A multi-objective optimization model for green demand responsive airport shuttle scheduling with a stop location problem

We proposed a multi-objective optimization framework for green demand responsive airport shuttle scheduling, which simultaneously aims at assigning demand points to selected stops and routing airport shuttles to visit these stops in their overlapping time windows to transport all passengers from their homes or workplaces to the airport. Our objectives were to minimize total travel time for passengers, the punishment expense of violating the time-window as well as carbon emissions for all shuttles. Since such issues belongs to the NP-problem, a two-stage Multi-objective ant lion optimizer (MOALO)-based algorithm incorporating dynamic programming search method was developed to acquire the optimal scheduling schemes. Finally, a case study of airport shuttle service in Tianjin Airport, China, was used to demonstrate the validity of the model and algorithm

Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models

Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux in NPC1 cells resulted in mitochondrial dysfunction due to impairment of mitophagy, leading to the depletion of both the reduced and oxidised forms of NAD as identified via metabolic profiling. Consequently, exhaustion of the NAD pools triggered mitochondrial depolarisation and apoptotic cell death. Our chemical screening identified two FDA-approved drugs, celecoxib and memantine, as autophagy activators which effectively restored autophagic flux, NAD levels, and cell viability of NPC1 cells. Of biomedical relevance, either pharmacological rescue of the autophagy deficiency or NAD precursor supplementation restored NAD levels and improved the viability of NPC1 patient fibroblasts and induced pluripotent stem cell (iPSC)-derived cortical neurons. Together, our findings identify the autophagy-NAD axis as a mechanism of cell death and a target for therapeutic interventions in NPC1 disease, with a potential relevance to other neurodegenerative disorders

Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome

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Dynamic Analysis of the Seismo-Dynamic Response of Anti-Dip Bedding Rock Slopes Using a Three-Dimensional Discrete-Element Method

Earthquakes are a major external factor that induce landslides. In order to systematically study the dynamic effects and failure mechanism of anti-dip bedding rock slopes (the slope trend is the same as the joint trend, while the slope dip direction is opposite to the joint dip direction) under seismic action (as well as the spatial effects of the structural planes in the anti-dip bedding rock slopes), three-dimensional (3D) discrete-element numerical calculations were performed to analyze anti-dip bedding rock slopes with different slope angles, joint angles, and joint trends subjected to the action of natural seismic and sinusoidal waves. The results were analyzed to investigate the amplification effect, change in Fourier spectrum, failure mechanism, and permanent displacement of the slope under the applied seismic action. The permanent displacement of the slope was calculated using Newmark’s method and the results obtained were discussed and compared with those obtained from a dynamic analysis performed using the 3D discrete-element method. The results showed that the regularity of the spatial distribution of the amplification effect was less clear than that encountered in the planar problem (unidirectional or bidirectional dynamical loading), and this leads to the effect of having an overall rhythmical nature. The seismic wave decays in the high-frequency part from the bottom up of the slope, while the dominant frequency of the seismic wave decreases. The value of the permanent displacement obtained using Newmark’s method is much smaller than that obtained using the dynamic 3D discrete-element analysis approach. The angle between the joint and slope trends has a significant effect on the amplification effect, failure mode, permanent displacement, and stability of slopes subjected to seismic action

Dynamic Analysis of the Seismo-Dynamic Response of Anti-Dip Bedding Rock Slopes Using a Three-Dimensional Discrete-Element Method

Earthquakes are a major external factor that induce landslides. In order to systematically study the dynamic effects and failure mechanism of anti-dip bedding rock slopes (the slope trend is the same as the joint trend, while the slope dip direction is opposite to the joint dip direction) under seismic action (as well as the spatial effects of the structural planes in the anti-dip bedding rock slopes), three-dimensional (3D) discrete-element numerical calculations were performed to analyze anti-dip bedding rock slopes with different slope angles, joint angles, and joint trends subjected to the action of natural seismic and sinusoidal waves. The results were analyzed to investigate the amplification effect, change in Fourier spectrum, failure mechanism, and permanent displacement of the slope under the applied seismic action. The permanent displacement of the slope was calculated using Newmark’s method and the results obtained were discussed and compared with those obtained from a dynamic analysis performed using the 3D discrete-element method. The results showed that the regularity of the spatial distribution of the amplification effect was less clear than that encountered in the planar problem (unidirectional or bidirectional dynamical loading), and this leads to the effect of having an overall rhythmical nature. The seismic wave decays in the high-frequency part from the bottom up of the slope, while the dominant frequency of the seismic wave decreases. The value of the permanent displacement obtained using Newmark’s method is much smaller than that obtained using the dynamic 3D discrete-element analysis approach. The angle between the joint and slope trends has a significant effect on the amplification effect, failure mode, permanent displacement, and stability of slopes subjected to seismic action