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.     

Benign glandular inclusions in inguinal and abdominopelvic lymph nodes in gynecologic pathology

From 4 cases recently seen at the Institut Gustave-Roussy, this report describes the pathological and evolutive features of benign glandular inclusions in inguinal, pelvic or abdominal lymph nodes. These lesions are defined by the presence of tubular formations in lymph nodes, lined by a single layer of epithelium which is cuboidal or columnar and resembled that of tubal epithelium with ciliated, secretory and intercalary cells. In most cases, benign glandular inclusions in lymph nodes still quiescent. In rare instances, they may proliferate and become papillary. The association of proliferating glandular inclusions in lymph nodes with borderline tumor of the ovary raises the problem of their primary or metastatic origin. However, their pathological features argues for a primary origin in lymph nodes. Thus, we think that a metastatic potential of borderline tumors of the ovary is not supported by any convincing argument.     

A Micellar Route to Ordered Arrays of Magnetic Nanoparticles: From Size‐Selected Pure Cobalt Dots to Cobalt–Cobalt Oxide Core–Shell Systems

Starting with Co‐salt‐loaded inverse micelles, which form if the diblock copolymer polystyrene‐block‐poly(2‐vinylpyridine) is dissolved in a selective solvent like toluene and CoCl₂ is added to the solution, monomicellar arrays of such micelles exhibiting a significant hexagonal order can be prepared on top of various substrates with tailored intermicellar distances and structure heights. In order to remove the polymer matrix and to finally obtain arrays of pure Co nanoparticles, the micelles are first exposed to an oxygen plasma, followed by a treatment in a hydrogen plasma. Applying in‐situ X‐ray photoelectron spectroscopy, it is demonstrated that: 1) The oxygen plasma completely removes the polymer, though conserving the original order of the micellar array. Furthermore, the resulting nanoparticles are entirely oxidized with a chemical shift of the Co 2p_3/2 line pointing to the formation of Co₃O₄. 2) By the subsequent hydrogen plasma treatment the nanoparticles are fully reduced to metallic Co. 3) By exposing the pure Co nanoparticles for 100 s to various oxygen partial pressures pequation/tex2gif-inf-5.gif, a stepwise oxidation is observed with a still metallic Co core surrounded by an oxide shell. The data allow the extraction of the thickness of the oxide shell as a function of the total exposure to oxygen (pequation/tex2gif-inf-7.gif × time), thus giving the opportunity to control the ferromagnetic–antiferromagnetic composition of an exchange‐biased magnetic system.     

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.     

Covalent Adaptable Microstructures via Combining Two-Photon Laser Printing and Alkoxyamine Chemistry: Toward Living 3D Microstructures

Manufacturing programmable materials, whose mechanical properties can be adapted on demand, is highly desired for their application in areas ranging from robotics, to biomedicine, or microfluidics. Herein, the inclusion of dynamic and living bonds, such as alkoxyamines, in a printable formulation suitable for two-photon 3D laser printing is exploited. On one hand, taking advantage of the dynamic covalent character of alkoxyamines, the nitroxide exchange reaction is investigated. As a consequence, a reduction of the Young´s Modulus by 50%, is measured by nanoindentation. On the other hand, due to its “living” characteristic, the chain extension becomes possible via nitroxide mediated polymerization. In particular, living nitroxide mediated polymerization of styrene results not only in a dramatic increase of the volume (≈8 times) of the 3D printed microstructure but also an increase of the Young's Modulus by two orders of magnitude (from 14 MPa to 2.7 GPa), while maintaining the shape including fine structural details. Thus, the approach introduces a new dimension by enabling to create microstructures with dynamically tunable size and mechanical properties.     

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.