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.     

Design of High Sensitive Temperature Sensor Based on Two-Dimensional Photonic Crystal

In this effort, a two-dimensional photonic crystal ring resonator (2DPCRR) is simulated. This device is developed for temperature detection in harsh enviro     

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)     

Mobility management support and performance analysis for wireless MPLS networks

Multi‐Protocol Label Switching (MPLS) is deployed in the Internet backbone to support service differentiation and traffic engineering. In recent years, there has been interest in extending the MPLS capability to wireless access networks for mobility management support. In this paper, we present analysis of Micro Mobile MPLS, a new micro‐mobility management scheme which integrates the Mobile IP and MPLS protocols by using two‐level hierarchy architecture. Our proposal supports two protocol variants. First, the fast handoff process, which anticipates the LSP procedure set‐up with neighboring locations where a mobile node (MN) may move to, is provided to reduce service disruption. Second, a new mechanism based on the forwarding chain concept is proposed to track efficiently the host mobility within a domain. This concept can significantly reduce registration update costs and provide low handoff latency. Analytical models are developed and simulations are conducted to justify the benefits of our proposed mechanisms. Copyright © 2006 John Wiley & Sons, Ltd.     

Cost optimal, parallel reliability systems with fixed repair sanction

Optimisation methods under varied criteria for different parameters in stochastic reliability systems are being increasingly developed and have been reported in recent literature. The large interest evinced in this fascinating area is primarily due to its applicational value and operational role in the decision making process. Recently a parallel system has been considered and the optimal number of units discussed, as well as optimal replacement times for the system based on acquisition and replacement costs.In this paper we consider an improved version of the model formulation, by bringing in additionally the maintenance and per unit repair time costs, and develop a procedure to obtain the optimal number of components in the system with the condition that the system is allowed to undergo a prefixed maximum number of repairs, after which the system is to be replaced.The applicational use of the results is illustrated through numerical work, specialising to some known laws governing the system parameters and corresponding to different fixed number of repair sanctions.     

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.     

Selectivity of partial hydrogenation reactions performed in a pore-through-flow catalytic membrane reactor

The selectivity of partial hydrogenation reactions of unsaturated substrates was studied in a membrane reactor operating at 323 K and 40 bar hydrogen pressure. The reactor system was constructed as a loop of a saturation vessel and a membrane module in which the reaction mixture was resaturated with hydrogen up to 100 times. In a porous membrane made from cross-linked polyacrylic acid palladium nanoparticles were incorporated as catalysts. A well-defined residence time within the membrane was achieved due to a defined pore structure of the membrane and a convective mass flow of the reaction mixture through the membrane. The selectivity for the partially hydrogenated products was investigated as a function of the pore size of the PAA membrane and was compared to commercially available catalysts. Compared to experiments with supported catalysts (Pd/C and Pd/Al₂O₃) in a slurry and a fixed bed reactor the selectivity for the desired products could be increased by 3% (1-octyne) up to 40% (geraniol).     

Framework Model for Asset Maintenance Management

This paper presents the development of a generic framework for asset maintenance management. The framework has been presented in the form of an IDEF0 process model. The process model served to illustrate the interaction and dependencies among a diverse set of knowledge areas. In this framework, outputs from one management process become inputs to another in a subsequent hierarchy. The structure of the framework model exhibited the characteristics of flexibility and robustness. Updates in knowledge can be accommodated within the framework through incorporating new management processes and/or activities, as well as establishing new sequencing logic for these processes and/or activities. In a supporting effort to the development of the framework model, the writers have objectively reviewed the general capabilities of three commercially available software applications that are known within the asset management (AM) industry. These three applications, while encompassing a wide selection of capabilities, represent a typical selection of information technology (IT) tools and techniques that are widely used in strategic AM practices. The objective of this review is to study the operational characteristics and functionalities, and to assess the capability of software interoperability, of a representative sample of IT tools known within the AM industry.