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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   
2.
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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4.
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   
5.
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   
6.
Learning to Perceive and Act by Trial and Error   总被引:5,自引:1,他引:4  
This article considers adaptive control architectures that integrate active sensory-motor systems with decision systems based on reinforcement learning. One unavoidable consequence of active perception is that the agent's internal representation often confounds external world states. We call this phoenomenon perceptual aliasingand show that it destabilizes existing reinforcement learning algorithms with respect to the optimal decision policy. We then describe a new decision system that overcomes these difficulties for a restricted class of decision problems. The system incorporates a perceptual subcycle within the overall decision cycle and uses a modified learning algorithm to suppress the effects of perceptual aliasing. The result is a control architecture that learns not only how to solve a task but also where to focus its visual attention in order to collect necessary sensory information.  相似文献   
7.
At times, people keep their emotions from showing during social interactions. The authors' analysis suggests that such expressive suppression should disrupt communication and increase stress levels. To test this hypothesis, the authors conducted 2 studies in which unacquainted pairs of women discussed an upsetting topic. In Study 1, one member of each pair was randomly assigned to (a) suppress her emotional behavior, (b) respond naturally, or (c) cognitively reappraise in a way that reduced emotional responding. Suppression alone disrupted communication and magnified blood pressure responses in the suppressors' partners. In Study 2, suppression had a negative impact on the regulators' emotional experience and increased blood pressure in both regulators and their partners. Suppression also reduced rapport and inhibited relationship formation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
8.
Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is an herbicide associated with both accidental and intentional ingestion, leading to severe and often fatal toxicity. Prognosis is largely dependent on the amount of paraquat absorbed. Rapid identification of the symptoms of paraquat toxicity (burns or ulceration at the site of ingestion or injection, acute respiratory distress, and renal failure) can facilitate early treatment intervention to limit absorption. We report a case of a 71-year-old man with a suicidal ingestion of paraquat 2 days prior to presentation. Serum paraquat levels, time elapsed since ingestion, and clinical symptoms all indicated poor prognosis. The patient developed severe respiratory distress and progressive renal failure, and died 6 days after admission to the hospital.  相似文献   
9.
One requirement in designing and operating and operating system is to minimize the moisture change in stored grain. Moisture transfer during the aeration process is generally believed to be caused by the partial pressure difference between water in grain and water in air (P3-P4). A mathematical model was developed for rough rice, which predicts the partial pressure difference under various grain and ambient conditions. Observations of moisture change over 10 aeration tests confirmed the good correlation between sorption phenomena and partial pressure differences. Studies indicated that air relative humidity, air temperature, grain temperature and grain moisture are significant factors influencing the partial pressure differences and, thus, affecting  相似文献   
10.
Experiments were conducted to investigate the fate of ethylbenzoate and soil microorganisms in shallow aquifers. Biodegradation and volatilization have been identified as the major mechanisms in attenuating ethylbenzoate in contaminated soils. The rate of volatilization was experimentally found to be limited by gas-phase diffusion. The parameters of an available model, i.e., the maximum specific growth rate and the saturation constant, have been estimated by fitting the model to the experimental data obtained with ethylbenzoate as the carbon source; the former was 0.49 h−1, and the latter was 62 mg L−1. Various facets of biodegradation, including the effects of mass-transfer resistance and initial distribution of microorganisms, have been numerically analyzed on the basis of the model.  相似文献   
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