In recent years, due to the drastic rise in the number of vehicles and the lack of sufficient infrastructure, traffic jams, air pollution, and fuel consumption have increased in cities.
The optimization of timing for traffic lights is one of the solutions for the mentioned problems. Many methods have been introduced to deal with these problems, including reinforcement learning. Although a great number of learning-based methods have been used in traffic signal control, they suffer from poor performance and slow learning convergence. In this paper, a transfer learning-based method for traffic signal control has been proposed. Multi-agent system has also been used for modelling the traffic network and transfer learning has been used to make reinforcement learning agents transfer their experience to each other. Furthermore, a classifier has been utilized to classify the transferred experiences. The results show that using the proposed method leads to a significant improvement on average delay time and convergence time of the learning process.
The development of a computational multibody knee model able to capture some of the fundamental properties of the human knee articulation is presented. This desideratum is reached by including the kinetics of the real knee articulation. The research question is whether an accurate modeling of the condyle contact in the knee will lead to reproduction of the complex combination of flexion/extension, abduction/adduction, and tibial rotation observed in the real knee. The model is composed by two anatomic segments, the tibia and the femur, whose characteristics are functions of the geometric and anatomic properties of the real bones. The biomechanical model characterization is developed under the framework of multibody systems methodologies using Cartesian coordinates. The type of approach used in the proposed knee model is the joint surface contact conditions between ellipsoids, representing the two femoral condyles, and points, representing the tibial plateau and the menisci. These elements are closely fitted to the actual knee geometry. This task is undertaken by considering a parameter optimization process to replicate experimental data published in the literature, namely that by Lafortune and his coworkers in 1992. Then kinematic data in the form of flexion/extension patterns are imposed on the model corresponding to the stance phase of the human gait. From the results obtained, by performing several computational simulations, it can be observed that the knee model approximates the average secondary motion patterns observed in the literature. Because the literature reports considerable inter-individual differences in the secondary motion patterns, the knee model presented here is also used to check whether it is possible to reproduce the observed differences with reasonable variations of bone shape parameters. This task is accomplished by a parameter study, in which the main variables that define the geometry of condyles are taken into account. It was observed that the data reveal a difference in secondary kinematics of the knee in flexion versus extension. The likely explanation for this fact is the elastic component of the secondary motions created by the combination of joint forces and soft tissue deformations. The proposed knee model is, therefore, used to investigate whether this observed behavior can be explained by reasonable elastic deformations of the points representing the menisci in the model. 相似文献
The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immune-incompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities—in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44+/CD24−/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints. 相似文献
Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7’s role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor. 相似文献
The histidine phosphocarrier protein (HPr) kinase/phosphorylase (HPrK/P) modulates the phosphorylation state of the HPr protein, and it is involved in the use of carbon sources by Gram-positive bacteria. Its X-ray structure, as concluded from crystals of proteins from several species, is a hexamer; however, there are no studies about its conformational stability, and how its structure is modified by the pH. We have embarked on the conformational characterization of HPrK/P of Bacillus subtilis (bsHPrK/P) in solution by using several spectroscopic (namely, fluorescence and circular dichroism (CD)) and biophysical techniques (namely, small-angle X-ray-scattering (SAXS) and dynamic light-scattering (DLS)). bsHPrK/P was mainly a hexamer in solution at pH 7.0, in the presence of phosphate. The protein had a high conformational stability, with an apparent thermal denaturation midpoint of ~70 °C, at pH 7.0, as monitored by fluorescence and CD. The protein was very pH-sensitive, precipitated between pH 3.5 and 6.5; below pH 3.5, it had a molten-globule-like conformation; and it acquired a native-like structure in a narrow pH range (between pH 7.0 and 8.0). Guanidinium hydrochloride (GdmCl) denaturation occurred through an oligomeric intermediate. On the other hand, urea denaturation occurred as a single transition, in the range of concentrations between 1.8 and 18 µM, as detected by far-UV CD and fluorescence. 相似文献
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer. 相似文献
Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (ApcMin/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 107 CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in ApcMin/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/β-catenin signaling pathway in the colon of ApcMin/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in ApcMin/+ mice. 相似文献
We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments. 相似文献
A transient permeation method presented here not only determines the adsorption and diffusion properties of the pores that are the transport pathways through zeolite membranes, but nondestructively estimates the effective thickness of the membrane. Transient responses of the permeate concentration to step changes in the feed were measured on two H-ZSM-5 tubular membranes and modeled assuming Maxwell-Stefan diffusion and Langmuir adsorption. The adsorption isotherms determined from these transient measurements at 298 K of N2 and CO2 were nearly identical to those measured by calorimetry on H-ZSM-5 powders. The CH4 isotherm at 298 K was similar to isotherms measured by calorimetry and gravimetric techniques on Na-ZSM-5 and silicalite powders. The similarity of the isotherms indicates that transport of these light gases occurs mainly through zeolite pores. The Maxwell-Stefan diffusion coefficients DMS depended on concentration and were higher for higher feed partial pressures. Average DMS values for the two membranes were 7.5, 5 and 1.5×10−10 m2/s for N2, CH4, and CO2, respectively; these are in the same range and order as diffusion coefficients measured in zeolite crystals. 相似文献