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.     

Partial replacement of metakaolin with red ceramic waste in geopolymer

Metakaolin was incrementally replaced (33.3%, 50% and 66.6%) by red ceramic waste in geopolymer formulation to study the effect on geopolymerisation and its resultant properties. The geopolymer binders composed of two calcined aluminosilicates (viz. Metakaolin and Red ceramic waste), NaOH and sodium silicate. In the experimental compositions, metakaolin was replaced gradually up to 66.6% in the clay fraction, the Si/Al increased from 3.36 to 5.16 and Na/Al increased from 0.93 to 1.38. The FTIR spectroscopic studies of geopolymer pastes along with XRD analysis indicated that the red ceramic waste partly reacts with alkali and takes part in geopolymer formation. Replacement of 33.3% metakaolin by the red ceramic waste in geopolymer binder did not reduce the compressive strength with respect to the pure metakaolin geopolymer here. Additional replacement resulted in a drastic decrease in the compressive strength of the geopolymer binder. However, the compressive strength of geopolymer mortars revealed interesting synergy between the amount of binder and particle packing in the mortar. Despite having a lower amount of binder phase, mortars with 33% and 50% red ceramic waste exhibited maximum compressive strength values. This has been attributed to improved particle packing through incorporation of red ceramic waste particles.     

More Harvard humbug.

Replies to J. Sonnenfeld's (1982) critique of D. Bramel and R. Friend's (see record 1982-08638-001) article on the studies performed at the Hawthorne plant of Western Electric. Sonnenfeld fails to recognize the unique aspects of Bramel and Friend's reinterpretation of what happened at Hawthorne. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Three-dimensional finite-element analysis of laminated composites

A three-dimensional finite-element analysis treating the mechanical response of thick laminated composite plates in bending is presented. An isoparametric solid element with a cubic displacement expansion in planform and a linear variation through the thickness is used to model each layer of the laminate. The degrees-of-freedom of the element are retained at its boundaries so that interconnections between lamina with different fiber orientations can be made at their interfaces. An incore version of the conjugate gradient technique, which does not have bandwidth restrictions, is used to minimize the total potential energy of the system with the number of iterations to convergence being about one-fifth the total global degrees-of-freedom. Because a three-dimensional analysis is used, the effects of thickness-stretching, transverse shear, extension, and bending deformations are obtained. Comparisons with three-dimensional elasticity solutions are in excellent agreement and show the necessity of having individual elements for each layer when they have different fiber orientations and when the plates are thick.     

An assessment of the feasibility of solar absorption and vapor compression cooling systems

For absorption cooling systems to operate and produce their cooling effects they need both thermal and electrical energy, while vapor compression systems need electrical energy only. When operating on solar energy the absorption system may receive all its thermal energy needs from solar sources while its electrical needs (parasitic power) are to be supplied from conventional sources. In order to conduct a fair comparison between the two cooling systems, it is proposed to supply both systems with equal amounts of conventional power and to supplement the rest of their needs from solar sources. A solar coefficient of performance, defined as the ratio of the refrigeration effect to the solar radiation input, is introduced and used for comparing some parameters of engineering ane economic importance in both systems. Economic analysis of solar cooling systems indicates that their initial cost is a function of both their design capacities and the number of hours of full load operation required to fulfill the total daily cooling demand. It indicates, also, that the initial cost of both solar cooling systems would break even before the cost of their respective solar conversion devices do.     

Conditioned suppression of humoral immunity in the rat.

180 Charles River rats were conditioned by pairing consumption of a novel sodium saccharin drinking solution with the effects of an ip injection of 75 mg/kg cyclophosphamide, an immunosuppressive drug. Five and 10 days after conditioning, an experimental group (Group CS) was reexposed to the saccharin drinking solution. Control Ss (Group CSo) were conditioned but were not reexposed to saccharin. On Days 10, 15, or 25 after conditioning, Ss were injected ip with sheep erythrocytes, and independent subgroups were sampled for hemagglutinating antibody titer 4, 6, or 8 days later. Antibody titers 4 days after immunization were lower than values observed 6 and 8 days after immunization, and CS Ss had an attenuated antibody response. There were no significant differences between Group CSo and a group of placebo-treated Ss, but CS Ss had lower antibody titers than placebo-treated animals 4, 6, and 8 days after antigenic stimulation. Results suggest that reexposure to a CS may have long-lasting effects, and provide further documentation of conditioned immunopharmacologic effects and the impact of behavioral factors in modifying immunologic reactivity. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Designing mobile technologies to support co-present collaboration

Mobile technologies offer new opportunities for childrens educational activities in that they can be used across different locations and times. Naturally, some instances of mobile technology use will necessitate, or be enhanced by, the sharing of information. Social interaction is important for sharing ideas, constructing and shaping understanding and fundamental for educational development. However the physical size of mobile technologies presents interesting challenges when designing for collaborative activities. When designing mobile technologies the importance of collaborative tasks has often been overlooked. The replacement of low-tech artefacts with digital devices, for supporting multiple users, can inhibit the shareability of information. We present three projects where mobile technologies have been used as part of a larger mixed reality experience. Novel technologies were used to support childrens collaborative activities in storytelling, an adventure game and during an outdoor field trip. Interaction with mobile devices within each project is reviewed and the authors highlight important considerations for their design and use across multiple contexts.     

A miniature photorefractive circuit for principal component extraction

The optical feature extractor is a photorefractive ring oscillator that can identify the strongest spatiotemporal component of its input space. The theoretical sections discuss the design and performance limitations of the signal extractor. A simple model of the filter's nonlinear functioning enables the reader to go directly to the experimental section that describes the making of the filter and experimental results. The device, also called the auto-tuning filter, is 5 cm2 in size, has a 3 GHz processing bandwidth, and requires less than 5 mW of continuous optical power to operate.     

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.     

Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase

Arachidonic acid (AA) can trigger activation of the phagocyte NADPH oxidase in a cell-free assay. However, a role for AA in activation of the oxidase in intact cells has not been established, nor has the AA generating enzyme critical to this process been identified. The human myeloid cell line PLB-985 was transfected to express p85 cytosolic phospholipase A2 (cPLA2) antisense mRNA and stable clones were selected that lack detectable cPLA2. cPLA2-deficient PLB-985 cells differentiate similarly to control PLB-985 cells in response to retinoic acid or 1,25-dihydroxyvitamin D3, indicating that cPLA2 is not involved in the differentiation process. Neither cPLA2 nor stimulated [3H]AA release were detectable in differentiated cPLA2-deficient PLB-985 cells, demonstrating that cPLA2 is the major type of PLA2 activated in phagocytic-like cells. Despite the normal synthesis of NADPH oxidase subunits during differentiation of cPLA2-deficient PLB-985 cells, these cells fail to activate NADPH oxidase in response to a variety of soluble and particulate stimuli, but the addition of exogenous AA fully restores oxidase activity. This establishes an essential requirement of cPLA2-generated AA for activation of phagocyte NADPH oxidase.