Calcium hexaluminate (CA6) is an intrinsically densification-resistant material, therefore, its porous structures are key materials for applications as high-temperature thermal insulators. This article reports on the combination of calcined alumina and calcium aluminate cement (CAC) in castable aqueous suspensions for the in situ production of porous CA6. The CAC content (10–34 vol%) and the curing conditions ensure structural integrity prior to sintering and maximize the development of hydrated phases. Changes in physical properties, crystalline phases, and microstructure were investigated after isothermal treatments (120–1500 °C), and three sequential porogenic events were observed. The hydration of CAC preserved the water-derived pores (up to 120 °C), and the dehydroxylation of CAC hydrates (250–700 °C) generated inter-particles pores. Moreover, the in situ expansive formation of CA2 and CA6 (900–1500 °C) hindered densification and generated intra-particle pores. Such events differed from those observed with other CaO sources, and resulted in significantly higher pores content and lower thermal conductivity. 相似文献
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials. 相似文献
The compositional limits of a previously reported (J. Am. Ceram. Soc., 61, 5-8. (1978)) but relatively unstudied sodium-bismuth titanate pyrochlore solid solution are revised and their electrical properties presented. The pyrochlore solid solution we report forms via a different mechanism to that originally reported and occurs in a different location within the Na2O-Bi2O3-TiO2 ternary system. In both cases, relatively large amounts of vacancies are required on the A-sites and on the oxygen sites, similar to that reported for undoped ‘Bi2Ti2O7’ pyrochlore. In contrast to ‘Bi2Ti2O7’, this ternary pyrochlore solid solution can be prepared and ceramics sintered using conventional solid-state methods; however, the processing requires several challenges to be overcome to obtain dense ceramics. This cubic pyrochlore series has low electrical conductivity (and does not exhibit any evidence of oxide-ion conduction) and exhibits relaxor ferroelectric behavior with a broad permittivity maximum of ~100 near room temperature. Variable temperature neutron diffraction data do not provide any conclusive evidence for a phase transition in the pyrochlore solid solution between ~4 and 873 K. 相似文献
Bone is an inorganic template containing organic material inside which can be converted into hydroxyapatite‐rich material by pyrolysis. Nowadays, there is a growing research interest in the use of hydroxyapatite, the chemical formula of which is Ca10(PO4)6(OH)2. In the present work, pork bone, an abundant biomass source and food waste, has been converted into structured porous hydroxyapatite by a three‐step process including precharring under mild conditions, chemical activation, and thermal activation. The investigated activating agents were NaOH, KOH, K2CO3, H2SO4, and H3PO4. A thorough investigation of the influence of different activating protocols on the chemical and textural properties of the produced material was carried out by nitrogen adsorption–desorption at 77 K, potentiometric titrations, Fourier transform infrared, and X‐ray diffraction techniques. Chemical activation with NaOH, K2CO3, and H2SO4 increased the specific surface area up to 53%. H3PO4 reduced both surface area and pore volume, and KOH showed little influence on the pore structure. The produced materials were evaluated by methylene blue adsorption tests and showed significant improvement as a result of chemical activation. As a main effect, acid treatment increased methylene blue adsorption kinetics, probably owing to an increase in micropororosity, whereas alkali activation enhanced the adsorption capacity of the resultant biochar. 相似文献
In this paper, analytical functions for the estimation of the temperature-dependent behaviors of poorly and highly dispersed graphene oxide reinforced nanocomposite (GORNC) materials are studied in the framework of a machine learning-based approach. The validity of the presented models is shown comparing the results achieved from this modeling with those reported in the open literature. Also, the application of the obtained functions in solving the thermal buckling problem of beams constructed from such nanocomposites is demonstrated based on an energy-based method incorporated with a shear deformable beam hypothesis. The verification of the results indicates that the presented mechanical model can approximate the buckling behaviors of nanocomposite beams with remarkable precision. It can be realized from the results that the temperature plays an indispensable role in the determination of the buckling load which can be endured by the nanocomposite structure.
Herein we present the design, synthesis, and biological evaluation of potent and highly selective β-secretase 2 (memapsin 1, beta-site amyloid precursor protein cleaving enzyme 2, or BACE 2) inhibitors. BACE2 has been recognized as an exciting new target for type 2 diabetes. The X-ray structure of BACE1 bound to inhibitor 2 a {N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)propyl]amino]propyl]-5-[methyl(methylsulfonyl)amino]-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide} containing a hydroxyethylamine isostere was determined. Based on this structure, a computational docking study was performed which led to inhibitor 2 a -bound BACE2 models. These were used to optimize the potency and selectivity of inhibitors. A systematic structure–activity relationship study led to the identification of determinants of the inhibitors’ potency and selectivity toward the BACE2 enzyme. Inhibitors 2 d [N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)pentyl]amino]propyl]-N1-methyl-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide; Ki=0.031 nm , selectivity over BACE1: ≈174 000-fold] and 3 l [N1-((2S,3R)-3-hydroxy-1-phenyl-4-((3-(trifluoromethyl)benzyl)amino)butan-2-yl)-N3,5-dimethyl-N3-((R)-1-phenylethyl)isophthalamide; Ki=1.6 nm , selectivity over BACE1: >500-fold] displayed outstanding potency and selectivity. Inhibitor 3 l is nonpeptide in nature and may pave the way to the development of a new class of potent and selective BACE2 inhibitors with clinical potential. 相似文献