Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue.</p> <p>Methods</p> <p>H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer.</p> <p>Results</p> <p>H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth.</p> <p>Conclusion</p> <p>These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.</p

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

Arquitetos pioneiros na construção do estado de Roraima: décadas de 1980 e 1990

Este artigo tem por objetivo evidenciar a importância dos arquitetos pioneiros de Roraima, que foram responsáveis pela consolidação da estrutura dos órgãos técnicos no surgimento do estado e que contribuíram para a imagem da arquitetura local, entre o final da década de 1980 e ao longo da década de 1990. Inseridos num segundo momento de influxo desenvolvimentista, estes arquitetos se destacaram pela coordenação e autoria de obras modernas que serviram de alicerce infraestrutural e arranque para o desenvolvimento socioeconômico roraimense, especialmente na década de 1990, com destaque às obras arquitetônicas dos edifícios institucionais, que constituiram um conjunto arquitetônico simbólico para a capital. A necessidade desse registro deve-se à escassez de documentação histórica desse período importante, sendo necessário o registro dessas contribuições, cujas fontes foram pesquisas bibliográficas e análises documentais, como entrevistas com os profissionais da época e registros fotográficos. Desse modo, o trabalho visa destacar como se deu o processo da Arquitetura Moderna tardia em Roraima nesse período, assim como o papel dos arquitetos dos órgãos públicos de infraestrutura como precursores na construção e consolidação do, então, novo estado brasileiro