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1.
A quantitative immunocytochemical procedure was used for evaluation of the blood-brain barrier (BBB) to endogenous albumin in plaque-forming (PF) and non-plaque-forming (NPF) groups of scrapie-infected mice at the clinical stage of disease. Ultrathin sections of brain samples (cerebral cortex, hippocampus and cerebellum) embedded in resin (Lowicryl K4M) were exposed to anti-mouse albumin antiserum followed by protein A-gold. Using morphometry, the density of immunosignals (gold particles per microns2) was recorded over four compartments: vascular lumen, endothelium, subendothelial space, and brain parenchyma (neuropil). Morphometric and statistical analyses did not reveal significant differences in the barrier function of the microvasculature of the cerebral cortex and hippocampus in either group of mice, although a slight increase in the number of leaking vessels in the PF group was noted. In contrast, in the cerebellum, the permeability of the microvessels to albumin was significantly higher in the PF than in the NPF mouse group, and this was paralleled by the infiltration of the walls of numerous vascular profiles with amyloid deposits (amyloid angiopathy). These data also indicate the existence of distinct regional differences in BBB function in the brain of scrapie-infected mice. The vascular amyloid deposits and the amyloid plaques present in the cerebral cortex of PF mice were labeled with numerous immunosignals suggesting the affinity of extravasated albumin to these deposits. In conclusion, no convincing evidence was obtained indicating that impairment of the BBB, manifested by increased permeability of vascular segments, is directly related to the deposition of amyloid in the vascular wall and in plaques. Segmental impairment of the barrier function seems to be rather the result of disturbed structural integrity of the components of the vascular wall.  相似文献   
2.
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   
3.
Although alcohol and distraction are often cited as significant risk factors for traffic crashes, most research has considered them in isolation. It is therefore necessary to consider the interactions between alcohol and distraction impairment sources, especially when examining the relationship between behavior and crash risk. In a driving simulator, the primary goal was to maintain a safe headway to a lead vehicle and the secondary goal was to maintain stable lane position. All participants engaged in distractions that represented different levels of resource competition and half of the participants consumed alcohol (target BAC 0.08 g/dl). Specific comparisons were made between sober driving while distracted and driving intoxicated without distraction. Distraction tasks produced more changes in driving behavior than did alcohol for both longitudinal (primary) and lateral (secondary) driving goals. Alcohol impairment was evident only in relation to lateral driving performance, however there was an amplification of impairment when alcohol and distraction conditions were combined. Distraction resulted in a general level of impairment across all driving goals, whereas participants with alcohol appeared to shed secondary driving goals to “protect” primary driving goals. Drivers’ strategies to cope with alcohol (and distraction) may not be sufficient to offset the increased crash risk.  相似文献   
4.
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   
5.
The effect of high-intensity pulsed electric field (PEF) treatment on the survival of Enterobacter sakazakii suspended in buffered peptone water (BPW) and powdered infant formula milk (IFM) was evaluated. Reference medium and IFM samples were treated with PEF. Electric field intensity and treatment time were varied from 10 to 40 kV cm−1 and from 60 to 3895 μs, respectively. Samples of buffered peptone water (3 g L−1) and IFM were inoculated with E. sakazakii (CECT 858) (109 cfu mL−1) and then treated with PEF. The inactivation data were adjusted to the Weibull frequency distribution function and Bigelow model, and constants were calculated for both substrates. A maximum 2.7 log (cfu mL−1) reduction was achieved in BPW after exposure of E. sakazakii to PEF for 360 μs (2.5 μs pulse width) at 40 kV cm−1. In IFM, exposure of E. sakazakii to PEF, with the same conditions, led to a 1.2 log (cfu mL−1) reduction. The greater the field strength and treatment time, the greater the inactivation achieved in both substrates. Even though further research will be necessary, according to the results, there are good prospects for the use of PEF in hospitals to achieve safe reconstituted infant formula before storage at refrigerated temperatures.  相似文献   
6.
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   
7.
An analytical method for the calculation of thermal stress in polarization-maintaining optical fibers is presented. The method is based on the thermoelastic potential and is appropriate for structures with a noncircular stress-cladding boundary. The analytical solution is compared with the results of the finite element method (FEM) for the case of an elliptical boundary  相似文献   
8.
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   
9.
This article presents a study on the novel method of model reference adaptive control (MRAC). As a new contribution, the derivative action is included into MRAC control to improve the controller performance and efficiency. The stability is analysed using a recent technique called immersion and invariance. The simulations of derived laws are presented based on nonlinear models.  相似文献   
10.
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   
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