Global gene expression profiling of a mouse model of ovarian clear cell carcinoma caused by ARID1A and PIK3CA mutations implicates a role for inflammatory cytokine signaling

Ovarian clear-cell carcinoma (OCCC) is an aggressive form of epithelial ovarian cancer (EOC). OCCC represents 5-25% of all EOC incidences and is the second leading cause of death from ovarian cancer (Glasspool and McNeish, 2013) [1]. A recent publication by Chandler et al. reported the first mouse model of OCCC that resembles human OCCC both genetically and histologically by inducing a localized deletion of ARID1A and the expression of the PIK3CAH1047R substitution mutation (Chandler et al., 2015) [2]. We utilized Affymetrix Mouse Gene 2.1 ST arrays for the global gene expression profiling of mouse primary OCCC tumor samples and animal-matched normal ovaries to identify cancer-dependent gene expression. We describe the approach used to generate the differentially expressed genes from the publicly available data deposited at the Gene Expression Omnibus (GEO) database under the accession number GSE57380. These data were used in cross-species comparisons to publically available human OCCC gene expression data and allowed the identification of coordinately regulated genes in both mouse and human OCCC and supportive of a role for inflammatory cytokine signaling in OCCC pathogenesis (Chandler et al., 2015) [2]

Space-time Phase Transitions in Driven Kinetically Constrained Lattice Models

Kinetically constrained models (KCMs) have been used to study and understand the origin of glassy dynamics. Despite having trivial thermodynamic properties, their dynamics slows down dramatically at low temperatures while displaying dynamical heterogeneity as seen in glass forming supercooled liquids. This dynamics has its origin in an ergodic-nonergodic first-order phase transition between phases of distinct dynamical "activity". This is a "space-time" transition as it corresponds to a singular change in ensembles of trajectories of the dynamics rather than ensembles of configurations. Here we extend these ideas to driven glassy systems by considering KCMs driven into non-equilibrium steady states through non-conservative forces. By classifying trajectories through their entropy production we prove that driven KCMs also display an analogous first-order space-time transition between dynamical phases of finite and vanishing entropy production. We also discuss how trajectories with rare values of entropy production can be realized as typical trajectories of a mapped system with modified forces

Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins

Water and water-mediated interactions determine thermodynamic and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano droplets. Solvation of hydrophobic and charged species change drastically in nano water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. Interaction between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores

Observational diagnostics of gas in protoplanetary disks

Protoplanetary disks are composed primarily of gas (99% of the mass). Nevertheless, relatively few observational constraints exist for the gas in disks. In this review, I discuss several observational diagnostics in the UV, optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to study the gas in the disks of young stellar objects. I concentrate in diagnostics that probe the inner 20 AU of the disk, the region where planets are expected to form. I discuss the potential and limitations of each gas tracer and present prospects for future research.Comment: Review written for the proceedings of the conference "Origin and Evolution of Planets 2008", Ascona, Switzerland, June 29 - July 4, 2008. Date manuscript: October 2008. 17 Pages, 6 graphics, 134 reference

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

The views and experiences of suicidal children and young people of mental health support services: A meta-ethnography.

Background: Suicide is amongst the leading causes of death in young people globally and a health priority worldwide. For children and young people (CYP) attempting or considering suicide there is no agreed treatment model. Development of treatment models should be informed by the views and experiences of CYP using services. Methods: Meta-ethnography was used to systematically identify and synthesise studies reporting the views of CYP who used mental health services following suicidal behaviour. Relevant studies were quality appraised. First order (participants) and second order (original author) data were translated to identify common and disconfirming themes and concepts. Translated findings were synthesised and led to a new hypothesis supported by additional ‘linguistic analysis’ of texts to construct a novel third order line-of-argument. Results: Four studies conducted since 2006 in three countries involving 44 young people aged 11-24 years were synthesised. Translation revealed that suicidal CYP do not know where or how to access help, they cannot access help directly and when seen by mental health practitioners they do not feel listened to. Line-of-argument synthesis identified a silence around suicidality within the conversations CYP have with mental health practitioners and within academic research reporting. Use of the term ‘self-harm’ to encompass suicidal behaviours potentially contributes to this silence by avoiding the word ‘suicide’. Conclusions: CYP who are suicidal need to have easy access to mental health services. When using services, they want to feel listened to and have suicidal feelings acknowledged. This involves professionals referring explicitly to suicide not just self-harm