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1.
Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.  相似文献   
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We investigate the effect of dopant random fluctuation on threshold voltage and drain current variation in a two-gate nanoscale transistor. We used a quantum-corrected technology computer aided design simulation to run the simulation (10000 randomizations). With this simulation, we could study the effects of varying the dimensions (length and width), and thicknesses of oxide and dopant factors of a transistor on the threshold voltage and drain current in subthreshold region (off) and overthreshold (on). It was found that in the subthreshold region the variability of the drain current and threshold voltage is relatively fixed while in the overthreshold region the variability of the threshold voltage and drain current decreases remarkably, despite the slight reduction of gate voltage diffusion (compared with that of the subthreshold). These results have been interpreted by using previously reported models for threshold current variability, load displacement, and simple analytical calculations. Scaling analysis shows that the variability of the characteristics of this semiconductor increases as the effects of the short channel increases. Therefore, with a slight increase of length and a reduction of width, oxide thickness, and dopant factor, we could correct the effect of the short channel.  相似文献   
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Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.  相似文献   
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The Journal of Supercomputing - With the expansion in the use of IoT, increasing the efficiency of these networks has become even more significant. Objects need reliable communications at suitable...  相似文献   
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The mechanistic pathway of MgO-Al2O3 reaction in solid state to form MgAl2O4 spinel was investigated to correlate the kinetic parameters with ratio of reactants (MgO:Al2O3) and with the presence of a doping agent, TiO2. The time-temperature-expansion data of oxide compacts was analyzed using several model free analyses and model based (linear and non-linear) kinetic algorithms. These indicated that spinel formation process can be best described by single step with n-dimensional Avrami equation for every MgO:Al2O3 ratio, irrespective of titania dopant. The activation energy (Ea) of the process was proportional to % spinel formed in each system and validated with quantitative XRD analysis. The higher value of Avrami coefficient (n) in 90 wt% Al2O3 compositions has been explained with geometric considerations of powder packing. Incorporations of 1% TiO2 in the MgO: Al2O3 oxide compact did not markedly affect the reaction model, frequency factor and Activation energy.  相似文献   
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The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging.  相似文献   
10.
An information-processing paradigm was used to examine attentional biases in clinically depressed participants, participants with generalized anxiety disorder (GAD), and nonpsychiatric control participants for faces expressing sadness, anger, and happiness. Faces were presented for 1,000 ms, at which point depressed participants had directed their attention selectively to depression-relevant (i.e., sad) faces. This attentional bias was specific to the emotion of sadness; the depressed participants did not exhibit attentional biases to the angry or happy faces. This bias was also specific to depression; at 1,000 ms, participants with GAD were not attending selectively to sad, happy, or anxiety-relevant (i.e., angry) faces. Implications of these findings for both the cognitive and the interpersonal functioning of depressed individuals are discussed and directions for future research are advanced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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