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1.
Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.  相似文献   
2.
Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.  相似文献   
3.
A survey on the occurrence of ochratoxin A (OTA) in 240 grape‐based beverages was carried out. Red and white wines from four different Spanish Designations of Origin (n = 160), musts (n = 20), grape juices (n = 10), ordinary wines (n = 20), special wines (Malaga, muscatel, sherry, vermouth, etc) (n = 20) and sparkling wines (n = 10) were assayed for OTA content using immunoaffinity column clean‐up and high‐performance liquid chromatography with fluorimetric detection (detection limit 0.05 µg l?1). Forty‐three (17.9%) of the samples tested contained detectable levels of OTA. The overall mean OTA concentration in red and white wines of Designations of Origin was 0.30 and 0.18 µg l?1 respectively (ranges 0.05–3.19 and 0.05–1.13 µg l?1 respectively). The percentage of wine samples with detectable amounts of OTA was higher for red (18.3%) than for white (10%) wines. OTA was also found in two of 10 red ordinary wines (0.68 and 4.24 µg l?1), whereas none of 10 white ordinary wines contained OTA. The mean OTA amount detected in sparkling wines was 0.44 µg l?1 (range 0.14–0.71 µg l?1). Two of 20 must samples contained OTA at low levels (0.08 and 0.18 µg l?1), while none of 10 grape juice samples contained OTA. Highest amounts of OTA were found in special wines (45%), with a maximum of 15.25 µg l?1 in a muscatel sample. Copyright © 2004 Society of Chemical Industry  相似文献   
4.
The use of magnetic nanoparticles in the development of ultra-high-density recording media is the subject of intense research. Much of the attention of this research is devoted to the stability of magnetic moments, often neglecting the influence of dipolar interactions. Here, we explore the magnetic microstructure of different assemblies of monodisperse cobalt single-domain nanoparticles by magnetic force microscopy and magnetometric measurements. We observe that when the density of particles per unit area is higher than a determined threshold, the two-dimensional self-assemblies behave as a continuous ferromagnetic thin film. Correlated areas (similar to domains) of parallel magnetization roughly ten particles in diameter appear. As this magnetic percolation is mediated by dipolar interactions, the magnetic microstructure, its distribution and stability, is strongly dependent on the topological distribution of the dipoles. Thus, the magnetic structures of three-dimensional assemblies are magnetically soft, and an evolution of the magnetic microstructure is observed with consecutive scans of the microscope tip.  相似文献   
5.
The combination of lithography and ion implantation is demonstrated to be a suitable method to prepare lateral multilayers. A laterally, compositionally, and magnetically modulated microscale pattern consisting of alternating Co (1.6 µm wide) and Co‐CoO (2.4 µm wide) lines has been obtained by oxygen ion implantation into a lithographically masked Au‐sandwiched Co thin film. Magnetoresistance along the lines (i.e., current and applied magnetic field are parallel to the lines) reveals an effective positive giant magnetoresistance (GMR) behavior at room temperature. Conversely, anisotropic magnetoresistance and GMR contributions are distinguished at low temperature (i.e., 10 K) since the O‐implanted areas become exchange coupled. This planar GMR is principally ascribed to the spatial modulation of coercivity in a spring‐magnet‐type configuration, which results in 180° Néel extrinsic domain walls at the Co/Co‐CoO interfaces. The versatility, in terms of pattern size, morphology, and composition adjustment, of this method offers a unique route to fabricate planar systems for, among others, spintronic research and applications.  相似文献   
6.
The IL-15 receptor alpha subunit (IL-15Ralpha) mediates high-affinity binding of IL-15, a pleiotropic cytokine implicated in the development of innate immune cells. We have generated IL-15Ralpha null (IL-15Ralpha-/-) mice to understand the role of IL-15Ralpha in immune development and function. IL-15Ralpha-/- mice are markedly lymphopenic despite grossly normal T and B lymphocyte development. This lymphopenia is due to decreased proliferation and decreased homing of IL-15Ralpha-/- lymphocytes to peripheral lymph nodes. These mice are also deficient in natural killer cells, natural killer T cells, CD8+ T lymphocytes, and TCRgammadelta intraepithelial lymphocytes. In addition, memory phenotype CD8+ T cells are selectively reduced in number. Thus, IL-15Ralpha has pleiotropic roles in immune development and function, including the positive maintenance of lymphocyte homeostasis.  相似文献   
7.
Dose uniformity within the treatment volume for tangent breast irradiation can be significantly improved through dynamic compensating collimation using all four independent jaws to define a superposition of sequentially reduced Enhanced dynamic wedge fields. The enhanced dynamic wedge angle is determined which optimizes dose uniformity in the central axis transverse plane, then the sequential reduction of the superior and inferior jaws is determined to optimize the sagittal dose uniformity. This technique could be applied under computer control through a record and verify system.  相似文献   
8.
A simple bisection algorithm for the synthesis of planar inductors using a fast electromagnetic analysis algorithm is presented in this work. Both bisection and electromagnetic analysis algorithms are based on a set of heuristic and physical rules obtained from the study of the electromagnetic behavior of these planar devices. With this procedure, the benefits are two fold: (i) the number of iterations is kept moderately low in the synthesis loop, and (ii) the analysis at each iteration step is speed up without compromising accuracy. The algorithm is applied to the development of an inductor library for a low temperature co-fired ceramic process technology.  相似文献   
9.
Proteome analysis is now emerging as key technology for deciphering biological processes and the discovery of biomarkers for diseases from tissues and body fluids. The complexity and wide dynamic range of protein expression poses a formidable challenge to both peptide separation technologies and mass spectrometry (MS). Here we review the efforts that have been undertaken to date, focussing on capillary electrophoresis coupled to mass spectrometry (CE-MS). We discuss CE-MS from an application point of view evaluating its merits and vices in regard to biomarker discovery and clinical applications. As examples, we present the use of CE-MS for the determination of protein patterns in urine, serum, and other body fluids. Finally, the benefits and limitations of CE-MS for the analysis of proteins in clinical samples are discussed against the background of alternative technologies.  相似文献   
10.
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