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Do seismic slip deficits indicate an underestimated earthquake potential along the Vienna Basin Transfer Fault System? (2003)

Hinsch, R. ; Decker, K.

Oxford, UK : Blackwell Science Ltd

Terra nova 15 (2003), S. 0

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ISSN: 1365-3121

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Geosciences

Notes: Seismic slip rates of about 0.2 mm yr−1 calculated from cumulative seismic moments of earthquakes along the Vienna Basin Transfer Fault (VBTF) between the Alps and the Carpathians are very low compared to geologically and geodetically determined slip rates of 1–2 mm yr−1, proving a significant seismic slip deficit. Additional seismic slip calculations for arbitrarily selected fault sectors reveal large differences along strike ranging from c. 0.02 to 0.5 mm slip yr−1. As the earthquake frequency distribution suggests seismically coupled deformation, these variations might indicate locked fault segments. Results suggest that (1) the seismic cycle of the VBTF exceeds the length of available seismological observation, and (2) larger earthquakes than those recorded may occur along the fault. Thus, current local seismic hazard estimates, which are solely based on this historical database, probably underestimate the earthquake potential of the fault system.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1365-3121.2003.00504.x

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Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions (2012)

Decker, K. F., Zheng, D., He, Y., Bowman, T., Edwards, J. R., Jia, L.

Oxford University Press

In: Nucleic Acids Research

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Publication Date: 2012-11-25

Description: The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signaling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. Although previous studies have focused on ligand-dependent AR signaling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal.

Print ISSN: 0305-1048

Electronic ISSN: 1362-4962

Topics: Biology

Published by Oxford University Press

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Discovering high-resolution patterns of differential DNA methylation that correlate with gene expression changes (2013)

Vander; Kraats, N. D., Hiken, J. F., Decker, K. F., Edwards, J. R.

Oxford University Press

In: Nucleic Acids Research

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Publication Date: 2013-08-09

Description: Methylation of the CpG-rich region (CpG island) overlapping a gene’s promoter is a generally accepted mechanism for silencing expression. While recent technological advances have enabled measurement of DNA methylation and expression changes genome-wide, only modest correlations between differential methylation at gene promoters and expression have been found. We hypothesize that stronger associations are not observed because existing analysis methods oversimplify their representation of the data and do not capture the diversity of existing methylation patterns. Recently, other patterns such as CpG island shore methylation and long partially hypomethylated domains have also been linked with gene silencing. Here, we detail a new approach for discovering differential methylation patterns associated with expression change using genome-wide high-resolution methylation data: we represent differential methylation as an interpolated curve, or signature, and then identify groups of genes with similarly shaped signatures and corresponding expression changes. Our technique uncovers a diverse set of patterns that are conserved across embryonic stem cell and cancer data sets. Overall, we find strong associations between these methylation patterns and expression. We further show that an extension of our method also outperforms other approaches by generating a longer list of genes with higher quality associations between differential methylation and expression.

Print ISSN: 0305-1048

Electronic ISSN: 1362-4962

Topics: Biology