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.     

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.     

Potential for integration of electrophoretic deposition into electronic device manufacture; demonstrations using silver/palladium

A silver palladium (Ag/Pd) alloy powder is used as an example material to illustrate potential applications of electrophoretic deposition (EPD) in electronics manufacturing, in particular the forming of multilayer devices. The dispersion and deposition of the Ag/Pd powder in acetic acid is characterized. It is found that deposition can be explained by the direct action of electrostatic force on individual particles. Depositions of this Ag/Pd powder are then used to demonstrate: forming of a continuous layer on a rigid substrate; forming of continuous layers in laminated and sintered BaTiO₃ multilayers; and incorporation of patterned depositions into a multilayer by either overcasting the patterned deposition with a particulate slip to form a multicomponent tape, or direct lamination of the patterned deposition to a low temperature co-fired ceramic (LTCC) tape. It is shown that electrically conducting layers can be formed at an average thickness of only two times the diameter of the starting powder. Continuous conductor lines thirty times the average diameter of the starting powder were formed.     

Studies on adsorption equilibrium of xylenes in AEL framework using biased GCMC and energy minimization

The adsorption of xylene isomers in AlPO₄-11 (AEL network) was investigated using biased grand canonical Monte Carlo (GCMC) simulations. Preferential o-xylene adsorption was predicted by the simulations, in agreement with previously reported experimental data. In AlPO₄-11 the selective adsorption behavior comes from the smaller length of the o-xylene molecule along the crystallographic c-axis compared to p-xylene. This is in contrast to AlPO₄-5 and AlPO₄-8, where the ortho-selectivity is caused by the characteristic face-to-face positioning of o-xylene. Energy minimization studies were also performed in a flexible AlPO₄-11 lattice to study the structural changes upon xylene adsorption. The energy minimization study showed that the AlPO₄-11 crystal distorts upon p- and o-xylene adsorption. The distortion mechanism is related to the strong interaction between xylene methyl groups and the sieve oxygen atoms in the O3 position in the wide region of the pore.     

Distinctiveness and Correlation in Conceptual Structure: Behavioral and Computational Studies.

Patients with category-specific deficits have motivated a range of hypotheses about the structure of the conceptual system. One class of models claims that apparent category dissociations emerge from the internal structure of concepts rather than fractionation of the system into separate substores. This account claims that distinctive properties of concepts in the living domain are vulnerable because of their weak correlation with other features. Given the assumption that mutual activation among correlated properties produces faster activation in the normal system, the authors predicted a disadvantage for the distinctive features of living things for unimpaired adults. Results of a speeded feature verification study supported this prediction, as did a computational simulation in which networks mapped from orthography to semantics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working Memory Capacity and the Antisaccade Task: Individual Differences in Voluntary Saccade Control.

Performance on antisaccade trials requires the inhibition of a prepotent response (i.e., don't look at the flashing cue) and the generation and execution of a correct saccade in the opposite direction. The authors attempted to further specify the role of working memory (WM) span differences in the antisaccade task. They tested high- and low-span individuals on variants of prosaccade and antisaccade trials in which an eye movement is the sole requirement. In 3 experiments, they demonstrated the importance of WM span differences in both suppression of a reflexive saccade and generation of a volitional eye movement. The results support the contention that individual differences in WM span are not exclusively due to differences in inhibition but also reflect differences in directing the focus of attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)