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.     

Smoothed aggregation multigrid for a Stokes problem

We discuss advantages of using algebraic multigrid based on smoothed aggregation for solving indefinite linear problems. The ingredients of smoothed aggregation are used to construct a black-box monolithic multigrid method with indefinite coarse problems. Several techniques enforcing inf–sup stability conditions on coarse levels are presented. Numerical experiments are designed to support recent stability results for coupled algebraic multigrid. Comparison of the proposed multigrid preconditioner with other methods shows its robust behaviour even for very elongated geometries, where the pressure mass matrix is no longer a good preconditioner for the pressure Schur complement. Supported by the Swiss CTI grant no. 6437.1 IWS-IW, in collaboration with Alcan-Péchiney.     

Linkage of familial hemophagocytic lymphohistiocytosis to 10q21-22 and evidence for heterogeneity

An interleukin-6 (IL-6) response was detected in 81 patients with febrile urinary tract infections (UTIs). Bacteremic patients (n=24) had higher serum IL-6 at inclusion and throughout the first 24 h (P<. 01) and higher urine IL-6 from 6 h after start of therapy (P<.01) than did nonbacteremic patients (n=57). The serum and urine IL-6 responses remained elevated longer in the bacteremic group. Patients with clinical signs of pyelonephritis had higher serum and urine IL-6 concentrations than did other patients in the study population (P=.058, P<.01, respectively). IL-6 high responders had higher temperatures (P<.05) and C-reactive protein levels (P<.05, P<.01) than did low responders. The results demonstrate that IL-6 responses accompany febrile UTIs regardless of bacteremia and that the response reflects disease severity. The results suggest that IL-6 produced in the urinary tract can trigger the systemic host response in the absence of bacteremia.     

Testing basic visual functions in the evaluation of extrapyramidal side effects of antipsychotic agents

A female patient presenting with B-CLL and coincident eosinophilia-myalgia syndrome (EMS) after ingestion of L-tryptophan is described. The manifestations of EMS disappeared completely during treatment with cyclophosphamide/prednisone. and there was an intermittent clinical remission of CLL with absence of the monoclonal B-cell population. A few years later, the B-CLL relapsed, but without sign and symptoms of EMS. Whereas other eosinophilic syndromes such as eosinophilic fasciitis, panniculitis, or cellulitis Wells have been found to occur in relation to malignant underlying diseases, only a single patient with malignant fibrous histiocytoma following EMS has been described. There are no reports about an increased occurrence of B-CLL or other non-Hodgkin's lymphomas combined with or following EMS or related to L-tryptophan itself. The variant types of eosinophilic syndromes occurring due to malignant disorders, the differentiation from EMS, and the possible association between B-CLL and L-tryptophan-related EMS are discussed.     

Virtual Impactor as an Accessory to Optical Particle Counters

A method to improve the sensitivity of optical particle counters for large particles is presented. The basic idea is to increase the concentration in the sample air by connecting a virtual impactor to the sample inlet of an optical particle counter. For particles with D _p > 3 μm, the number concentration is increased by a factor of 20. The improvement in statistical accuracy is particularly useful in Alter testing and clean room measurements. The differences in the size distributions measured with and without the virtual impactor are used in estimating the relationship between the aerodynamic and optical sizes of different aerosols.     

Visual-Perceptual Dysfunctions Are Possible Endophenotypes of Schizophrenia: Evidence From the Psychophysical Investigation of Magnocellular and Parvocellular Pathways.

Visual information processing is impaired in schizophrenia patients and their biological relatives. The authors measured vernier thresholds in 72 schizophrenia patients, their 86 siblings, and 60 healthy control subjects. Subjects were asked to detect the direction of the horizontal displacement of 2 stimuli (left or right). During magnocellular (M) pathway tests, stimuli were dots with low contrast (5%) or counterphase-modulated gratings (25 Hz). For parvocellular (P) pathway tests, isoluminant blue-red dots with yellow-green background were used. Results revealed that patients with schizophrenia and their siblings were more impaired in M pathway conditions than in P pathway conditions. There was no color-specific impairment. The patients and their siblings displayed lower performances on tests of executive functions, psychomotor speed, and verbal memory compared with the controls. Visual-perceptual and neuropsychological data did not correlate. In conclusion, M pathway dysfunction is a potential endophenotype of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of a new composite material for bits of supporting and centering devices

Research has been conducted on the development of a new composite material for bits of well-supporting and -centering devices. The highly durable composite makes it possible to reduce frictional energy losses on straightline wellbore sections while ensuring a highly destructive effect at wellbore sections that are being explored. High-carbon high-alloy cast irons reinforced with titanium carbide have been proposed as the composite matrix. It has been shown that the hardness of the new material is comparable to that of hard alloys, while the minimum power losses for sliding friction under abrasion are lower than for hard alloys and diamond-bearing materials.     

Characterization and Response Model of the PPS-M Aerosol Sensor

The Pegasor PPS-M sensor is an electrical aerosol sensor based on diffusion charging and current measurement without particle collection. In this study, the role and effect of each component in the instrument is discussed shortly and the results from a thorough calibration measurements are presented. A comprehensive response model for the operation of the PPS-M sensor was developed based on the calibration results and computational fluid dynamics (CFD) modeling results. The obtained response model, covering the effects of the particle charger, the mobility analyzer, and both diffusion and inertial losses, was tested in the laboratory measurements with polydisperse test aerosols, where a good correlation between the model and the measured results was found.

Copyright 2014 American Association for Aerosol Research