In the upcoming decades, connected vehicles will join regular vehicles to appear on roads, and the characteristics of traffic flow will be changed accordingly. To model the heterogeneous traffic ...mixing regular and connected vehicles, a generic car-following framework is first proposed in this paper. A linear stability condition is theoretically derived, which indicates that the stability of the heterogeneous traffic is closely related to the penetration rate and the spatial distribution of connected vehicles. The generic car-following framework is applied by taking the Intelligent Driver Model as an example, and it is shown that connected vehicles can obviously enhance the stability of traffic flow and improve traffic efficiency in particular when traffic is in congestion. Moreover, a driver assistance strategy based on distributed feedback control is developed for connected vehicles, and the simulation results show that the proposed driver assistance strategy performs satisfactorily in stabilizing traffic as well as improving traffic efficiency.
Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of nucleotide metabolism, our understanding of ...nucleotide metabolism in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness of nucleotide antimetabolites for enhancing immunotherapy. A growing body of evidence now supports the concept that targeting nucleotide metabolism can increase the antitumor immune response by (1) activating host immune systems via maintaining the concentrations of several important metabolites, such as adenosine and ATP, (2) promoting immunogenicity caused by increased mutability and genomic instability by disrupting the purine and pyrimidine pool, and (3) releasing nucleoside analogs via microbes to regulate immunity. Therapeutic approaches targeting nucleotide metabolism combined with immunotherapy have achieved exciting success in preclinical animal models. Here, we review how dysregulated nucleotide metabolism can promote tumor growth and interact with the host immune system, and we provide future insights into targeting nucleotide metabolism for immunotherapeutic treatment of various malignancies.
Simulated moving bed (SMB) technology is considered one of the most successful techniques in chromatographic separation. However, due to the nonlinearity caused by discrete events and sensitivity to ...numerous separation performance parameters, purity control in SMB systems has been a challenging issue. Fuzzy controllers are increasingly popular in industrial environments due to their simplicity and effectiveness in handling nonlinearity. However, traditional fuzzy controllers used in industry often overlook considerations of error acceleration, resulting in slight deviations from target values under steady-state conditions and oscillatory behavior when system parameters change. This study proposes an advanced fuzzy controller, where in a series of experiments, the purity control targets for component B are set at 94% and 96%, and for component A are set at 96% and 96%, respectively. Experimental results indicate that the advanced fuzzy controller achieves higher precision, with an average deviation of around 0.1%, for both components B and A. Importantly, under variations in adsorbent parameter(from 0.01 to 0.03), feed concentration(from 4.5 to 5.2), and switching time(from 178 to 182), the experimental results demonstrate smoother control with the advanced controller, particularly when oscillations occur with conventional fuzzy controllers due to switching time variations, indicating robust control with the advanced fuzzy controller.
To address sustainable development issues of urban traffic, electric buses will join traditional bus system, and the scheduling of bus fleet should be adjusted due to the distinct features of ...electric buses. To this end, this paper develops a Multi-objective Bi-level programming model to collaboratively optimize the vehicle scheduling and charging scheduling of the mixed bus fleet under the operating conditions of a single depot. The upper level determines the vehicle scheduling to minimize the operating cost and carbon emissions under the constraints of connecting time between trips and the limited driving range of electric buses. The lower level is a charging scheduling problem that considers the charging time and the limited driving distance constraint to minimize the charging cost. The proposed model is solved with an integrated heuristic algorithm. The vehicle scheduling problem is addressed with the iterative neighborhood search algorithm based on simulated annealing, while the charging scheduling problem is solved with a greedy dynamic selection strategy based on the approach of multi-stage decision. Finally, case study is carried out based on a mixed bus fleet in Beijing, and the results validate the availability of the proposed model and solution algorithm.
The role of white matter of brain has always been neglected by scholars.With the development of neuroimaging technology,the role of white matter has attracted increasing attention.Perioperative ...neurocognitive disorders have been a hot issue in the research on anesthesia,and recent studies have suggested that white matter may be involved in the effects of general anesthetics on cognitive function.This paper reviews the progress in the relationship between white matter,general anesthesia,and cognitive function from clinical practice and research,aiming to provide new ideas for the research on the mechanism.
•Polysaccharides extracted from traditional Chinese medicine are expected to be used to treat brain I/R injury.•Inhibiting oxidative stress, inflammatory and neuronal apoptosis are the key to ...polysaccharides against brain I/R injury.•There is a little research on inhibiting glutamate neurotoxicity and promoting angiogenesis.•There may be synergy between different polysaccharides.
Cerebral ischemia-reperfusion injury can lead to a series of serious brain diseases and cause death or different degrees of disability. Polysaccharide is a kind of biological macromolecule with multiple pharmacological activities and has been proven that it may be used for the treatment of cerebral I/R injury in the future. By sorting out all relevant research from 2000 to 2020, we selected 74 references and identified 22 kinds of polysaccharides. Almost all of these polysaccharides are extracted from traditional Chinese medicine. Research shows that these polysaccharides can improve cerebral ischemia-reperfusion injury through anti-oxidative stress, inhibiting the neuroinflammation, glutamate neurotoxicity and neuronal apoptosis, and exerting neurotrophic effect. The specific mechanisms include clearing ROS and RNS, inhibiting the expression of inflammatory factors, maintaining mitochondrial homeostasis and blocking caspase cascade, regulating NMDA receptor and promoting angiogenesis. We hoped this review is instructive for researchers to design, research and develop polysaccharides.
α‐linolenic acid (ALA, 18:3n‐3) is a carboxylic acid composed of 18 carbon atoms and three cis double bonds, and is an essential fatty acid indispensable to the human body. This study aims to ...systematically review related studies on the dietary sources, metabolism, and pharmacological effects of ALA. Information on ALA was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library, and Europe PMC using a combination of keywords including “pharmacology,” “metabolism,” “sources.” The following findings are mainly contained. (a) ALA can only be ingested from food and then converted into eicosapentaenoic acid and docosahexaenoic acid in the body. (b) This conversion process is relatively limited and affected by many factors such as dose, gender, and disease. (c) Pharmacological research shows that ALA has the anti‐metabolic syndrome, anticancer, antiinflammatory, anti‐oxidant, anti‐obesity, neuroprotection, and regulation of the intestinal flora properties. (d) There are the most studies that prove ALA has anti‐metabolic syndrome effects, including experimental studies and clinical trials. (e) The therapeutic effect of ALA will be affected by the dosage. In short, ALA is expected to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of ALA.
The damage evolving on rock slopes, including unstable mass failure events, is expected to be associated with a rigidity loss of geomaterials. Therefore, velocity changes (dv/v) inferred from ambient ...noise interferometry allow remotely assessing the damage state of the slope. However, the time scale and amplitude of the dv/v evolution associated with the slope destabilizations are not well known, and their detection and characterization require both high precision and high temporal resolution in dv/v. We herein report an in-situ one-year monitoring of the dv/v on the slow-moving Pubugou rock slope with a high temporal resolution up to 20-min by using two seismic stations in the mountainous region of Sichuan, China, where the slope is affected by both earthquakes and rainfall. The results confirm the feasibility of (1) detecting a possible precursor dv/v drop (−0.5%) ∼40 min before a slope destabilization; (2) characterizing the dv/v caused by the superimposed effects of moderate earthquakes and rainfall; and (3) quantifying the daily dv/v fluctuations of the slope caused by the environmental thermal forcing through thermoelastic effects. In addition, the measurement error and the detectable depth resolution of the dv/v are also addressed in this study. Finally, we suggest the high-resolution technique as a complementary means to be used for operational rock slope damage surveillance in the future.
•One-year dv/v on a rock slope with a temporal resolution of 20-min in SW China.•A possible precursor dv/v drop (−0.5%) ∼ 40 min before a slope destabilization.•Superimposed moderate earthquakes and rainfall maintain an unstable slope.•The thermoelastic effects drive daily dv/v fluctuations of the slope.
The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic ...characterization of multifocal HCC is important for understanding immune escape in different lesions and developing immunotherapy.
We combined whole-exome/transcriptome sequencing, multiplex immunostaining, immunopeptidomes, T cell receptor (TCR) sequencing and bioinformatic analyses of 47 tumors from 15 patients with HCC and multifocal lesions.
IM and MO demonstrated distinct clonal architecture, mutational spectrum and genetic susceptibility. The immune microenvironment also displayed spatiotemporal heterogeneity, such as less T cell and more M2 macrophage infiltration in IM and higher expression of inhibitory immune checkpoints in MO. Similar to mutational profiles, shared neoantigens and TCR repertoires among tumors from the same patients were abundant in IM but scarce in MO. Combining neoantigen prediction and immunopeptidomes identified T cell-specific neoepitopes and achieved a high verification rate in vitro. Immunoediting mainly occurred in MO but not IM, due to the relatively low immune infiltration. Loss of heterozygosity of human leukocyte antigen (HLA) alleles, identified in 17% of multifocal HCC, hampered the ability of major histocompatibility complex to present neoantigens, especially in IM. An integrated analysis of Immunoscore, immunoediting, TCR clonality and HLA loss of heterozygosity in each tumor could stratify patients into 2 groups based on whether they have a high or low risk of recurrence (p = 0.038).
Our study comprehensively characterized the genetic structure, neoepitope landscape, T cell profile and immunoediting status that collectively shape tumor evolution and could be used to optimize personalized immunotherapies for multifocal HCC.
Immunogenomic features of multifocal hepatocellular carcinoma (HCC) are important for understanding immune-escape mechanisms and developing more effective immunotherapy. Herein, comprehensive immunogenomic characterization showed that diverse genomic structures within multifocal HCC would leave footprints on the immune landscape. Only a few tumors were under the control of immunosurveillance, while others evaded the immune system through multiple mechanisms that led to poor prognosis. Our study revealed heterogeneous immunogenomic landscapes and immune-constrained tumor evolution, the understanding of which could be used to optimize personalized immunotherapies for multifocal HCC.
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•Immunogenomic discrepancies among multifocal HCC vary within patients and shape tumor evolutionary trajectories.•Immune escape involves HLA alterations, M2 macrophage infiltration, inhibitory ligands and immunoediting.•Immune context imprinted by genetics can exert selective pressures.•Immune evasion correlates with tumor regression and can predict postoperative recurrence.•Personalized immunotherapy strategies should be adopted for multifocal HCC to maximize efficacy.
The Java subduction zone is located in the southern part of Southeast Asia, where the strong plate convergence results in clustered arc volcanoes and intense seismicity. To better understand the arc ...magmatism and seismogenesis in this region, we determine a high-resolution 3-D P-wave velocity (Vp) model of the crust and upper mantle down to 600 km depth beneath Java. The geometry of the subducting Australian slab is taken into account in the starting model to obtain a better tomographic result by inverting a large number of travel-time data of local and teleseismic events. Our results show lower intra-slab Vp anomalies at depths of ∼100–200 km than other parts of the slab, which may reflect dehydration embrittlement and a slab hole. Feeble low-Vp anomalies appear below the subducting Australian slab, which is probably due to the slab hole where subslab hot materials flow into the mantle wedge. This feature may be related to the occurrence of potassium-rich back-arc volcanoes and the lack of giant megathrust earthquakes (Mw ≥ 8.5) in Java. Our tomographic results also support the hot finger model for explaining the arc magmatism in Java.
•A detailed 3-D P wave velocity model of the Java subduction zone is determined.•The distribution pattern of low-velocity zones in the mantle wedge supports the hot finger model.•A lower-Vp anomaly exists within the high-V slab that is smaller than the well-known seismicity gap.
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