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A NaVO3/Gr composite exhibits enhanced electrochemical performance in SIB.

A reliable, efficient, and simple control is presented and validated for a quarter-car active suspension system equipped with an electro-hydraulic actuator. Unlike the existing techniques, this control does not use any function approximation, e.g., neural networks (NNs) or fuzzy-logic systems (FLSs), while the unmolded dynamics, including the hydraulic actuator behavior, can be accommodated effectively. Hence, the heavy computational costs and tedious parameter tuning phase can be remedied. Moreover, both the transient and steady-state suspension performance can be retained by incorporating prescribed performance functions (PPFs) into the control implementation. This guaranteed performance is particularly useful for guaranteeing the safe operation of suspension systems. Apart from theoretical studies, some practical considerations of control implementation and several parameter tuning guidelines are suggested. Experimental results based on a practical quarter-car active suspension test-rig demonstrate that this control can obtain a superior performance and has better computational efficiency over several other control methods.

BACKGROUND AND OBJECTIVE: Multiple agents have been developed for treating non-small cell lung cancer (NSCLC). However, patients’ response to these therapies vary drastically, which indicates a need to tailor therapy. Sex is a readily usable clinical characteristic that has been shown to impact patients’ response to drugs. The main objective of this narrative review is to summarize the current state of knowledge, compiled from meta-analyses, on sex differences in treatment efficacy for targeted therapy and immunotherapy in NSCLC. We discuss the interplay of patient characteristics, both molecular and demographic, with sex on how they impact therapeutic response. METHODS: PubMed search was performed with the term “sex/gender differences” with currently FDA approved targeting therapy and immunotherapy agents in treating NSCLC. KEY CONTENT AND FINDINGS: For targeted therapy, women tend to benefit more in terms of progression-free survival upon receiving first-generation anti-epidermal growth factor receptor (EGFR) treatment than men. On the other hand, there is an ongoing debate on sex differences in response to immunotherapy. Although preliminary, whether sex differences were observed depends on treatment settings, patient characteristics, and molecular features. Importantly, incorporating sex as a biological component in the biomarker discovery seems to reveal novel insights in immunotherapy response. CONCLUSIONS: Taken together, sex differences in responding to standard care have been observed in clinical settings for NSCLC patients. A better understanding of sex-associated treatment response and the underlying biology will improve cancer prognosis and eliminate these sex differences.

Prostate cancer (PC) is the most frequently diagnosed malignancy and a leading cause of cancer deaths in US men. Many PC cases metastasize and develop resistance to systemic hormonal therapy, a stage known as castration-resistant prostate cancer (CRPC). Therefore, there is an urgent need to develop effective therapeutic strategies for CRPC. Traditional drug discovery pipelines require significant time and capital input, which highlights a need for novel methods to evaluate the repositioning potential of existing drugs. Here, we present a computational framework to predict drug sensitivities of clinical CRPC tumors to various existing compounds and identify treatment options with high potential for clinical impact. We applied this method to a CRPC patient cohort and nominated drugs to combat resistance to hormonal therapies including abiraterone and enzalutamide. The utility of this method was demonstrated by nomination of multiple drugs that are currently undergoing clinical trials for CRPC. Additionally, this method identified the tetracycline derivative COL-3, for which we validated higher efficacy in an isogenic cell line model of enzalutamide-resistant vs. enzalutamide-sensitive CRPC. In enzalutamide-resistant CRPC cells, COL-3 displayed higher activity for inhibiting cell growth and migration, and for inducing G1-phase cell cycle arrest and apoptosis. Collectively, these findings demonstrate the utility of a computational framework for independent validation of drugs being tested in CRPC clinical trials, and for nominating drugs with enhanced biological activity in models of enzalutamide-resistant CRPC. The efficiency of this method relative to traditional drug development approaches indicates a high potential for accelerating drug development for CRPC.

BACKGROUND: Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD. METHODS: Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators. FINDINGS: No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR(1) = 0.60 [95% CI 0.50–0.72], p(1) = 2.07 × 10(−8); OR(2) = 0.57 [95% CI 0.39–0.82], p(2) = 3.00 × 10(−3)). A significant MR association (OR = 0.71 [95% CI, 0.58–0.87], p = 1.20 × 10(−3)) and strong colocalisation association (PP.H(4) = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk. INTERPRETATION: Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects. FUNDING: Capital’s Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

This article presents a novel proportional-integral approximation-free control (PIAFC) for nonlinear robotic systems with unknown Coriolis and gravity dynamics. One key merit is to transform the original motion tracking problem into an alternative system stabilization problem by introducing prescribed performance functions (PPFs) and the associated error transformation. Another idea is to develop a proportional-integral error compensation mechanism and incorporate it into the approximation-free control synthesis, such that the tracking error converges to zero in the steady-state. In this framework, only the inertia matrix is required and the computationally demanding function approximators are avoided, while the unknown Coriolis and gravity dynamics can be effectively handled. Moreover, the transient tracking error can be retained within a preset boundary. Stability analysis of the closed-loop control system is carried out in terms of the Lyapunov theorem. Finally, extensive comparative simulations and experimental results on a realistic SCARA robotic test-rig illustrate the superiority of the suggested method over several other methods.

Functional studies of long noncoding RNAs (lncRNAs) are often performed in the context of only a single cancer type. However, the tissue-specific expression patterns of lncRNAs raise the question of whether lncRNA associations identified in one cancer type are relevant to other cancer types. Here, we examine the relationships between the expression levels of 50 cancer-related lncRNAs and survival data from 24 types of cancer in The Cancer Genome Atlas (TCGA) with the goal of identifying prognosis related lncRNAs. Our results suggest that high expression levels of certain lncRNAs are consistently associated with worse/better survival in a number of cancers, while other lncRNAs have different prognostic roles in different types of cancer. Our analysis also identifies 20 novel unadjusted associations that have not been reported before. In addition, in low-grade glioma (LGG), prognostic-related lncRNAs are identified after conditioning on known clinical biomarker and common therapy, revealing that 2 lncRNAs, FOXP4-AS1, and NEAT1, are associated with temozolomide response-a standard-of-care in LGG. Pathway analysis suggests NF-kB/STAT3 signaling pathway enrichment in LGG patients with high NEAT1 expression and DNA repair/myc gene set enrichment in LGG patients with high expression of FOXP4-AS1. Our work demonstrates the context dependency of lncRNAs across cancer types and highlights a number of lncRNAs as potential novel cancer prognosis markers.

In this paper, we propose an alternative, simple, yet efficient estimation method to handle unknown dynamics and external disturbances for motion control of robotic systems. An unknown system dynamics estimator (USDE) is first proposed by introducing filter operations and simple algebraic calculations, where the external disturbances and unknown Coriolis/gravity dynamics can be estimated simultaneously. In the specific case where only the external disturbance is unknown, a further modified unknown disturbance estimator (MUDE) is introduced. These proposed USDE and MUDE can be easily implemented and their parameter tuning is straightforward compared with the nonlinear disturbance observer that requires calculation of the inverse of the inertia matrix. The acceleration signal of robotic joints is not used in the design of estimators. Moreover, we also show that the proposed estimators can be incorporated into the design of composite controllers to achieve satisfactory motion tracking response. The closed-loop control system stability and convergence of both the tracking error and estimation error are all guaranteed. Finally, the effectiveness of the two proposed methods is validated by using simulations and experiments based on a SCARA robot test-rig.

This article proposes a new control approach for full-car active suspension systems with unknown nonlinearities. The main advantage of this approach is that the uncertainties and nonlinearities in the system can be handled without using any function approximator (e.g., neural networks and fuzzy logic systems), and the associated online adaptation. Hence, the heavy computational costs and sluggish learning phase to achieve convergence can be remedied. To maintain the transient and steady-state suspension responses, a coordinate suspension error transformation with prescribed performance functions is adopted. Then an approximation-free control is developed to achieve stabilization of the transformed system so as to retain a predefined suspension response. Extreme Value Theorem is used together with the Lyapunov theorem to prove the stability and convergence of the closed-loop control system. To validate the proposed method and show its practical applicability, a dynamic simulator is built by using a commercial vehicle software, Carsim, where an E-SUV type vehicle is configured to describe realistic vehicle dynamics. Simulation results reveal that the proposed control can achieve better suspension performance and require less model information compared with some existing approaches.

This article studies the multi-H∞ controls for the input-interference nonlinear systems via adaptive dynamic programming (ADP) method, which allows for multiple inputs to have the individual selfish component of the strategy to resist weighted interference. In this line, the ADP scheme is used to learn the Nash-optimization solutions of the input-interference nonlinear system such that multiple H∞ performance indices can reach the defined Nash equilibrium. First, the input-interference nonlinear system is given and the Nash equilibrium is defined. An adaptive neural network (NN) observer is introduced to identify the input-interference nonlinear dynamics. Then, the critic NNs are used to learn the multiple H∞ performance indices. A novel adaptive law is designed to update the critic NN weights by minimizing the Hamiltonian-Jacobi-Isaacs (HJI) equation, which can be used to directly calculate the multi-H∞ controls effectively by using input-output data such that the actor structure is avoided. Moreover, the control system stability and updated parameter convergence are proved. Finally, two numerical examples are simulated to verify the proposed ADP scheme for the input-interference nonlinear system.\ud

This paper proposes an adaptive estimation and control method for vehicle active suspension systems with unknown time-varying parameter. Unlike the conventional methods that rely on polynomial-based parameter estimation framework, a novel parameter estimation algorithm is developed to achieve the accurate estimation of unknown time-varying parameter (e.g., vehicle mass). To realize this purpose, low-pass filter operation is imposed on system dynamics, by which the auxiliary variables can be constructed to extract the parameter estimation error information. With this method, a novel adaptive parameter estimation algorithm can be designed to online update the unknown time-varying parameter. Then, the estimated parameter is incorporated into an adaptive controller to regulate the vehicle motion. Theoretical analysis is conducted via the Lyapunov theorem to prove the convergence of both control error and parameter estimation error. Comparative simulation is carried out to demonstrate the effectiveness of the proposed method.