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61.
    
Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment. This may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution, underlying the influence of the context and the timeline in anti-tumor therapeutic approaches. Besides the cancer metabolic strategies, here we review the modifications found in the GBM-associated glia, focusing on morphological, molecular, and metabolic features. We propose to analyze the GBM metabolic rewiring processes from a systems biology perspective. We aim at defining the crosstalk between GBM and the glial cells as modules. The complex networking may be expressed by metabolic modules corresponding to the GBM growth and spreading phases. Variation in the oxidative phosphorylation (OXPHOS) rate and regulation appears to be the most important part of the metabolic and functional heterogeneity, correlating with glycolysis and response to hypoxia. Integrated metabolic modules along with molecular and morphological features could allow the identification of key factors for controlling the GBM-stroma metabolism in multi-targeted, time-dependent therapies.  相似文献   
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The continuous evolution of manufacturing environments leads to a more efficient production process that controls an increasing number of parameters. Production resources usually represent an important constraint in a manufacturing activity, specially talking about the management of human resources and their skills. In order to study the impact of this subject, this paper considers an open shop scheduling problem based on a mechanical production workshop to minimise the total flow time including a multi-skill resource constraint. Then, we count with a number of workers that have a versatility to carry out different tasks, and according to their assignment a schedule is generated. In that way, we have formulated the problem as a linear as and a non-linear mathematical model which applies the classic scheduling constraints, adding some different resources constraints related to personnel staff competences and their availability to execute one task. In addition, we introduce a genetic algorithm and an ant colony optimisation (ACO) method to solve large size problems. Finally, the best method (ACO) has been used to solve a real industrial case that is presented at the end.  相似文献   
64.
The current standards for machine tool performance evaluation do not consider productivity and dynamic capability at high feed rates. Therefore, industry does not have a basis for machine tool comparison. Testing was conducted with the Heidenhain KGM 181 grid encoder to record the actual path of the machine at high feed rates (up to 16 m/min). This paper shows the significance of linear vs. circular interpolation, acceleration and rate of change in acceleration (jerk) on the productivity and dynamic capability of this type of machine. Under high feed rate interpolations, the actual cycle time can differ significantly from the ideal cycle time (calculated with the traveled distance and programmed feed rate). A modeling approach with simple testing protocols is presented in order to predict the cycle time during machining with high feed rates. The proposed modeling approach provides less than 6% error in estimating cycle time.  相似文献   
65.
Rapid manufacturing is an advanced manufacturing technology based on layer-by-layer manufacturing to produce a part. This paper presents experimental work carried out to investigate the effects of scan speed, layer thickness, and building direction on the following part features: dimensional error, surface roughness, and mechanical properties for DMLS with DS H20 powder and SLM with CL 20 powder (1.4404/AISI 316L). Findings were evaluated using ANOVA analysis. According to the experimental results, build direction has a significant effect on part quality, in terms of dimensional error and surface roughness. For the SLM process, the build direction has no influence on mechanical properties. Results of this research support industry estimating part quality and mechanical properties before the production of parts with additive manufacturing, using iron-based powders.  相似文献   
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Cloud-based services have proved useful in several research fields, such as engineering, health science, and astrophysics, to mention a few examples. The computational environmental science community developed a strong need for cloud facilities to store, process, and manage data from observations and numerical models for simulations and forecasts. Weather forecast models and global sensor networks deal with multidimensional geo-referenced data∖sets. However, environmental data consumer applications usually require a relatively small amount of multidimensional input data slice to analyze a specific area or time interval. Hence, reducing data dimension for information retrieval is mandatory. This paper presents a twofold solution: a technique to load and retrieve the sliced multidimensional data set on different cloud services such as Amazon Web Service (AWS), Google Cloud Platform, and Microsoft Azure. The experimental results performed on these cloud services highlight that the proposed method can significantly speed up the process of loading and retrieving the data slices compared to working with the entire data set in bulk or OPeNDAP server.  相似文献   
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A masterslave synchronisation control problem is addressed for current-fed DC and permanent magnet synchronous motors with all uncertain parameters. A measurable exogenous rotor position reference signal, which belongs to the class of biased sinusoidal signals with uncertain bias, amplitude, angular frequency, phase, is to be tracked without assuming its a priori knowledge. An innovative modification of disturbance cancellation techniques allows to prove that an output feedback adaptive nonlinear control scheme, which simply generalises the classical internal-model-based input law, solves the aforementioned problem, with an overall stability proof concerning the entire closed-loop system. The practical effectiveness of the proposed approach is illustrated by experimental results.  相似文献   
69.
Heat‐shock protein 90 (Hsp90) is a molecular chaperone involved in the stabilization of key oncogenic signaling proteins, and therefore, inhibition of Hsp90 represents a new strategy in cancer therapy. 2‐Amino‐7‐[4‐fluoro‐2‐(3‐pyridyl)phenyl]‐4‐methyl‐7,8‐dihydro‐6H‐quinazolin‐5‐one oxime is a racemic Hsp90 inhibitor that targets the N‐terminal adenosine triphosphatase site. We developed a method to resolve the enantiomers and evaluated their inhibitory activity on Hsp90 and the consequent antitumor effects. The (S) stereoisomer emerged as a potent Hsp90 inhibitor in biochemical and cellular assays. In addition, this enantiomer exhibited high oral bioavailability in mice and excellent antitumor activity in two different human cancer xenograft models.  相似文献   
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