measured. Results: The radiation pulmonary fibrosis rat model was successfully established. The lung indexes of the control group were lower than those of the irradiated and intervention groups at 5 d post-irradiation (t = 3.046, 2.252, P < 0.05). The lung indexes of the intervention group were lower than those of the irradiated group (t = 4.120, 5.226, 5.719, P < 0.05). Pulmonary fibrosis scores of intervention group were lower than those of irradiated group (t = 3.212, 4.959, P < 0.05). The serum concentrations of TGF-β1 of irradiated group were higher than those of the intervention group (t = 4.138, 5.924, 4.138, 5.924, P < 0.05). The Hyp in the lung of irradiated group was higher than that of intervention group (t = 7.527, 8.416, P < 0.05). Conclusions: CpG ODN1826 will not worse the radiation pulmonary fibrosis, on the contrary, it could reduce the serum concentrations of TGF-β1 and the lung content of Hyp in radiation pulmonary fibrosis, and protects rat against radiation pulmonary fibrosis. (authors)

  19. CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci.

    Science.gov (United States)

    Kawasaki, Takako; Ohnishi, Mutsuko; Nosho, Katsuhiko; Suemoto, Yuko; Kirkner, Gregory J; Meyerhardt, Jeffrey A; Fuchs, Charles S; Ogino, Shuji

    2008-03-01

    The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index>4. Low-level methylation (methylation index>0, CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (> or =6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (PCIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared to CIMP-high and CIMP-0 tumors, CIMP-low colorectal cancers show not only few methylated CIMP-high-specific CpG islands, but also more frequent low-level methylation at individual loci. Our data may provide supporting evidence for a difference in pathogenesis of DNA methylation between CIMP-low and CIMP-high tumors.

  20. Effects of CPG ODN on biological behavior of PANC-1 and expression of TLR9 in pancreatic cancer.

    Science.gov (United States)

    Wu, Han-Qing; Wang, Bo; Zhu, Shi-Kai; Tian, Yuan; Zhang, Jing-Hui; Wu, He-Shui

    2011-02-28

    To determine the expression of toll-like receptor 9 (TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216 (CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance. The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein in pancreatic cancer tissues, and immunofluorescence staining was performed to detect the TLR9 protein expression in pancreatic carcinoma cell line PANC-1. To assess the effects of CPG ODN2216 on the invasive property of Panc-1 cells, in vitro cell adhesion, wound-healing scrape, and invasion and cell colony formation were evaluated. TLR9 was highly expressed in pancreatic cancer tissues and PANC-1 cells. The percentage of positive cells expressing TLR9 protein in human pancreatic tissues, paracancerous tissues and normal tissues were 73.3%, 33.3% and 20.0%, respectively, and the protein expression level of TLR9 was gradually descending (P PANC-1 cells in CPG ODN 2216 treatment group were significantly lower than in the control group (P PANC-1 cells in treatment group was significantly decreased and CPG ODN2216 had an inhibitive effect in the growth of Panc-1 cells in a dose and time-dependent manner (P Panc-1 cells.

  1. Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I-deficient and -proficient HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Šímová, Jana; Bubeník, Jan

    2006-01-01

    Roč. 118, č. 7 (2006), s. 1836-1842 ISSN 0020-7136 R&D Projects: GA ČR(CZ) GA301/04/0492 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * immunotherapy * CpG oligodeoxynucleotides Subject RIV: EC - Immunology Impact factor: 4.693, year: 2006

  2. Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

  3. A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide

    Science.gov (United States)

    Shen, Hong; Iwasaki, Akiko

    2006-01-01

    Topical microbicides represent a promising new approach to preventing HIV and other sexually transmitted infections. TLR agonists are ideal candidates for microbicides, as they trigger a multitude of antiviral genes effective against a broad range of viruses. Although vaginal application of CpG oligodeoxynucleotides (ODNs) and poly I:C has been shown to protect mice from genital herpes infection, the mechanism by which these agents provide protection remains unclear. Here, we show that plasmacytoid DCs (pDCs) are required for CpG ODN–mediated protection against lethal vaginal challenge with herpes simplex virus type 2 (HSV-2). Moreover, we demonstrate that cells of both the hematopoietic and stromal compartments must respond to CpG ODN via TLR9 and to type I IFNs through IFN-αβ receptor (IFN-αβR) for protection. Thus, crosstalk between pDCs and vaginal stromal cells provides for optimal microbicide efficacy. Our results imply that temporally and spatially controlled targeting of CpG ODN to pDCs and epithelial cells can potentially maximize their effectiveness as microbicides while minimizing the associated inflammatory responses. PMID:16878177

  4. CPG-Based Locomotion Control of a Robotic Fish : Using Linear Oscillators and Reducing Control Parameters via PSO

    NARCIS (Netherlands)

    Wang, Chen; Xie, G.; Wang, L.; Cao, M.

    The aim of the present study is to investigate the locomotion control of a robotic fish. To achieve this goal, we design a control architecture based on a novel central pattern generator (CPG) and implement it as a system of coupled linear oscillators. This design differs significantly from the

  5. Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP)

    NARCIS (Netherlands)

    Hughes, L.A.E.; Simons, C.C.J.M.; Brandt, P.A. van den; Goldbohm, R.A.; Goeij, A.F. de; Bruïne, A.P. de; Engeland, M. van; Weijenberg, M.P.

    2011-01-01

    Background: We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Methods: In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.3 years of follow-up, 603

  6. Long-range autocorrelations of CpG islands in the human genome.

    Directory of Open Access Journals (Sweden)

    Benjamin Koester

    Full Text Available In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes.

  7. CpG Island Methylation in Colorectal Cancer: Past, Present and Future

    Directory of Open Access Journals (Sweden)

    Karen Curtin

    2011-01-01

    Full Text Available The concept of a CpG island methylator phenotype, or CIMP, quickly became the focus of several colorectal cancer studies describing its clinical and pathological features after its introduction in 1999 by Toyota and colleagues. Further characterization of CIMP in tumors lead to widespread acceptance of the concept, as expressed by Shen and Issa in their 2005 editorial, “CIMP, at last.” Since that time, extensive research efforts have brought great insights into the epidemiology and prognosis of CIMP+ tumors and other epigenetic mechanisms underlying tumorigenesis. With the advances in technology and subsequent cataloging of the human methylome in cancer and normal tissue, new directions in research to understand CIMP and its role in complex biological systems yield hope for future epigenetically based diagnostics and treatments.

  8. The CpG island methylator phenotype (CIMP) in colorectal cancer.

    Science.gov (United States)

    Nazemalhosseini Mojarad, Ehsan; Kuppen, Peter Jk; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

    2013-01-01

    It is clear that colorectal cancer (CRC) develops through multiple genetic and epigenetic pathways. These pathways may be determined on the basis of three molecular features: (i) mutations in DNA mismatch repair genes, leading to a DNA microsatellite instability (MSI) phenotype, (ii) mutations in APC and other genes that activate Wnt pathway, characterized by chromosomal instability (CIN) phenotype, and (iii) global genome hypermethylation, resulting in switch off of tumor suppressor genes, indicated as CpG island methylator phenotype (CIMP). Each of these pathways is characterized by specific pathological features, mechanisms of carcinogenesis and process of tumor development. The molecular aspects of these pathways have been used clinically in the diagnosis, screening and management of patients with colorectal cancer. In this review we especially describe various aspects of CIMP, one of the important and rather recently discovered pathways that lead to colorectal cancer.

  9. Euthyroid goitre with and without functional autonomy: A comparison

    International Nuclear Information System (INIS)

    Hillenhinrichs, H.; Emrich, D.

    1998-01-01

    Analysis of functional autonomy in euthyroid goitre. Methods: In an area of moderate iodine deficiency 163 goitrous patients without and 179 with functional autonomy all clinically euthyroid were compared by sex, age, signs and symptoms, sonographic results, qualitative and quantitative scintigraphy without and with suppression, TRH test, hormone concentrations and iodine excretion in the urine. Results: Age, signs and symptoms, thyroid volume and structure did not contribute sufficiently to diagnosis. To detect functional autonomy quantitative scintigraphy under suppression was superior to the TRH test. Increased hormone concentrations were observed in 15% of patients with functional autonomy. A global 99m Tc thyroid uptake of ≥3% under suppression indicates a higher risk of spontaneous hyperthyroidism. It was present in 20% of patients with functional autonomy. Conclusion: to diagnose and treat adequately functional autonomy in euthyroid goitre quantitative scintigraphy, determination of TSH and hormone concentrations are inevitable. (orig.) [de

  10. Autonomy and Housing Accessibility Among Powered Mobility Device Users

    Science.gov (United States)

    Brandt, Åse; Lexell, Eva Månsson; Iwarsson, Susanne

    2015-01-01

    OBJECTIVE. To describe environmental barriers, accessibility problems, and powered mobility device (PMD) users’ autonomy indoors and outdoors; to determine the home environmental barriers that generated the most housing accessibility problems indoors, at entrances, and in the close exterior surroundings; and to examine personal factors and environmental components and their association with indoor and outdoor autonomy. METHOD. This cross-sectional study was based on data collected from a sample of 48 PMD users with a spinal cord injury (SCI) using the Impact of Participation and Autonomy and the Housing Enabler instruments. Descriptive statistics and logistic regression were used. RESULTS. More years living with SCI predicted less restriction in autonomy indoors, whereas more functional limitations and accessibility problems related to entrance doors predicted more restriction in autonomy outdoors. CONCLUSION. To enable optimized PMD use, practitioners must pay attention to the relationship between client autonomy and housing accessibility problems. PMID:26356666

  11. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    James Crooks

    2017-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

  12. Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

    Science.gov (United States)

    Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

    2013-11-01

    Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Autonomy and job satisfaction for a sample of Greek teachers.

    Science.gov (United States)

    Koustelios, Athanasios D; Karabatzaki, Despina; Kousteliou, Ioanna

    2004-12-01

    Analysing the relation between Job Satisfaction and Autonomy in a sample of 300 Greek teachers (114 men and 186 women, 28 to 59 years old) from primary and secondary schools, showed statistically significant positive correlations between Job Satisfaction and Autonomy. Particularly, Autonomy was correlated with Job Itself (.21), Supervision (.22), and the Organizational as a Whole (.27), aspects of Job Satisfaction. Findings are in line with previous studies conducted in different cultural contexts. Percent common variance accounted for is small.

  14. Autonomy support for autonomous motivation in medical education.

    Science.gov (United States)

    Kusurkar, Rashmi A; Croiset, Gerda

    2015-01-01

    Medical students often study only to fare well in their examinations or pursue a specific specialty, or study only those topics that they perceive to be useful in medical practice. The motivation for study in these cases comes from external or internal pressures or from the desire to obtain rewards. Self-determination theory (SDT) classifies this type of motivation as controlled motivation and the type of motivation that comes from genuine interest or personal value as autonomous motivation. Autonomous motivation, in comparison with controlled motivation, has been associated with better learning, academic success, and less exhaustion. SDT endorses autonomous motivation and suggests that autonomy support is important for autonomous motivation. The meaning of autonomy is misinterpreted by many. This article tries to focus on how to be autonomy-supportive in medical education. Autonomy support refers to the perception of choice in learning. Some of the ways of supporting autonomy in medical education are small group teaching, problem-based learning, and gradual increase in responsibility of patients. Autonomy-supportive teaching behavior is not a trait and can be learned. Autonomy support in medical education is not limited to bringing in changes in the medical curriculum for students; it is about an overall change in the way of thinking and working in medical schools that foster autonomy among those involved in education. Research into autonomy in medical education is limited. Some topics that need to be investigated are the ideas and perceptions of students and teachers about autonomy in learning. Autonomy support in medical education can enhance autonomous motivation of students for medical study and practice and make them autonomy-supportive in their future medical practice and teaching.

  15. Autonomy support for autonomous motivation in medical education

    Directory of Open Access Journals (Sweden)

    Rashmi A. Kusurkar

    2015-05-01

    Full Text Available Background: Medical students often study only to fare well in their examinations or pursue a specific specialty, or study only those topics that they perceive to be useful in medical practice. The motivation for study in these cases comes from external or internal pressures or from the desire to obtain rewards. Self-determination theory (SDT classifies this type of motivation as controlled motivation and the type of motivation that comes from genuine interest or personal value as autonomous motivation. Autonomous motivation, in comparison with controlled motivation, has been associated with better learning, academic success, and less exhaustion. SDT endorses autonomous motivation and suggests that autonomy support is important for autonomous motivation. The meaning of autonomy is misinterpreted by many. This article tries to focus on how to be autonomy-supportive in medical education. Discussion: Autonomy support refers to the perception of choice in learning. Some of the ways of supporting autonomy in medical education are small group teaching, problem-based learning, and gradual increase in responsibility of patients. Autonomy-supportive teaching behavior is not a trait and can be learned. Autonomy support in medical education is not limited to bringing in changes in the medical curriculum for students; it is about an overall change in the way of thinking and working in medical schools that foster autonomy among those involved in education. Research into autonomy in medical education is limited. Some topics that need to be investigated are the ideas and perceptions of students and teachers about autonomy in learning. Conclusion: Autonomy support in medical education can enhance autonomous motivation of students for medical study and practice and make them autonomy-supportive in their future medical practice and teaching.

  16. Learner Autonomy in Language Education : A Cross-Cultural Perspective

    OpenAIRE

    Kojima, Hideo

    2006-01-01

    In recent years, the importance of developing learner autonomy in language education hasbeen one of its more prominent themes in Japan as well as in the West. In spite of agreementconcerning its importance, there remains a good deal of uncertainty about its meaning inteaching and learning English as a foreign language (EFL). This paper aims to consider theconcept of learner autonomy amongst different cultures. Autonomy has a social as well as anindividual dimension. The promotion of learner a...

  17. Learner Autonomy in Foreign Language Education and in Cultural Context

    OpenAIRE

    Ivanovska, Biljana

    2015-01-01

    The present paper is a brief review of the theoretical concepts about learner autonomy focusing on highlighting the main themes on learner autonomy in foreign language education and in cultural context as a globalized construct. These themes are based on the concepts of learner responsibility and independence, the importance of the autonomy in foreign language education in both the Western and Eastern style and the role of the culture in the concept of learner independence. The present study ...

  18. Psychological autonomy and hierarchical relatedness as organizers of developmental pathways

    OpenAIRE

    Keller, Heidi

    2016-01-01

    The definition of self and others can be regarded as embodying the two dimensions of autonomy and relatedness. Autonomy and relatedness are two basic human needs and cultural constructs at the same time. This implies that they may be differently defined yet remain equally important. The respective understanding of autonomy and relatedness is socialized during the everyday experiences of daily life routines from birth on. In this paper, two developmental pathways are portrayed that emphasize d...

  19. School staff autonomy and educational performance: within school type evidence

    OpenAIRE

    VERSCHELDE, Marijn; HINDRIKS, Jean; RAYP, Glenn; SCHOORS, Koen

    2012-01-01

    This paper shows the effect of school staff autonomy on educational performance. The distinctive feature with existing literature is that we employ variation in autonomy within the same country and within the same school type to reduce the omitted variables problems. To fully capture the informational advantage of local actors, we define autonomy as the operational empowerment of the school’s direction and teachers. The Flemish secondary school system in Belgium is analyzed as it displays uni...

  20. Adolescent autonomy revisited: clinicians need clearer guidance.

    Science.gov (United States)

    Brierley, Joe; Larcher, Victor

    2016-08-01

    In 1996, Brazier and Bridge raised the question 'is adolescent autonomy truly dead and buried' following judicial decisions which had seemed to reverse the Gillick-inspired trend for greater child autonomy in healthcare. Subsequent decisions by the courts have reinforced the view that those below 18 years in England and Wales remain children with limited rights to refuse treatment compared with adults. This is at variance with the daily experience of those working with young people who increasingly seek to actively involve them in making freely informed decisions about their healthcare, in accordance with the principles enunciated in the UN Convention of the Rights of the Child and the UK Children Acts. We review the derivation of the law in England and Wales in this area, in the light of another recent family court judgement enforcing treatment on a 'competent' child without his or her consent and ask: 'How can the Common Law and the ethical practice of those caring for young people have diverged so far?' Either young people can decide whether to have a recommended treatment, or they cannot. Given Ian McEwan's book, the Children Act, has stimulated wider social debate in this area might this be an opportune moment to seek public policy resolution with regards to healthcare decision making by young people? We argue that events since the Gillick case have underlined the need for a comprehensive review of legal policy and practice in this area. While absolute autonomy and freedom of choice are arguably inconsistent with the protection rights that society has agreed are owed to children, healthcare practitioners need clarity over the circumstances in which society expects that autonomous choices of adolescents can be overridden. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Experienced job autonomy among maternity care professionals in The Netherlands.

    Science.gov (United States)

    Perdok, Hilde; Cronie, Doug; van der Speld, Cecile; van Dillen, Jeroen; de Jonge, Ank; Rijnders, Marlies; de Graaf, Irene; Schellevis, François G; Verhoeven, Corine J

    2017-11-01

    High levels of experienced job autonomy are found to be beneficial for healthcare professionals and for the relationship with their patients. The aim of this study was to assess how maternity care professionals in the Netherlands perceive their job autonomy in the Dutch maternity care system and whether they expect a new system of integrated maternity care to affect their experienced job autonomy. A cross-sectional survey. The Leiden Quality of Work Life Questionnaire was used to assess experienced job autonomy among maternity care professionals. Data were collected in the Netherlands in 2015. 799 professionals participated of whom 362 were primary care midwives, 240 obstetricians, 93 clinical midwives and 104 obstetric nurses. The mean score for experienced job autonomy was highest for primary care midwives, followed by obstetricians, clinical midwives and obstetric nurses. Primary care midwives scored highest in expecting to lose their job autonomy in an integrated care system. There are significant differences in experienced job autonomy between maternity care professionals. When changing the maternity care system it will be a challenge to maintain a high level of experienced job autonomy for professionals. A decrease in job autonomy could lead to a reduction in job related wellbeing and in satisfaction with care among pregnant women. Copyright © 2017. Published by Elsevier Ltd.

  2. Autonomy and reason: treatment choice in breast cancer.

    Science.gov (United States)

    Twomey, Mary

    2012-10-01

    The practice of offering choice to those women with breast cancer for whom either breast conserving surgery or mastectomy would be equally beneficial has come to be seen as an important aspect of medical care. As well as improving satisfaction with treatment, this is seen as satisfying the ethical principle of respect for autonomy. A number of studies, however, show that women are not always comfortable with such choice, preferring to leave treatment decisions to their surgeons. A question then arises as to the extent that these women can be seen as autonomous or as exercising autonomy. This paper argues, however, that the understanding of autonomy which is applied in current approaches to breast cancer care does not adequately support the exercise of autonomy, and that the clinical context of care means that women are not able to engage in the kind of reasoning that might promote the exercise of autonomy. Where respect for autonomy is limited to informed consent and choice, there is a danger that women's interests are overlooked in those aspects of their care where choice is not appropriate, with very real, long-term consequences for some women. Promoting the exercise of autonomy, it is argued, needs to go beyond the conception of autonomy as rational individuals making their own decisions, and clinicians need to work with an understanding of autonomy as relational in order to better involve women in their care. © 2012 Blackwell Publishing Ltd.

  3. [Autonomy: to what extent is the concept relevant in psychiatry?].

    Science.gov (United States)

    de Wit, F A

    2012-01-01

    Autonomy is an important concept in psychiatry, but because it is a somewhat abstract and ambiguous notion, it is not applicable in its entirety in a psychiatric context. This becomes obvious in situations where patients are receiving long term care and treatment. To modify the concept of autonomy in such a way that it acquires an extra dimension that renders it applicable to daily psychiatric practice. The literature was reviewed in order to find articles that reveal the tensions that arise between autonomy and dependence in psychiatry and that reflect the human characteristics that are concealed behind the modern concepts of autonomy, freedom and respect for autonomy. Concepts such as person, identity, acknowledgement, dialogical ethics and life histories are used as an addition to the concepts of autonomy of Kant and Mill. A phenomenological and a context sensitive conception of autonomy is needed within the perspective of dialogical ethics. A dialogical perspective requires from psychiatric professionals a susceptibility for what the patient as a human being really has to say. On the basis of a dialogue where there is space and attention for life histories, backgrounds and the potentials of patients, a new perspective can be developed that is shared by the persons involved. In psychiatry, statements about real autonomy and genuine respect for autonomy are only truly meaningful within the context of doctors, nurses and patients. A hermeneutic approach to patients which involves dialogue creates new opportunities in the field of staff-patient relations.

  4. Concept analysis: patient autonomy in a caring context.

    Science.gov (United States)

    Lindberg, Catharina; Fagerström, Cecilia; Sivberg, Bengt; Willman, Ania

    2014-10-01

    This paper is a report of an analysis of the concept of patient autonomy Many problems regarding patient autonomy in healthcare contexts derive from the patient's dependent condition as well as the traditional authoritarian position of healthcare professionals. Existing knowledge and experience reveal a lack of consensus among nurses regarding the meaning of this ethical concept. Concept analysis. Medline, CINAHL, The Cochrane Library and PsycINFO were searched (2005-June 2013) using the search blocks 'autonomy', 'patient' and 'nursing/caring'. A total of 41 articles were retrieved. The Evolutionary Method of Concept Analysis by Rodgers was used to identify and construct the meaning of the concept of patient autonomy in a caring context. Five attributes were identified, thus creating the following descriptive definition: 'Patient autonomy is a gradual, time-changing process of (re-)constructing autonomy through the interplay of to be seen as a person, the capacity to act and the obligation to take responsibility for one's actions'. Patient vulnerability was shown to be the antecedent of patient autonomy and arises due to an impairment of a person's physical and/or mental state. The consequences of patient autonomy were discussed in relation to preserving control and freedom. Patient autonomy in a caring context does not need to be the same before, during and after a care episode. A tentative model has been constructed, thus extending the understanding of this ethical concept in a caring context. © 2014 John Wiley & Sons Ltd.

  5. Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT).

    Science.gov (United States)

    Francis, R J; Mather, S J; Chester, K; Sharma, S K; Bhatia, J; Pedley, R B; Waibel, R; Green, A J; Begent, R H J

    2004-08-01

    MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

  6. Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT)

    International Nuclear Information System (INIS)

    Francis, R.J.; Chester, K.; Sharma, S.K.; Bhatia, J.; Pedley, R.B.; Green, A.J.; Begent, R.H.J.; Mather, S.J.; Waibel, R.

    2004-01-01

    MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99m Tc-carbonyl [ 99m Tc(H 2 O) 3 (CO) 3 ] + (abbreviated to TcCO) mediated labelling of 99m Tc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins. (orig.)

  7. Autonomie du groupe restreint et performance

    Directory of Open Access Journals (Sweden)

    Elke Nissen

    2005-09-01

    Full Text Available Un groupe est autonome lorsqu'il prend lui-même en charge sa gestion (Abric, 1996 et lorsque celle-ci fonctionne bien. L'autonomie du groupe restreint est une caractéristique revendiquée dans le cadre actuel de l'expansion de dispositifs collaboratifs à distance entre apprenants. La question qui se pose alors est de savoir si un groupe restreint autonome est plus performant qu'un groupe moins autonome. L'autonomie d'un groupe d'apprentissage en ligne est-elle en relation avec la qualité de la réalisation de la tâche ? Est-elle en relation avec les progrès réalisés par les membres du groupe ? Dans le cadre de notre étude expérimentale, menée dans deux dispositifs pédagogiques différents (l'environnement d'apprentissage Babbelnet et une formation sur la plate-forme Acolad, des étudiants ont réalisé en groupes restreints, avec l'accompagnement d'un tuteur, une tâche de type actionnel – en l'occurrence une rédaction en langue étrangère (allemand ou anglais. Pour ce faire, ils disposaient d'aides méthodologiques et linguistiques dans l'environnement pédagogique en ligne. Ils ont interagi par le biais d'Internet au moyen de différents outils de communication. Une analyse de l'interaction qui a eu lieu dans chaque groupe, l'évaluation des rédactions réalisées conjointement, deux tests réalisés respectivement avant et après la phase de travail en groupe ainsi qu'un formulaire auto-administré nous permettent de mettre en lien l'autonomie des groupes, d'une part, et leur performance, voire leur apprentissage, d'autre part. Au vu de cette étude, il apparaît que l'autonomie du groupe n'a pas d'influence directe sur l'apprentissage des groupes restreints. En revanche, un rapport est visible entre l'appréciation du fonctionnement du groupe par ses membres et l'évolution de la performance des groupes.

  8. Learner autonomy, self regulation and metacognition

    Directory of Open Access Journals (Sweden)

    Feryal Çubukcu

    2009-10-01

    Full Text Available Different theories try to explain why some students are more successful than the others. Phenomenologists (Mc Combs, 1989 study self concepts of the students and find such students prone to achieve more. Attributional Theorists (Dweck, 1986; Weiner, 2005 focus on personal outcome such as effort or ability. Metacognitive theorists (Pressley, 2000; Schunk, Pintrich & Meece, 2007 examine students’ self regulated learning strategies whereas Constructivists (Maxim, 2009; Paris & Byrnes, 1989 believe supportive environments are important to be successful. In this study, the metacognitive theory will be given more importance and the purpose of the article is to find the correlation between self regulation, metacognition and autonomy.

  9. Resident Autonomy in the Operating Room: Expectations Versus Reality.

    Science.gov (United States)

    Meyerson, Shari L; Sternbach, Joel M; Zwischenberger, Joseph B; Bender, Edward M

    2017-09-01

    There is concern about graduating thoracic trainees' independent operative skills due to limited autonomy in training. This study compared faculty and trainee expected levels of autonomy with intraoperative measurements of autonomy for common cardiothoracic operations. Participants underwent frame-of-reference training on the 4-point Zwisch scale of operative autonomy (show and tell → active help → passive help → supervision only) and evaluated autonomy in actual cases using the Zwisch Me!! mobile application. A separate "expected autonomy" survey elicited faculty and resident perceptions of how much autonomy a resident should have for six common operations: decortication, wedge resection, thoracoscopic lobectomy, coronary artery bypass grafting, aortic valve replacement, and mitral valve repair. Thirty-three trainees from 7 institutions submitted evaluations of 596 cases over 18 months (March 2015 to September 2016). Thirty attendings subsequently provided their evaluation of 476 of those cases (79.9% response rate). Expected autonomy surveys were completed by 21 attendings and 19 trainees from 5 institutions. The six operations included in the survey constituted 47% (226 of 476) of the cases evaluated. Trainee and attending expectations did not differ significantly for senior trainees. Both groups expected significantly higher levels of autonomy than observed in the operating room for all six types of cases. Although faculty and trainees both expect similar levels of autonomy in the operating room, real-time measurements of autonomy show a gap between expectations and reality. Decreasing this gap will require a concerted effort by both faculty and residents to focus on the development of independent operative skills. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Bankruptcy Prediction Based on the Autonomy Ratio

    Directory of Open Access Journals (Sweden)

    Daniel Brîndescu Olariu

    2016-11-01

    Full Text Available The theory and practice of the financial ratio analysis suggest the existence of a negative correlation between the autonomy ratio and the bankruptcy risk. Previous studies conducted on a sample of companies from Timis County (largest county in Romania confirm this hypothesis and recommend the autonomy ratio as a useful tool for measuring the bankruptcy risk two years in advance. The objective of the current research was to develop a methodology for measuring the bankruptcy risk that would be applicable for the companies from the Timis County (specific methodologies are considered necessary for each region. The target population consisted of all the companies from Timis County with annual sales of over 10,000 lei (aprox. 2,200 Euros. The research was performed over all the target population. The study has thus included 53,252 yearly financial statements from the period 2007 – 2010. The results of the study allow for the setting of benchmarks, as well as the configuration of a methodology of analysis. The proposed methodology cannot predict with perfect accuracy the state of the company, but it allows for a valuation of the risk level to which the company is subjected.

  11. Mount Athos: Between autonomy and statehood

    Directory of Open Access Journals (Sweden)

    Avramović Dragutin

    2013-01-01

    Full Text Available Legal status of the Mount Athos is characterized by many special features that make it internationally unique legal regime. The author analyzes peculiarities of Mount Athos territorial status, legal position of residents and visitors, as well as organization of Mount Athos authorities. The author concludes that the Mount Athos is characterized by a kind of para-sovereignty. Its autonomy involves not only the internal organization, autonomous governance and religious autonomy, but it also includes many elements of secular life of their visitors. Mount Athos has its own, separate legislative, administrative and judicial powers, while the Statute of the Mount Athos has greater legal force than all the other laws of the Greek state, because the state can not unilaterally change its provisions. Having in mind that the wide self-government is vested in church authorities and that the monks have very specific way of living, the author takes a position that the Mount Athos represent 'monastic state', but without statehood. The author also states that the Mount Athos will be faced with many challenges in the context of spreading of an assimilating, universal conception of human rights.

  12. [Respecting minors' autonomy in child custody cases].

    Science.gov (United States)

    Santa Rosa, Bárbara; Corte-Real, Francisco; Vieira, Duarte Nuno

    2013-01-01

    Child custody decisions are among the most difficult for judges to make. The possibility of child abuse allegations or parents' deviant/ psychopathologic behaviours within this context, make the decision further complicated. Based on jurisprudence the listening of children opinion is a way to protect their best interest. In fact children have the right to express an opinion in all matters affecting their life. It should be given proper consideration to children opinion according with his/her age and maturity. Nonetheless custody disputes are emotionally draining issues. Asking the child to express an opinion during a public hearing, most likely in the presence of both parents, its not recommended because this is a potential stressful experience. Child interviews should take place in a proper environment and be set to their age. Medicine and Psychology have an important role in assessing children cognitive, emotional and volitional abilities, which is essential to properly account their opinions according to autonomy degree. This essay analyses the contribution of medico-legal and/or psychological exams to respect the autonomy of the child in cases of regulation of parental responsibilities. The conclusion is the need to establish a symbiotic relationship between the medical and legal perspectives of the (open) concept of child's best interests.

  13. CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

    Directory of Open Access Journals (Sweden)

    Monica Molano

    Full Text Available Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC are associated with human papillomavirus (HPV. Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS and laser capture microdissected (LCM tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

  14. The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells

    International Nuclear Information System (INIS)

    Yokoyama, Seiya; Yonezawa, Suguru; Kitamoto, Sho; Yamada, Norishige; Houjou, Izumi; Sugai, Tamotsu; Nakamura, Shin-ichi; Arisaka, Yoshifumi; Takaori, Kyoichi; Higashi, Michiyo

    2012-01-01

    Methylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. Here, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis) using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE). The MSE method is comprised of the following steps: (a) bisulfite treatment of genomic DNA, (b) amplification of the target DNA by a nested PCR approach and (c) applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices. The MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is < 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We also show that MSE can be used for analysis of challenging samples such as human isolated colonic crypts or human pancreatic juices, from which only a small amount of DNA can be extracted. The MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical

  15. Experienced job autonomy among maternity care professionals in The Netherlands

    NARCIS (Netherlands)

    Perdok, H.; Cronie, D.; Speld, C. van der; Dillen, J. van; Jonge, A . de; Rijnders, M.; Graaf, I. de; Schellevis, F.G.; Verhoeven, C.J.

    2017-01-01

    OBJECTIVE: High levels of experienced job autonomy are found to be beneficial for healthcare professionals and for the relationship with their patients. The aim of this study was to assess how maternity care professionals in the Netherlands perceive their job autonomy in the Dutch maternity care

  16. Experienced job autonomy among maternity care professionals in The Netherlands

    NARCIS (Netherlands)

    Perdok, Hilde; Cronie, Doug; van der Speld, Cecile; van Dillen, Jeroen; de Jonge, Ank; Rijnders, Marlies; de Graaf, Irene; Schellevis, François G.; Verhoeven, Corine J.

    2017-01-01

    Objective: High levels of experienced job autonomy are found to be beneficial for healthcare professionals and for the relationship with their patients. The aim of this study was to assess how maternity care professionals in the Netherlands perceive their job autonomy in the Dutch maternity care

  17. Experienced job autonomy among maternity care professionals in The Netherlands

    NARCIS (Netherlands)

    Perdok, H.; Cronie, D.; Speld, C. van der; Dillen, J. van; Jonge, A. de; Rijnders, M.; Graaf, I. de; Schellevis, F.G.; Verhoeven, G.

    2017-01-01

    Objective High levels of experienced job autonomy are found to be beneficial for healthcare professionals and for the relationship with their patients. The aim of this study was to assess how maternity care professionals in the Netherlands perceive their job autonomy in the Dutch maternity care

  18. Experienced job autonomy among maternity care professionals in The Netherlands.

    NARCIS (Netherlands)

    Perdok, H.; Cronie, D.; Speld, C. van der; Dillen, J. van; Jonge, A. de; Rijnders, M.; Graaf, J. de; Schellevis, F.; Verhoeven, C.

    2017-01-01

    Objective: High levels of experienced job autonomy are found to be beneficial for healthcare professionals and for the relationship with their patients. The aim of this study was to assess how maternity care professionals in the Netherlands perceive their job autonomy in the Dutch maternity care

  19. 40 CFR 73.86 - State regulatory autonomy.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State regulatory autonomy. 73.86 Section 73.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulatory autonomy. Nothing in this subpart shall preclude a State or State regulatory authority from...

  20. Attachment, Autonomy, and Emotional Reliance: A Multilevel Model

    Science.gov (United States)

    Lynch, Martin F.

    2013-01-01

    This article reports a test of a multilevel model investigating how attachment security and autonomy contribute to emotional reliance, or the willingness to seek interpersonal support. Participants ("N" = 247) completed online measures of attachment, autonomy, emotional reliance, and vitality with respect to several everyday…

  1. The Need for Authenticity-Based Autonomy in Medical Ethics.

    Science.gov (United States)

    White, Lucie

    2017-08-11

    The notion of respect for autonomy dominates bioethical discussion, though what qualifies precisely as autonomous action is notoriously elusive. In recent decades, the notion of autonomy in medical contexts has often been defined in opposition to the notion of autonomy favoured by theoretical philosophers. Where many contemporary theoretical accounts of autonomy place emphasis on a condition of "authenticity", the special relation a desire must have to the self, bioethicists often regard such a focus as irrelevant to the concerns of medical ethics, and too stringent for use in practical contexts. I argue, however, that the very condition of authenticity that forms a focus in theoretical philosophy is also essential to autonomy and competence in medical ethics. After tracing the contours of contemporary authenticity-based theories of autonomy, I consider and respond to objections against the incorporation of a notion of authenticity into accounts of autonomy designed for use in medical contexts. By looking at the typical problems that arise when making judgments concerning autonomy or competence in a medical setting, I reveal the need for a condition of authenticity-as a means of protecting choices, particularly high-stakes choices, from being restricted or overridden on the basis of intersubjective disagreement. I then turn to the treatment of false and contestable beliefs, arguing that it is only through reference to authenticity that we can make important distinctions in this domain. Finally, I consider a potential problem with my proposed approach; its ability to deal with anorexic and depressive desires.

  2. Dutch dilemmas: Decentralization, school autonomy and professionalization of teachers

    NARCIS (Netherlands)

    Sleegers, P.; Wesselingh, A.

    1995-01-01

    The policy of decentralisation of the Dutch Ministry of Education, Culture and Science is aimed at increasing the autonomy of schools. This policy is also considered an appropriate strategy for the revitalisation of the teaching profession. Decentralisation, school autonomy and professionalisation

  3. A Study of Autonomy English Learning on the Internet

    Science.gov (United States)

    Zhong, Yunsheng

    2008-01-01

    With the variety of environment and method of English learning, Autonomy English learning on the Internet is playing a more and more important role in modern English learning. It challenges the traditional learning approach, and also is forwardness. This paper points out that autonomy English learning on the Internet facilitates the improvement of…

  4. School Autonomy: A Comparison between China and the United States

    Science.gov (United States)

    Xia, Jiangang; Gao, Xingyuan; Shen, Jianping

    2017-01-01

    This study examined and compared school autonomy in China and the United States. Based on the international PISA 2012 school data, the authors examined three aspects of school autonomy. We found that in comparison with the United States, (1) principals from China were less likely to have responsibility over eleven school decisions (hiring…

  5. On the relations between parents' ideals and children's autonomy

    NARCIS (Netherlands)

    de Ruyter, D.J.; Schinkel, A.

    2013-01-01

    In this article Doret J. de Ruyter and Anders Schinkel argue that parents' ideals can enhance children's autonomy, but that they may also have a detrimental effect on the development of children's autonomy. After describing the concept of ideals and elucidating a systems theoretical conception of

  6. Relations among Autonomy, Attribution Style, and Happiness in College Students

    Science.gov (United States)

    O'Donnell, Susan L.; Chang, Kelly B.; Miller, Kristen S.

    2013-01-01

    Research suggests that a personal sense of autonomy supports individuals' success in a variety of domains, but information regarding these processes remains unclear. This paper attempts to establish a link between personal autonomy and cognitive processes, in the form of attributions for success and failure, in establishing a sense of subjective…

  7. "The Pleasure Is All Mine": Music and Female Sexual Autonomy

    OpenAIRE

    Strube, Miriam

    2004-01-01

    To analyze sexual autonomy this paper concentrates on the recent concept of relational autonomy, which is different from the classic tradition in its multilevel perspective on persons as embodied, desiring, creative as well as rational creatures. I then apply this concept to music asking in which way women performers are both relational and (sexually) autonomous.

  8. Measuring local autonomy: A decision-making approach

    NARCIS (Netherlands)

    Fleurke, F.; Willemse, R.

    2006-01-01

    In studies on central-local relations it is common to assess local autonomy in a deductive way. The extent of local autonomy is determined by measuring the central legal and financial competence, after which the remaining room for local decision-making is determined. The outcome of this indirect

  9. Review of "Charter School Autonomy: A Half-Broken Promise"

    Science.gov (United States)

    Gulosino, Charisse

    2010-01-01

    This report concludes that autonomy is a prerequisite for innovative and effective charter schools to emerge. Especially important is freedom from external bureaucratic control. Yet there is nothing in this report that addresses levels of autonomy in relationship to financial performance, resource allocation practices, academic results, and other…

  10. Documenting Different Domains of Promotion of Autonomy in Families

    Science.gov (United States)

    Manzi, Claudia; Regalia, Camillo; Pelucchi, Sara; Fincham, Frank D.

    2012-01-01

    Parental promotion of autonomy for offspring well-being has been widely recognized in developmental psychology. Recent studies, however, show that this association varies across cultures. Such variation may reflect inappropriate measurement of this dimension of parenting. Therefore, three existing measures of promotion of autonomy were used to…

  11. Issues of promoting learner autonomy in EFL context

    Directory of Open Access Journals (Sweden)

    Pichugova Inna L.

    2016-01-01

    Full Text Available The paper is focuded on investigating the phenomenon of learner autonomy, which has mostly been explored in Europe and the USA and is now attracting attention of researchers and academics in many other countries including Russia. Learner autonomy through a focus on learner reflection and taking responsibility for one’s own learning processes has become a central concern in the recent history of language teaching. However, many language teachers, who are committed to concepts of learnercentredness and autonomy, struggle with the ways to foster learner autonomy or at least to encourage the idea of learner autonomy in language classroom. The study aims at investigating what the most important issues which have a great impact on developing learner autonomy are. Having given special attention to conditions which can insure development of learner autonomy, a model covering seven issues relating to the subject matter has been designed. The authors state that such aspects as choice, goals and needs, support, emotional climate, learning strategies, learner attitude and motivation, and self-esteem should be considered as the goal to promote learner autonomy in EFL context.

  12. the doctrine of party autonomy in international commercial arbitration

    African Journals Online (AJOL)

    RAYAN_

    provoke discussions in many fora on the applicability of party autonomy in international ... questions, this article analyses the principle of party autonomy. The ultimate aim of .... 12 Odoe, (n 1) 48; English Arbitration Act 1996 s 6. 13 Odoe ibid ...

  13. Workload Measurement in Human Autonomy Teaming: How and Why?

    Science.gov (United States)

    Shively, Jay

    2016-01-01

    This is an invited talk on autonomy and workload for an AFRL Blue Sky workshop sponsored by the Florida Institute for Human Machine Studies. The presentation reviews various metrics of workload and how to move forward with measuring workload in a human-autonomy teaming environment.

  14. School Autonomy, Leadership and Student Achievement: Reflections from Finland

    Science.gov (United States)

    Saarivirta, Toni; Kumpulainen, Kristiina

    2016-01-01

    Purpose: The purpose of this paper is to provide national information on school autonomy, leadership and student achievements in Finland. Design/methodology/approach: The paper is a literature review on Finnish studies focusing on school autonomy, leadership and student achievement. The studies have been reviewed on the basis of a content…

  15. Italian Adaptation of the "Autonomy and Relatedness Coding System"

    Directory of Open Access Journals (Sweden)

    Sonia Ingoglia

    2013-08-01

    Full Text Available The study examined the applicability of the observational technique developed by Allen and colleagues (Allen, Hauser, Bell, & O’Connor, 1994; Allen, Hauser, et al., 2003 to investigate the issues of autonomy and relatedness in parent-adolescent relationship in the Italian context. Thirty-five mother-adolescent dyads participated to a task in which they discussed a family issue about which they disagree. Adolescents were also administered a self-report measure assessing their relationship with mothers. Mothers reported significantly higher levels of promoting and inhibiting autonomy, and promoting relatedness behaviors than their children. Results also suggested a partial behavioral reciprocity within the dyads, regarding promoting and inhibiting relatedness, and inhibiting autonomy. Finally, mothers’ inhibiting autonomy behaviors positively correlated to teens’ perception of their relationship as conflicting; adolescents’ inhibiting and promoting autonomy and inhibiting relatedness behaviors positively correlated to open confrontation, rejection and coolness, while promoting relatedness behaviors negatively correlated to open confrontation, rejection and coolness. The results suggest that, for Italian mothers, behaviors linked to autonomy seem to be associated with being involved in a more negative relationship with their children, even if not characterized by open hostility, while for Italian adolescents, behaviors linked to autonomy seem to be associated with threatening the closeness of the relationship. Globally, the findings suggest that the application of this observational procedure may help our understanding of youth autonomy and relatedness development in Italy, but they leave unanswered questions regarding its appropriate adaptation and the role played by cultural differences.

  16. Autonomy of nurse practitioners in primary care: An integrative review.

    Science.gov (United States)

    Choi, Min; De Gagne, Jennie C

    2016-03-01

    This integrative review of the existing literature was conducted to identify dimensions related to nurse practitioner (NP) autonomy and to recommend future areas of research related to the important topic of NP autonomy in this era of cost-conscious healthcare reform. Articles were identified from the following databases: CINAHL, MEDLINE, PubMed, Ovid, Scopus, Google Scholar, and EBSCO. Over 24 articles were found; 12 peer-reviewed articles met the inclusion criteria of research conducted with NPs, physicians, and patients. The results revealed three categories of association with regard to NP autonomy: job satisfaction, patient satisfaction, and physician-NP collaboration. This review was undertaken to advance understanding of autonomy among NPs and the dynamics involved in their delivery of care. Further research into the associations between NP autonomy and its dimensions are necessary to indicate a future direction to the NP role. ©2015 American Association of Nurse Practitioners.

  17. Autonomy, Respect, and Arrogance in the Danish Cartoon Controversy

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    2009-01-01

    is understood as something we should presume everyone possesses, it provides a strong basis for equal respect among people from diverse cultures. A Kantian conception of autonomy can justify the right to freedom of expression while it at the same time requires that we in the exercise of freedom of expression......Autonomy is increasingly rejected as a fundamental principle by liberal political theorists, because it is regarded as incompatible with respect for diversity. This article seeks, via an analysis of the Danish cartoon controversy, to show that the relationship between autonomy and diversity is more...... complex than often posited. Particularly, it asks whether the autonomy defense of freedom of expression encourages disrespect for religious feelings. Autonomy leads to disrespect for diversity only when it is understood as a character ideal that must be promoted as an end in itself. If it by contrast...

  18. Patient autonomy and informed consent in critically lll

    Directory of Open Access Journals (Sweden)

    Todorović Zoran M.

    2017-01-01

    Full Text Available Patient autonomy has been a cornerstone of contemporary clinical ethics since the Nuremberg trial, especially in American school of bioethics. Topic: Patient autonomy has been defined in the Nuremberg Code, and re-defined in the Declaration of Helsinki, Belmont Report and Barcelona Declaration. Founders and followers of the rights-oriented bioethics (for example, Hellegers, Beauchamp and Childers have established and promoted the patient autonomy as the main principle of bio(medical ethics since 1970s. However, there is a lot of controversy surrounding such a principle, especially in vulnerable patients. We aimed at evaluating the real meaning and value of patient autonomy in critical care settings regarding the communication between health workers and their patients and families. Conclusion: Protection of patients autonomy in critically ill is a complex issue. Careful benefit-risk assessment is needed in order to find the most appropriate way of obtaining the informed consent, proxy consent or to omit or delay it.

  19. [Psychiatric advance directives and the role of autonomy].

    Science.gov (United States)

    Ambrosini, Daniel L; Crocker, Anne G

    2009-01-01

    Although psychiatric advance directives (PADs) are grounded in the ethics of autonomy, the relationship between the two is unclear. PADs are legal documents that allow individuals with mental illness to record their treatment preferences should they become incompetent in the future. The relationship between autonomy and PADs has been discussed in ethical, legal, and philosophical terms, but has not been clearly operationalized for clinical purposes. Autonomy is a fundamental ethical value that includes having the independence from outside controlling influences and the mental capacity to direct one's personal actions. Individuals with mental illness sometimes require assistance to understand their ethical and legal rights with respect to autonomous choice, and professional stakeholders need education regarding the importance of autonomy for clinical practice. Competency to consent to treatment is the mental prerequisite that ensures individuals with mental illness are able to complete PADs with insight, whereas autonomy is the value that empowers individuals to work towards their recovery.

  20. Intelligent autonomy for unmanned naval systems

    Science.gov (United States)

    Steinberg, Marc

    2006-05-01

    This paper provides an overview of the development and demonstration of intelligent autonomy technologies for control of heterogeneous unmanned naval air and sea vehicles and describes some of the current limitations of such technologies. The focus is on modular technologies that support highly automated retasking and fully autonomous dynamic replanning for up to ten heterogeneous unmanned systems based on high-level mission objectives, priorities, constraints, and Rules-of-Engagement. A key aspect of the demonstrations is incorporating frequent naval operator evaluations in order to gain better understanding of the integrated man/machine system and its tactical utility. These evaluations help ensure that the automation can provide information to the user in a meaningful way and that the user has a sufficient level of control and situation awareness to task the system as needed to complete complex mission tasks. Another important aspect of the program is examination of the interactions of higher-level autonomy algorithms with other relevant components that would be needed within the decision-making and control loops. Examples of these are vision and other sensor processing algorithms, sensor fusion, obstacle avoidance, and other lower level vehicle autonomous navigation, guidance, and control functions. Initial experiments have been completed using medium and high-fidelity vehicle simulations in a virtual warfare environment and inexpensive surrogate vehicles in flight and in-water demonstrations. Simulation experiments included integration of multi-vehicle task allocation, dynamic replanning under constraints, lower level autonomous vehicle control, automatic assessment of the impact of contingencies on plans, management of situation awareness data, operator alert management, and a mixed-initiative operator interface. In-water demonstrations of a maritime situation awareness capability were completed in both a river and a harbor environment using unmanned surface

  1. Why job autonomy matters for young companies' performance: company maturity as a moderator between job autonomy and company performance

    NARCIS (Netherlands)

    Preenen, P.T.Y.; Howaldt, J.; Oeij, P.R.A.; Dhondt, S.; Kraan, K.O.; Jansen, E.

    2016-01-01

    Although the positive impact of job autonomy has been widely shown for individual-level employee outcomes, research on job autonomy and company-level outcomes has been surprisingly scarce. Therefore, among 3,311 companies in the Netherlands, we investigate the relationship between employees' job

  2. LEARNER AUTONOMY ON ESSAY WRITING ACCURACY

    Directory of Open Access Journals (Sweden)

    Mohammad Hafidz

    2018-01-01

    Full Text Available Abstract: Learner autonomy on writing is independently teaching and learning that keeps students’ control to explore their knowledge and experiences in written language, find out and evaluate their errors based on the conceptual courses to make accurately simple essay. The aim was to know the effectiveness of the learner autonomy on writing accuracy. This quantitative research conducted in one group pretest and posttest design. The number of samples was 21 students in Bangkalan. The instrument were tests to gain students’ writing score before and after treatment. Researcher statistically analyzed the data using SPSS 23 version by running a Paired Samples Test. The result shown the means of pretes score was 66,83 and posttest score was 74,57, Paired Samples Correlations was 0,614 (strong correlation. Significance was 0,005, it means that  a (0,05 is higher than r value (0,005 with high variance of mean value (14,091. As a result, the hypothesis (H1­ was received that learner autonomy contributed effectively to learners’ in organizing own ideas (Ene, 2006 such as making a topic  map becomes some explanable sub-topics, writing down main and supporting idea, clustering some objects, editing next and learners  absolutely accumulate some selected vocabularies inappropriate topics  (Chengping W, 2008. Keyword: Learner Autonomy, Learning process, outcomes Absrak: Pembelajaran otonomi  adalah pembelajaran mandiri yang mengontrol mahasiswa untuk menyampaikan gagasan dan pengalamannya, mencatat dan mengevaluasi kesalahan yang terjadi dalam penulisan esai sederhana berdasarkan pembelajaran yang tersetruktur. Tujuan adalah untuk mengetahui efektifitas pembelajaran otonomi terhadap akurasi tulisan secara statistik. Penelitian ini dilakukan dengan menggunakan desain tes awal dan akhir. Jumlah sampel terdiri dari 21 siswa di Bangkalan. Isntrumen yang digunakan adalah tes untuk mengetahui hasil nilai mahasiswa sebelum dan sesudah melakukan

  3. Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

    Science.gov (United States)

    Huang, R C; Garratt, E S; Pan, H; Wu, Y; Davis, E A; Barton, S J; Burdge, G C; Godfrey, K M; Holbrook, J D; Lillycrop, K A

    2015-01-01

    Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 - 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 - 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

  4. In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases.

    Directory of Open Access Journals (Sweden)

    Julia Arand

    2012-06-01

    Full Text Available The enzymatic control of the setting and maintenance of symmetric and non-symmetric DNA methylation patterns in a particular genome context is not well understood. Here, we describe a comprehensive analysis of DNA methylation patterns generated by high resolution sequencing of hairpin-bisulfite amplicons of selected single copy genes and repetitive elements (LINE1, B1, IAP-LTR-retrotransposons, and major satellites. The analysis unambiguously identifies a substantial amount of regional incomplete methylation maintenance, i.e. hemimethylated CpG positions, with variant degrees among cell types. Moreover, non-CpG cytosine methylation is confined to ESCs and exclusively catalysed by Dnmt3a and Dnmt3b. This sequence position-, cell type-, and region-dependent non-CpG methylation is strongly linked to neighboring CpG methylation and requires the presence of Dnmt3L. The generation of a comprehensive data set of 146,000 CpG dyads was used to apply and develop parameter estimated hidden Markov models (HMM to calculate the relative contribution of DNA methyltransferases (Dnmts for de novo and maintenance DNA methylation. The comparative modelling included wild-type ESCs and mutant ESCs deficient for Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3a/3b, respectively. The HMM analysis identifies a considerable de novo methylation activity for Dnmt1 at certain repetitive elements and single copy sequences. Dnmt3a and Dnmt3b contribute de novo function. However, both enzymes are also essential to maintain symmetrical CpG methylation at distinct repetitive and single copy sequences in ESCs.

  5. eMethylsorb: electrochemical quantification of DNA methylation at CpG resolution using DNA-gold affinity interactions.

    Science.gov (United States)

    Sina, Abu Ali Ibn; Howell, Sidney; Carrascosa, Laura G; Rauf, Sakandar; Shiddiky, Muhammad J A; Trau, Matt

    2014-11-07

    We report a simple electrochemical method referred to as "eMethylsorb" for the detection of DNA methylation. The method relies on the base dependent affinity interaction of DNA with gold. The methylation status of DNA is quantified by monitoring the electrochemical current as a function of the relative adsorption level of bisulphite treated DNA samples onto a bare gold electrode. This method can successfully distinguish methylated and unmethylated epigenotypes at single CpG resolution.

  6. Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma

    OpenAIRE

    Ricketts, Christopher J.; Morris, Mark R.; Gentle, Dean; Brown, Michael; Wake, Naomi; Woodward, Emma R.; Clarke, Noel; Latif, Farida; Maher, Eamonn R.

    2012-01-01

    In order to identify novel candidate tumor suppressor genes (TSGs) implicated in renal cell carcinoma (RCC), we performed genome-wide methylation profiling of RCC using the HumanMethylation27 BeadChips to assess methylation at >14,000 genes. Two hundred and twenty hypermethylated probes representing 205 loci/genes were identified in genomic CpG islands. A subset of TSGs investigated in detail exhibited frequent tumor methylation, promoter methylation associated transcriptional silencing an...

  7. A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps

    OpenAIRE

    HOKAZONO, KOJI; UEKI, TAKASHI; NAGAYOSHI, KINUKO; NISHIOKA, YASUNOBU; HATAE, TATSUNOBU; KOGA, YUTAKA; HIRAHASHI, MINAKO; ODA, YOSHINAO; TANAKA, MASAO

    2014-01-01

    A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically examined precursor lesions of CIMP. In total, 104 CRCs treated between January 1996 and December 2004 were examined. Aberrant promoter methylation of 15 cancer-related genes was analyzed. CIMP sta...

  8. Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review

    OpenAIRE

    Jia, Min; Gao, Xu; Zhang, Yan; Hoffmeister, Michael; Brenner, Hermann

    2016-01-01

    Contradictory results were reported for the prognostic role of CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Differences in the definitions of CIMP were the most common explanation for these discrepancies. The aim of this systematic review was to give an overview of the published studies on CRC prognosis according to the different definitions of CIMP. A systematic literature search was performed in MEDLINE and ISI Web of Science for articles published until 3 ...

  9. Reconceptualizing Autonomy: A Relational Turn in Bioethics.

    Science.gov (United States)

    Jennings, Bruce

    2016-05-01

    History's judgment on the success of bioethics will not depend solely on the conceptual creativity and innovation in the field at the level of ethical and political theory, but this intellectual work is not insignificant. One important new development is what I shall refer to as the relational turn in bioethics. This development represents a renewed emphasis on the ideographic approach, which interprets the meaning of right and wrong in human actions as they are inscribed in social and cultural practices and in structures of lived meaning and interdependence; in an ideographic approach, the task of bioethics is to bring practice into theory, not the other way around. The relational turn in bioethics may profoundly affect the critical questions that the field asks and the ethical guidance it offers society, politics, and policy. The relational turn provides a way of correcting the excessive atomism of many individualistic perspectives that have been, and continue to be, influential in bioethics. Nonetheless, I would argue that most of the work reflecting the relational turn remains distinctively liberal in its respect for the ethical significance of the human individual. It moves away from individualism, but not from the value of individuality.In this review essay, I shall focus on how the relational turn has manifested itself in work on core concepts in bioethics, especially liberty and autonomy. Following a general review, I conclude with a brief consideration of two important recent books in this area: Jennifer Nedelsky's Law's Relations and Rachel Haliburton's Autonomy and the Situated Self. © 2016 The Hastings Center.

  10. Euthanasia--he illusion of autonomy.

    Science.gov (United States)

    Hartling, O J

    2006-03-01

    The paper deals with some of the more common arguments used for the legalisation of voluntary euthanasia. It looks at these arguments from an ethical and philosophical point of view. First, the argument that to offer a person the possibility of euthanasia is to respect that person's autonomy is questionable. Can a person's decision on euthanasia be really autonomous? If euthanasia were legal everybody would be conscious of this option: the patient, the doctor, the family and the nursing staff. Thus, there could be indirect pressure on the patient to make a decision. The choice is meant to be free but the patient is not free not to make the choice. Secondly, a choice that seeks to alleviate suffering and thus improve life by annihilating it is irrational. Thirdly, autonomy as to one's own death is hardly exercised freely. Even an otherwise competent person may not be competent in deciding on his own death on account of despair, hopelessness, fear or maybe a feeling of being weak, superfluous and unwanted. This is a very uncertain base for decision-making, especially in the irrevocable decision of euthanasia. Finally, a competent person usually makes any choice in a responsible way and after due consideration; a 'good' decision should consider and respect the wishes and feelings of others. This will be no less the case in making a decision on the so-called free choice of euthanasia. Thus 'normal' behaviour in decision making will only add to the tendency of the already depressed person to feel a burden on his family, the staff and even on society.

  11. Model Based Autonomy for Robust Mars Operations

    Science.gov (United States)

    Kurien, James A.; Nayak, P. Pandurang; Williams, Brian C.; Lau, Sonie (Technical Monitor)

    1998-01-01

    Space missions have historically relied upon a large ground staff, numbering in the hundreds for complex missions, to maintain routine operations. When an anomaly occurs, this small army of engineers attempts to identify and work around the problem. A piloted Mars mission, with its multiyear duration, cost pressures, half-hour communication delays and two-week blackouts cannot be closely controlled by a battalion of engineers on Earth. Flight crew involvement in routine system operations must also be minimized to maximize science return. It also may be unrealistic to require the crew have the expertise in each mission subsystem needed to diagnose a system failure and effect a timely repair, as engineers did for Apollo 13. Enter model-based autonomy, which allows complex systems to autonomously maintain operation despite failures or anomalous conditions, contributing to safe, robust, and minimally supervised operation of spacecraft, life support, In Situ Resource Utilization (ISRU) and power systems. Autonomous reasoning is central to the approach. A reasoning algorithm uses a logical or mathematical model of a system to infer how to operate the system, diagnose failures and generate appropriate behavior to repair or reconfigure the system in response. The 'plug and play' nature of the models enables low cost development of autonomy for multiple platforms. Declarative, reusable models capture relevant aspects of the behavior of simple devices (e.g. valves or thrusters). Reasoning algorithms combine device models to create a model of the system-wide interactions and behavior of a complex, unique artifact such as a spacecraft. Rather than requiring engineers to all possible interactions and failures at design time or perform analysis during the mission, the reasoning engine generates the appropriate response to the current situation, taking into account its system-wide knowledge, the current state, and even sensor failures or unexpected behavior.

  12. Predicting DNA Methylation State of CpG Dinucleotide Using Genome Topological Features and Deep Networks.

    Science.gov (United States)

    Wang, Yiheng; Liu, Tong; Xu, Dong; Shi, Huidong; Zhang, Chaoyang; Mo, Yin-Yuan; Wang, Zheng

    2016-01-22

    The hypo- or hyper-methylation of the human genome is one of the epigenetic features of leukemia. However, experimental approaches have only determined the methylation state of a small portion of the human genome. We developed deep learning based (stacked denoising autoencoders, or SdAs) software named "DeepMethyl" to predict the methylation state of DNA CpG dinucleotides using features inferred from three-dimensional genome topology (based on Hi-C) and DNA sequence patterns. We used the experimental data from immortalised myelogenous leukemia (K562) and healthy lymphoblastoid (GM12878) cell lines to train the learning models and assess prediction performance. We have tested various SdA architectures with different configurations of hidden layer(s) and amount of pre-training data and compared the performance of deep networks relative to support vector machines (SVMs). Using the methylation states of sequentially neighboring regions as one of the learning features, an SdA achieved a blind test accuracy of 89.7% for GM12878 and 88.6% for K562. When the methylation states of sequentially neighboring regions are unknown, the accuracies are 84.82% for GM12878 and 72.01% for K562. We also analyzed the contribution of genome topological features inferred from Hi-C. DeepMethyl can be accessed at http://dna.cs.usm.edu/deepmethyl/.

  13. Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

    International Nuclear Information System (INIS)

    Ward, Alejandra; Morettin, Alan; Shum, David; Hudson, John W

    2011-01-01

    Hepatocellular carcinoma (HCC), one of the most common cancers world-wide occurs twice as often in men compared to women. Predisposing conditions such as alcoholism, chronic viral hepatitis, aflatoxin B1 ingestion, and cirrhosis all contribute to the development of HCC. We used a combination of methylation specific PCR and bisulfite sequencing, qReal-Time PCR (qPCR), and Western blot analysis to examine epigenetic changes for the Polo-like kinases (Plks) during the development of hepatocellular carcinoma (HCC) in Plk4 heterozygous mice and murine embryonic fibroblasts (MEFs). Here we report that the promoter methylation of Plk4 CpG islands increases with age, was more prevalent in males and that Plk4 epigenetic modification and subsequent downregulation of expression was associated with the development of HCC in Plk4 mutant mice. Interestingly, the opposite occurs with another Plk family member, Plk1 which was typically hypermethylated in normal liver tissue but became hypomethylated and upregulated in liver tumours. Furthermore, upon alcohol exposure murine embryonic fibroblasts exhibited increased Plk4 hypermethylation and downregulation along with increased centrosome numbers and multinucleation. These results suggest that aberrant Plk methylation is correlated with the development of HCC in mice

  14. Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications.

    Science.gov (United States)

    Malta, Tathiane M; de Souza, Camila F; Sabedot, Thais S; Silva, Tiago C; Mosella, Maritza S; Kalkanis, Steven N; Snyder, James; Castro, Ana Valeria B; Noushmehr, Houtan

    2018-04-09

    Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties. Despite advances in surgical techniques and clinical regimens, treatment of high-grade glioma remains challenging and carries dismal rates of therapeutic success and overall survival. Challenges include the molecular complexity of gliomas, as well as inconsistencies in histopathological grading, resulting in an inaccurate prediction of disease progression and failure in the use of standard therapy. The updated 2016 World Health Organization (WHO) classification of tumors of the central nervous system reflects a refinement of tumor diagnostics by integrating the genotypic and phenotypic features, thereby narrowing the defined subgroups. The new classification recommends molecular diagnosis of isocitrate dehydrogenase (IDH) mutational status in gliomas. IDH-mutant gliomas manifest the cytosine-phosphate-guanine (CpG) island methylator phenotype (G-CIMP). Notably, the recent identification of clinically relevant subsets of G-CIMP tumors (G-CIMP-high and G-CIMP-low) provides a further refinement in glioma classification that is independent of grade and histology. This scheme may be useful for predicting patient outcome and may be translated into effective therapeutic strategies tailored to each patient. In this review, we highlight the evolution of our understanding of the G-CIMP subsets and how recent advances in characterizing the genome and epigenome of gliomas may influence future basic and translational research.

  15. CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas.

    Science.gov (United States)

    Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

    2014-05-01

    CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance.

  16. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Gregory E D Mullen

    2008-08-01

    Full Text Available Apical Membrane Antigen 1 (AMA1, a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15, 80 microg of AMA1-C1/Alhydrogel (n = 30, or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30.Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG were detected by enzyme-linked immunosorbent assay (ELISA, and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.ClinicalTrials.gov NCT00344539.

  17. CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

    Science.gov (United States)

    Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

    2009-01-01

    Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

  18. Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Chiang

    Full Text Available The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus.

  19. The rates of G:C[yields]T:A and G:C[yields]C:G transversions at CpG dinucleotides in the human factor IX gene

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1994-05-01

    The authors have identified eight independent transversions at CpG in 290 consecutive families with hemophilia B. These eight transversions account for 16.3% of all independent transversions in the sample, yet the expected frequency of CpG transversions at random in the factor IX gene is only 2.6% (P<0.1). The aggregate data suggest that the two types of CpG transversions (G:C[yields]T:A and G:C[yields]C:G) possess similar mutation rates (24.8 [times] 10[sup [minus]10] and 20.6 [times] 10[sup [minus]10], respectively), which are about fivefold greater than the comparable rates for transversions at non-CpG dinucleotides. The enhancement of transversions at CpG suggest that the model by which mutations occur at CpG may need to be reevaluated. The relationship, if any, between deamination of 5-methyl cytosine and enhancement of transversions at CpG remains to be defined. 28 refs., 2 tabs.

  20. Ensemble approach combining multiple methods improves human transcription start site prediction.

    LENUS (Irish Health Repository)

    Dineen, David G

    2010-01-01

    The computational prediction of transcription start sites is an important unsolved problem. Some recent progress has been made, but many promoters, particularly those not associated with CpG islands, are still difficult to locate using current methods. These methods use different features and training sets, along with a variety of machine learning techniques and result in different prediction sets.

  1. Cloning of the anhidrotic ectodermal dysplasia gene: Identification of cDNAs associated with CpG islands mapped near translocation breakpoint in two female patients

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, A.K.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); Kere, J. [Univ. of Helsinki (Finland)] [and others

    1994-09-01

    The gene for the X chromosomal developmental disorder anhidrotic ectodermal dysplasia (EDA) has been mapped to Xq12-q13 by linkage analysis and is expressed in a few females with chromosomal translocations involving band Xq12-q13. A yeast artificial chromosome (YAC) contig (2.0 Mb) spanning two translocation breakpoints has been assembled by sequence-tagged site (STS)-based chromosomal walking. The two translocation breakpoints (X:autosome translocations from the affected female patients) have been mapped less than 60 kb apart within a YAC contig. Unique probes and intragenic STSs (mapped between the two translocations) have been developed and a somatic cell hybrid carrying the translocated X chromosome from the AK patient has been analyzed by isolating unique probes that span the breakpoint. Several STSs made from intragenic sequences have been found to be conserved in mouse, hamster and monkey, but we have detected no mRNAs in a number of tissues tested. However, a probe and STS developed from the DNA spanning the AK breakpoint is conserved in mouse, hamster and monkey, and we have detected expressed sequences in skin cells and cDNA libraries. In addition, unique sequences have been obtained from two CpG islands in the region that maps proximal to the breakpoints. cDNAs containing these sequences are being studied as candidates for the gene affected in the etiology of EDA.

  2. Authenticity and autonomy in deep-brain stimulation.

    Science.gov (United States)

    Wardrope, Alistair

    2014-08-01

    Felicitas Kraemer draws on the experiences of patients undergoing deep-brain stimulation (DBS) to propose two distinct and potentially conflicting principles of respect: for an individual's autonomy (interpreted as mental competence), and for their authenticity. I argue instead that, according to commonly-invoked justifications of respect for autonomy, authenticity is itself in part constitutive of an analysis of autonomy worthy of respect; Kraemer's argument thus highlights the shortcomings of practical applications of respect for autonomy that emphasise competence while neglecting other important dimensions of autonomy such as authenticity, since it shows that competence alone cannot be interpreted as a reliable indicator of an individual's capacity for exercising autonomy. I draw from relational accounts to suggest how respect for a more expansive conception of autonomy might be interpreted for individuals undergoing DBS and in general. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Autonomy and social functioning of recently admitted nursing home residents.

    Science.gov (United States)

    Paque, Kristel; Goossens, Katrien; Elseviers, Monique; Van Bogaert, Peter; Dilles, Tinne

    2017-09-01

    This paper examines recently admitted nursing home residents' practical autonomy, their remaining social environment and their social functioning. In a cross-sectional design, 391 newly admitted residents of 67 nursing homes participated. All respondents were ≥65 years old, had mini-mental state examination ≥18 and were living in the nursing home for at least 1 month. Data were collected using a structured questionnaire and validated measuring tools. The mean age was 84, 64% were female, 23% had a partner, 80% children, 75% grandchildren and 59% siblings. The mean social functioning score was 3/9 (or 33%) and the autonomy and importance of autonomy score 6/9 (or 67%). More autonomy was observed when residents could perform activities of daily living more independently, and cognitive functioning, quality of life and social functioning were high. Residents with depressive feelings scored lower on autonomy and social functioning compared to those without depressive feelings. Having siblings and the frequency of visits positively correlated with social functioning. In turn, social functioning correlated positively with quality of life. Moreover, a higher score on social functioning lowered the probability of depression. Autonomy or self-determination and maintaining remaining social relationships were considered to be important by the new residents. The remaining social environment, social functioning, quality of life, autonomy and depressive feelings influenced each other, but the cause--effect relation was not clear.

  4. Are there limits to respect for autonomy in bioethics?

    Science.gov (United States)

    de Roubaix, Malcolm

    2008-06-01

    I discuss the significance of respect for personal autonomy in bioethics with reference to its practical expression: rational informed patient choice. The question is whether, given the apparent practical limitations to this notion, bioethical autonomy should be seen as an absolute. After a historical review of informed consent and its development, I discuss the requirements for informed consent. Some inherent tensions are evaluated, as is the applicability of the notion that in order to be legitimate, autonomy should do some ethical work. Limits to the notion of informed consent are explored with reference to six examples: the right of women to reproductive autonomy; the autonomy of legally minor Jehovah's Witnesses; autonomy in cosmetic surgery; inappropriate treatment; autonomy and human medical research, and euthanasia and other end-of-life options. The discussion is within a South African framework with reference to other jurisdictions and decisions where appropriate. I conclude that whilst some unusual instances of limitation of bioethical informed consent might be ethically justifiable, the arguments presented point to the opposite: the unfounded limitation of informed consent.

  5. Relational autonomy: moving beyond the limits of isolated individualism.

    Science.gov (United States)

    Walter, Jennifer K; Ross, Lainie Friedman

    2014-02-01

    Although clinicians may value respecting a patient's or surrogate's autonomy in decision-making, it is not always clear how to proceed in clinical practice. The confusion results, in part, from which conception of autonomy is used to guide ethical practice. Reliance on an individualistic conception such as the "in-control agent" model prioritizes self-sufficiency in decision-making and highlights a decision-maker's capacity to have reason transcend one's emotional experience. An alternative model of autonomy, relational autonomy, highlights the social context within which all individuals exist and acknowledges the emotional and embodied aspects of decision-makers. These 2 conceptions of autonomy lead to different interpretations of several aspects of ethical decision-making. The in-control agent model believes patients or surrogates should avoid both the influence of others and emotional persuasion in decision-making. As a result, providers have a limited role to play and are expected to provide medical expertise but not interfere with the individual's decision-making process. In contrast, a relational autonomy approach acknowledges the central role of others in decision-making, including clinicians, who have a responsibility to engage patients' and surrogates' emotional experiences and offer clear guidance when patients are confronting serious illness. In the pediatric setting, in which decision-making is complicated by having a surrogate decision-maker in addition to a patient, these conceptions of autonomy also may influence expectations about the role that adolescents can play in decision-making.

  6. The impact of financial constraints and incentives on professional autonomy.

    Science.gov (United States)

    Lewis, Jenny M; Marjoribanks, Tim

    2003-01-01

    General practice has been the subject of extensive reforms over the 1990s in Australia as elsewhere. Reforms have attempted to improve quality and contain the overall cost of health care, and have often been seen as reducing the autonomy of medical professionals. This paper examines the impact of financial constraints and incentives introduced during the 1990s on Australian GPs' perceptions of autonomy. An existing seven component definition of autonomy and six themes that emerged from reviewing publications were used to construct focus group questions. A total of 25 GPs participated in four focus groups. Those who participated believe that their financial autonomy has been diminished by policy changes and consumer expectations. They also perceive that their ability to control clinical decisions, which they regard as the most important aspect of professional autonomy, has been reduced along with financial autonomy. Organized medicine in Australia sees financial accountability and clinical decision making as polar opposites, and has continued to argue that fee-for-service payment is the only appropriate method of remuneration, despite increasing evidence that this does not guarantee clinical autonomy. Major changes to the financing of general practice in Australia are required to address the concerns of GPs, governments and patients.

  7. Clinical guidelines and the fate of medical autonomy in Ontario.

    Science.gov (United States)

    Rappolt, S G

    1997-04-01

    Conceptually, clinical guidelines and professional autonomy have a paradoxical relationship. Despite being the quintessence of medical knowledge at the corporate level, guidelines diminish the clinical autonomy of individual practitioners, and therefore threaten medicine's justification for its autonomy. Theorists have argued that professional autonomy will be retained through elite dominance of practitioners, while comparative research suggests that economic autonomy can be traded off to retain clinical autonomy. Under government pressure to regulate the growth of Ontario physicians' fee-for-service public expenditure, the profession's representative organization, the Ontario Medical Association (OMA), promoted voluntary clinical guidelines, hoping to both constrain costs and preserve professional control over the content of medical care. The OMA collaborated with the Ministry of Health in developing guidelines and establishing a provincial centre for health service research. Ontario's practitioners disregarded the OMA's exhortations to implement clinical guidelines, suggesting that in the absence of external constraints, practitioners can subvert elite dominance. However, practitioners' unchecked clinical and economic autonomy, combined with evidence of wide provincial variations in medical care, served to legitimize the government's increasingly unilateral control over the schedule of insured medical services, and, in 1993, their imposition of a global cap on physicians' fee-for-service income pool. When analysed in the context of ongoing Ministry-OMA relations, the failure of the OMA's guidelines strategy to constrain medical service costs has expedited an overall decline in medical autonomy in Ontario. The emergence and course of Ontario's clinical guidelines movement is consistent with the view that medical autonomy is contingent upon broad class forces, and the conceptualization of professional organizations as instruments for mediated occupational control.

  8. Perceived Autonomy Support in the NIMH RAISE Early Treatment Program.

    Science.gov (United States)

    Browne, Julia; Penn, David L; Bauer, Daniel J; Meyer-Kalos, Piper; Mueser, Kim T; Robinson, Delbert G; Addington, Jean; Schooler, Nina R; Glynn, Shirley M; Gingerich, Susan; Marcy, Patricia; Kane, John M

    2017-09-01

    This study examined perceived support for autonomy-the extent to which individuals feel empowered and supported to make informed choices-among participants in the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE ETP). The aims of this study were to evaluate whether NAVIGATE, the active treatment studied in RAISE ETP, was associated with greater improvements in perceived autonomy support over the two-year intervention, compared with community care, and to examine associations between perceived autonomy support and quality of life and symptoms over time and across treatment groups. This study examined perceived autonomy support among the 404 individuals with first-episode psychosis who participated in the RAISE ETP trial (NAVIGATE, N=223; community care, N=181). Three-level conditional linear growth modeling was used given the nested data structure. The results indicated that perceived autonomy support increased significantly over time for those in NAVIGATE but not in community care. Once treatment began, higher perceived autonomy support was related to higher quality of life at six, 12, and 18 months in NAVIGATE and at 12, 18, and 24 months in community care. Higher perceived autonomy support was related to improved scores on total symptoms and on excited symptoms regardless of treatment group and time. Overall, perceived autonomy support increased in NAVIGATE but not for those in community care and was related to improved quality of life and symptoms across both treatment groups. Future research should examine the impact of perceived autonomy support on a wider array of outcomes, including engagement, medication adherence, and functioning.

  9. [Physician and autonomy: on time perception and job satisfaction].

    Science.gov (United States)

    Huisman, Frank G

    2015-01-01

    Is it true that haste is sneaking into medicine? In this article, it is argued that it mainly concerns the perception of being rushed, which is caused by a loss of autonomy of the modern physician. In the fifties, physicians were busy as well, but because they enjoyed a greater degree of autonomy compared to their contemporary colleagues, they did not experience this in a negative way. Due to increased bureaucracy and the introduction of market dynamics, the medical profession has lost autonomy, which in turn led to a loss of job satisfaction.

  10. Does Country Context Distance Determine Subsidiary Decision-Making Autonomy?

    DEFF Research Database (Denmark)

    de Jong, Gjalt; Van Vo, Dut; Marek, Philipp

    2015-01-01

    enterprises, highlighting the importance of such intra-firm collaboration. The division of decision-making autonomy is a core issue in the management of headquarters–subsidiary relationships. The main contribution of our paper is that we confront two valid theoretical frameworks – business network theory......We studied an underrepresented area in the international business (IB) literature: the effect of country context distance on the distribution of decision-making autonomy across headquarters and foreign affiliates. Foreign affiliates directly contribute to the competitive advantages of multinational...... approach to the study of subsidiary decision-making autonomy...

  11. Autonomy and exclusion among Danish prisoners in education

    DEFF Research Database (Denmark)

    Riis, Anita Holm

    2018-01-01

    A prison sentence necessarily means that the person receiving the sentence is in essential ways excluded from the surrounding society. This exclusion means fewer choices and, in the long run, this may affect the person’s ability to actively make choices – therefore, autonomy is an important theme...... choices as well as a high degree of autonomy on the part of the individual inmate. This article focuses on the interplay between exclusion and autonomy in relation to Danish prison inmates who are in education. Alongside this, a more general insight into the educational life of Danish prisoners...

  12. Health equality, social justice and the poverty of autonomy.

    Science.gov (United States)

    Newdick, Christopher

    2017-10-01

    How does the concept of autonomy assist public responses to 'lifestyle' diseases? Autonomy is fundamental to bioethics, but its emphasis on self-determination and individuality hardly supports public health policies to eat and drink less and take more exercise. Autonomy rejects a 'nanny' state. Yet, the cost of non-communicable diseases is increasing to individuals personally and to public health systems generally. Health care systems are under mounting and unsustainable pressure. What is the proper responsibility of individuals, governments and corporate interests working within a global trading environment? When public health care resources are unlikely to increase, we cannot afford to be so diffident to the cost of avoidable diseases.

  13. Evaluation of Existing Situation of University Institutional Autonomy in Moldova

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Bugaian, Larisa; Gulieva, Valeria

    2014-01-01

    This chapter introduces four studies in which the current status of university institutional autonomy in Moldova is evaluated. At the same time it discusses the methodology employed in the study, provide a brief introduction to the higher education sector in Moldova and summaries key findings fro...... the evaluation of organizational, financial, HR and academic autonomy in Moldova.......This chapter introduces four studies in which the current status of university institutional autonomy in Moldova is evaluated. At the same time it discusses the methodology employed in the study, provide a brief introduction to the higher education sector in Moldova and summaries key findings from...

  14. CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.

    Science.gov (United States)

    Debouki-Joudi, Saoussen; Trifa, Fatma; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2017-01-01

    Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.

  15. The role of the CpG island methylator phenotype on survival outcome in colon cancer.

    Science.gov (United States)

    Kang, Ki Joo; Min, Byung Hoon; Ryu, Kyung Ju; Kim, Kyoung Mee; Chang, Dong Kyung; Kim, Jae J; Rhee, Jong Chul; Kim, Young Ho

    2015-03-01

    CpG island methylator phenotype (CIMP)- high colorectal cancers (CRCs) have distinct clinicopathologi-cal features from their CIMP-low/negative CRC counterparts. However, controversy exists regarding the prognosis of CRC according to the CIMP status. Therefore, this study examined the prognosis of Korean patients with colon cancer according to the CIMP status. Among a previous cohort pop-ulation with CRC, a total of 154 patients with colon cancer who had available tissue for DNA extraction were included in the study. CIMP-high was defined as ≥3/5 methylated mark-ers using the five-marker panel (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). CIMP-high and CIMP-low/neg-ative cancers were observed in 27 patients (17.5%) and 127 patients (82.5%), respectively. Multivariate analysis adjust-ing for age, gender, tumor location, tumor stage and CIMP and microsatellite instability (MSI) statuses indicated that CIMP-high colon cancers were associated with a significant increase in colon cancer-specific mortality (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.20 to 8.69; p=0.02). In microsatellite stable cancers, CIMP-high cancer had a poor survival outcome compared to CIMP-low/negative cancer (HR, 2.91; 95% CI, 1.02 to 8.27; p=0.04). Re-gardless of the MSI status, CIMP-high cancers had poor sur-vival outcomes in Korean patients. (Gut Liver, 2015;9202-207).

  16. CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China.

    Science.gov (United States)

    Li, Xia; Hu, Fulan; Wang, Yibaina; Yao, Xiaoping; Zhang, Zuoming; Wang, Fan; Sun, Guizhi; Cui, Bin-Bin; Dong, Xinshu; Zhao, Yashuang

    2014-01-01

    To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China. 282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI). 12.77% (36/282) of patients were CIMP-0, 74.1% (209/282) of patients were CIMP-L, and 13.12% (37/282) of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05-2.46; P = 0.03). CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19-7.89; P = 0.02) and CIMP-L (HR = 1.97; 95% CI: 1.11-3.48; P = 0.02), respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0), CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02-5.24; P = 0.04). CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.

  17. Aberrant TET1 Methylation Closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer.

    Science.gov (United States)

    Ichimura, Norihisa; Shinjo, Keiko; An, Byonggu; Shimizu, Yasuhiro; Yamao, Kenji; Ohka, Fumiharu; Katsushima, Keisuke; Hatanaka, Akira; Tojo, Masayuki; Yamamoto, Eiichiro; Suzuki, Hiromu; Ueda, Minoru; Kondo, Yutaka

    2015-08-01

    Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer. The relationship between TET inactivation and CIMP in colorectal cancers is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) colorectal cancers. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in colorectal cancers, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of colorectal cancers as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (23/55, 42%) than CIMP-N (2/113, 2%, P CIMP-P, 16/40, 40%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P colorectal cancers. Colorectal cancers with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in colorectal cancer. ©2015 American Association for Cancer Research.

  18. Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer.

    Science.gov (United States)

    Cha, Yongjun; Kim, Kyung-Ju; Han, Sae-Won; Rhee, Ye Young; Bae, Jeong Mo; Wen, Xianyu; Cho, Nam-Yun; Lee, Dae-Won; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue; Jeong, Seung-Yong; Park, Kyu Joo; Kang, Gyeong Hoon; Kim, Tae-You

    2016-07-12

    The association between the CpG island methylator phenotype (CIMP) and clinical outcomes in metastatic colorectal cancer remains unclear. We investigated the prognostic impact of CIMP in patients with metastatic colorectal cancer treated with systemic chemotherapy. Eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, CDKN2A, CRABP1, and MLH1) were examined. The CIMP status was determined by the number of methylated promoters as high (⩾5), low (1-4), and negative (0). A total of 153 patients were included (men/women, 103/50; median age, 61 years; range, 22-80 years). The CIMP status was negative/low/high in 77/ 69/7 patients, respectively. Overall survival (OS) was significantly different among the three CIMP groups, with median values of 35.7, 22.2, and 9.77 months for the negative, low, and high groups, respectively (PCIMP groups; the median OS was 37.9, 23.8, and 6.77 months for the negative, low, and high groups, respectively (PCIMP groups (53.4% vs 45.1% vs 16.7%, respectively; P=0.107). For patients treated with fluoropyrimidine and irinotecan second-line chemotherapy (N=86), only OS showed a difference according to the CIMP status, with median values of 20.4, 13.4, and 2.90 months for the negative, low, and high groups, respectively (PCIMP status is a negative prognostic factor for patients with metastatic colorectal cancer treated with chemotherapy.

  19. CpG Island Methylator Phenotype and Prognosis of Colorectal Cancer in Northeast China

    Directory of Open Access Journals (Sweden)

    Xia Li

    2014-01-01

    Full Text Available Purpose. To investigate the association between CpG island methylator phenotype (CIMP and the overall survival of sporadic colorectal cancer (CRC in Northeast China. Methods. 282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM. Proportional hazards-regression models were fitted with computing hazard ratios (HR and the corresponding 95% confidence intervals (95% CI. Results. 12.77% (36/282 of patients were CIMP-0, 74.1% (209/282 of patients were CIMP-L, and 13.12% (37/282 of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05–2.46; P=0.03. CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19–7.89; P=0.02 and CIMP-L (HR = 1.97; 95% CI: 1.11–3.48; P=0.02, respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0, CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02–5.24; P=0.04. Conclusion. CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.

  20. Don’t Always Prefer My Chosen Objects: Low Level of Trait Autonomy and Autonomy Deprivation Decreases Mere Choice Effect

    Science.gov (United States)

    Shang, Zhe; Tao, Tuoxin; Wang, Lei

    2016-01-01

    Choice effect is a robust phenomenon in which even “mere choice” that does not include actual choosing actions could result in more preference for the self-chosen objects over other-chosen objects. In the current research, we proposed that autonomy would impact the mere choice effect. We conducted two studies to examine the hypothesis. The results showed that the mere choice effect measured by Implicit Association Test (IAT) significantly decreased for participants with lower levels of trait autonomy (Study 1) and when participants were primed to experience autonomy deprivation (Study 2). The theoretical and practical implications are discussed. PMID:27148132

  1. Threats to Autonomy in Consumer Societies and Their Implications for Education

    Science.gov (United States)

    Schinkel, Anders; de Ruyter, Doret; Steutel, Jan

    2010-01-01

    The development of autonomy in children is a central concern of liberal philosophers of education. We endorse the liberal intuition that autonomy matters and that it is an appropriate aim of education. However, we divert from autonomy liberals, who defend a rather limited and demanding conception of autonomy that is closely connected with skills…

  2. the search for local government autonomy in nigeria

    African Journals Online (AJOL)

    RAYAN_

    autonomous. Keywords: Search, local government, autonomy, pathways and realization .... time. 6 There were, for instance, the Native Authority Ordinance, the Native Revenue .... Construction and maintenance of primary schools; and e.

  3. Emotional autonomy and problem behavior among Chinese adolescents.

    Science.gov (United States)

    Chou, Kee-Lee

    2003-12-01

    The author examined the association between emotional autonomy and problem behavior among Chinese adolescents living in Hong Kong. The respondents were 512 adolescents, 16 to 18 years of age, who were interviewed for a cross-sectional study. Three dimensions of emotional autonomy including individuation, nondependency on parents, and de-idealization of parents were significantly and positively correlated with the amount of problem behavior the participants engaged in during the past 6 months. Using a simple linear multiple regression model, the author found that problem behavior was associated with only one aspect of emotional autonomy-individuation. Results indicated that the relationship between problem behavior and three aspects of emotional autonomy was similar in both individualistic and collectivistic societies.

  4. Radioiodine therapy of benign thyroid disorders: functional thyroid autonomy

    International Nuclear Information System (INIS)

    Dunkelmann, S.

    2005-01-01

    In the last 15 years, several concepts have been developed to further improve the outcome of radioiodine therapy in functional thyroid autonomy. Results of radioiodine therapy in functional autonomy are considerably better than in Graves' disease. All of the currently-applied concepts offer healing rates of 75-100%, but they differ considerably in the hypothyreosis rates attained. The target volume can be precisely determined by sonography only in unifocal autonomy. In the case of multifocal and disseminated autonomy, the entire thyroid is taken as the target volume and the focal dose is reduced ('dosimetric compromise'). TcTUs-based dose concepts calculate the functionally autonomous volume from the TcTUs and replace the target volume by sonography, in the TcTUs-adapted dose concepts, sonographic target volume is left and the focal dose varied in dependence of the suppression uptake. The objective is to attain a high rate of success with a low rate of hypothyreosis. (orig.)

  5. Innovations in Computer Generated Autonomy at the MOVES Institute

    National Research Council Canada - National Science Library

    Hiles, John

    2001-01-01

    The M6VES Institute's Computer-Generated Autonomy Group has focused on a research goal of modeling intensely complex and adaptive behavior while at the same time making the behavior far easier to create and control...

  6. the Effect of Egyptian Married Women's Decision-Making Autonomy

    African Journals Online (AJOL)

    AJRH Managing Editor

    women's autonomy influences their use of modern contraception methods and to determine the mediating effect of education .... attention should be given to other social ..... possibly due to their greater exposure to media, ... prohibited in Islam.

  7. Autonomy-connectedness mediates sex differences in symptoms of psychopathology

    NARCIS (Netherlands)

    Bekker, Marrie H.J.; Van Assen, Marcel A.L.M.

    2017-01-01

    Objectives: This study aimed to examine if autonomy-connectedness, capacity for self-governance under the condition of connectedness, would mediate sex differences in symptoms of various mental disorders (depression, anxiety, eating disorders, antisocial personality disorder). Method: Participants

  8. Autonomy-connectedness mediates sex differences in symptoms of psychopathology

    NARCIS (Netherlands)

    Bekker, M.H.J.; van Assen, M.A.L.M.

    2017-01-01

    Objectives This study aimed to examine if autonomy-connectedness, capacity for self-governance under the condition of connectedness, would mediate sex differences in symptoms of various mental disorders (depression, anxiety, eating disorders, antisocial personality disorder). Method Participants (N

  9. Developing child autonomy in pediatric healthcare: towards an ethical model.

    Science.gov (United States)

    Martakis, Kyriakos; Brand, Helmut; Schröder-Bäck, Peter

    2018-06-01

    The changes initiated by the new National Civil and Commercial Code in Argentina underline the pediatric task to empower children's and adolescents' developing autonomy. In this paper, we have framed a model describing autonomy in child healthcare. We carried out a literature review focusing on i) the concept of autonomy referring to the absolute value of the autonomous individual, and ii) the age-driven process of competent decisionmaking development. We summarized our findings developing a conceptual model that includes the child, the pediatrician and the parents. The pediatricianchild relationship is based on different forms of guidance and cooperation, resulting in varying levels of activity and passivity. Parental authority influences the extent of autonomy, based on the level of respect of the child's moral equality. Contextual, existential, conceptual, and socialethical conditions shall be considered when applying the model to facilitate dialogue between pediatricians, children, parents and other actors. Sociedad Argentina de Pediatría.

  10. Contingency Management with Human Autonomy Teaming

    Science.gov (United States)

    Shively, Robert J.; Lachter, Joel B.

    2018-01-01

    Automation is playing an increasingly important role in many operations. It is often cheaper faster and more precise than human operators. However, automation is not perfect. There are many situations in which a human operator must step in. We refer to these instances as contingencies and the act of stepping in contingency management. Here we propose coupling Human Autonomy Teaming (HAT) with contingency management. We describe two aspects to HAT, bi-directional communication, and working agreements (or plays). Bi-directional communication like Crew Resource Management in traditional aviation, allows all parties to contribute to a decision. Working agreements specify roles and responsibilities. Importantly working agreements allow for the possibility of roles and responsibilities changing depending on environmental factors (e.g., situations the automation was not designed for, workload, risk, or trust). This allows for the automation to "automatically" become more autonomous as it becomes more trusted and/or it is updated to deal with a more complete set of possible situations. We present a concrete example using a prototype contingency management station one might find in a future airline operations center. Automation proposes reroutes for aircraft that encounter bad weather or are forced to divert for environmental or systems reasons. If specific conditions are met, these recommendations may be autonomously datalinked to the affected aircraft.

  11. Coercive treatment and autonomy in psychiatry.

    Science.gov (United States)

    Sjöstrand, Manne; Helgesson, Gert

    2008-02-01

    There are three lines of argument in defence of coercive treatment of patients with mental disorders: arguments regarding (1) societal interests to protect others, (2) the patients' own health interests, and (3) patient autonomy. In this paper, we analyse these arguments in relation to an idealized case, where a person with a mental disorder claims not to want medical treatment for religious reasons. We also discuss who should decide what in situations where patients with mental disorders deny treatment on seemingly rational grounds. We conclude that, in principle, coercive treatment cannot be defended for the sake of protecting others. While coercive actions can be acceptable in order to protect close family and others, medical treatment is not justified for such reasons but should be given only in the interest of patients. Coercive treatment may be required in order to promote the patient's health interests, but health interests have to waive if they go against the autonomous interests of the patient. We argue that non-autonomous patients can have reasons, rooted in their deeply-set values, to renounce compulsory institutional treatment, and that such reasons should be respected unless it can be assumed that their new predicaments have caused them to change their views.

  12. Reconfigurable Autonomy for Future Planetary Rovers

    Science.gov (United States)

    Burroughes, Guy

    Extra-terrestrial Planetary rover systems are uniquely remote, placing constraints in regard to communication, environmental uncertainty, and limited physical resources, and requiring a high level of fault tolerance and resistance to hardware degradation. This thesis presents a novel self-reconfiguring autonomous software architecture designed to meet the needs of extraterrestrial planetary environments. At runtime it can safely reconfigure low-level control systems, high-level decisional autonomy systems, and managed software architecture. The architecture can perform automatic Verification and Validation of self-reconfiguration at run-time, and enables a system to be self-optimising, self-protecting, and self-healing. A novel self-monitoring system, which is non-invasive, efficient, tunable, and autonomously deploying, is also presented. The architecture was validated through the use-case of a highly autonomous extra-terrestrial planetary exploration rover. Three major forms of reconfiguration were demonstrated and tested: first, high level adjustment of system internal architecture and goal; second, software module modification; and third, low level alteration of hardware control in response to degradation of hardware and environmental change. The architecture was demonstrated to be robust and effective in a Mars sample return mission use-case testing the operational aspects of a novel, reconfigurable guidance, navigation, and control system for a planetary rover, all operating in concert through a scenario that required reconfiguration of all elements of the system.

  13. Marketing human organs: the autonomy paradox.

    Science.gov (United States)

    Marshall, P A; Thomasma, D C; Daar, A S

    1996-03-01

    The severe shortage of organs for transplantation and the continual reluctance of the public to voluntarily donate has prompted consideration of alternative strategies for organ procurement. This paper explores the development of market approaches for procuring human organs for transplantation and considers the social and moral implications of organ donation as both a "gift of life" and a "commodity exchange." The problematic and paradoxical articulation of individual autonomy in relation to property rights and marketing human body parts is addressed. We argue that beliefs about proprietorship over human body parts and the capacity to provide consent for organ donation are culturally constructed. We contend that the political and economic framework of biomedicine, in western and non-western nations, influences access to transplantation technology and shapes the form and development of specific market approaches. Finally, we suggest that marketing approaches for organ procurement are and will be negotiated within cultural parameters constrained by several factors: beliefs about the physical body and personhood, religious traditions, economic conditions, and the availability of technological resources.

  14. Learner autonomy development through digital gameplay

    Directory of Open Access Journals (Sweden)

    Alice Chik

    2011-04-01

    Full Text Available Playing digital games is undeniably a popular leisure activity, and digital gaming is also gaining academic attention and recognition for enhancing digital literacies and learning motivation. One tricky issue when exploring digital gaming in Asian contexts is the popularity of English and Japanese games. Though Chinese and Korean online games are readily available, many of the more popular commercial off-the-shelf (COTS digital games are in English and Japanese. Students in Hong Kong are required to take English as a foreign language, which resulted in a huge range of proficiency, but Japanese is not offered at public schools. So, most Hong Kong gamers are playing foreign language games. Yet language barriers do not diminish the market demand for foreign language digital games. This paper explores the phenomenon of digital gaming in foreign languages. Based on findings from an on-going research project with ten undergraduate video gamers (F=4, M=6, this paper argues that gamers exercise learner autonomy by managing their gaming both as leisure and learning experiences.

  15. The Chains on All My People Are the Chains on Me: Restrictions to Collective Autonomy Undermine the Personal Autonomy and Psychological Well-Being of Group Members.

    Science.gov (United States)

    Kachanoff, Frank J; Taylor, Donald M; Caouette, Julie; Khullar, Thomas H; Wohl, Michael J A

    2018-01-11

    Four studies assessed the potentially detrimental effects that restrictions to collective autonomy (i.e., a group's freedom to determine and practice its own identity) may have for the personal autonomy and psychological well-being of group members. In Study 1, using 3 distinct samples (NSample1a = 123, NSample1b = 129, NSample1c = 370), correlational and cross-cultural evidence indicates that perceived restrictions to the collective autonomy of one's group is directly associated with reduced personal autonomy, and indirectly associated with diminished well-being through personal autonomy. In Study 2 (N = 411), a longitudinal assessment of group members over 3 time-points during a 4-month period found that group members who perceived greater collective autonomy restriction also experienced reduced personal autonomy, and in turn, reduced psychological well-being over time. In Study 3 (N = 255), group members described a time during which their ingroup had (or did not have) its collective autonomy unduly restricted by other groups. Participants who were primed to think that their group lacked collective autonomy reported reduced feelings of personal autonomy, and reduced psychological well-being (compared with those primed to think their group had collective autonomy). In Study 4 (N = 389), collective autonomy was manipulated within the context of an intensive laboratory simulation. Collective autonomy-restricted group members experienced less personal autonomy than those who did not have their collective autonomy restricted. Together these findings suggest that restrictions to a group's collective autonomy may have detrimental consequences for the personal autonomy and psychological well-being of group members. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  16. Exploring the relationship between university internationalization and university autonomy

    DEFF Research Database (Denmark)

    Turcan, Romeo V.; Gullieva, Valeria

    This paper explores a research gap at the intersection of university internationalization and university autonomy. A process model of university internationalization is put forward whereby the process of university internationalization is mediated by university internationalization capacity...... and moderated by target country institutional autonomy and globalization; and entry modes, timing and pace, as well as product mix of internationalization define university’s internationalization pattern. A systematic review is conducted to identify empirical studies at this intersection. One of the questions...

  17. Direct-to-consumer genomics on the scales of autonomy

    Science.gov (United States)

    Vayena, Effy

    2015-01-01

    Direct-to-consumer (DTC) genetic services have generated enormous controversy from their first emergence. A dramatic recent manifestation of this is the Food and Drug Administration's (FDA) cease and desist order against 23andMe, the leading provider in the market. Critics have argued for the restrictive regulation of such services, and even their prohibition, on the grounds of the harm they pose to consumers. Their advocates, by contrast, defend them as a means of enhancing the autonomy of those same consumers. Autonomy emerges as a key battle-field in this debate, because many of the ‘harm’ arguments can be interpreted as identifying threats to autonomy. This paper assesses whether DTC genomic services are a threat to, or instead, an enhancement of, personal autonomy. It deploys Joseph Raz's account of personal autonomy, with its emphasis on choice from a range of valuable options. It then seeks to counter claims that DTC genomics threatens autonomy because it involves manipulation in contravention of consumers’ independence or because it does not generate valuable options which can be meaningfully engaged with by consumers. It is stressed that the value of the options generated by DTC genomics should not be judged exclusively from the perspective of medical actionability, but should take into consideration plural utilities. Finally, the paper ends by broaching policy recommendations, suggesting that there is a strong autonomy-based argument for permitting DTC genomic services, and that the key question is the nature of the regulatory conditions under which they should be permitted. The discussion of autonomy in this paper helps illuminate some of these conditions. PMID:24797610

  18. Teacher autonomy in the era of New Public Management

    OpenAIRE

    Lundström, Ulf

    2015-01-01

    This article examines how upper secondary school teachers perceive and respond to the consequences for their professional autonomy of recent school reforms and restructurings. Based on empirical material from interviews of 119 teachers in three studies conducted between 2002 and 2014, the findings indicate that teacher autonomy has been reduced by school reforms and restructurings since the late 1980s. Regardless of their individual aims, these reforms have collectively created a power struct...

  19. Managing the accountability-autonomy tensions in university research commercialisation

    OpenAIRE

    Narayan, Anil K.; Northcott, Deryl; Parker, Lee D.

    2017-01-01

    This article investigates organisational responses to emerging concerns about how accountability–autonomy tensions can be managed within the context of university research commercialisation. The findings suggest that changed expectations of university research practices, which result from the introduction of a commercialisation logic, can be managed via the homogenisation of research goals and strategies. The successful management of accountability–autonomy tensions also depends on utilising ...

  20. Autonomy, religious values, and refusal of lifesaving medical treatment.

    OpenAIRE

    Wreen, M J

    1991-01-01

    The principal question of this paper is: Why are religious values special in refusal of lifesaving medical treatment? This question is approached through a critical examination of a common kind of refusal of treatment case, one involving a rational adult. The central value cited in defence of honouring such a patient's refusal is autonomy. Once autonomy is isolated from other justificatory factors, however, possible cases can be imagined which cast doubt on the great valuational weight assign...

  1. Factors Contributing to Learners’ Autonomy in EFL Reading

    OpenAIRE

    Sri Endah Tabiati

    2016-01-01

    Abstract: This study aims to discover factors that assist learners develop their autonomy in EFL reading. The approach employed is qualitative involving EFL learners in an English Department of the Faculty of Cultural Studies, Brawijaya University Malang. There are two stages in the study: the subject selection stage intended to gain potential subjects and the main study intended to find the answer of the research questions. The findings of the study show that the autonomy of EFL learners in ...

  2. Monetary Autonomy in Select Asian Economies : Role of International Reserves

    OpenAIRE

    Hiroyuki Taguchi; Geethanjali Nataraj; Pravakar Sahoo

    2010-01-01

    This paper examines the trends in monetary autonomy and its interaction with financial integration, currency regime and foreign reserves for the past two decades in select Asian countries viz., Thailand, Korea, Indonesia, Philippines, and India. Our main findings are as follows : First, Thailand, Korea and Indonesia, who experienced the change in currency regime towards a floating regime, have lowered the sensitivities of their interest rates (have raised monetary autonomy) after the regime c...

  3. Between Autonomy and Vulnerability : the Space of Movement

    OpenAIRE

    Kevin McDonald

    2011-01-01

    Analyses of the contemporary alterglobalization movement increasingly emphasize dimensions of autonomy, whose ultimate origins lie in theories of agency understood as sovereignty. This paper argues that critical dimensions of the alterglobalization movement involve practices of embodied action and forms of responsibility that point beyond autonomy, to a paradigm of relational vulnerability. Recognising this is central to understanding ethics, agency, and subjectivity and to understanding move...

  4. Between Autonomy and Vulnerability : the Space of Movement

    Directory of Open Access Journals (Sweden)

    Kevin McDonald

    2011-03-01

    Full Text Available Analyses of the contemporary alterglobalization movement increasingly emphasize dimensions of autonomy, whose ultimate origins lie in theories of agency understood as sovereignty. This paper argues that critical dimensions of the alterglobalization movement involve practices of embodied action and forms of responsibility that point beyond autonomy, to a paradigm of relational vulnerability. Recognising this is central to understanding ethics, agency, and subjectivity and to understanding movements as a space of experience.

  5. Effect of Autonomy Support on Self-Determined Motivation in Elementary Physical Education.

    Science.gov (United States)

    Chang, Yu-Kai; Chen, Senlin; Tu, Kun-Wei; Chi, Li-Kang

    2016-09-01

    Using the quasi-experimental design, this study examined the effect of autonomy support on self-determined motivation in elementary school physical education (PE) students. One hundred and twenty six participants were assigned to either the autonomy support group (n = 61) or the control group (n = 65) for a six-week intervention period. Perceived teacher autonomy, perceived autonomy in PE, and self-determined motivation in PE were pre- and post-tested using validated questionnaires. Significant increases in perceived teacher autonomy and perceived autonomy in PE were observed in the autonomy support group, but not in the control group. Intrinsic motivation was higher in the autonomy support group than that in the control group. From an experimental perspective, these findings suggest that the autonomy support was successfully manipulated in the PE classes, which in turn increased the students' perceived autonomy and intrinsic motivation.

  6. Effect of Autonomy Support on Self-Determined Motivation in Elementary Physical Education

    Directory of Open Access Journals (Sweden)

    Yu-Kai Chang, Senlin Chen, Kun-Wei Tu, Li-Kang Chi

    2016-09-01

    Full Text Available Using the quasi-experimental design, this study examined the effect of autonomy support on self-determined motivation in elementary school physical education (PE students. One hundred and twenty six participants were assigned to either the autonomy support group (n = 61 or the control group (n = 65 for a six-week intervention period. Perceived teacher autonomy, perceived autonomy in PE, and self-determined motivation in PE were pre- and post-tested using validated questionnaires. Significant increases in perceived teacher autonomy and perceived autonomy in PE were observed in the autonomy support group, but not in the control group. Intrinsic motivation was higher in the autonomy support group than that in the control group. From an experimental perspective, these findings suggest that the autonomy support was successfully manipulated in the PE classes, which in turn increased the students’ perceived autonomy and intrinsic motivation.

  7. Volitional Trust, Autonomy Satisfaction, and Engagement at Work.

    Science.gov (United States)

    Heyns, Marita; Rothmann, Sebastiaan

    2018-02-01

    This study tested a structural model that identifies the nature of relationships between trust, autonomy satisfaction, and personal engagement at work. A cross-sectional survey design with a convenience sample ( n = 252) was used. The Behavioral Trust Inventory, Work-Related Basic Need Satisfaction Scale, and Work Engagement Scale were administered. While reliance-based trust did not have a significant influence on engagement, disclosure-based trust in a focal leader was found to predict satisfaction of autonomy needs and employee engagement. Mediation analyses revealed that satisfaction of the need for autonomy facilitates the influence of trust on work outcomes. More specifically, disclosure (a dimension of trust) impacted engagement via autonomy satisfaction. Overall, the model explained 44% of total variance in engagement, to which the variables proportionately contributed as follows: autonomy satisfaction = 79.58%, disclosure = 18.22%, and reliance = 2.20%. The findings provide possible directions for how leaders can leverage trust to facilitate autonomy support and higher levels of engagement.

  8. Radioiodine-treatment (RIT) of functional thyroidal autonomy

    International Nuclear Information System (INIS)

    Meller, J.; Sahlmann, C.O.; Becker, W.

    2002-01-01

    Since 1942, therapy with radioiodine (RIT) has gained a major role in the treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves' disease or toxic multinodular goitre (thyroid autonomy). In iodine deficient areas thyroid autonomy accounts for 40-50% of all cases with hyperthyroidism. RIT has become a cost-effective first-line procedure in autonomy-patients with latent or overt hyperthyroidism, especially in the absence of a large goitre, after thyroid surgery and in elderly patients with associated conditions who carry a high intra- or perioperative risk. Decisions concerning the definitive treatment of thyroid autonomy should take into account previous episodes of hyperthyroidism, objective parameters of risk stratification in euthyroid patients as well as concomitant diseases and the probability of iodine exposure in the future. In Central Europe the majority of investigators prefer to estimate the therapeutic activity individually by a radioiodine test. TCTUs (global 99m-Tc-pertechnetate thyroid uptake under suppression) - based dose concepts have been proven to be highly effective in the elimination of autonomy and carry a low (< 10%) risk of postradioiodtherapeutic hypothyroidism. Radioiodine therapy for autonomy has been found to be both effective and safe and without major early or late side effects. The most frequent complication is hypothyroidism requiring lifelong follow-up. (author)

  9. What does respect for the patient's autonomy require?

    Science.gov (United States)

    Cheng, Kam-Yuen

    2013-11-01

    Personal autonomy presupposes the notion of rationality. What is not so clear is whether, and how, a compromise of rationality to various degrees will diminish a person's autonomy. In bioethical literature, three major types of threat to the rationality of a patient's medical decision are identified: insufficient information, irrational beliefs/desires, and influence of different framing effects. To overcome the first problem, it is suggested that patients be provided with information about their diseases and treatment choices according to the objective standard. I shall explain how this should be finessed. Regarding the negative impact of irrational beliefs/desires, some philosophers have argued that holding irrational beliefs can still be an expression of autonomy. I reject this argument because the degree of autonomy of a decision depends on the degree of rationality of the beliefs or desires on which the decision is based. Hence, to promote patient autonomy, we need to eliminate irrational beliefs by the provision of evidence and good arguments. Finally, I argue that the way to smooth out the framing effects is to present the same information in different perspectives: it is too often assumed that medical information can always be given in a complete and unadorned manner. This article concludes with a cautionary note that the protection of patient autonomy requires much more time and effort than the current practice usually allows. © 2012 John Wiley & Sons Ltd.

  10. Psychological autonomy and hierarchical relatedness as organizers of developmental pathways.

    Science.gov (United States)

    Keller, Heidi

    2016-01-19

    The definition of self and others can be regarded as embodying the two dimensions of autonomy and relatedness. Autonomy and relatedness are two basic human needs and cultural constructs at the same time. This implies that they may be differently defined yet remain equally important. The respective understanding of autonomy and relatedness is socialized during the everyday experiences of daily life routines from birth on. In this paper, two developmental pathways are portrayed that emphasize different conceptions of autonomy and relatedness that are adaptive in two different environmental contexts with very different affordances and constraints. Western middle-class children are socialized towards psychological autonomy, i.e. the primacy of own intentions, wishes, individual preferences and emotions affording a definition of relatedness as psychological negotiable construct. Non-Western subsistence farmer children are socialized towards hierarchical relatedness, i.e. positioning oneself into the hierarchical structure of a communal system affording a definition of autonomy as action oriented, based on responsibility and obligations. Infancy can be regarded as a cultural lens through which to study the different socialization agendas. Parenting strategies that aim at supporting these different socialization goals in German and Euro-American parents on the one hand and Nso farmers from North Western Cameroon on the other hand are described. It is concluded that different pathways need to be considered in order to understand human psychology from a global perspective. © 2015 The Author(s).

  11. CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways.

    Science.gov (United States)

    Qi, Xu-Feng; Zheng, Li; Kim, Cheol-Su; Lee, Kyu-Jae; Kim, Dong-Heui; Cai, Dong-Qing; Qin, Jun-Wen; Yu, Yan-Hong; Wu, Zheng; Kim, Soo-Ki

    2013-07-01

    Recent studies have suggested that the anti-cancer activity of CpG-oligodeoxynucleotides (CpG-ODNs) is owing to their immunomodulatory effects in tumor-bearing host. The purpose of this study is to investigate the directly cytotoxic activity of KSK-CpG, a novel CpG-ODN with an alternative CpG motif, against A20 and EL4 lymphoma cells in comparison with previously used murine CpG motif (1826-CpG). To evaluate the potential cytotoxic effects of KSK-CpG on lymphoma cells, cell viability assay, confocal microscopy, flow cytometry, DNA fragmentation, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used. We found that KSK-CpG induced direct cytotoxicity in A20 lymphoma cells, but not in EL4 lymphoma cells, at least in part via TLR9-mediated pathways. Apoptotic cell death was demonstrated to play an important role in CpG-ODNs-induced cytotoxicity. In addition, both mitochondrial membrane potential decrease and G1-phase arrest were involved in KSK-CpG-induced apoptosis in A20 cells. The activities of apoptotic molecules such as caspase-3, PARP, and Bax were increased, but the activation of p27 Kip1 and ERK were decreased in KSK-CpG-treated A20 cells. Furthermore, autocrine IFN-γ partially contributed to apoptotic cell death in KSK-CpG-treated A20 cells. Collectively, our findings suggest that KSK-CpG induces apoptotic cell death in A20 lymphoma cells at least in part by inducing G1-phase arrest and autocrine IFN-γ via increasing TLR9 expression, without the need for immune system of tumor-bearing host. This new understanding supports the development of TLR9-targeted therapy with CpG-ODN as a direct therapeutic agent for treating B lymphoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Autonomy and the human element in space

    Science.gov (United States)

    1985-01-01

    productivity. Extended operations can in turn enhance critical technologies and contribute to the competitive economic abilities of the United States. A high degree of automation and autonomy may be required to reduce dependence on ground systems, reduce mission costs, diminish complexity as perceived by the crew, increase mission lifetime and expand mission versatility. However, technologies dealing with heavily automated, long duration habitable spacecraft have not yet been thoroughly investigated by NASA. A highly automated station must amalgamate the diverse capabilities of people, machines, and computers to yield an efficient system which capitalizes on unique human characteristics. The station also must have an initial design which allows evolution to a larger and more sophisticated space presence. In the early years it is likely that AI-based subsystems will be used primarily in an advisory or planning capacity. As human confidence in automated systems grows and as technology advances, machines will take on more critical and interdependent roles. The question is whether, and how much, system autonomy will lead to improved station effectiveness.

  13. Controlling the autonomy of a reconnaissance robot

    Science.gov (United States)

    Dalgalarrondo, Andre; Dufourd, Delphine; Filliat, David

    2004-09-01

    In this paper, we present our research on the control of a mobile robot for indoor reconnaissance missions. Based on previous work concerning our robot control architecture HARPIC, we have developed a man machine interface and software components that allow a human operator to control a robot at different levels of autonomy. This work aims at studying how a robot could be helpful in indoor reconnaissance and surveillance missions in hostile environment. In such missions, since a soldier faces many threats and must protect himself while looking around and holding his weapon, he cannot devote his attention to the teleoperation of the robot. Moreover, robots are not yet able to conduct complex missions in a fully autonomous mode. Thus, in a pragmatic way, we have built a software that allows dynamic swapping between control modes (manual, safeguarded and behavior-based) while automatically performing map building and localization of the robot. It also includes surveillance functions like movement detection and is designed for multirobot extensions. We first describe the design of our agent-based robot control architecture and discuss the various ways to control and interact with a robot. The main modules and functionalities implementing those ideas in our architecture are detailed. More precisely, we show how we combine manual controls, obstacle avoidance, wall and corridor following, way point and planned travelling. Some experiments on a Pioneer robot equipped with various sensors are presented. Finally, we suggest some promising directions for the development of robots and user interfaces for hostile environment and discuss our planned future improvements.

  14. Autonomy in robots and other agents.

    Science.gov (United States)

    Smithers, T

    1997-06-01

    The word "autonomous" has become widely used in artificial intelligence, robotics, and, more recently, artificial life and is typically used to qualify types of systems, agents, or robots: we see terms like "autonomous systems," "autonomous agents," and "autonomous robots." Its use in these fields is, however, both weak, with no distinctions being made that are not better and more precisely made with other existing terms, and varied, with no single underlying concept being involved. This ill-disciplined usage contrasts strongly with the use of the same term in other fields such as biology, philosophy, ethics, law, and human rights, for example. In all these quite different areas the concept of autonomy is essentially the same, though the language used and the aspects and issues of concern, of course, differ. In all these cases the underlying notion is one of self-law making and the closely related concept of self-identity. In this paper I argue that the loose and varied use of the term autonomous in artificial intelligence, robotics, and artificial life has effectively robbed these fields of an important concept. A concept essentially the same as we find it in biology, philosophy, ethics, and law, and one that is needed to distinguish a particular kind of agent or robot from those developed and built so far. I suggest that robots and other agents will have to be autonomous, i.e., self-law making, not just self-regulating, if they are to be able effectively to deal with the kinds of environments in which we live and work: environments which have significant large scale spatial and temporal invariant structure, but which also have large amounts of local spatial and temporal dynamic variation and unpredictability, and which lead to the frequent occurrence of previously unexperienced situations for the agents that interact with them.

  15. Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Andresen, Lars; Matthiessen, M W

    2005-01-01

    Recognition of repeat CpG motifs, which are common in bacterial, but not in mammalian, DNA, through Toll-like receptor (TLR)9 is an integral part of the innate immune system. As the role of TLR9 in the human gut is unknown, we determined the spectrum of TLR9 expression in normal and inflamed colo...... in vitro despite spontaneous TLR9 gene expression. This suggests that the human epithelium is able to avoid inappropriate immune responses to luminal bacterial products through modulation of the TLR9 pathway....

  16. Proinflammatory Stimulation of Toll-Like Receptor 9 with High Dose CpG ODN 1826 Impairs Endothelial Regeneration and Promotes Atherosclerosis in Mice.

    Directory of Open Access Journals (Sweden)

    Alexander O Krogmann

    Full Text Available Toll-like receptors (TLR of the innate immune system have been closely linked with the development of atherosclerotic lesions. TLR9 is activated by unmethylated CpG motifs within ssDNA, but also by CpG motifs in nucleic acids released during vascular apoptosis and necrosis. The role of TLR9 in vascular disease remains controversial and we sought to investigate the effects of a proinflammatory TLR9 stimulation in mice.TLR9-stimulation with high dose CpG ODN at concentrations between 6.25 nM to 30 nM induced a significant proinflammatory cytokine response in mice. This was associated with impaired reendothelialization upon acute denudation of the carotid and increased numbers of circulating endothelial microparticles, as a marker for amplified endothelial damage. Chronic TLR9 agonism in apolipoprotein E-deficient (ApoE-/- mice fed a cholesterol-rich diet increased aortic production of reactive oxygen species, the number of circulating endothelial microparticles, circulating sca-1/flk-1 positive cells, and most importantly augmented atherosclerotic plaque formation when compared to vehicle treated animals. Importantly, high concentrations of CpG ODN are required for these proatherogenic effects.Systemic stimulation of TLR9 with high dose CpG ODN impaired reendothelialization upon acute vascular injury and increased atherosclerotic plaque development in ApoE-/- mice. Further studies are necessary to fully decipher the contradictory finding of TLR9 agonism in vascular biology.

  17. Hypermethylation of the 5′ CpG island of the p14ARF flanking exon 1β in human colorectal cancer displaying a restricted pattern of p53 overexpression concomitant with increased MDM2 expression

    Directory of Open Access Journals (Sweden)

    Nyiraneza Christine

    2012-06-01

    Full Text Available Abstract Background It has been suggested that inactivation of p14ARF, a tumor suppressor central to regulating p53 protein stability through interaction with the MDM2 oncoprotein, abrogates p53 activity in human tumors retaining the wild-type TP53 gene. Differences in expression of tumor suppressor genes are frequently associated with cancer. We previously reported on a pattern of restricted p53 immunohistochemical overexpression significantly associated with microsatellite instability (MSI, low TP53 mutation frequency, and MDM2 overexpression in colorectal cancers (CRCs. In this study, we investigated whether p14ARF alterations could be a mechanism for disabling the p53 pathway in this subgroup of CRCs. Results Detailed maps of the alterations in the p14ARF gene were determined in a cohort of 98 CRCs to detect both nucleotide and copy-number changes. Methylation-specific PCR combined with bisulfite sequencing was used to evaluate the prevalence and distribution of p14ARF methylation. p14ARF alterations were then correlated with MSI status, TP53 mutations, and immunohistochemical expression of p53 and MDM2. The frequency of p14ARF mutations was extremely low (1/98; 1%, whereas coexistence of methylated and unmethylated alleles in both tumors and normal colon mucosa was common (91/98; 93%. Only seven of ninety-eight tumors (7% had a distinct pattern of methylation compared with normal colon mucosa. Evaluation of the prevalence and distribution of p14ARF promoter methylation in a region containing 27 CpG sites in 35 patients showed a range of methylated CpG sites in tumors (0 to 25 (95% CI 1 to 13 versus 0 to 17 (95% CI 0 to 2 in adjacent colon mucosa (P = 0.004. Hypermethylation of the p14ARF promoter was significantly correlated with the restricted p53 overexpression pattern (P = 0.03, and MDM2 overexpression (P = 0.02, independently of MSI phenotype. Although no significant correlation between p14ARF methylation and TP53 mutational

  18. Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Farrar William L

    2010-10-01

    Full Text Available Abstract Background Recently, much attention has been focused on gaining a better understanding of the different populations of cells within a tumor and their contribution to cancer progression. One of the most commonly used methods to isolate a more aggressive sub-population of cells utilizes cell sorting based on expression of certain cell adhesion molecules. A recently established method we developed is to isolate these more aggressive cells based on their properties of increased invasive ability. These more invasive cells have been previously characterized as tumor initiating cells (TICs that have a stem-like genomic signature and express a number of stem cell genes including Oct3/4 and Nanog and are more tumorigenic compared to their 'non-invasive' counterpart. They also have a profile reminiscent of cells undergoing a classic pattern of epithelial to mesenchymal transition or EMT. Using this model of invasion, we sought to investigate which genes are under epigenetic control in this rare population of cells. Epigenetic modifications, specifically DNA methylation, are key events regulating the process of normal human development. To determine the specific methylation pattern in these invasive prostate cells, and if any developmental genes were being differentially regulated, we analyzed differences in global CpG promoter methylation. Results Differentially methylated genes were determined and select genes were chosen for additional analyses. The non-receptor tyrosine kinase BMX and transcription factor SOX1 were found to play a significant role in invasion. Ingenuity pathway analysis revealed the methylated gene list frequently displayed genes from the IL-6/STAT3 pathway. Cells which have decreased levels of the targets BMX and SOX1 also display loss of STAT3 activity. Finally, using Oncomine, it was determined that more aggressive metastatic prostate cancers in humans also have higher levels of both Stat3 and Sox1. Conclusions Using this

  19. Patient autonomy in home care: Nurses' relational practices of responsibility.

    Science.gov (United States)

    Jacobs, Gaby

    2018-01-01

    Over the last decade, new healthcare policies are transforming healthcare practices towards independent living and self-care of older people and people with a chronic disease or disability within the community. For professional caregivers in home care, such as nurses, this requires a shift from a caring attitude towards the promotion of patient autonomy. To explore how nurses in home care deal with the transformation towards fostering patient autonomy and self-care. Research design and context: A case study was conducted in a professional development course ('learning circle') for home care nurses, including participant observations and focus groups. The theoretical notion of 'relational agency' and the moral concept of 'practices of responsibility' were used to conduct a narrative analysis on the nurses' stories about autonomy. Eight nurses, two coaches and two university lecturers who participated in the learning circle. Ethical considerations: Informed consent was sought at the start of the course and again, at specific moments during the course of the learning circle. Three main themes were found that expressed the moral demands experienced and negotiated by the nurses: adapting to the person, activating patients' strengths and collaboration with patients and informal caregivers. On a policy and organisational level, the moral discourse on patient autonomy gets intertwined with the instrumental discourse on healthcare budget savings. This is manifested in the ambiguities the nurses face in fostering patient autonomy in their daily home care practice. To support nurses, critical thinking, moral sensitivity and trans-professional working should be part of their professional development. The turn towards autonomy in healthcare raises moral questions about responsibilities for care. Promoting patient autonomy should be a collaborative endeavour and deliberation of patients, professional and informal caregivers together.

  20. A biochemistry laboratory course designed to enhance students autonomy

    Directory of Open Access Journals (Sweden)

    T. Silva

    2015-08-01

    Full Text Available INTRODUCTION: Laboratory sessions are responsible for promoting instrumentation skills desirable in biochemistry and biochemistry related careers. They are traditionally based on experimental protocols that lead to the expected results, and students usually have not autonomy to plan and execute their experiments. GOALS: This work aimed to enhance a traditional biochemistry lab course, applying pre-lab quizzes on protein biochemistry and lab techniques in order to have students better prepared to plan, execute and interpret experiments. This approach also aims to bring the laboratory sessions into an inquiry-based environment capable to improve students’ independent capabilities in 2 autonomy domains: learning and communication. MATERIAL AND METHODS: Online quizzes are delivered one week before each laboratory session, containing questions regarding the experimental techniques and theoretical basis related to them. Laboratory activities are presented in an inquiry-based approach where the first class of each activity is dedicated to plan experiments in order to answer the research questions presented by instructors. Activities are also organized in order to enhance students’ autonomy. The first activity is the simplest and more instructor-controlled and the last one is the most complex and less driven, transferring gradually to students the responsibility for their decisions in laboratory, supporting students’ autonomy. RESULTS: Online quizzes allowed instructors to identify students’ difficulties and to timely intervene. Scientific reports presented by students at the end of each activity showed that they performed better on less driven activities in which autonomy support were more complex than in the instructor controlled activities. CONCLUSIONS: Scientific reports analysis reveals students capabilities related to different scopes of autonomy, such as: discuss different strategies; find multiple solutions to solve problems; make their

  1. Evidence-Responsiveness and the Ongoing Autonomy of Treatment Preferences.

    Science.gov (United States)

    Weimer, Steven

    2017-06-14

    To be an autonomous agent is to determine one's own path in life. However, this cannot plausibly be seen as a one-off affair. An autonomous agent does not merely set herself on a particular course and then lock the steering wheel in place, so to speak, but must maintain some form of ongoing control over her direction in life-must keep her eyes on the road and her hands on the wheel. Circumstances often change in important and unexpected ways, after all, and it is reasonable to think that a crucial part of autonomy consists of the ability and disposition to recognize and properly respond to such changes. This implies, I contend, that a patient whose initial decision to undergo a given treatment satisfied plausible requirements of autonomy, but who is now unable to recognize that available evidence indicates the need to reconsider her medical situation and options has come to lack autonomy with respect to her desire to continue that treatment. However, and despite its importance with respect to both theoretical understandings of autonomy and applications of the concept to clinical ethics, this ongoing aspect of autonomy has received little attention. This paper aims to go some way toward remedying that. I first critically review two of the few theories of autonomy that do address "evidence-responsiveness" so as to identify and elaborate what I take to be the most promising way in which to account for this aspect of autonomy. After considering and responding to a possible objection to the evidence-responsiveness condition I propose, I conclude by discussing its clinical implications. That condition, I argue, is not merely theoretically sound, but can and should be applied to clinical practice.

  2. Instructors' Support of Student Autonomy in an Introductory Physics Course

    Science.gov (United States)

    Hall, Nicholas; Webb, David

    2014-12-01

    The role of autonomy in the student experience in a large-enrollment undergraduate introductory physics course was studied from a self-determination theory perspective. A correlational study investigated whether certain aspects of the student experience correlated with how autonomy supportive (versus controlling) students perceived their instructors to be. An autonomy-supportive instructor acknowledges students' perspectives and feelings and provides students with information and opportunities for choice while minimizing external pressures (e.g., incentives or deadlines). It was found that the degree to which students perceived their instructors as autonomy supportive was positively correlated with student interest and enjoyment in learning physics (β =0.31***) and negatively correlated with student anxiety about taking physics (β =-0.23**). It was also positively correlated with how autonomous (versus controlled) students' reasons for studying physics became over the duration of the course (i.e., studying physics more because they wanted to versus had to; β =0.24***). This change in autonomous reasons for studying physics was in turn positively correlated with student performance in the course (β =0.17*). Additionally, the degree to which students perceived their instructors as autonomy supportive was directly correlated with performance for those students entering the course with relatively autonomous reasons for studying physics (β =0.25**). In summary, students who perceived their instructors as more autonomy supportive tended to have a more favorable motivational, affective, and performance experience in the course. The findings of the present study are consistent with experimental studies in other contexts that argue for autonomy-supportive instructor behaviors as the cause of a more favorable student experience.

  3. Regions’ Economic Autonomy in the New Reality

    Directory of Open Access Journals (Sweden)

    Vladimir Stepanovich Bochko

    2016-06-01

    Full Text Available The paper discloses the understanding of new reality (normality for Russia that consists in the strengthening of the role of a man-personality and in the expansion of the economic autonomy of the territories in their interaction with the federal center. The rationale is based on a hypothesis according to which in the conditions of new reality, the increase of the well-being of the population and the overcoming of economic inequality between the territories are provided by the expansion of their economic independence as it leads to the increase of their intellectual, engineering and manufacturing potential. In the research, the author used the basic concepts of the classical economic theory, the theory of behavioural economics, interdisciplinary approach and statistical grouping method. The dynamics of the economic independence of the territories, which is manifested in the decrease in a number of donor regions and the socio-economic dividing of the territories, is shown. The assumption is proved that the consequences of the territorial stratification are the restraining of the growth of their socio-economic development and possibility probable emergence of «regional peripheral economy» with the property of the dependence of the periphery on the center, the decrease in a local initiative, the inhibition of technological development. The need to use the social psychology of the population, the psychological sets of economic development, «the second invisible hand of the market» and soft power to overcome the «regional peripheral economy» is revealed. The result of the research is the proof that the expansion of the economic independence of the territories is not only the increase of the self-isolation of regions and municipalities, but also the need to save the considerable part of the income from the production of goods and services created by the local population under control of the regional and municipal authorities and direct it to the

  4. Measuring the e-Learning Autonomy of Distance Education Students

    Directory of Open Access Journals (Sweden)

    Mehmet Firat

    2016-08-01

    Full Text Available Previous studies have provided evidence that learner autonomy is an important factor in academic achievement. However, few studies have investigated the autonomy of distance education students in e-learning environments. The purpose of this study is to evaluate the e-learning autonomy of distance education students who are responsible for their own learning. For this purpose, as the first step of the study, an e-learning autonomy scale was developed. Analyses of the validity and reliability of the scale were carried out with the participation of 1,152 distance education students from Anadolu University, Open Education System. The scale has an internal consistency coefficient of α = 0.952 and a single factorial model that explains 66.58% of the total variance. The scale was implemented with 3,293 students from 42 different programs. According to the findings, student autonomy in e-learning environments is directly proportional to level of ICT use but not affected by program or gender.

  5. ARMD Strategic Thrust 6: Assured Autonomy for Aviation Transformation

    Science.gov (United States)

    Ballin, Mark; Holbrook, Jon; Sharma, Shivanjli

    2016-01-01

    In collaboration with the external community and other government agencies, NASA will develop enabling technologies, standards, and design guidelines to support cost-effective applications of automation and limited autonomy for individual components of aviation systems. NASA will also provide foundational knowledge and methods to support the next epoch. Research will address issues of verification and validation, operational evaluation, national policy, and societal cost-benefit. Two research and development approaches to aviation autonomy will advance in parallel. The Increasing Autonomy (IA) approach will seek to advance knowledge and technology through incremental increases in machine-based support of existing human-centered tasks, leading to long-term reallocation of functions between humans and machines. The Autonomy as a New Technology (ANT) approach seeks advances by developing technology to achieve goals that are not currently possible using human-centered concepts of operation. IA applications are mission-enhancing, and their selection will be based on benefits achievable relative to existing operations. ANT applications are mission-enabling, and their value will be assessed based on societal benefit resulting from a new capability. The expected demand for small autonomous unmanned aircraft systems (UAS) provides an opportunity for development of ANT applications. Supervisory autonomy may be implemented as an expansion of the number of functions or systems that may be controlled by an individual human operator. Convergent technology approaches, such as the use of electronic flight bags and existing network servers, will be leveraged to the maximum extent possible.

  6. Recentralization within decentralization: County hospital autonomy under devolution in Kenya

    Science.gov (United States)

    Manyara, Anthony M.; Molyneux, Sassy; Tsofa, Benjamin

    2017-01-01

    Background In 2013, Kenya transitioned into a devolved system of government with a central government and 47 semi-autonomous county governments. In this paper, we report early experiences of devolution in the Kenyan health sector, with a focus on public county hospitals. Specifically, we examine changes in hospital autonomy as a result of devolution, and how these have affected hospital functioning. Methods We used a qualitative case study approach to examine the level of autonomy that hospitals had over key management functions and how this had affected hospital functioning in three county hospitals in coastal Kenya. We collected data by in-depth interviews of county health managers and hospital managers in the case study hospitals (n = 21). We adopted the framework proposed by Chawla et al (1995) to examine the autonomy that hospitals had over five management domains (strategic management, finance, procurement, human resource, and administration), and how these influenced hospital functioning. Findings Devolution had resulted in a substantial reduction in the autonomy of county hospitals over the five key functions examined. This resulted in weakened hospital management and leadership, reduced community participation in hospital affairs, compromised quality of services, reduced motivation among hospital staff, non-alignment of county and hospital priorities, staff insubordination, and compromised quality of care. Conclusion Increasing the autonomy of county hospitals in Kenya will improve their functioning. County governments should develop legislation that give hospitals greater control over resources and key management functions. PMID:28771558

  7. Patient autonomy in chronic care: solving a paradox

    Directory of Open Access Journals (Sweden)

    Reach G

    2013-12-01

    Full Text Available Gérard Reach Department of Endocrinology, Diabetes, and Metabolic Diseases, Avicenne Hospital AP-HP, and EA 3412, CRNH-IdF, Paris 13 University, Sorbonne Paris Cité, Bobigny, France Abstract: The application of the principle of autonomy, which is considered a cornerstone of contemporary bioethics, is sometimes in obvious contradiction with the principle of beneficence. Indeed, it may happen in chronic care that the preferences of the health care provider (HCP, who is largely focused on the prevention of long term complications of diseases, differ from those, more present oriented, preferences of the patient. The aims of this narrative review are as follows: 1 to show that the exercise of autonomy by the patient is not always possible; 2 where the latter is not possible, to examine how, in the context of the autonomy principle, someone (a HCP can decide what is good (a treatment for someone else (a patient without falling into paternalism. Actually this analysis leads to a paradox: not only is the principle of beneficence sometimes conflicting with the principle of autonomy, but physician's beneficence may enter into conflict with the mere respect of the patient; and 3 to propose a solution to this paradox by revisiting the very concepts of the autonomous person, patient education, and trust in the patient–physician relationship: this article provides an ethical definition of patient education. Keywords: preference, autonomy, person, reflexivity, empathy, sympathy, patient education, trust, respect, care

  8. The potential of immunostimulatory CpG DNA for inducing immunity against genital herpes: opportunities and challenges.

    Science.gov (United States)

    Harandi, Ali M

    2004-07-01

    Herpes simplex virus type 2 (HSV-2) invades human genital tract mucosa and following local replications can be rapidly transmitted via peripheral nerve axons to the sacral ganglia where it can establish latency. Reactivation of the latent viral reservoir results in recurrent ulcers in the genital region. Innate immunity, the first line of defence during both primary and recurrent genital herpes infections, is crucial during the period of acute infection to limit early virus replication and to facilitate the development of an appropriate specific acquired immunity. Recent developments in immunology reveal that the mammalian innate immune systems use Toll-like receptor (TLR) to specifically sense evolutionary conserved molecules such as bacterial DNA in pathogens. Recently, local-vaginal delivery of CpG containing oligodeoxynucleotide (ODN), a synthetic mimic of bacterial DNA, holds substantial promise as a strong inducer of innate immunity against genital herpes infections in the animal models of the disease. These preclinical observations provide a scientific ground work for introduction of this novel intervention strategy to clinic. This review aims to highlight recent developments and future challenges in use of immunostimulatory CpG ODN for inducing immunity against genital herpes infection and disease.

  9. Methylation of the estrogen receptor CpG island distinguishes spontaneous and plutonium-induced tumors from nitrosamine-induced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S.A.; Baylin, S.B.; Issa, J.J. [Johns Hopkins Univ., Baltimore, MD (United States)

    1995-12-01

    CpG islands located in the promoter region of genes constitute one mechanism for regulating transcription. These islands are normally free of methylation, regardless of the expression state of the gene. Hypermethylation of CpG islands, the addition of a methyl group to the internal cytosine within CpG dinucleotides, can cause silencing of a gene. Hypermethylation has been detected as an early event at specific chromosome loci during the development of colon cancer and represents one mechanism used by neoplatic cells to inactivate tumor suppressor genes. Recent studies have demonstrated this mechanism in inactivation of the VHL tumor suppressor gene in 19% of sporadic renal tumors and the p16 {sup INK4a} tumor suppressor gene in 30% of non-small cell lung cancers. A recent report indicates that the estrogen receptor gene could also be inactivated through methylation. In addition, estrogen receptor CpG island methylation arises as a direct function of age in normal colonic mucosa and is present in virtually all colonic tumors. In cultured colon cancer cells, methylation-associated loss of expression of the estrogen receptor gene results in deregulated growth, suggesting a role for the estrogen receptor in colon cancer development. These results provide further evidence that gene silencing through methylation could be a predominant epigenetic mechanism underlying the development of many different types of cancer. The purpose of the current investigation was to determine whether estrogen receptor CpG island methylation is involved in the development of lung cancer. The frequency for methylation of the estrogen receptor CpG island in rodent lung tumors is summarized.

  10. Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Zhifu Sun

    Full Text Available We used deep sequencing technology to profile the transcriptome, gene copy number, and CpG island methylation status simultaneously in eight commonly used breast cell lines to develop a model for how these genomic features are integrated in estrogen receptor positive (ER+ and negative breast cancer. Total mRNA sequence, gene copy number, and genomic CpG island methylation were carried out using the Illumina Genome Analyzer. Sequences were mapped to the human genome to obtain digitized gene expression data, DNA copy number in reference to the non-tumor cell line (MCF10A, and methylation status of 21,570 CpG islands to identify differentially expressed genes that were correlated with methylation or copy number changes. These were evaluated in a dataset from 129 primary breast tumors. Gene expression in cell lines was dominated by ER-associated genes. ER+ and ER- cell lines formed two distinct, stable clusters, and 1,873 genes were differentially expressed in the two groups. Part of chromosome 8 was deleted in all ER- cells and part of chromosome 17 amplified in all ER+ cells. These loci encoded 30 genes that were overexpressed in ER+ cells; 9 of these genes were overexpressed in ER+ tumors. We identified 149 differentially expressed genes that exhibited differential methylation of one or more CpG islands within 5 kb of the 5' end of the gene and for which mRNA abundance was inversely correlated with CpG island methylation status. In primary tumors we identified 84 genes that appear to be robust components of the methylation signature that we identified in ER+ cell lines. Our analyses reveal a global pattern of differential CpG island methylation that contributes to the transcriptome landscape of ER+ and ER- breast cancer cells and tumors. The role of gene amplification/deletion appears to more modest, although several potentially significant genes appear to be regulated by copy number aberrations.

  11. Improvement of the Immunogenicity of Porcine Circovirus Type 2 DNA Vaccine by Recombinant ORF2 Gene and CpG Motifs.

    Science.gov (United States)

    Li, Jun; Shi, Jian-Li; Wu, Xiao-Yan; Fu, Fang; Yu, Jiang; Yuan, Xiao-Yuan; Peng, Zhe; Cong, Xiao-Yan; Xu, Shao-Jian; Sun, Wen-Bo; Cheng, Kai-Hui; Du, Yi-Jun; Wu, Jia-Qiang; Wang, Jin-Bao; Huang, Bao-Hua

    2015-06-01

    Nowadays, adjuvant is still important for boosting immunity and improving resistance in animals. In order to boost the immunity of porcine circovirus type 2 (PCV2) DNA vaccine, CpG motifs were inserted. In this study, the dose-effect was studied, and the immunity of PCV2 DNA vaccines by recombinant open reading frame 2 (ORF2) gene and CpG motifs was evaluated. Three-week-old Changbai piglets were inoculated intramuscularly with 200 μg, 400 μg, and 800 μg DNA vaccines containing 14 and 18 CpG motifs, respectively. Average gain and rectum temperature were recorded everyday during the experiments. Blood was collected from the piglets after vaccination to detect the changes of specific antibodies, interleukin-2, and immune cells every week. Tissues were collected for histopathology and polymerase chain reaction. The results indicated that compared to those of the control piglets, all concentrations of two DNA vaccines could induce PCV2-specific antibodies. A cellular immunity test showed that PCV2-specific lymphocytes proliferated the number of TH, TC, and CD3+ positive T-cells raised in the blood of DNA vaccine immune groups. There was no distinct pathological damage and viremia occurring in pigs that were inoculated with DNA vaccines, but there was some minor pathological damage in the control group. The results demonstrated that CpG motifs as an adjuvant could boost the humoral and cellular immunity of pigs to PCV2, especially in terms of cellular immunity. Comparing two DNA vaccines that were constructed, the one containing 18 CpG motifs was more effective. This is the first report that CpG motifs as an adjuvant insert to the PCV2 DNA vaccine could boost immunity.

  12. A downstream CpG island controls transcript initiation and elongation and the methylation state of the imprinted Airn macro ncRNA promoter.

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    Martha V Koerner

    Full Text Available A CpG island (CGI lies at the 5' end of the Airn macro non-protein-coding (nc RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start.

  13. CpG island methylator phenotype, Helicobacter pylori, Epstein-Barr virus, and microsatellite instability and prognosis in gastric cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Liang Zong

    Full Text Available BACKGROUND: The controversy of CpG island methylator phenotype (CIMP in gastric cancer persists, despite the fact that many studies have been conducted on its relation with helicobacter pylori (H. pylori, Epstein-Barr virus (EBV, and microsatellite instability (MSI and prognosis. To drive a more precise estimate of this postulated relationship, a meta-analysis was performed based on existing relevant studies. METHODS: We combined individual patient data from 12 studies which involved 1000 patients with gastric cancer, which met the criteria. We tabulated and analyzed parameters from each study, including H. pylori, EBV, MSI, and clinical information of patients. RESULTS: The overall OR for H. pylori infection in CIMP positive group vs. negative group revealed that significantly elevated risks of positive H. pylori infection in the former were achieved (OR 2.23 95% CI, 1.25-4.00; P = 0.007, Pheterogeneity = 0.05. Similarly, strong relation between EBV infection and CIMP was achieved by OR 51.27 (95% CI, 9.39-279.86; P<0.00001, Pheterogeneity = 0.39. The overall OR for MSI in CIMP positive group vs. negative group was 4.44 (95% CI, 1.17-16.88; P = 0.03, Pheterogeneity = 0.01. However, there did not appear to be any correlations with clinical parameters such as tumor site, pathological type, cell differentiation, TNM stage, distant metastasis, lymph node metastasis, and 5-year survival. CONCLUSIONS: The meta-analysis highlights the strong relation of CIMP with H. pylori, EBV, and MSI, but CIMP can not be used as a prognostic marker for gastric cancer.

  14. Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo

    International Nuclear Information System (INIS)

    Du, Yantao; Liu, Zhaojun; Gu, Liankun; Zhou, Jing; Zhu, Bu-dong; Ji, Jiafu; Deng, Dajun

    2012-01-01

    Many miR genes are located within or around CpG islands. It is unclear whether methylation of these CpG islands represses miR transcription regularly. The aims of this study are to characterize gastric carcinoma (GC)-related methylation of miR CpG islands and its relationship with miRNA expression. Methylation status of 9 representative miR CpG islands in a panel of cell lines and human gastric samples (including 13 normal biopsies, 38 gastritis biopsies, 112 pairs of GCs and their surgical margin samples) was analyzed by bisulfite-DHPLC and sequencing. Mature miRNA levels were determined with quantitative RT-PCR. Relationships between miR methylation, transcription, GC development, and clinicopathological characteristics were statistically analyzed. Methylation frequency of 5 miR CpG islands (miR-9-1, miR-9-3, miR-137, miR-34b, and miR-210) gradually increased while the proportion of methylated miR-200b gradually decreased during gastric carcinogenesis (Ps < 0.01). More miR-9-1 methylation was detected in 62%-64% of the GC samples and 4% of the normal or gastritis samples (18/28 versus 2/48; Odds ratio, 41.4; P < 0.01). miR-210 methylation showed high correlation with H. pylori infection. miR-375, miR-203, and miR-193b methylation might be host adaptation to the development of GCs. Methylation of these miR CpG islands was consistently shown to significantly decrease the corresponding miRNA levels presented in human cell lines. The inverse relationship was also observed for miR-9-1, miR-9-3, miR-137, and miR-200b in gastric samples. Among 112 GC patients, miR-9-1 methylation was an independent favourable predictor of overall survival of GC patients in both univariate and multivariate analysis (P < 0.02). In conclusion, alteration of methylation status of 6 of 9 tested miR CpG islands was characterized in gastric carcinogenesis. miR-210 methylation correlated with H. pylori infection. miR-9-1 methylation may be a GC-specific event. Methylation of miR CpG islands may

  15. The appearance of Kant's deontology in contemporary Kantianism: concepts of patient autonomy in bioethics.

    Science.gov (United States)

    Secker, B

    1999-02-01

    Kant's concept of autonomy and the Kantian notion of autonomy are often conflated in bioethics. However, the contemporary Kantian notion has very little at all to do with Kant's original. In order to further bioethics discourse on autonomy, I critically distinguish the contemporary Kantian notion from Kant's original concept of moral autonomy. I then evaluate the practical relevance of both concepts of autonomy for use in bioethics. I argue that it is not appropriate to appeal to either concept toward assessing which patients we ought to respect as autonomous. Finally, I sketch criteria for what I take to be a more promising concept of autonomy for patients.

  16. Focusing on relationships, not information, respects autonomy during antenatal consultations.

    Science.gov (United States)

    Gaucher, Nathalie; Payot, Antoine

    2017-01-01

    Policy statements regarding antenatal consultations for preterm labour are guided by physicians' concerns for upholding the legal doctrine of informed consent, through the provision of standardised homogeneous medical information. This approach, led by classical in-control conceptions of patient autonomy, conceives moral agents as rational, independent, self-sufficient decision-makers. Recent studies on these antenatal consultations have explored patients' perspectives, and these differ from guidelines' suggestions. Relational autonomy - which understands moral agents as rational, emotional, creative and interdependent - resonates impressively with these new data. A model for antenatal consultations is proposed. This approach encourages clinicians to explore individual patients' lived experiences and engage in trusting empowering relationships. Moreover, it calls on physicians to enhance patients' relational autonomy by becoming advocates for their patients within healthcare institutions and professional organisations, while calling for broadscale policy changes to encourage further funding and support in investigations of the patient's voice. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  17. Education and Reproductive Autonomy: The Case of Married Nigerian Women.

    Science.gov (United States)

    Princewill, Chitu Womehoma; De Clercq, Eva; Riecher-Rössler, Anita; Jegede, Ayodele Samuel; Wangmo, Tenzin; Elger, Bernice Simone

    2017-01-01

    In this article, we examine the influence of education on the exercise of married women's reproductive autonomy. We carried out 34 in-depth interviews (IDIs) with purposively sampled married Ikwerre women in Rivers State, Nigeria. The participants were between the ages of 22 and 60, had different educational backgrounds, and were in monogamous and polygynous marriages. Data were analyzed using MAXQDA 11 software. We found that although formal education enhanced women's ability to exercise reproductive autonomy, the culture of demanding absolute respect for men remains a major barrier. Formal education provides women with the knowledge that they need in order to access adequate health services for themselves and their children. Participants also believed that educating men was critical for the exercise of women's reproductive autonomy. The cultural aspects that promote female subordination and patriarchy should be addressed more openly in Nigeria.

  18. Our experience with radioiodine therapy of thyroid functional autonomies

    International Nuclear Information System (INIS)

    Kraft, Otakar

    2005-01-01

    Full text: In this paper the author presents his experience with radioiodine therapy of thyroid functional autonomies. The objectives of this study were to establish the efficacy and determine the adverse effects of radioiodine therapy of patients with thyroid functional autonomies. The main pathologic attribute of thyroid functional autonomies is the loss of regulation in the axis of hypothalamus-hypophysis-thyroid. The main cause of functional autonomy of the thyroid is iodine deficiency. Over a period of 30 years (1974-2004) 799 patients (age from 33 to 86 years; average age 58.7 years; the female: male ration was 7.4:1) with unifocal functional autonomy (UFA), multifocal functional autonomy (MFA) and disseminated functional autonomy (DFA) received at least one treatment of radioiodine. For diagnostics and the evaluation of radioiodine therapeutic effect of functional autonomies a thyroid scintigraphy is the basic and necessary procedure. In some patients a common scintigraphy with special imaging modulation, in some patients a scintigraphy after suppression or stimulation by means of thyroid hormones or TSH were done. We have also performed a thyroid ultrasonography, an assessment of a serum level of a total and free thyroxine, total triiodothyronine, TSH, radioiodine accumulation test, estimation of radioiodine effective half-life, in some patients TRH-TSH test. The follow-up examinations were done in all patients after 4-6 months, another examination after one year in 545 patients and after two years in 254 patients. One therapeutic dose received 733 patients (91.74%) and it was sufficient for an elimination of functional autonomies. Some patients were retreated if there was the evidence of small or no treatment effect and no elimination of functional autonomies. Two radioiodine treatments received 62 patients (7.76%) and three treatments 4 patients (0.5%). We advocate individual pre-therapeutic dosimetry to determine the activity necessary to achieve a

  19. Effective Autonomy, Organisational Relationships and Skilled Jobs in Subsidiaries

    DEFF Research Database (Denmark)

    Gammelgaard, Jens; McDonald, Frank; Tüselmann, Heinz

    2011-01-01

    Purpose – The purpose of this paper is to explore how the proportion of skilled jobs in subsidiaries is influenced by resource gaps created by subsidiary development. Design/methodology/approach – This paper develops a range of propositions that connect the constructs of effective autonomy...... implications – The conceptual model can help parent company managers assess the likely effects of developments in effective autonomy and organisational relationships in their subsidiaries. Subsidiary managers can assess the possible impact of such factors as development of entrepreneurial activities......, specialization within the multinational corporation supply chain and enhancement of absorptive capacity on the proportion of skilled jobs. Originality/value – This paper is the first to describe subsidiary development from a skilled job perspective. It further develops the concept of autonomy and introduces...

  20. A Feasible Approach for Implementing Greater Levels of Satellite Autonomy

    Science.gov (United States)

    Lindsay, Steve; Zetocha, Paul

    2002-01-01

    In this paper, we propose a means for achieving increasingly autonomous satellite operations. We begin with a brief discussion of the current state-of-the-art in satellite ground operations and flight software, as well as the real and perceived technical and political obstacles to increasing the levels of autonomy on today's satellites. We then present a list of system requirements that address these hindrances and include the artificial intelligence (AI) technologies with the potential to satisfy these requirements. We conclude with a discussion of how the space industry can use this information to incorporate increased autonomy. From past experience we know that autonomy will not just "happen," and we know that the expensive course of manually intensive operations simply cannot continue. Our goal is to present the aerospace industry with an analysis that will begin moving us in the direction of autonomous operations.

  1. LOCAL PUBLIC 0 EXPENDITURE AUTONOMY – MEASURING APPROACH

    Directory of Open Access Journals (Sweden)

    Irina BILAN

    2013-06-01

    Full Text Available The decentralization process was continuous in Romania starting with 1990, generating the implication of local authorities in local public finance, as a result of exclusives, shared and delegate competences and, so, the necessity of ensuring a good management of resources and expenditures. Therefore, the decentralization of competences / responsibilities from State to local governments was a major Romanian political theme and a first rank component of management of local public finance, as main driving instrument for local development. Specific legal framework of local responsibilities is established both to European and national level. Researchers based on regulation and practice have tried to quantify the responsibilities developing different models to measure local revenue and expenditures autonomy. The paper aims is to identify some models for measuring local expenditure autonomy and to apply for Romania. The study is oriented to measure local expenditure autonomy in Romania using Bell, Ebel, Kaiser and Rojchaichainthorn's model.

  2. Autonomy among physically frail older people in nursing home settings

    DEFF Research Database (Denmark)

    Andresen, Mette; Puggaard, Lis

    2008-01-01

    BACKGROUND: Experiencing autonomy is recognised to promote health and well-being for all age groups. Perceived lack of control has been found to be detrimental to physical and mental health. There is a lack of evidence-based knowledge elucidating how frail older people in nursing home settings...... participants aged 65 years or older were included in the study. All the participants were restricted in performing at least one P-ADL activity unassisted and had a Mini Mental State Examination-score above 16. Perceived autonomy was measured at baseline, after 12 weeks and after 24 weeks by The Autonomy Sub......-dimension in the Measure of Actualisation of Potential test. Programmes were based on participants' individual assessment of their most important daily activities. Staff at all nursing homes who usually organize physical training, social or creative activities carried out individually tailored programmes using their usual...

  3. A cybernetic theory of morality and moral autonomy.

    Science.gov (United States)

    Chambers, J

    2001-04-01

    Human morality may be thought of as a negative feedback control system in which moral rules are reference values, and moral disapproval, blame, and punishment are forms of negative feedback given for violations of the moral rules. In such a system, if moral agents held each other accountable, moral norms would be enforced effectively. However, even a properly functioning social negative feedback system could not explain acts in which individual agents uphold moral rules in the face of contrary social pressure. Dr. Frances Kelsey, who withheld FDA approval for thalidomide against intense social pressure, is an example of the degree of individual moral autonomy possible in a hostile environment. Such extreme moral autonomy is possible only if there is internal, psychological negative feedback, in addition to external, social feedback. Such a cybernetic model of morality and moral autonomy is consistent with certain aspects of classical ethical theories.

  4. The history of autonomy in medicine from antiquity to principlism.

    Science.gov (United States)

    Saad, Toni C

    2018-03-01

    Respect for Autonomy (RFA) has been a mainstay of medical ethics since its enshrinement as one of the four principles of biomedical ethics by Beauchamp and Childress' in the late 1970s. This paper traces the development of this modern concept from Antiquity to the present day, paying attention to its Enlightenment origins in Kant and Rousseau. The rapid C20th developments of bioethics and RFA are then considered in the context of the post-war period and American socio-political thought. The validity and utility of the RFA are discussed in light of this philosophical-historical account. It is concluded that it is not necessary to embrace an ethic of autonomy in order to guard patients from coercion or paternalism, and that, on the contrary, the dominance of autonomy threatens to undermine those very things which have helped doctors come to view and respect their patients as persons.

  5. The Impact of Autonomy on Women’s Agency

    Directory of Open Access Journals (Sweden)

    Jeyle Ortiz-Rodríguez

    2017-01-01

    Full Text Available Kabeer’s simple and illustrative definition of empowerment is “the expansion in people’s ability to make strategic life choices in a context where this ability was previously denied to them” (Kabeer, 1999: 437. Women’s empowerment, then, is conceptualized as an increase in agency over time. Little is it known about the importance of the effect of ‘self directed motivations and desires’ and autonomy on women’s agency. The purpose of this paper is to analyze the relationships among women’s autonomy and labor force participation along with their effects on women’s agency in Nuevo Leon, Mexico. For this, we use the structural equation modeling approach. Our results reveal that women’s autonomy and participation in the labor market positively influence their agency levels.

  6. Post-sterilization autonomy among young mothers in South India.

    Science.gov (United States)

    Pallikadavath, Saseendran; Rajan, Irudaya; Singh, Abhishek; Ogollah, Reuben; Page, Samantha

    2015-01-01

    This study examined the post-sterilization autonomy of women in south India in the context of early sterilization and low fertility. Quantitative data were taken from the third round of the National Family Health Survey (NFHS-3) carried out in 2005-06, and qualitative data from one village each in Kerala and Tamil Nadu during 2010-11. The incident rate ratios and thematic analysis showed that among currently married women under the age of 30 years, those who had been sterilized had significantly higher autonomy in household decision-making and freedom of mobility compared with women who had never used any modern family planning method. Early age at sterilization and low fertility enables women to achieve the social status that is generally attained at later stages in the life-cycle. Policies to capitalize on women's autonomy and free time resulting from early sterilization and low fertility should be adopted in south India.

  7. Child Schooling in Ethiopia: The Role of Maternal Autonomy.

    Science.gov (United States)

    Gebremedhin, Tesfaye Alemayehu; Mohanty, Itismita

    2016-01-01

    This paper examines the effects of maternal autonomy on child schooling outcomes in Ethiopia using a nationally representative Ethiopian Demographic and Health survey for 2011. The empirical strategy uses a Hurdle Negative Binomial Regression model to estimate years of schooling. An ordered probit model is also estimated to examine age grade distortion using a trichotomous dependent variable that captures three states of child schooling. The large sample size and the range of questions available in this dataset allow us to explore the influence of individual and household level social, economic and cultural factors on child schooling. The analysis finds statistically significant effects of maternal autonomy variables on child schooling in Ethiopia. The roles of maternal autonomy and other household-level factors on child schooling are important issues in Ethiopia, where health and education outcomes are poor for large segments of the population.

  8. Teaching quality: High school students' autonomy and competence.

    Science.gov (United States)

    León, Jaime; Medina-Garrido, Elena; Ortega, Miriam

    2018-05-01

    How teachers manage class learning and interact with students affects students’ motivation and engagement. However, it could be that the effect of students’ representation of teaching quality on the students’ motivation varies between classes. Students from 90 classes participated in the study. We used multilevel random structural equation modeling to analyze whether the relationship of the students’ perception of teaching quality (as an indicator of the students’ mental representation) and students’ motivation varies between classes, and if this variability depends on the class assessment of teaching quality (as an indicator of teaching quality). The effect of teachers’ structure on the regression slope of student perception of student competence was .127. The effect of teachers’ autonomy support on the regression slope of student perception of student autonomy was .066. With this study we contribute a more detailed description of the relationship between teaching quality, competence and autonomy.

  9. Limits to relational autonomy--the Singaporean experience.

    Science.gov (United States)

    Krishna, Lalit Kumar Radha; Watkinson, Deborah S; Beng, Ng Lee

    2015-05-01

    Recognition that the Principle of Respect for Autonomy fails to work in family-centric societies such as Singapore has recently led to the promotion of relational autonomy as a suitable framework within which to place healthcare decision making. However, empirical data, relating to patient and family opinions and the practices of healthcare professionals in Confucian-inspired Singapore, demonstrate clear limitations on the ability of a relational autonomy framework to provide the anticipated compromise between prevailing family decision-making norms and adopted Western led atomistic concepts of autonomy. Evidence suggests that despite a growing infusion of Western influence, there is still little to indicate any major shift to individual decision making, particularly in light of the way society and healthcare are structured. Similarly, the lack of employing a shared decision-making model and data that discredit the notion that the complex psychosocial and cultural factors that affect the decision making may be considered "content neutral" not only prevents the application of relational autonomy but questions the viability of the values behind the Principle of Respect for Autonomy. Taking into account local data and drawing upon a wider concept of personhood that extends beyond prevailing family-centric ideals along with the complex interests that are focused upon the preservation of the unique nature of personhood that arises from the Ring Theory of Personhood, we propose and "operationalize" the employing of an authoritative welfare-based approach, within the confines of best interest decision making, to better meet the current care needs within Singapore. © The Author(s) 2014.

  10. The impact of patient autonomy on older adults with asthma.

    Science.gov (United States)

    Karamched, Keerthi R; Hao, Wei; Song, Peter X; Carpenter, Laurie; Steinberg, Joel; Baptist, Alan P

    2018-05-03

    Understanding patient preferences and desire for involvement in making medical decisions is important when managing chronic conditions. Previous studies have utilized the Autonomy Preference Index (API) in younger asthmatic patients to evaluate these preferences. To identify factors associated with autonomy, and to determine if autonomy is related to asthma outcomes among older adults. 189 older adults (>55 yr) with persistent asthma were included. Preferences for autonomy were assessed using the API, with a higher score indicating higher desire for autonomy. Scores were separated into two domains of 'information seeking' and 'decision making' preferences. The separated scores were correlated with asthma outcomes and demographic variables. To control for confounding factors, a linear regression analysis was performed. Higher 'decision making' preference scores correlated with female gender (p=0.007), higher education level (p=0.01), and lower depression scores (p=0.04). Regarding outcomes, 'decision making' scores positively correlated with asthma quality of life questionnaire (AQLQ) scores (p=0.01). On linear regression analysis, the AQLQ score remained significantly associated with 'decision making' preference scores (p=0.03). There was no association with asthma control test scores, spirometry values, and healthcare utilization. 'Information seeking' preference scores correlated with education level (p=0.03), but there was no correlation with asthma outcomes. Older asthmatic adults with a greater desire for involvement in decision making have a higher asthma related quality of life. Future studies with the intention to increase patient autonomy may help establish a causal relationship. Copyright © 2018. Published by Elsevier Inc.

  11. Negotiating autonomy at the margins of the state

    DEFF Research Database (Denmark)

    Eilenberg, Michael

    2009-01-01

    Recent processes of decentralization have dramatically changed local political configurations and access to resources throughout Indonesia. In particular, the resource-rich regions at the margins of the state have, in the name of regional autonomy, experienced new spaces for manoeuvre in their cl......Recent processes of decentralization have dramatically changed local political configurations and access to resources throughout Indonesia. In particular, the resource-rich regions at the margins of the state have, in the name of regional autonomy, experienced new spaces for manoeuvre...

  12. Professional Autonomy and Security Risks of Journalists in Colombia

    Directory of Open Access Journals (Sweden)

    Miguel E. Garcés Prettel

    2017-01-01

    Full Text Available This paper analyzes the relationship between professional autonomy and security risks of journalists in Colombia. A correlational-transversal research was conducted with a sample of 751 journalists who filled out the questionnaire “Worlds of Journalism Study”. The results show significant differences on the attacks received by the journalists depending on gender, news beat, region, news media, years of experience, capacity and educational level of journalists. Attacks on journalists correlates positively with the autonomy to publish and write news on governments, armed forces, criminal gangs and structural social problems (poverty, status of ethnic minorities, socioeconomic inequality, environmental damage the latter being a predictor of high risk security.

  13. Robot Science Autonomy in the Atacama Desert and Beyond

    Science.gov (United States)

    Thompson, David R.; Wettergreen, David S.

    2013-01-01

    Science-guided autonomy augments rovers with reasoning to make observations and take actions related to the objectives of scientific exploration. When rovers can directly interpret instrument measurements then scientific goals can inform and adapt ongoing navigation decisions. These autonomous explorers will make better scientific observations and collect massive, accurate datasets. In current astrobiology studies in the Atacama Desert we are applying algorithms for science autonomy to choose effective observations and measurements. Rovers are able to decide when and where to take follow-up actions that deepen scientific understanding. These techniques apply to planetary rovers, which we can illustrate with algorithms now used by Mars rovers and by discussing future missions.

  14. Enhancing Learner Autonomy in an On-line Editing Programme

    Directory of Open Access Journals (Sweden)

    Hebe Wong

    2011-09-01

    Full Text Available Little (1999 argues that in formal educational contexts, “the basis of learner autonomy is acceptance of responsibility for one’s own learning” (p.11. An autonomous learner takes responsibility for various aspects of learning (Benson & Voller, 1997; Holec, 1981. This study examines how learner autonomy opportunities were provided at various stages of writing in an on-line editing programme for a group of electronic engineering students and how the students took charge of their language learning when receiving feedback on their technical writing. The impact on their own learning effectiveness of the decisions students made is also discussed.

  15. Representations of Patients' Experiences of Autonomy in Graphic Medicine.

    Science.gov (United States)

    Tschaepe, Mark

    2018-02-01

    I advocate using graphic medicine in introductory medical ethics courses to help trainees learn about patients' experiences of autonomy. Graphic narratives about this content offer trainees opportunities to gain insights into making diagnoses and recommending treatments. Graphic medicine can also illuminate aspects of patients' experiences of autonomy differently than other genres. Specifically, comics allow readers to consider visual and text-based representations of a patient's actions, speech, thoughts, and emotions. Here, I use Ellen Forney's Marbles: Mania, Depression, Michelangelo, and Me: A Graphic Memoir and Peter Dunlap-Shohl's My Degeneration: A Journey Through Parkinson's as two examples that can serve as pedagogical resources. © 2018 American Medical Association. All Rights Reserved.

  16. Autonomy and Vulnerability of Elderly People: Emblematic Judicial Responses

    Directory of Open Access Journals (Sweden)

    María Isolina Dabove

    2018-03-01

    Full Text Available This paper discusses the private autonomy of older people when they are in situations of dependency according to the “Law of Old Age”. For this, the author presents the autonomy system: the capacity, the will, the guardianship and the schemes of support, assistance and representation according to the Argentinean Civil and Commercial Code, in force since August 2015, its scope and the jurisprudence. In addition, it is considered the recent Inter-American Convention on the Protection of the Human Rights of Older Persons (CIDHPM of the OAS, in force since January 11, 2017.

  17. The autonomy of religions from the state: the normative framework

    OpenAIRE

    Carp, Radu

    2010-01-01

    The principle of the autonomy of religious cults from the state is found in many of the Constitutions of European states and it has also been asserted by ECHR. In the case of Romania, this principle was noted for the first time by the 1869 Organic Statute of the Romanian Greek Orthodox Church of Hungary and Transylvania. This was not the case after 1918 when the term autonomy cannot be found in the 1923 Constitution, the 1928 Law on the general regime of religions or in the 1925 Statute of th...

  18. An agent-based Model of Energy Autonomy in Germany

    OpenAIRE

    Huijie, Li; Pfenning, Uwe

    2014-01-01

    Ein kurzer sozio-techischer Einblick in dasw Verständnis und die damit verbundenen Risiken von Energie-Autonomie. Auf lokaler Ebene mündet das Bestreben nach Autonomie in einer systemischen Anomie, auf regionaler Ebene finden sich Synergieeffekte, auf nationaler Ebene sind Energiekooperationen sinnvoll und effektiv. Die Risiken liegen in einer Schaffung von Überkapazitäten und erhöhten Kosten. Die Chancen liegen in Kooperation und Synergien für ein funktionierendes, sicheres EE-EVS.

  19. The Decisonal Autonomy Defending the Right to Die With Dignity

    Directory of Open Access Journals (Sweden)

    Riva Sobrado de Freitas

    2016-12-01

    Full Text Available This article aims to verify the possibility that the terminal patient, provided with decisional autonomy, can claim the right to die with dignity. To achieve the intent, it was done a bibliographic exploratory-explanatory research, qualitative, using the deductive method. Concluding that, even if the subject is polemic, the decisional autonomy deserves to be considered, including in the execution of the right to die with dignity, since it is intended to safeguard the human being in the most intimate aspects of one’s life and, because, choose the death with dignity doesn’t mean to give up from the right to life.

  20. Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

    Directory of Open Access Journals (Sweden)

    Jolly Kate

    2009-06-01

    Full Text Available Abstract Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT-based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n = 7 or to the SDT-based intervention (n = 6. Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833.