Regulatory mechanisms mediated by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer

Considerable progress has been made during the past twenty years towards elucidating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of mRNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes. Molecular mechanisms have since been discovered to explain how this nuclear receptor can be targeted for preventing and treating skin cancer. This includes the regulation of terminal differentiation, mitotic signaling, endoplasmic reticulum stress, and cellular senescence. Interestingly, the effects of activating PPARβ/δ can preferentially target keratinocytes with genetic mutations associated with skin cancer. This review provides the history and current understanding of how PPARβ/δ can be targeted for both non-melanoma skin cancer and melanoma, and postulates how future approaches that modulate PPARβ/δ signaling may be developed for the prevention and treatment of these diseases

Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4

Abstract Background The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPARβ/δ in high concentration. Results Microarray analysis elucidated eight different types of regulation that modulated PPARβ/δ-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPARβ/δ for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPARβ/δ bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPARβ/δ target genes. Conclusions PPARβ/δ regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPARβ/δ is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPARβ/δ.http://deepblue.lib.umich.edu/bitstream/2027.42/112940/1/12864_2012_Article_4648.pd

Dynamical model and nonextensive statistical mechanics of a market index on large time windows

The shape and tails of partial distribution functions (PDF) for a financial signal, i.e. the S&P500 and the turbulent nature of the markets are linked through a model encompassing Tsallis nonextensive statistics and leading to evolution equations of the Langevin and Fokker-Planck type. A model originally proposed to describe the intermittent behavior of turbulent flows describes the behavior of normalized log-returns for such a financial market index, for small and large time windows, both for small and large log-returns. These turbulent market volatility (of normalized log-returns) distributions can be sufficiently well fitted with a $\chi^2$-distribution. The transition between the small time scale model of nonextensive, intermittent process and the large scale Gaussian extensive homogeneous fluctuation picture is found to be at $ca.$ a 200 day time lag. The intermittency exponent ($\kappa$) in the framework of the Kolmogorov log-normal model is found to be related to the scaling exponent of the PDF moments, -thereby giving weight to the model. The large value of $\kappa$ points to a large number of cascades in the turbulent process. The first Kramers-Moyal coefficient in the Fokker-Planck equation is almost equal to zero, indicating ''no restoring force''. A comparison is made between normalized log-returns and mere price increments.Comment: 40 pages, 14 figures; accepted for publication in Phys Rev

Planned Use of Pulsed Crab Cavities for Short X-Ray Pulse Generation at the Advanced Photon Source

Recently, we have explored application to the Advanced Photon Source (APS) of Zholents'[1] crab cavity scheme for production of short x-ray pulses. We assumed use of superconducting (SC) cavities in order to have a continuous stream of crabbed bunches and flexibility of operating modes. The challenges of the SC approach are related to the size, cost, and development time of the cavities and associated systems. A good case can be made [2] for a pulsed system using room-temperature cavities. APS has elected to pursue such a system in the near term, with the SC-based system planned for a later date. This paper describes the motivation for the pulsed system and gives an overview of the planned implementation and issues. Among these are overall configuration options and constraints, cavity design options, frequency choice, cavity design challenges, tolerances, instabilities, and diagnostics plans

Support for smoke-free policies in the Cyprus hospitality industry

Objectives The present study used attitudinal and behavioural indicators to measure support for smoke-free policies among employers and employees in the hospitality industry in Cyprus. Methods A representative sample of 600 participants (95 % response rate) completed anonymous structured questionnaires on demographic variables, smoking status, exposure to second-hand smoke at work and related health beliefs, social norms, and smoke-free policy support. Results Participants were predominantly males (68.3 %), with a mean age of 40 years (SD = 12.69), and 39.7 % were employers/owners of the hospitality venue. Analysis of variance showed that employers and smokers were less supportive of smoke-free policies, as compared to employees and non-smokers. Linear regression models showed that attitudes towards smoke-free policy were predicted by smoking status, SHS exposure and related health beliefs, and social norm variables. Logistic regression analysis showed that willingness to confront a policy violator was predicted by SHS exposure, perceived prevalence of smoker clients, and smoke-free policy attitudes. Conclusions SHS exposure and related health beliefs, and normative factors should be targeted by interventions aiming to promote policy support in the hospitality industry in Cyprus