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.     

Telephone booster sessions for optimizing smoking cessation for patients in rehabilitation centers.

Smokers with smoking-related diseases who are hospitalized in rehabilitation centers should be offered smoking cessation. This is the first study evaluating whether telephone booster sessions after intensive inpatient treatment are an effective strategy. The present study was conducted in 13 rehabilitation centers for somatic disorders as a prospective multicenter study with a randomized treatment-control group design. We compared abstinence rates after hospital discharge from treatment that included a group smoking cessation program with (treatment group) and without telephone booster sessions (control group). Data from 290 smokers were analyzed. After 6 and 12 months the treatment group achieved abstinence rates twice as high as those of the control group. Men profited more from telephone booster sessions than did women. Results indicated that telephone booster sessions were highly effective (even) after an inherently intensive group program during a hospital stay. Further research should focus on the special needs of women receiving telephone counseling.     

An evaluation of ruminally degradable intake protein and metabolizable amino acid requirements of feedlot calves

Ruminally degradable intake protein (DIP) and metabolizable indispensable amino acid (MIAA) requirements of feedlot steers were evaluated. Dietary treatments consisted of isocaloric 80% concentrate steam-flaked corn-based diets containing either .8% urea, 1.5% fish meal (FM), 3.0% FM, 4.5% FM, or 4.5% soybean meal (SBM). Treatment effects on characteristics of ruminal and total tract digestion were evaluated using four Holstein steers (249 kg) with cannulas in the rumen and proximal duodenum. Ruminal digestibility of OM (RDOM; P < .05) and feed N (P < .01) and microbial N flow (MNF; P < .01) to the small intestine were greater with urea as the supplemental N source. The level of DIP was closely associated (R2 = .89) with MNF. Postruminal digestibility of OM was greater (P < .05) for FM than for urea-supplemented diets, compensating for lower RDOM. There were no treatment effects (P > .10) on DOM. As the level of FM was increased, MIAA increased linearly (P < .01). Intestinal MIAA were similar (P > .10) for urea- and SBM-supplemented diets. Treatment effects on 56-d growth performance were evaluated using 100 medium-framed crossbred steers (231 kg). Daily weight gain (linear effect; P < .01), DM intake (linear effect; P < .10), feed efficiency (linear effect; P < .05), and diet NE (linear effect; P < .05) increased with level of FM supplementation. Daily weight gain (P < .10) and DM intake (P < .05) were greater for urea- than for SBM-supplemented diets. Using bovine tissue as the reference protein, the biological value (based on chemical score) of the intestinal chyme protein averaged 73%; methionine was first-limiting. There was a close association (R2 = .99) between methionine supply to the small intestine and observed/expected dietary NE. The metabolizable methionine requirement (MMETR, g/d) of medium-framed feedlot steers can be reliably predicted from measures of BW and ADG (MMETR = 1.565 + .0234ADG[268 - (29.4 x .0557BW(.75)ADG(1.097))/ADG] + .0896BW(.75)). There was a very close association (R2 = .89) between DIP and MNF (MNF = 13.7DIP - .66DIP(2) + 25.9). At maximal observed synthesis, DIP accounted for 76% of the MNF. A minimum of 100 g DIP/kg of total tract digestible OM was required to maximize RDOM and MNF.     

Tyrosine kinase inhibition produces specific alterations in axon guidance in the grasshopper embryo

Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development. We have examined the roles of tyrosine kinase activity in programming growth cone guidance decisions in an intact nervous system in which neurons can be individually identified. We applied the tyrosine kinase inhibitors herbimycin A and genistein to whole 40% grasshopper embryos placed in medium, or injected the inhibitors into intact grasshopper eggs. Both inhibitors caused interneuronal axons that normally would grow along the longitudinal connectives to instead leave the central nervous system (CNS) within the segmental nerve root and grow out toward the body wall muscles. In addition, herbimycin A produced pathfinding errors in which many longitudinal axons crossed the CNS midline. To study how this drug affected guidance decisions made by individual growth cones, we dye-filled the pCC interneuron, which normally extends an axon anteriorly along the ipsilateral longitudinal connective. In the presence of herbimycin A, the pCC growth cone was redirected across the anterior commissure. These phenotypes suggest that tyrosine kinase inhibition blocks a signaling mechanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline.     

Multi-Stage Phase-Segregation of Mixed Halide Perovskites under Illumination: A Quantitative Comparison of Experimental Observations and Thermodynamic Models

Photo- and charge-carrier-induced ion migration is a major challenge when utilizing metal halide perovskite semiconductors for optoelectronic applications. For mixed iodide/bromide perovskites, the compositional instability due to light- or electrical bias induced phase-segregation restricts the exploitation of the entire bandgap range. Previous experimental and theoretical work suggests that excited states or charge carriers trigger the process, but the exact mechanism is still under debate. To identify the mechanism and cause of light-induced phase-segregation phenomena, the full compositional range of methylammonium lead bromide/iodide samples are investigated, MAPb(Br_xI_1-x)₃ with x = 0…1, by simultaneous in situ X-ray diffraction (XRD) and photoluminescence (PL) spectroscopy during illumination. The quantitative comparison of composition-dependent in situ XRD and PL shows that at excitation densities of 1 sun, only the initial stage of photo-segregation is rationalized with the previously established thermodynamic models. However, a progression of the phase segregation is observed that is rationalized by considering long-lived accumulative photo-induced material alterations. It is suggested that (additional) photo-induced defects, possibly halide vacancies and interstitials, need to be considered to fully rationalize light-induced phase segregation and anticipate the findings to provide crucial insight for the development of more sophisticated models.     

Modification of Iron with Degradable Silver Phases Processed via Laser Beam Melting for Implants with Adapted Degradation Rate

In medical technology, implants are used to improve the quality of patients’ lives. The development of materials with adapted properties can further increase the benefit of implants. If implants are only needed temporarily, biodegradable materials are beneficial. In this context, iron-based materials are promising due to their biocompatibility and mechanical properties, but the degradation rate needs to be accelerated. Apart from alloying, the creation of noble phases to cause anodic dissolution of the iron-based matrix is promising. Due to its high electrochemical potential, immiscibility with iron, biocompatibility, and antibacterial properties, silver is suited for the creation of such phases. A suitable technology for processing immiscible material combinations is powder-bed-based procedure like laser beam melting. This procedure offers short exposure times to high temperatures and therefore a limited time for diffusion of alloying elements. As the silver phases remain after the dissolution of the iron matrix, a modification is needed to ensure their degradability. Following this strategy, pure iron with 5 wt% of a degradable silver–calcium–lanthanum alloy is processed via laser beam melting. Investigation of the microstructure yields achievement of the intended microstructure and long-term degradation tests indicates an impact on the degradation, but no increased degradation rate.     

Using Selective Electron Beam Melting to Enhance the High-Temperature Strength and Creep Resistance of NiAl–28Cr–6Mo In Situ Composites

By increasing the density of interfaces in NiAl–CrMo in situ composites, the mechanical properties can be significantly improved compared to conventionally cast material. The refined microstructure is achieved by manufacturing through electron beam powder bed fusion (PBF-EB). By varying the process parameters, an equiaxed or columnar cell morphology can be obtained, exhibiting a plate-like or an interconnected network of the (Cr,Mo) reinforcement phase which is embedded in a NiAl matrix. The microstructure of the different cell morphologies is investigated in detail using scanning electron microscope, transmission electron microscopy, and atom probe tomography. For both morphologies, the mechanical properties at elevated temperatures are analyzed by compression and creep experiments parallel and perpendicular to the building direction. In comparison to cast NiAl and NiAl–(Cr, Mo), the yield strength of the PBF-EB fabricated specimens is significantly improved at temperatures up to 1,027 °C. While the columnar morphology exhibits the best improved mechanical properties at high temperatures, the equiaxial morphology shows nearly ideal isotropic mechanical behavior, which is a substantial advantage over directionally solidified material.     

Concrete Beams Exposed to Live Loading during Carbon Fiber Reinforced Polymer Strengthening

The need for structural rehabilitation of concrete structures all over the world is well known. Extensive amounts of research have been carried out and are ongoing in this field. Most of the laboratory research has been undertaken on structural elements without live load during the strengthening process. Normally owners of structures want to continue their activity or service during strengthening. Full-scale applications have shown that this is possible, but there is a lack of understanding as to how cyclic loads are distributed during strengthening; for example, traffic loads affect the final strengthening result. This paper presents laboratory tests on concrete beams strengthened with carbon fiber-reinforced polymer laminates and near-surface mounted reinforcement. The beams were subjected to a cyclic load during setting of the adhesive, and after additional hardening were then loaded by deformation control up to failure.