Undevelopable stiffened curved shells have been widely used in engineering fields. The shape of the undevelopable curved surface is generally characterized with the non-straight generatrix and ...variable cross sections, which makes it challenging to automatically model and optimize stiffeners on the undevelopable curved surface. Therefore, the data-driven modelling and optimization framework are proposed for undevelopable stiffened curved shells in this paper. Firstly, a novel mesh deformation method is developed for the data-driven modelling of undevelopable stiffened curved shells based on RBF neural network machine learning method. Its main idea is to firstly define a developable curved shell (background mesh domain) having similar topological characteristics with the undevelopable curved shell (target mesh domain), and then train the mapping relationship between the background mesh domain and the target mesh domain by RBF neural network, and finally the complicated modelling problem of the undevelopable stiffened curved shell can be transformed into a simple modelling problem of developable stiffened curved shell by means of the mapping relationship. Moreover, based on the efficient global optimization (EGO) surrogate method, a data-driven layout optimization method is established for minimizing the structural weight of undevelopable stiffened curved shells. Finally, three representative optimization examples are carried out, including modelling and optimization of stiffeners on hyperbolic parabolic curved surfaces, blade-shaped curved surfaces and S-shaped variable cross-sectional curved surfaces. Optimal results indicate that the structural weight of undevelopable stiffened curved shells decreases significantly after the optimization, indicating the effectiveness of the proposed modelling and optimization framework.
Introduction
Cerebral ischemic injury is associated with long-term disability. Dexmedetomidine (Dex) can exert neuroprotective effects on cerebral ischemic/reperfusion injury. The present study ...explored the mechanism of Dex in cerebral ischemic injury.
Materials and methods
To this end, the permanent middle cerebral artery occlusion (p-MCAO) mouse model was established and treated with Dex or/and Nrf2 inhibitor ML385. Subsequently, microglia were subjected to oxygen–glucose deprivation (OGD) in sugar-free environment and thereafter treated with Dex, Nrf2 inhibitor, and NLRP3 lentiviral overexpression vector, respectively.
Results
Dex alleviated the neurobehavioral deficit of p-MCAO mice, reduced brain water content, relieved pathological changes, and reduced cerebral infarction size. Dex promoted the polarization of microglia from M1 to M2, thus ameliorating oxidative stress and inflammatory responses. Our results showed that Dex promoted M2-polarization of microglia in vivo and in vitro by promoting HO-1 expression via Nrf2 nuclear import. Moreover, the Nrf2/HO-1 axis inhibited the activation of NLRP2 inflammasome and NLRP3 overexpression reversed the effect of Dex.
Conclusion
In conclusion, Dex promoted M2-polarization of microglia and attenuated oxidative stress and inflammation, and thus protected against cerebral ischemic injury by activating the Nrf2/HO-1 pathway and inhibiting NLRP3 inflammasome.
In recent decades, the explosion of the waste generation rate and corresponding environmental impacts worldwide have turned waste management into one of the most vital services in urban areas to ...alleviate the waste-related issues. In this study, a novel integrated model is developed to improve the municipal solid waste system by considering the facility location, shift scheduling, and vehicle routing decisions. The problem is formulated as a tri-objective mixed-integer linear programming model, striving to optimize the sustainable development goals in the waste system. These objectives encompass the total profit, air pollution emissions, citizen satisfaction, and social risk factors. The findings from this study illustrate that the proposed integrated framework empowers decision makers to maintain the resilience of the municipal solid waste system by concurrently addressing three critical sustainability aspects.
Parkinson's disease (PD), a chronic and progressive neurodegenerative disease, can reduce the population of dopaminergic neurons in the substantia nigra. The cause of this neuronal death remains ...unclear. 1-Methyl-4-phenylpyridinium ion (MPP+) is a potent neurotoxin that can destroy dopaminergic (DA) neurons and promote PD. Garcinol, a polyisoprenylated benzophenone derivative, was extracted from Garcinia indica and is an important active compound it has been used as an anticancer, antioxidant, and anti-inflammatory, agent and it can suppress reactive oxygen species (ROS) mediated cell death in a PD model. Human neuroblastoma (SH-SY5Y) cells (1 × 10
cells) were treated with MPP+ (1 mM) for 24 h to induce cellular ROS production. The formation of ROS was suppressed by pretreatment with different concentrations of garcinol (0.5 and 1.0 μM) for 3 h in SH-SY5Y cells. The present study found that MPP+ treatment increased the formation of reactive oxygen species (ROS), and the increased ROS began to promote cell death in SH-SY5Y cells. However, our natural compound garcinol effectively blocked MPP+-mediated ROS formation by activating the DJ-1/SIRT1 and PGC-1α mediated antioxidant pathway. Further findings indicate that the activated SIRT1 can also regulate p-AMPK-mediated autophagy to protect the neurons from the damage it concludes that garcinol sub-sequential regulates intracellular autophagy in this model, and the productive efficacy of garcinol was confirmed by western blot analysis and MitoSOX DCFDA and MTT assays. The results showed garcinol increased protection due to the prevention of MPP+-induced ROS and the promotion of cell survival.
The lightweight design of turbine disks is challenging due to the extreme thermomechanical service environment which leads to high stress and temperature-dependency of material properties. The ...simplified engineering design method which uses uniform material properties at fixed temperature would lead to either unsafe or conservative designs. In this article, a stress-constrained thermo-elastic topology optimization method is proposed for axisymmetric disks considering temperature-dependent material properties. The temperature-dependent property functions fitted from the material test data are used to determine the material properties of each element according to the element's average temperature. The strain energy constraint is added into the optimization formulation in order to prevent isolated material and severe violation of stress constraint caused by abrupt volume change. The Helmholtz filter and Heaviside projection are utilized to eliminate the checkerboard pattern and ensure distinct solid/void interfaces in the optimization results, respectively. The geometry extraction from the optimization results is easily implemented by the Least Square Fitting with B-spline Method. In the illustrative examples, the effectiveness of the proposed method in obtaining lighter disk designs is demonstrated in comparison to the design obtained by the simplified engineering method and the traditional single-web disk design. The ability of the proposed method to deal with arbitrary nonuniform temperature field is also demonstrated and it is learned that lighter disk design can be obtained if the temperature field has a lower radial temperature gradient at the disk hub.
Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual ...characteristics. Type A platelet‐derived growth factor (PDGF‐AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF‐AA or its congenital receptor PDGFR‐α leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF‐AA/PDGFR‐α signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR‐α are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF‐AA/PDGFR‐α signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF‐AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF‐AA‐activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF‐AA/PDGFR‐α signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.
In this paper, the integrated design of curvilinearly grid-stiffened panels is investigated, including stiffener layout design and profile design. The layout design includes the curvilinear path and ...non-uniform distribution of stiffeners. Firstly, the path of curvilinear stiffeners is defined by the piecewise linear function, and the non-uniform distribution of curvilinear stiffener cluster is described by the proposed representation method based on the PCHIP interpolation function. In addition to the layout design, the variable profile design method of grid-stiffened structures is also proposed in this paper. The variations of the thickness and height of stiffeners are represented by curves respectively. Similarly, the variable profile design of stiffeners is realized by designing the curves. On this basis, various novel configuration of curvilinearly grid-stiffened panels can be obtained by the integrated layout and profile design. The effectiveness of the proposed integrated design framework is validated by numerical examples. Compared with the initial design, the final integrated design improves the critical buckling factor of the grid-stiffened panel by 73.09%, which shows a great design potential of this kind of variable-stiffness structure compared to constant-stiffness structures.
Display omitted
•An efficient layout representation method of curvilinearly grid-stiffened panel with non-uniform distribution is proposed.•A concept of variable profile design of stiffeners based on interpolation curve is proposed.•Various novel configuration of curvilinearly grid-stiffened panels can be obtained by the integrated design framework.
Abstract
This study evaluated the hydraulic conductivity of bentonite–polymer (B-P) geosynthetic clay liners (GCLs) subjected to wet-dry cycles that simulated seasonal conditions on a GCL installed ...in a landfill cover system. Hydraulic conductivity tests were conducted on B-P GCLs and NaB GCLs at 10 kPa in accordance with the ASTM D5084 standard. Two wet–dry methods were used to investigate the hydraulic conductivity of the GCLs under different field exposure conditions. The hydraulic conductivities of the NaB and B-P GCLs gradually increased during four wet–dry cycles. However, the hydraulic conductivity of the B-P GCL (
K
= 2.3 × 10
-12
m/s) was lower than that of the NaB GCL (
K
= 6.3 × 10
-11
m/s) by two orders of magnitude after four permeation–drying cycles. In addition, the hydraulic conductivity of the B-P GCL was lower (
K
= 5.8 × 10
-12
m/s) than that of the NaB GCL (
K
= 7.8 × 10
-10
m/s) by two orders of magnitude after four saturation–drying cycles. The results suggest that B-P GCLs can enhance the effectiveness of landfill cover systems compared to Na-B GCLs in managing conditions during wet and dry seasons.
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