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Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.

Establishing an execution time certificate in deploying model predictive control (MPC) is a pressing and challenging requirement. As nonlinear MPC (NMPC) results in nonlinear programs, differing from quadratic programs encountered in linear MPC, deriving an execution time certificate for NMPC seems an impossible task. Our prior work \cite{wu2023direct} introduced an input-constrained MPC algorithm with the exact and only \textit{dimension-dependent} (\textit{data-independent}) number of floating-point operations ([flops]). This paper extends it to input-constrained NMPC problems via the real-time iteration (RTI) scheme, which results in \textit{data-varying} (but \textit{dimension-invariant}) input-constrained MPC problems. Therefore, applying our previous algorithm can certify the execution time based on the assumption that processors perform fixed [flops] in constant time. As the RTI-based scheme generally results in MPC with a long prediction horizon, this paper employs the efficient factorized Riccati recursion, whose computational cost scales linearly with the prediction horizon, to solve the Newton system at each iteration. The execution-time certified capability of the algorithm is theoretically and numerically validated through a case study involving nonlinear control of the chaotic Lorenz system., Comment: 7 pages

This article addresses the nonadaptive and robust output regulation problem of the general nonlinear output feedback system with error output. The global robust output regulation problem for a class of general output feedback nonlinear systems with an uncertain exosystem and high relative degree can be tackled by constructing a linear generic internal model provided that a continuous nonlinear mapping exists. Leveraging the presented nonadaptive framework facilitates the conversion of the nonlinear robust output regulation problem into a robust nonadaptive stabilization endeavour for the augmented system endowed with Input-to-State Stable dynamics, removing the need for constructing a specific Lyapunov function with positive semidefinite derivatives. To ensure the feasibility of the nonlinear mapping, the approach is extended by incorporating the nonparametric learning framework. Moreover, the introduced nonparametric learning framework provides the ability to learn the dynamics of the steady-state/input behaviour from the signal generated from the internal model only using the output error feedback. As a result, the nonadaptive/nonparametric approach can be advantageous by guaranteeing convergence of the estimation and tracking error even when the underlying controlled system dynamics are complex or poorly understood. The effectiveness of the theoretical results is illustrated for a controlled duffing system and a continuously stirred tank reactor, Comment: 11 pages, 10 figures

This article studies the leaderless consensus problem of heterogeneous multiple networked Euler-Lagrange systems subject to persistent disturbances with unknown constant biases, amplitudes, initial phases, and frequencies. The main characteristic of this study is that none of the agents has information of a common reference model or of a common reference trajectory. Therefore, the agents must simultaneously and in a distributed way: achieve consensus to a common reference model (group model); achieve consensus to a common reference trajectory; and reject the unknown disturbances. We show that this is possible via a suitable combination of techniques of distributed 'observers,' internal model principle and adaptive regulation. The proposed design generalizes recent results on group model learning, which have been studied for linear agents over undirected networks. In this article, group model learning is achieved for Euler-Lagrange dynamics over directed networks in the presence of persistent unknown disturbances., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Team Bart De Schutter

This paper deals with a distributed state estimation problem for jointly observable multi-agent systems operated over various time-varying network topologies. The results apply when the system matrix of the system to be observed contains eigenvalues with positive real parts. They also can apply to situations where the communication networks are disconnected at every instant. We present sufficient conditions for the existence of distributed observers for general linear systems over periodic communication networks. Using an averaging approach, it is shown that the proposed distributed observer can provide exponentially converging state estimates of the state of the linear system when the network is uniformly connected on average. This average connectedness condition offers a more relaxed assumption that includes periodic switching, Markovian switching and Cox process switching as special cases. All the agents in the network share the estimated state with their neighbours through the network and cooperatively reconstruct the entire state locally. Furthermore, this study presents two exponential stability results for two classes of switched systems, providing valuable tools in related distributed state estimation approaches. A toy example and three practical applications are provided to illustrate the effectiveness of the theoretical results., Comment: 12 pages,12 figures

In this paper, a bipartite output regulation problem is solved for a class of nonlinear multi-agent systems subject to static signed communication networks. A nonlinear distributed observer is proposed for a nonlinear exosystem with cooperation-competition interactions to address the problem. Sufficient conditions are provided to guarantee its existence and stability. The exponential stability of the observer is established. As a practical application, a leader-following bipartite consensus problem is solved for a class of nonlinear multi-agent systems based on the observer. Finally, a network of multiple pendulum systems is treated to support the feasibility of the proposed design. The possible application of the approach to generate specific Turing patterns is also presented., Comment: 8 pages,six figures

This paper proposes a non-adaptive control solution framework to the practical output regulation problem (PORP) for a class of nonlinear systems with uncertain parameters, unknown control directions and uncertain exosystem dynamics. The concurrence of the unknown control directions and uncertainties in both the system dynamics and the exosystem pose a significant challenge to the problem. In light of a nonlinear internal model approach, we first convert the robust PORP into a robust non-adaptive stabilization problem for the augmented system with integral Input-to-State Stable (iISS) inverse dynamics. By employing an extremum-seeking control (ESC) approach, the construction of our solution method avoids the use of Nussbaum-type gain techniques to address the robust PORP subject to unknown control directions with time-varying coefficients. The stability of the non-adaptive output regulation design is proven via a Lie bracket averaging technique where uniform ultimate boundedness of the closed-loop signals is guaranteed. As a result, both the estimation and tracking errors converge to zero exponentially, provided that the frequency of the dither signal goes to infinity. Finally, a simulation example with unknown coefficients is provided to exemplify the validity of the proposed control solution frameworks., Comment: 11 pages, 7 figures

This paper proposes a nonparametric learning solution framework for a generic internal model design of nonlinear robust output regulation. The global robust output regulation problem for a class of nonlinear systems with output feedback subject to a nonlinear exosystem can be tackled by constructing a linear generic internal model, provided that a continuous nonlinear mapping exists. An explicit continuous nonlinear mapping was constructed recently in [1] under the assumption that the steady-state generator is linear in the exogenous signal. We further relax such an assumption to a relaxed assumption that the steady-state generator is polynomial in the exogenous signal. A nonparametric learning framework is proposed to solve a linear time-varying equation to make the nonlinear continuous mapping always exist. With the help of the proposed framework, the nonlinear robust output regulation problem can be converted into a robust non-adaptive stabilization problem for the augmented system with integral Input-to-State Stable (iISS) inverse dynamics. Moreover, a dynamic gain approach can adaptively raise the gain to a sufficiently large constant to achieve stabilization without requiring any a priori knowledge of the uncertainties appearing in the dynamics of the exosystem and the system. We further apply the nonparametric learning framework to globally reconstruct and estimate multiple sinusoidal signals with unknown frequencies without using adaptive techniques. An explicit nonlinear mapping can directly provide the estimated parameters, which will exponentially converge to the unknown frequencies. As a result, a feedforward control design is proposed to solve the output regulation using our nonparametric learning framework., Comment: 15 pages; Nonlinear control; iISS stability; output regulation; parameter estimation; Non-adaptive control

This paper deals with the state estimation of linear time-invariant systems using distributed observers with local sampled-data measurement and aperiodic communication. Each observer agent perceives partial information of the system to be observed but does not satisfy the observability condition. Consequently, distributed observers are designed to exponentially estimate the state of the system to be observed by time-varying sampling and asynchronous communication. Additionally, explicit upper bounds on allowable sampling periods for convergent estimation errors are given. Finally, a numerical example is provided to demonstrate the validity of the theoretical results, Comment: 9 pages, 4 figures

Knowledge-based leader-following synchronization of heterogeneous nonlinear multi-agent systems is a challenging problem since the leader's dynamic information is unknown to any follower node. This paper proposes a learning-based fully distributed observer for a class of nonlinear leader systems, which can simultaneously learn the leader's dynamics and states. This class of leader dynamics is rather general and does not require a bounded Jacobian matrix. Based on this learning-based distributed observer, we further synthesize an adaptive distributed control law for solving the leader-following synchronization problem of multiple Euler-Lagrange systems subject to an uncertain nonlinear leader system. The results are illustrated by a simulation example.

This paper studies the leaderless consensus problem of {heterogeneous} multiple networked Euler-Lagrange systems subject to persistent disturbances with unknown constant biases, amplitudes, initial phases, and frequencies. The main characteristic of this study is that none of the agents has information of a common reference model or of a common reference trajectory. Therefore, the agents must simultaneously and in a distributed way: achieve consensus to a common reference model (group model); achieve consensus to a common reference trajectory; {and} reject the unknown disturbances. We show that this is possible via a suitable combination of techniques of distributed `observers', internal model principle, and adaptive regulation. The proposed design generalizes recent results on group model learning, which have been studied for linear agents over undirected networks. In this work, group model learning is achieved for Euler-Lagrange dynamics over directed networks in the presence of persistent unknown disturbances.

For an autonomous linear time-invariant (LTI) system, a distributed observer with time-triggered periodic observations and event-triggered communication is proposed to estimate the state of the system. It is shown that the sampling period is critical for the existence of desirable observers. A necessary and sufficient condition is established to give all feasible sampling periods that lead to convergent error dynamics and characterize delicate relationships among sampling periods, topologies, and system matrices. An event-triggering mechanism based on locally sampled data is designed to regulate the communication among agents, and the convergence of the estimation errors under the mechanism holds for a class of positive and convergent triggering functions, which include the commonly used exponential function as a special case. The mixed time- and event-triggered architecture naturally excludes the existence of Zeno behavior as the system updates at discrete instants. When the triggering function is bounded by exponential functions, analytical characterization of the relationship among sampling, event triggering, and inter-event behaviour is established. Finally, several examples are provided to illustrate the effectiveness and merits of the theoretical results., Comment: 17 pages, 10 figures

This paper studies cooperative tracking problem of heterogeneous Euler-Lagrange systems with an uncertain leader. Different from most existing works, system dynamic knowledge of the leader node is unaccessible to any follower node in our paper. Distributed adaptive observers are designed for all follower nodes, simultaneously estimate the state and parameters of the leader node. The observer design does not rely on the frequency knowledge of the leader node, and the estimation errors are shown to converge to zero exponentially. Moreover, the results are applied to general directed graphs, where the symmetry of Laplacian matrix does not hold. This is due to two newly developed Lyapunov equations, which solely depend on communication network topologies. Interestingly, using these Lyapunov equations, many results of multi-agent systems over undirected graphs can be extended to general directed graphs. Finally, this paper also advances the knowledge base of adaptive control systems by providing a main tool in the analysis of parameter convergence for adaptive observers.

In this note, the problem of simultaneous leader-following consensus and parameter estimation is studied for a class of multi-agent systems subject to an uncertain leader system. The leader system is described by a sum of sinusoids with unknown amplitudes, frequencies and phases. A distributed adaptive observer is established for each agent to estimate the unknown frequencies of the leader. It is shown that if the signal of the leader is sufficiently rich, the estimation errors of the unknown frequencies converge to zero asymptotically for all the agents. Based on the designed distributed adaptive observer, a distributed adaptive control law is synthesized for each agent to solve the leader-following consensus problem., Comment: 8 page

In this paper, we study the leader-following consensus problem of multiple Euler-Lagrange systems subject to an uncertain leader system. We first establish an adaptive distributed observer for a neutrally stable linear leader system whose system matrix is not known exactly. Under standard assumptions, this adaptive distributed observer can estimate and pass the leader's state to each follower through the communication network of the system without knowing the leader's system matrix exactly. Under the additional assumption that the leader's state is persistently exciting, this adaptive distributed observer can also asymptotically learn the parameters of the leader's system matrix. On the basis of this adaptive distributed observer, we further synthesize an adaptive distributed control law to solve our problem via the certainty equivalence principle. Our result allows the leader-following consensus problem of multiple Euler-Lagrange systems to be solved even if none of the followers knows the system matrix of the leader system exactly.

In this paper, we first consider the containment control problem of singular heterogeneous multi-agent systems, where all the followers converge to the convex hull spanned by the leaders. To solve this problem, we propose two distributed control laws: one is based on the state feedback control framework, which is suitable for the case that the full state information of each follower is accessible; and the other is based on the output regulation framework, where each follower only can access to its output. Furthermore, the distributed observers are designed for every follower to estimate the convex combination of the leader states which is determined by the communication graph. It should be noted that our results can also regard the non-singular multi-agent systems’ containment control problem as a special case. Finally, simulation results corroborate the effectiveness of our analytical results.

Guoming Hu,1 Kefang Zhong,1 Wei Chen,1 Shimin Wang,2 Liming Huang1 1Department of General Surgery (Breast and Thyroid Surgery), 2Department of Nephrology, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Zhejiang, China Background: Cancer-associated fibroblasts (CAFs) are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin-positive CAFs in human lung cancer still remains controversial. Methods: Herein, we performed a meta-analysis including 12 published studies with 1,802 patients identified from PubMed and EBSCO to assess the prognostic impact of podoplanin-positive CAFs in lung cancer patients. Results: We found that podoplanin+ fibroblast infiltration significantly decreased overall survival (OS), disease-free survival (DFS), and progression-free survival in patients. In stratified analyses, podoplanin+ fibroblast infiltration was significantly associated with worse OS and DFS in both squamous cell carcinoma and adenocarcinoma of lung. In addition, high density of podoplanin-positive CAFs significantly correlated with unfavorable clinicopathological features such as lymph node metastasis, and lymphatic, vascular, and pleural invasion of patients. Conclusion: Podoplanin+ fibroblast infiltration leads to worse clinical outcome in lung cancer patients, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment. Keywords: podoplanin-positive cancer-associated fibroblasts, worse outcome, lung cancer, meta-analysis

Résumé: Récemment, plusieurs évidences ont démontré que certaines hormones tels que l'Endothéline-1 (ET-1), le facteur activateur de plaquettes (PAF), la Bradykinine (BK) et l'Angiotensine II (Angll) peuvent influencer le fonctionnement cardiovasculaire. Cependant, les effets de ces hormones sur les courants ioniques dans les cellules cardiaques demeurent inconnus. La présente étude sert à explorer ces propriétés. Afin de mieux étudier les effets des substances cardioactives, nous avons continué de caractériser les propriétés électrophysiologiques fondamentales des courants ioniques dans les cardiomyocytes provenant de l'embryon de poulet et du fœtus humain. Deux types de courants calciques sont identifiés dans ces derniers. Le premier était un courant calcique (Ca) à bas seuil d'activation (ou type T). Le second est un courant calcique à haut seuil d'activation (ou type L). Ces deux courants peuvent être distingués à partir de leurs propriétés cinétiques et électriques. De plus, les propriétés des canaux calciques de type T et L détectées dans les cellules cardiaques d'embryons de poulet âgés de 10 jours ont été reconfirmées dans les cellules cardiaques de fœtus humain, puisque les propriétés observées dans chacune de ces préparations étaient semblables. Tous les résultats obtenus sont consistant avec ceux observés auparavant dans ce laboratoire. Il avait déjà été observé dans ce laboratoire que l'ET-1 augmente la concentration de Ca2+ intracellulaire ( [ Ca2+]i) dans des cellules de muscle lisse vasculaire provenant de l'aorte de lapin en activant le canal calcique de type R. L'ET-1 ne semble pas affecter le courant calcique de type T et L vasculaire. Ceci ne peut pas expliquer l'effet inotrope positif connu de l'ET-1 sur le cœur. Dans cette étude, nous avons observé, dans les cardiomyocytes d'embryons de poulet et humain, que l'ET-1 a induit une augmentation très significative du courant Ca de type L. L'ET-1 a aussi provoqué la potentialisation du courant Ca de t

Leaf a) Wang Hui (1632-1717): Buddhist Temple on a Clear Evening after Oubolaoren [Zhao Mengfu, 1254-1322] Executed Spring of 1674 Leaf b) Wang Hui (1632-1717): Sand Banks and Rocks after Chiweng [Huang Gongwang, 1269-1354] Leaf c) Wang Hui (1632-1717): Shady Summer Woods after Shuming [Wang Meng, ca. 1308-1385] Leaf d) Wang Hui (1632-1717): Pavilion Amid Woods and Verdant Peaks Following the Brush Ideas of Guan Tong (10th century) Leaf e) Wang Hui (1632-1717): Deserted Mountain, Old Trees and Village after Zhuran [active ca. 960-80] Mountain torrent and deserted mountain path; using the brush manner of Zhuran to write the poetic idea of Shaoling [Du Fu, 712-770] Leaf f) Wang Hui (1632-1717): Cloudy Mountains after Gaokegong [Gao Kegong, 1248-1310] When mountains put forth clouds, clouds put forth mountains, Transformed into continuous rain they encompass all mankind; From this one knows that the gods assembled banners and pendants Are not in golden halls or rooms of jade. After Gao [Kegong] Xiangshu Leaf g) Wang Hui (1632-1717): Peach Blossom Spring following Zhao Chengzhi's methods of using color [Zhao (Mengfu) Chengzhi, 1254-1322] When spring comes, peach blossom waters are everywhere; If this is not an immortal's spring, what piece is? Leaf h) Wang Hui (1632-1717): Level Vista with Trees and Water Buffalo after Zhao Danian [Zhao (Lingrang) active ca. 1070-1100] Leaf i) Wang Hui (1632-1717): Wintry Grove on Ancient Banks after Li Xianxi [Cheng, ca. 919-967] Leaf j) Wang Hui (1632-1717): Snowy Studio in a Mountain Village after Wang Youcheng [Wei, 699-759] "This painting bears a second inscription by Wang Hui: Youweng laoren [Wang Shimin] gave me a blank album and asked for some paintings. At the time I was traveling in Yangzhou and wasn't able to comply. This spring I received an express letter [from him] so I quickly did these small scenes after various masters. Your disciple's embarrassing brush and ink is not worthy of entering your collection. Done by a rainy, Please note that if this image is under copyright, you may need to contact one or more copyright owners for any use that is not permitted under the ARTstor Terms and Conditions of Use or not otherwise permitted by law. While ARTstor tries to update contact information, it cannot guarantee that such information is always accurate. Determining whether those permissions are necessary, and obtaining such permissions, is your sole responsibility.

Leaf a) Wang Hui (1632-1717): Buddhist Temple on a Clear Evening after Oubolaoren [Zhao Mengfu, 1254-1322] Executed Spring of 1674 Leaf b) Wang Hui (1632-1717): Sand Banks and Rocks after Chiweng [Huang Gongwang, 1269-1354] Leaf c) Wang Hui (1632-1717): Shady Summer Woods after Shuming [Wang Meng, ca. 1308-1385] Leaf d) Wang Hui (1632-1717): Pavilion Amid Woods and Verdant Peaks Following the Brush Ideas of Guan Tong (10th century) Leaf e) Wang Hui (1632-1717): Deserted Mountain, Old Trees and Village after Zhuran [active ca. 960-80] Mountain torrent and deserted mountain path; using the brush manner of Zhuran to write the poetic idea of Shaoling [Du Fu, 712-770] Leaf f) Wang Hui (1632-1717): Cloudy Mountains after Gaokegong [Gao Kegong, 1248-1310] When mountains put forth clouds, clouds put forth mountains, Transformed into continuous rain they encompass all mankind; From this one knows that the gods assembled banners and pendants Are not in golden halls or rooms of jade. After Gao [Kegong] Xiangshu Leaf g) Wang Hui (1632-1717): Peach Blossom Spring following Zhao Chengzhi's methods of using color [Zhao (Mengfu) Chengzhi, 1254-1322] When spring comes, peach blossom waters are everywhere; If this is not an immortal's spring, what piece is? Leaf h) Wang Hui (1632-1717): Level Vista with Trees and Water Buffalo after Zhao Danian [Zhao (Lingrang) active ca. 1070-1100] Leaf i) Wang Hui (1632-1717): Wintry Grove on Ancient Banks after Li Xianxi [Cheng, ca. 919-967] Leaf j) Wang Hui (1632-1717): Snowy Studio in a Mountain Village after Wang Youcheng [Wei, 699-759] "This painting bears a second inscription by Wang Hui: Youweng laoren [Wang Shimin] gave me a blank album and asked for some paintings. At the time I was traveling in Yangzhou and wasn't able to comply. This spring I received an express letter [from him] so I quickly did these small scenes after various masters. Your disciple's embarrassing brush and ink is not worthy of entering your collection. Done by a rainy, Please note that if this image is under copyright, you may need to contact one or more copyright owners for any use that is not permitted under the ARTstor Terms and Conditions of Use or not otherwise permitted by law. While ARTstor tries to update contact information, it cannot guarantee that such information is always accurate. Determining whether those permissions are necessary, and obtaining such permissions, is your sole responsibility.

Leaf a) Wang Hui (1632-1717): Buddhist Temple on a Clear Evening after Oubolaoren [Zhao Mengfu, 1254-1322] Executed Spring of 1674 Leaf b) Wang Hui (1632-1717): Sand Banks and Rocks after Chiweng [Huang Gongwang, 1269-1354] Leaf c) Wang Hui (1632-1717): Shady Summer Woods after Shuming [Wang Meng, ca. 1308-1385] Leaf d) Wang Hui (1632-1717): Pavilion Amid Woods and Verdant Peaks Following the Brush Ideas of Guan Tong (10th century) Leaf e) Wang Hui (1632-1717): Deserted Mountain, Old Trees and Village after Zhuran [active ca. 960-80] Mountain torrent and deserted mountain path; using the brush manner of Zhuran to write the poetic idea of Shaoling [Du Fu, 712-770] Leaf f) Wang Hui (1632-1717): Cloudy Mountains after Gaokegong [Gao Kegong, 1248-1310] When mountains put forth clouds, clouds put forth mountains, Transformed into continuous rain they encompass all mankind; From this one knows that the gods assembled banners and pendants Are not in golden halls or rooms of jade. After Gao [Kegong] Xiangshu Leaf g) Wang Hui (1632-1717): Peach Blossom Spring following Zhao Chengzhi's methods of using color [Zhao (Mengfu) Chengzhi, 1254-1322] When spring comes, peach blossom waters are everywhere; If this is not an immortal's spring, what piece is? Leaf h) Wang Hui (1632-1717): Level Vista with Trees and Water Buffalo after Zhao Danian [Zhao (Lingrang) active ca. 1070-1100] Leaf i) Wang Hui (1632-1717): Wintry Grove on Ancient Banks after Li Xianxi [Cheng, ca. 919-967] Leaf j) Wang Hui (1632-1717): Snowy Studio in a Mountain Village after Wang Youcheng [Wei, 699-759] "This painting bears a second inscription by Wang Hui: Youweng laoren [Wang Shimin] gave me a blank album and asked for some paintings. At the time I was traveling in Yangzhou and wasn't able to comply. This spring I received an express letter [from him] so I quickly did these small scenes after various masters. Your disciple's embarrassing brush and ink is not worthy of entering your collection. Done by a rainy, Please note that if this image is under copyright, you may need to contact one or more copyright owners for any use that is not permitted under the ARTstor Terms and Conditions of Use or not otherwise permitted by law. While ARTstor tries to update contact information, it cannot guarantee that such information is always accurate. Determining whether those permissions are necessary, and obtaining such permissions, is your sole responsibility.