Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

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.     

Defining Dry Eye from a Clinical Perspective

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.     

Practical Application of the Probabilistic‐Statistical Model of the Suspension Separation in Hydrocyclones

An effective practical approach that allows not only a significant reduction in the scope of practical experiments in the course of studying suspension separation processes in hydrocyclones, but also makes it possible to assess the intensity of random components of the processes and define the interrelation between such components and hydrodynamics of flows in a hydrocyclone is presented. Within the frames of the developed probabilistic‐statistical model of suspension separation in hydrocyclones on the basis of statistical self‐similarity properties, a relationship was found between determined and random components of the processes. This allowed transitioning from three‐parameter probability density functions for suspension particles in hydrocyclones to two‐parameter functions; thus significantly improving the efficiency of practical application of the developed model.     

Kinetic analysis of magnesium aluminate spinel formation: Effect of MgO:Al2O3 ratio and titania dopant

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 (E_a) 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.     

Attentional Biases for Negative Interpersonal Stimuli in Clinical Depression.

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)     

Learning to Perceive and Act by Trial and Error

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.     

Decision Making Effectiveness in Wildfire Incident Management Teams

During large scale wildfires, suppression activities are carried out under the direction of an Incident Management Team (IMT). The aim of the research was to increase understanding of decision processes potentially related to IMT effectiveness. An IMT comprises four major functions: Command, Operations, Planning, and Logistics. Four methodologies were used to study IMT processes: computer simulation experiments; analyses of wildfire reports; interviews with IMT members; and cognitive ethnographic studies of IMTs. Three processes were important determinants of IMT effectiveness: information management and cognitive overload; matching component function goals to overall goals; and team metacognition to detect and counter task‐disruptive developments. These processes appear to be complex multi‐person analogues of individual Incident Command processes identified previously. The findings have implications for issues such as: creating IMTs; training IMTs; managing IMTs; and providing decision support to IMTs.     

Effect of trichloroethylene on the exploratory and locomotor activity of rats exposed during development

Trichloroethylene (TCE) is a common contaminant of underground water supplies. To examine the effect of TCE on the developing central nervous system, rats were exposed to TCE throughout gestation until 21 days postpartum via their dams' drinking water. TCE concentrations of 312 mg/l, 625 mg/l and 1250 mg/l were tested. Exploratory behavior was higher in 60- and 90-day old male rats which were exposed to any level of TCE. The effect of TCE-exposure on locomotor activity (running wheel) was also examined in 60-day old males (625 and 1250 ppm exposure groups). Locomotor activity was significantly higher in rats exposed to 1250 ppm TCE. These data suggest that TCE has long-term effects on behaviour.