ORB5: a global electromagnetic gyrokinetic code using the PIC approach in toroidal geometry

This paper presents the current state of the global gyrokinetic code ORB5 as an update of the previous reference [Jolliet et al., Comp. Phys. Commun. 177 409 (2007)]. The ORB5 code solves the electromagnetic Vlasov-Maxwell system of equations using a PIC scheme and also includes collisions and strong flows. The code assumes multiple gyrokinetic ion species at all wavelengths for the polarization density and drift-kinetic electrons. Variants of the physical model can be selected for electrons such as assuming an adiabatic response or a ``hybrid'' model in which passing electrons are assumed adiabatic and trapped electrons are drift-kinetic. A Fourier filter as well as various control variates and noise reduction techniques enable simulations with good signal-to-noise ratios at a limited numerical cost. They are completed with different momentum and zonal flow-conserving heat sources allowing for temperature-gradient and flux-driven simulations. The code, which runs on both CPUs and GPUs, is well benchmarked against other similar codes and analytical predictions, and shows good scalability up to thousands of nodes

Amenability of algebras of approximable operators

We give a necessary and sufficient condition for amenability of the Banach algebra of approximable operators on a Banach space. We further investigate the relationship between amenability of this algebra and factorization of operators, strengthening known results and developing new techniques to determine whether or not a given Banach space carries an amenable algebra of approximable operators. Using these techniques, we are able to show, among other things, the non-amenability of the algebra of approximable operators on Tsirelson's space.Comment: 20 pages, to appear in Israel Journal of Mathematic

Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization

Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with alpha-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis

How university’s activities support the development of students’ entrepreneurial abilities: case of Slovenia and Croatia

The paper reports how the offered university activities support the development of students’ entrepreneurship abilities. Data were collected from 306 students from Slovenian and 609 students from Croatian universities. The study reduces the gap between theoretical researches about the academic entrepreneurship education and individual empirical studies about the student’s estimation of the offered academic activities for development of their entrepreneurial abilities. The empirical research revealed differences in Slovenian and Croatian students’ perception about (a) needed academic activities and (b) significance of the offered university activities, for the development of their entrepreneurial abilities. Additionally, the results reveal that the impact of students’ gender and study level on their perception about the importance of the offered academic activities is not significant for most of the considered activities. The main practical implication is focused on further improvement of universities’ entrepreneurship education programs through selection and utilization of activities which can fill in the recognized gaps between the students’ needed and the offered academic activities for the development of students’ entrepreneurial abilities

An Assessment of Food Safety Handling Practices at Farmers\u27 Markets in Rhode Island Using a Smartphone Application

The number of foodborne illness outbreaks increased in the US from 2001 to 2010, and 17% of them were associated with produce. Higher risk, whole produce sold at farmers\u27 markets presents unique challenges to food safety practices in regard to temperature controls, potable water, and exposure to contaminants. The purpose of this study is to use direct observations to identify unsafe food handling practices among vendors selling higher risk produce at Rhode Island farmers\u27 markets. This study used, as a tool for data acquisition, a Smartphone application developed to allow concealed direct observations of actual vendors\u27 practices at farmers\u27 markets. Observations were made at fourteen (7 state and 7 private) farmers\u27 markets to collect data on food handling practices of 26 vendors selling higher-risk produce. The results of this study will be used as guidance for education programs targeting farmers\u27 market managers and vendors that promote best practices in regard to whole produce

Dual inhibition of histone deacetylases and phosphoinositide 3-kinase enhances therapeutic activity against B cell lymphoma

Phosphoinositide 3-kinase (PI3K) and Myc are known to cooperate in promoting the survival and growth of a variety of B-cell lymphomas. While currently there are no small molecule inhibitors of Myc protein, histone deacetylase (HDAC) inhibitors have been shown to reduce levels of Myc protein by suppressing its transcription. We assessed the efficacy of CUDC-907, a new rationally designed dual inhibitor of PI3K and HDACs, in a panel of lymphoma cell lines. CUDC-907 treatment resulted in a dose- and time-dependent growth inhibition and cell death of DLBCL cell lines, irrespective of the cell of origin. CUDC-907 treatment down-regulated the phosphorylation of PI3K downstream targets, including AKT, PRAS40, S6, and 4EBP1, increased histone 3 acetylation, and decreased Myc protein levels. SILAC-based quantitative mass spectrometry demonstrated that CUDC-907 treatment decreased the protein levels of several components of the B cell receptor (BCR) and Toll like receptor (TLR) pathways, including BTK, SYK, and MyD88 proteins. These cellular changes were associated with an inhibition of NF-kB activation. CUDC-907 demonstrated in vivo efficacy with no significant toxicity in a human DLBCL xenograft mouse model. Collectively, these data provide a mechanistic rationale for evaluating CUDC-907 for the treatment of patients with Myc and PI3K-dependent lymphomas

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target