156 research outputs found

    In Conversation with Mubin Shaikh: From Salafi Jihadist to Undercover Agent inside the "Toronto 18" Terrorist Group

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    This interview with former undercover agent Mubin Shaikh can help academics and security practitioners understand the key role played and the challenges faced by covert human intelligence sources within domestic terrorist groups. The interview highlights the identity crisis, the personal factors, and the allure of jihadi militancy that initially drove Shaikh to join a Salafi jihadist group. It investigates Shaikh’s process of disengagement from the Salafi jihadist belief system and his rediscovery of a moderate, inclusive, and benevolent form of Islam. It explores his work as an undercover agent for the Canadian Security Intelligence Service, the Royal Canadian Mounted Police, and the Integrated National Security Enforcement Team responsible for disrupting domestic terrorist groups. The “Toronto 18” terrorist cell, the key role played by undercover agents in preventing terrorist action, and the challenges posed by entrapment are also discussed

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

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    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

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

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    <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

    Lewis X antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involvement of the endothelial scavenger receptor C-Type lectin

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    Lewis x (Lex, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Lex in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Lex-dependent PMN interaction with HUVEC. Although both anti-Lex mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Lex-trisaccharide, interacts with specific glycoproteins of Mr␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.Fil: Elola, Maria Teresa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capurro, Mariana Isabel. University of Toronto; CanadáFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; ArgentinaFil: Coombs, Peter J.. Imperial College London; Reino UnidoFil: Taylor, Maureen E.. Imperial College London; Reino UnidoFil: Drickamer, Kurt. Imperial College London; Reino UnidoFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentin

    Global turbulence features across marginality and non-local pedestal-core interactions

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    Spatially non-local aspects of turbulent transport in tokamak plasmas are examined with global gyrokinetic simulations using the ORB5 code. Inspired by very accurate measurements in the TCV tokamak in L-mode, we initialise plasma profiles with constant logarithmic gradients in the core and constant linear gradients in the 'pedestal' (ρ[0.8,1]\rho \in [0.8,\,1]). The main finding is that transport in the core is strongly affected by the presence of pedestal gradients. This non-local pedestal-core coupling appears to be correlated with the appearance of repetitive avalanches that propagate across both pedestal and core regions. Below a certain threshold value in pedestal gradient, no well-defined frequency is found for avalanches. Above this threshold, a well-defined frequency shows up, which roughly matches that of the local geodesic acoustic mode (GAM) frequency near the plasma edge and is thus well below the local GAM frequency in the core: this behaviour is very similar to the global coherent mode structure observed in TCV. Above this threshold in pedestal gradient, the core transport increases sharply: there is therefore a non-locality in marginality. The probability density functions (PDFs) of density, temperature, temperature gradient and potential are found to have nearly Gaussian distributions, whereas the heat flux can have, in the presence of avalanches, a more or less strongly positively skewed PDF, which could be fitted by a log-normal distribution. The skewness of the heat flux is found to be radially and non-locally dependent: its value in the plasma core critically depends on the presence of gradients in the pedestal. The relation flux versus gradient is examined in detail. The local instantaneous flux versus gradient relation shows a hysteresis behaviour during an avalanche but no clear correlation, unlike the flux and zonal flow (ZF) shearing rate, which are anti-correlated: flux is higher when shearing rate is lower. This leads to corrugated time-averaged radial profiles of transport, heat and temperature gradient, with heat diffusivity having local maxima where the ZF shearing rate goes to zero and temperature gradient has local minima. Finally, we show how the flux versus gradient relation can be analysed locally for series of simulations with different averaged gradients

    Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications

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