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.     

Pollution-prevention analysis and the quenching of steels

With the goal of improving process efficiency and reducing risk, this article describes a pollution-prevention analysis technique that can be applied to most secondary steel heat-treating operations involving quenching. Costs, risk assessments, and pollution-prevention options are discussed, as are the effects of quenching on two subsequent processes—parts cleaning and tempering. In contrast to many process comparisons, the issues of worker exposure, material safety and toxicity, liability, waste reduction, reclamation, and disposal are emphasized.     

Compartmentation of phosphoglycerate kinase in Trypanosoma brucei plays a critical role in parasite energy metabolism

African trypanosomes compartmentalize glycolysis in a microbody, the glycosome. When growing in the mammalian bloodstream, trypanosomes contain only a rudimentary mitochondrion, and the first seven glycolytic enzymes, including phosphoglycerate kinase, are located in the glycosome. Procyclic trypanosomes, growing in the gut of tsetse flies, possess a fully developed mitochondrion that is active in oxidative phosphorylation. The first six glycolytic enzymes are still glycosomal, but phosphoglycerate kinase is now found in the cytosol. We demonstrate here that bloodstream trypanosomes are killed by expression of cytosolic phosphoglycerate kinase. The toxicity depends on both enzyme activity and cytosolic location. One possible explanation is that cytosolic phosphoglycerate kinase creates an ATP-generating shunt in the cytosol, thus preventing full ATP regeneration in the glycosome and ultimately inhibiting the first, ATP-consuming, steps of glycolysis.     

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.     

Microwave-Assisted Fabrication of Superamphiphobic Surfaces on Aluminum Substrates

The field of superamphiphobic surface fabrication has evolved rapidly in the last decade; however, research on important issues such as sustainability and green chemistry procedures is still scarce. Herein, a simple method of microwave irradiation (MW) to minimize energy consumption during the preparation of superamphiphobic aluminum (Al) surfaces is reported. Al substrates are first etched in diluted HCl solutions to generate a microstructure and then irradiated in a commercial microwave unit for several time intervals, temperatures, and pressures. The surfaces are then coated with different compounds, and the wettability is tested with high and very-low surface tension liquids. Optical profilometry and scanning electron microscopy images show that the density of hierarchical micro-nanostructures increases with MW time, temperature, and pressure. At 170 °C and 7.9 bar, the surfaces present a high density of structures and re-entrant topographies. The obtained coatings display excellent repellence to liquids with surface tensions as low as 27.5 mN m⁻¹. X-ray photoelectron spectroscopy data show the importance of efficient surface functionalization for the production of superamphiphobicity in Al substrates. The results show that MW irradiation of Al substrates can be a green and efficient method for fabricating superamphiphobic surfaces.     

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.     

GOST 34.10—A brief overview of Russia's DSA

GOST 34.10 is Russia's DSA. Like its US counterpart, GOST is an ElGamal-like signature scheme used in Schnorr mode. It is similar to NIST DSA in many aspects. In this paper we will overview GOST 34.10 and discuss the three main differences between the two algorithms, (i) GOST's principal design criterion does not seem to be computational efficiency: the algorithm is 1.6 times slower than the DSA and produces 512-bit signatures. This is mainly due to the usage of the modulus q which is at least 254 bits long. During verification, modular inverses are computed by exponentiation (while the Extended Euclidian algorithm is roughly 100 times faster for this parameter size) and the generation of the public parameters is much more complicated than in the DSA. This choice of the parameters makes GOST 34.10 very secure. (ii) GOST signers do not have to generate modular inverses as the basic signature equation is s = xr + mk (mod q) instead of (mod q). (iii) GOST's hash function (the Russian equivalent of the SHA) is the standard GOST 34.11 which uses the block cipher GOST 28147 (partially classified) as a building block. The hash function will be briefly described. Copyright     

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.