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51.
Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy.  相似文献   
52.
This study proposes a novel method to mechanically characterize the performance of individual bonds in low‐density, thermomechanically bonded nonwoven fabrics. Commercial bicomponent, polyethylene/polypropylene (PE/PP), nonwoven fabric was laser cut into bowtie‐shaped specimens for uniaxial tensile testing so that the central region of each specimen contained an individual bond. Three groups, each composed of 20 specimens, were tested with their longitudinal axes oriented along the machine direction (MD), the cross direction (CD), and at 45° between these two directions (DD). Prior to testing, the intrinsic variation in areal density and fiber orientation in the region surrounding the individual bond were quantified via orientation and relative basis weight parameters. During testing, images of the specimens were acquired to determine the occurrence of fiber breakage, bond deformation, and bond cohesive failure. Maximum force, stiffness, and orientation parameters were found to be significantly different among the three specimen groups (p < 0.01) but the relative basis weight was not (p > 0.01). The stiffness and maximum load were linearly correlated with both the areal density and fiber orientation. Pre‐existing voids or windows within the bond lowered the maximum force for specimens with the longitudinal axes aligned with the MD. These voids had no influence on the maximum force achieved by the specimens aligned with the CD and DD. The bonds in these specimens were observed to deform less than the bonds in the specimens with the longitudinal axes aligned with the MD. The results indicate the importance of the fiber structure surrounding the bond on the tensile properties, deformation and failure mode of individual bonds within the nonwoven fabric. POLYM. ENG. SCI., 59:311–322, 2019. © 2018 Society of Plastics Engineers  相似文献   
53.
A novel rheometer to study the behavior of granular materials in an aerated bed of particles has been developed. The device, called the aerated bed virtual Couette rheometer, is shown to be able to measure the shear stresses in the quasi-static and in the intermediate flow regimes. To validate the instrument, a Newtonian fluid of known viscosity was first sheared. The device was then used for measuring the shear stress of nonaerated glass beads with three -3D printed cells of different sizes to validate the optimal radial position, r*, where both shear rate and shear stress are independent of the cell radius. The results for the nonaerated glass beads displayed Coulomb behavior. The same behavior was observed when the bed was aerated. These experiments also showed that for a fixed shear rate the shear stress decreases as the aeration velocity, U. increases.  相似文献   
54.
55.
The success of collaboration between firms and scientific partners is still debated. Although a firm's social context seems to be crucial to explain the success or failure of such collaboration in terms of innovation performance, a deep analysis of the context role is still lacking. Therefore, the aim of this paper is to analyse whether a firm's internal climate as well as the quality of the relationships with scientific partners can mediate the relationship between collaboration and innovation performance. Results, based on survey research developed in Finland, Italy and Sweden, suggest that collaborations with scientific partners achieve good results in terms of innovation performance, through an explanation path which involves a firm's social context.  相似文献   
56.
Composite gas separation membranes with a 0.1–3 μm thick film of Hyflon AD 60X on a porous hollow fibre ultrafiltration membrane support of amorphous poly(ether ether ketone), were prepared. The influence of the coating conditions on the film thickness and on the pure gas transport properties was studied. The gas transport properties were related to the film thickness and to the morphology of the supporting UF membrane.  相似文献   
57.
We consider the problem of designing approximation schemes for the values of mean-payoff games. It was recently shown that (1) mean-payoff with rational weights scaled on [−1,1][1,1] admit additive fully-polynomial approximation schemes, and (2) mean-payoff games with positive weights admit relative fully-polynomial approximation schemes. We show that the problem of designing additive/relative approximation schemes for general mean-payoff games (i.e. with no constraint on their edge-weights) is P-time equivalent to determining their exact solution.  相似文献   
58.
Amyloids are associated with severe degenerative diseases and show exceptional mechanical properties, in particular great stiffhess. Amyloid fibrils, forming protein nanotube structures, are elongated fibers with a diameter of ≈8 nm with a characteristic dense hydrogen-bond (H-bond)patterning in the form of beta-sheets (β-sheets). Here we report a series of molecular dynamics simulations to study mechanical failure properties of a twofold symmetric Aβ(l–40) amyloid fibril, a pathogen associated with Alzheimer’s disease. We carry out computational experiments to study the response of the amyloid fibril to compressive loading. Our investigations reveal atomistic details of the failure process, and confirm that the breakdown of H-bonds plays a critical role during the failure process of amyloid fibrils. We obtain a Young’s modulus of ≈12.43 GPa, in dose agreement with earlier experimental results. Our simulations show that failure by buck-ling and subsequent shearing in one of the layers initiates at ≈1% compressive strain, suggesting that amyloid fibrils can be rather brittle mechanical elements.  相似文献   
59.
This paper uses a partially ordered set of syntactic categories to accommodate optionality and licensing in natural language syntax. A complex but well-studied data set pertaining to the syntax of quantifier scope and negative polarity licensing in Hungarian is used to illustrate the proposal. The presentation is geared towards both linguists and logicians. The paper highlights that the main ideas can be implemented in different grammar formalisms, and discusses in detail an implementation where the partial ordering on categories is given by the derivability relation of a calculus with residuated and Galois-connected unary operators.  相似文献   
60.
This paper describes the development and application of a new analytical method for the analysis of the volatile fractions of pesto, a typical Italian basil-based pasta sauce, and its ingredients. The extraction of the volatile fraction was realized by headspace sorptive extraction (HSSE) and the extracted volatiles were then thermodesorbed, cryoconcentrated in a cooled injector and analysed by gas chromatography-mass spectrometry.  相似文献   
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