L\'{e}vy flights in inhomogeneous environments

We study the long time asymptotics of probability density functions (pdfs) of L\'{e}vy flights in different confining potentials. For that we use two models: Langevin - driven and (L\'{e}vy - Schr\"odinger) semigroup - driven dynamics. It turns out that the semigroup modeling provides much stronger confining properties than the standard Langevin one. Since contractive semigroups set a link between L\'{e}vy flights and fractional (pseudo-differential) Hamiltonian systems, we can use the latter to control the long - time asymptotics of the pertinent pdfs. To do so, we need to impose suitable restrictions upon the Hamiltonian and its potential. That provides verifiable criteria for an invariant pdf to be actually an asymptotic pdf of the semigroup-driven jump-type process. For computational and visualization purposes our observations are exemplified for the Cauchy driver and its response to external polynomial potentials (referring to L\'{e}vy oscillators), with respect to both dynamical mechanisms.Comment: Major revisio

Erwachsenenbildung im Kontext: theoretische Rahmungen, empirische Spielräume und praktische Regulative; Festschrift zum 60. Geburtstag von Jürgen Wittpoth

Ein Rahmen ist keine Grenze - er kann auch zur Auseinandersetzung mit dem gerahmten Inhalt und zur Rahmenüberschreitung anregen. Die Werke von Piet Mondrian gehören zu den bekanntesten "rahmensprengenden" Bildern. In der Erwachsenenbildung stehen die Arbeiten von Jürgen Wittpoth für rahmenüberschreitende Gedanken und Konzepte. Schon 1994 beschäftigt sich Jürgen Wittpoth in seiner Habilitationsschrift "Rahmungen und Spielräume des Selbst" kritisch mit den Grenzen, die empirische Befunde der Erwachsenenbildung setzen. In diesem Sammelband, der zum 60. Geburtstag von Jürgen Wittpoth erschienen ist, betrachten namhafte Wegbeleiter seine wegweisenden Arbeiten im Kontext von Theorie, Empirie und praktischen Regulativen

Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone

Genome-scale mapping of pre-replication complex proteins has not been reported in mammalian cells. Poor enrichment of these proteins at specific sites may be due to dispersed binding, poor epitope availability or cell cycle stage-specific binding. Here, we have mapped sites of biotin-tagged ORC and MCM protein binding in G1-synchronized populations of Chinese hamster cells harboring amplified copies of the dihydrofolate reductase (DHFR) locus, using avidin-affinity purification of biotinylated chromatin followed by high-density microarray analysis across the DHFR locus. We have identified several sites of significant enrichment for both complexes distributed throughout the previously identified initiation zone. Analysis of the frequency of initiations across stretched DNA fibers from the DHFR locus confirmed a broad zone of de-localized initiation activity surrounding the sites of ORC and MCM enrichment. Mapping positions of mononucleosomal DNA empirically and computing nucleosome-positioning information in silico revealed that ORC and MCM map to regions of low measured and predicted nucleosome occupancy. Our results demonstrate that specific sites of ORC and MCM enrichment can be detected within a mammalian intitiation zone, and suggest that initiation zones may be regions of generally low nucleosome occupancy where flexible nucleosome positioning permits flexible pre-RC assembly sites

The function of miR-143, miR-145 and the MiR-143 host gene in cardiovascular development and disease

Noncoding RNAs (long noncoding RNAs and small RNAs) are emerging as critical modulators of phenotypic changes associated with physiological and pathological contexts in a variety of cardiovascular diseases (CVDs). Although it has been well established that hereditable genetic alterations and exposure to risk factors are crucial in the development of CVDs, other critical regulators of cell function impact on disease processes. Here we discuss noncoding RNAs have only recently been identified as key players involved in the progression of disease. In particular, we discuss micro RNA (miR)-143/145 since they represent one of the most characterised microRNA clusters regulating smooth muscle cell (SMC) differentiation and phenotypic switch in response to vascular injury and remodelling. MiR143HG is a well conserved long noncoding RNA (lncRNA), which is the host gene for miR-143/145 and recently implicated in cardiac specification during heart development. Although the lncRNA-miRNA interactions have not been completely characterised, their crosstalk is now beginning to emerge and likely requires further research focus. In this review we give an overview of the biology of the genomic axis that is miR-143/145 and MiR143HG, focusing on their important functional role(s) in the cardiovascular system

Study of FoxA Pioneer Factor at Silent Genes Reveals Rfx-Repressed Enhancer at Cdx2 and a Potential Indicator of Esophageal Adenocarcinoma Development

Understanding how silent genes can be competent for activation provides insight into development as well as cellular reprogramming and pathogenesis. We performed genomic location analysis of the pioneer transcription factor FoxA in the adult mouse liver and found that about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. Virtually all of the FoxA-bound silent sites are within conserved sequences, suggesting possible function. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors. We found one such target site at a cryptic “shadow” enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA. The Cdx2 shadow enhancer exhibits a subset of regulatory properties of the upstream Cdx2 promoter region. While Cdx2 is ectopically induced in the early metaplastic condition of Barrett's esophagus, its expression is not necessarily present in progressive Barrett's with dysplasia or adenocarcinoma. By contrast, we find that Rfx1 expression in the esophageal epithelium becomes gradually extinguished during progression to cancer, i.e, expression of Rfx1 decreased markedly in dysplasia and adenocarcinoma. We propose that this decreased expression of Rfx1 could be an indicator of progression from Barrett's esophagus to adenocarcinoma and that similar analyses of other transcription factors bound to silent genes can reveal unanticipated regulatory insights into oncogenic progression and cellular reprogramming

Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene

Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2) functions exclusively in DNA replication of normal cells due to its S phase-specific expression and late mitotic degradation. Herein, we demonstrate the control of R2 expression through alternative promoters, splicing and polyadenylation sites in zebrafish. Three functional R2 promoters were identified to generate six transcript variants with distinct 5′ termini. The proximal promoter contains a conserved E2F binding site and two CCAAT boxes, which are crucial for the transcription of R2 gene during cell cycle. Activity of the distal promoter can be induced by DNA damage to generate four transcript variants through alternative splicing. In addition, two novel splice variants were found to encode distinct N-truncated R2 isoforms containing residues for enzymatic activity but no KEN box essential for its proteolysis. These two N-truncated R2 isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit (R1). Thus, our results suggest that multilayered mechanisms control the differential expression and function of zebrafish R2 gene during cell cycle and under genotoxic stress

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe