Simulations of ion cyclotron emission from energetic ions in DIII-D tokamak plasmas

Ion cyclotron emission (ICE) was the first collective radiative instability, driven by confined fusion-born ions, that was observed from deuterium-tritium plasmas in both JET and TFTR. The excitation mechanism for ICE is the magnetoacoustic cyclotron instability (MCI). The diagnostic exploitation of ICE in future experiments relies on the understanding of the MCI. Recent advances in computational plasma physics have led to substantial progress in developing models to study instabilities driven by fusion-born ions in fusion plasmas. ICE is a potential diagnostic for confined alpha-particles in ITER, where measurements of ICE could yield information on energetic ion behaviour supplementing that obtainable from other diagnostics. Furthermore, it may be possible to use ICE to study fast ion redistribution and loss due to MHD activity in ITER. One way to study the MCI is by using particle-in-cell simulations, where the electron and ion dynamics are evolved using the Lorentz force and the electromagnetic fields are solved using the full set of Maxwell’s equations. In this thesis, highly resolved particle in cell simulations of edge and central ICE have been performed for JET and the DIII-D tokamak. The results are found to be in good agreement with the experiment and the theory of the magnetoacoustic cyclotron instability

COMPETENCIES AND SKILLS IN HIGHER EDUCATIONIN ACCOUNTING IN LEBANON

The purpose of this study is to show the competencies and skills developed for the undergraduates and postgraduates’ degrees in accounting education in the Lebanese universities. It emphasizes the role of the universities that is essential in developing the economic reforms. It seeks to address the job offers needed in the accounting departments for major employers in the public sector. The study focuses on the accounting education in the context of IPSAS adoption. The research adopted the qualitative methodology by using interviews with the Lebanese higher education senior officials in universities

COMPETENCIES AND SKILLS IN HIGHER EDUCATION IN ACCOUNTING IN LEBANON

The purpose of this study is to show the competencies and skills developed for the undergraduates and postgraduates’ degrees in accounting education in the Lebanese universities. It emphasizes the role of the universities that is essential in developing the economic reforms. It seeks to address the job offers needed in the accounting departments for major employers in the public sector. The study focuses on the accounting education in the context of IPSAS adoption. The research adopted the qualitative methodology by using interviews with the Lebanese higher education senior officials in universities

Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence

The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The alveolar subtype (ARMS) is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 that drives oncogenic cellular properties. Exosomes are small, secreted vesicles that affect paracrine signaling. We show that PAX3-FOXO1 transcript alters exosome content of C2C12 myoblasts, leading to pro-tumorigenic paracrine effects in recipient cells. Microarray analysis revealed alteration in miRNA content of exosomes, affecting cellular networks involved in cell metabolism, growth signaling, and cellular invasion. Overexpression and knockdown studies showed that miR-486-5p is an effector of PAX3-FOXO1, and mediates its paracrine effects in exosomes, including promoting recipient cell migration, invasion, and colony formation. Analysis of human RMS cells showed miR-486-5p is enriched in both cells and exosomes, and to a higher extent in ARMS subtypes. Analysis of human serum samples showed that miR-486-5p is enriched in exosomes of patients with RMS, and follow-up after chemotherapy showed decrease to control values. Our findings identify a novel role of both PAX3-FOXO1 and its downstream effector miR-486-5p in exosome-mediated oncogenic paracrine effects of RMS, and suggest its possible use as a biomarker. © 2019, The Author(s)

The histone deacetylase inhibitor Suberoylanilide Hydroxamic Acid (SAHA) as a therapeutic agent in rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is an aggressive childhood sarcoma with two distinct subtypes, embryonal (ERMS) and alveolar (ARMS) histologies. More effective treatment is needed to improve outcomes, beyond conventional cytotoxic chemotherapy. The pan-histone deacetylase inhibitor, Suberoylanilide Hydroxamic Acid (SAHA), has shown promising efficacy in limited preclinical studies. We used a panel of human ERMS and ARMS cell lines and xenografts to evaluate the effects of SAHA as a therapeutic agent in both RMS subtypes. SAHA decreased cell viability by inhibiting S-phase progression in all cell lines tested, and induced apoptosis in all but one cell line. Molecularly, SAHA-treated cells showed activation of a DNA damage response, induction of the cell cycle inhibitors p21 Cip1 and p27 Kip1 and downregulation of Cyclin D1. In a subset of RMS cell lines, SAHA promoted features of cellular senescence and myogenic differentiation. Interestingly, SAHA treatment profoundly decreased protein levels of the driver fusion oncoprotein PAX3-FOXO1 in ARMS cells at a post-translational level. In vivo, SAHA-treated xenografts showed increased histone acetylation and induction of a DNA damage response, along with variable upregulation of p21 Cip1 and p27 Kip1 . However, while the ARMS Rh41 xenograft tumor growth was significantly inhibited, there was no significant inhibition of the ERMS tumor xenograft RD. Thus, our work shows that, while SAHA is effective against ERMS and ARMS tumor cells in vitro, it has divergent in vivo effects. Together with the observed effects on the PAX3-FOXO1 fusion protein, these data suggest SAHA as a possible therapeutic agent for clinical testing in patients with fusion protein-positive RMS. © 2018, © 2018 Taylor & Francis Group, LLC

Explanation of core ion cyclotron emission from beam-ion heated plasmas in ASDEX Upgrade by the magnetoacoustic cyclotron instability

Bursts of ion cyclotron emission (ICE), with spectral peaks corresponding to the hydrogen cyclotron harmonic frequencies in the plasma core are detected from helium plasmas heated by sub-Alfvénic beam-injected hydrogen ions in the ASDEX Upgrade tokamak. Based on the fast ion distribution function obtained from TRANSP/NUBEAM code, together with a linear analytical theory of the magnetoacoustic cyclotron instability (MCI), the growth rates of MCI could be calculated. In our theoretical and experimental studies, we found that the excitation mechanism of core ICE driven by sub-Alfvénic beam ions in ASDEX Upgrade is MCI as the time evolution of MCI growth rates is broadly consistent with measured ICE amplitudes. The MCI growth rate is very sensitive to the energy and velocity distribution of beam-injected ions and is suppressed by the slowing down of the dominant beam-injected ion velocity and the spreading of the fast ion distribution profile. This may help to account for the experimental observation that ICE signals disappear within ~3 ms after the NBI turn-off time, much faster than the slowing down times of the beam ions

Regulation of CEACAM1 transcription in human breast epithelial cells

<p>Abstract</p> <p>Background</p> <p>Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a transmembrane protein with multiple functions in different cell types. CEACAM1 expression is frequently mis-regulated in cancer, with down-regulation reported in several tumors of epithelial origin and <it>de novo </it>expression of CEACAM1 in lung cancer and malignant melanoma. In this report we analyzed the regulation of CEACAM1 expression in three breast cancer cell lines that varied in CEACAM1 expression from none (MCF7) to moderate (MDA-MB-468) to high (MCF10A, comparable to normal breast).</p> <p>Results</p> <p>Using <it>in vivo </it>footprinting and chromatin immunoprecipitation experiments we show that the <it>CEACAM1 </it>proximal promoter in breast cells is bound in its active state by SP1, USF1/USF2, and IRF1/2. When down-regulated the <it>CEACAM1 </it>promoter remains accessible to USF2 and partially accessible to USF1. Interferon-γ up-regulates CEACAM1 mRNA by a mechanism involving further induction of IRF-1 and USF1 binding at the promoter. As predicted by this analysis, silencing of IRF1 and USF1 but not USF2 by RNAi resulted in a significant decrease in CEACAM1 protein expression in MDA-MB-468 cells. The inactive <it>CEACAM1 </it>promoter in MCF7 cells exhibits decreased histone acetylation at the promoter region, with no evidence of H3K9 or H3K27 trimethylation, histone modifications often linked to condensed chromatin structure.</p> <p>Conclusions</p> <p>Our data suggest that transcription activators USF1 and IRF1 interact to modulate CEACAM1 expression and that the chromatin structure of the promoter is likely maintained in a poised state that can promote rapid induction under appropriate conditions.</p

Novel internal measurements of ion cyclotron frequency range fast-ion driven modes

Novel internal measurements and analysis of ion cyclotron frequency range fast-ion driven modes in DIII-D are presented. Observations, including internal density fluctuation (˜n) measurements obtained via Doppler backscattering, are presented for modes at low harmonics of the ion cyclotron frequency localized in the edge. The measurements indicate that these waves, identified as coherent ion cyclotron emission (ICE), have high wave number, k⊥ρfast1, consistent with the cyclotron harmonic wave branch of the magnetoacoustic cyclotron instability, or electrostatic instability mechanisms. Measurements show extended spatial structure (at least ∼1/6 the minor radius). These edge ICE modes undergo amplitude modulation correlated with edge localized modes (ELM) that is qualitatively consistent with expectations for ELM-induced fast-ion transport