141 research outputs found

    Earlier onset of tumoral anglogenesis in matrix metalloproteinase-19-deficient mice

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    Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies

    Control of neoclassical tearing modes by Sawtooth control

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    The onset of a neoclassical tearing mode (NTM) depends on the existence of a large enough seed island. It is shown in the Joint European Torus that NTMs can be readily destabilized by long-period sawteeth, such as obtained by sawtooth stabilization from ion-cyclotron heating or current drive. This has important implications for burning plasma scenarios, as alpha particles strongly stabilize the sawteeth. It is also shown that, by adding heating and current drive just outside the inversion radius, sawteeth are destabilized, resulting in shorter sawtooth periods and larger beta values being obtained without NTMs

    Functional MRI evidence for the decline of word retrieval and generation during normal aging

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    International audienceThis fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing , due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming , and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automa-tisms and overlearned information. In terms of behav-ioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuro-psychological scores, and the overactivation of these uncorrelated regions would simply reveal dedifferentia-tion that occurs with aging. Altogether, our results suggest that normal aging is associated with a more difficult access to lexico-semantic operations and representations by a slowdown in executive functions, without any conceptual loss

    Simulation of ITER ICWC scenarios in JET

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    Encouraging results recently obtained with alternative ion cyclotron wall conditioning (ICWC) in the present-day tokamaks and stellarators have elevated ICWC to the status of one of the most promising techniques available to ITER for routine interpulse conditioning in the presence of the permanent high toroidal magnetic field. The paper presents a study of ICWC discharge performance and optimization of the conditioning output in the largest tokamak JET using the standard ICRF heating antenna A2 in a scenario envisaged at ITER full field, BT=5.3 T: on-axis location of the fundamental ICR for deuterium, ω=ωcD+. The perspective of application of the alternative technique in ITER is analyzed using the 3-D MWS electromagnetic code, 1-D RF full wave and 0-D plasma codes.Обнадёживающие результаты по альтернативной ионно-циклотронной (ИЦ) чистке поверхностей вакуумной камеры, полученные недавно на современных токамаках и стеллараторах, выдвинули этот метод в число наиболее вероятных технологий, планирующихся использовать в ITERe между импульсами в присутствии постоянного сильного тороидального магнитно поля. В настоящей работе представлены результаты исследований ВЧ-разряда и его оптимизаци по усилению эффекта чистки в крупнейшем из ныне действующих токамаке JET с использованием стандартных ИЦ A2 антенн. Эксперименты по ВЧ-чистке на JETе были осуществлены в режиме, моделирующем сценарий ИЦ-разряда в токамаке-реакторе ITER, при работе на полном магнитном поле BT=5.3 T и при расположении фундаментального ИЦ-резонанса для дейтерия ω=ωcD+ в центре вакуумной камеры. Перспективы применения альтернативной ВЧ-чистки в ITERе анализируются с помощью численных кодов: 3-D MWS- электромагнитного кода, 1-D ВЧ-кода и 0-D плазменного кода.Обнадійливі результати з альтернативної іонної циклотронної (ІЦ) чистки поверхонь вакуумної камери, отримані останнім часом в сучасних токамаках і стелараторах, висунули цей метод до числа найбільш вірогідних технологій, які планується використовувати в ІТЕРі між імпульсами в присутності постійного сильного тороїдального магнітного поля. В роботі представленo результати дослідження ВЧ-розряду та його оптимізації щодо підсилення ефекту чистки в найбільшому з нині діючих токамаці JET з використанням стандартних ІЦ А2 антен. Експерименти по ВЧ-чищенню на JETі були здійснені в режимі, що моделює сценарій ІЦ-розряду в токамаці-реакторі ITER, при роботі на повному магнітному полі BT=5.3 T та при розміщенні фундаментального ІЦ-резонансу для дейтерію ω=ωcD+ в центрі вакуумної камери. Перспективи застосування альтернативної ВЧ-чистки в ITERі аналізуються за допомогою числових кодів: 3-D MWS- електромагнітного коду, 1-D ВЧ-коду і 0-D плазмового коду

    ICRF Wall Conditioning: Present Status and Developments for Future Superconducting Fusion Machines

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    . 1 ABSTRACT. ITER and future superconducting fusion machines need efficient wall conditioning techniques for routine operation in between shots in the presence of permanent high magnetic field for wall cleaning, surface isotope exchange and to control the in-vessel long term tritium retention. Ion Cyclotron Wall Conditioning (ICWC) based on the ICRF discharge is fully compatible and needs the presence of the magnetic field. The present paper focuses on the principal aspects of the ICWC discharge performance in large-size fusion machines: (i) neutral gas RF breakdown with conventional ICRF heating antennas, (ii) antenna coupling with low density (~10 17 m -3 ) RF plasmas and (iii) ICWC scenarios with improved RF plasma homogeneity in the radial and poloidal directions. All these factors were identified as crucial to achieve an enhanced conditioning effect (e.g. removal rates of selected "marker" masses). All the observed effects are analyzed in terms of RF plasma wave excitation/absorption and compared with the predictions from 1-D RF full wave and 0-D RF plasma codes. Numerical modeling and empirical extrapolation from the existing machines give good evidence for the feasibility of using ICWC in ITER with the main ICRF antenna
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