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21.
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.  相似文献   
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Ambient condition, especially the wind condition, is an important factor to determine the behavior of hydrogen diffusion during hydrogen release. However, only few studies aim at the quantitative study of the hydrogen diffusion in a wind-exist condition. And very little researches aiming at the variable wind condition have been done. In this paper, the hydrogen diffusion in different wind condition which including the constant wind velocity and the variable wind velocity is investigated numerically. When considering the variable wind velocity, the UDF (user defined function) is compiled. Characteristics of the FGC (flammable gas cloud) and the HMF (hydrogen mass fraction) are analyzed in different wind condition and comparisons are made with the no-wind condition. Results indicate that the constant wind velocity and the variable wind velocity have totally different effect for the determination of hydrogen diffusion. Comparisons between the constant wind velocity and the variable wind velocity indicate that the variable wind velocity may cause a more dangerous situation since there has a larger FGC volume. More importantly, the wind condition has a non-negligible effect when considering the HMF along the radial direction. As the wind velocity increases, the distribution of the HMF along the radial direction is not Gaussian anymore when the distance between the release hole and the observation line exceeds to a critical value. This work can be a supplement of the research on the hydrogen release and diffusion and a valuable reference for the researchers.  相似文献   
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Poly(l ‐lactic acid) (PLLA) is a biodegradable and biocompatible thermoplastic polyester produced from renewable sources, widely used for biomedical devices, in food packaging and in agriculture. It is a semicrystalline polymer, and as such its properties are strongly affected by the developed semicrystalline morphology. As a function of the crystallization temperature, PLLA can form different crystal modifications, namely α′‐crystals below about 120 °C and α‐crystals at higher temperatures. The α′ modification is therefore of special importance as it may be the preferred polymorph developing at processing‐relevant conditions. It is a metastable modification which typically transforms into the more stable α‐crystals on annealing at elevated temperature. The structure, kinetics of formation and thermodynamics of α′‐ and α‐crystals of PLLA are reviewed in this contribution, together with the effect of α′‐/α‐crystal polymorphism on the properties of PLLA. © 2018 Society of Chemical Industry  相似文献   
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Photocatalytic H2 generation using semiconductor photocatalysts is considered as a cost-effective and eco-friendly technology for solar to energy conversion; however, the present photocatalysts have been recognized to depict low efficiency. Currently, porous coordination polymers known as metal-organic frameworks (MOFs) constituting flexible and modifiable porous structure and having excess active sites are considered to be appropriate for photocatalytic H2 production. This review highlights current progress in structural development of MOF materials along with modification strategies for enhanced photoactivity. Initially, the review discusses the photocatalytic H2 production mechanism with the concepts of thermodynamics and mass transfer with particular focus on MOFs. Elaboration of the structural categories of MOFs into Type I, Type II, Type III and classification of MOFs for H2 generation into transition metal based, post-transition metal based, noble-metal based and hetero-metal based has been systematically discussed. The review also critically deliberate various modification approaches of band engineering, improvement of charge separation, efficient irradiation utilization and overall efficiency of MOFs including metal modification, heterojunction formation, Z-scheme formation, by introducing electron mediator, and dye based composites. Also, the MOF synthesized derivatives for photocatalytic H2 generation are elaborated. Finally, future perspectives of MOFs for H2 generation and approaches for efficiency improvement have been suggested.  相似文献   
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Increasing the heat capacity of heat exchangers is a crucial need for modern devices. The thermal conductivity of the usual fluids and the Nusselt (Nu) number of flows containing such fluids are two bottlenecks in the way of increasing heat delivery in the heat exchangers. For this reason, nanofluids have been introduced. The effect of utilizing a Cu-water nanofluid as a coolant of two hot pipes in a square cavity is investigated numerically with a two-component lattice Boltzmann method. The volume fraction of nanoparticles is assumed to be constant (0.03) while the Richardson (Ri) number varies from 0.02 to 20. Results show that the effectiveness of nanoparticles is better observed in the natural convection mode. However, sedimentation is also very probable at high Ri numbers, which significantly reduces the effectiveness of the nanoparticles. Configurations which produce a natural convection stream similar to the forced convection one as well as the configurations with high spacing and hence, low heat stream interactions, are the best choices for a uniform heat rate from the pipes.  相似文献   
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This study presents an improved mathematical model to analyse the stress wave propagation in adhesively bonded functionally graded (FG) circular cylinders (butt joint) under an axial impulsive load. The volume fractions of the material constituents in the upper and lower cylinders were functionally tailored through the thickness of each cylinder using a power-law. The effective material properties of both cylinders, which are made of aluminum (Al) and silicon carbide (SiC), at any point were predicted by using the Mori–Tanaka homogenization scheme. In this improved model, the governing equations of the wave propagation include the spatial derivatives of local mechanical properties and were discretized by means of the finite difference method. The influence of these spatial derivatives and the compositional gradient exponent on the displacement and stress distributions of the joint was investigated. The material composition variations of both cylinders affected the displacement and stress fields whereas the compositional gradient exponent had a minor effect. The stress concentrations were alleviated in time, the displacement and stress distributions/variations around/along the upper and lower cylinder-adhesive interfaces were significantly affected by the adhesive layer. The spatial derivatives also affected the temporal histories of the displacement and stress components evaluated at the selected critical points of the upper cylinder, adhesive layer and lower cylinder. The consideration of the spatial local material derivatives provided a more accurate mathematical model of wave propagations through the graded layered structures.  相似文献   
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Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.  相似文献   
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