Search

Time constant equilibration reduction (TICER) is a local model reduction method based on Gaussian elimination for RC networks which was introduced in Sheehan (1999 IEEE/ACM international conference on computer-aided design. Digest of technical papers (Cat. No.99CH37051), pp 200–203, 1999). The main idea of TICER is selectively removing the non-port nodes of the circuits to produce a smaller RC circuit. Since proposed, TICER has been widely used in the electronic engineering, and lots of practices validate its reliability and robustness. It is a practical method to meet the needs of reduction and can produce a realizable RC circuit with good accuracy, and this is the reason why TICER has been used until now. Later, many scholars proposed RC-realizable reduction methods based on TICER. Quite surprisingly, as far as the authors know, there exists no rigorous analysis on this simple but wonderful method in the literature. In this short communication, we prove the optimal first-order asymptotic accuracy of TICER and present numerical evidences to validate our theoretical results. [ABSTRACT FROM AUTHOR]

In this paper the Stokes system in an unbounded domain is solved by the artificial boundary method. The novelty lies in an operator form of the exact Dirichlet-to-Neumann (DtN) mapping. With the help of the Chebyshev rational approximation of the square root function, we derive a highly accurate approximate DtN mapping, which can be numerically implemented without resorting to the eigen-decomposition in terms of the vectorial spherical harmonics. In addition, we develop an efficient block preconditioner for the augmented truncated saddle point problem. Numerical experiments demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

This paper is concerned with a fast finite element method for the three-dimensional Poisson equation in infinite domains. Both the exterior problem and the strip-tail problem are considered. Exact Dirichlet-to-Neumann (DtN)-type artificial boundary conditions (ABCs) are derived to reduce the original infinite-domain problems to suitable truncated-domain problems. Based on the best relative Chebyshev approximation for the square-root function, a fast algorithm is developed to approximate exact ABCs. One remarkable advantage is that one need not compute the full eigensystem associated with the surface Laplacian operator on artificial boundaries. In addition, compared with the modal expansion method and the method based on Pad |$\acute{\textrm{e}}$| approximation for the square-root function, the computational cost of the DtN mapping is further reduced. An error analysis is performed and numerical examples are presented to demonstrate the efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

Although adoptive transfer of therapeutic cells to cancer patients is demonstrated with great success and fortunately approved for the treatment of leukemia and B‐cell lymphoma, potential issues, including the unclear mechanism, complicated procedures, unfavorable therapeutic efficacy for solid tumors, and side effects, still hinder its extensive applications. The explosion of nanotechnology recently has led to advanced development of novel strategies to address these challenges, facilitating the design of nano‐therapeutics to improve adoptive cell therapy (ACT) for cancer treatment. In this review, the emerging nano‐enabled approaches, that design multiscale artificial antigen‐presenting cells for cell proliferation and stimulation in vitro, promote the transducing efficiency of tumor‐targeting domains, engineer therapeutic cells for in vivo imaging, tumor infiltration, and in vivo functional sustainability, as well as generate tumoricidal T cells in vivo, are summarized. Meanwhile, the current challenges and future perspectives of the nanostrategy‐based ACT for cancer treatment are also discussed in the end. [ABSTRACT FROM AUTHOR]

We propose a fast numerical algorithm for the multi-dimensional heat equation on unbounded domains with strips tails. The artificial boundary method is used to confine the computational domains. By applying BDF2 for the time discretization and performing the Z transform, we derive an exact semi-discrete artificial boundary condition which contains the discrete temporal convolution and the surface Laplacian operator. Based on the best relative Chebyshev approximation of the square-root function, we design a fast algorithm to approximate and localize the exact semi-discrete artificial boundary condition. The spatial discretization is realized by the Galerkin finite element method with a special boundary treatment. A complete error estimate for the fully discrete problems is performed, and numerical tests are presented to demonstrate the accuracy and efficiency of the proposed algorithm. [ABSTRACT FROM AUTHOR]

This paper is concerned with the numerical solution of the one-dimensional semi-discrete linear Schrödinger equation in unbounded domains. In order to compute the solution on the domain of physical interest, the artificial boundary method is applied to transform the original unbounded domain problem into an initial boundary value problem on a truncated finite domain. We prove the stability of the truncated semi-discrete problem. Then, a fast algorithm is proposed to approximate the nonlocal absorbing boundary condition. The novelty of this fast algorithm is that the stability of the approximate truncated semi-discrete problem is automatically maintained. In the end, numerical examples are presented to demonstrate the performance of the proposed algorithm. [ABSTRACT FROM AUTHOR]

We study the asymptotic behavior of the solution to some time harmonic wave problems when the wave number is taken as a small asymptotic parameter. Our basic strategy is to introduce suitable Lagrangian multipliers into the governing equations, and transforming them into saddle point problems. These saddle point problems are uniformly invertible with respect to the wave number k ∈ [ 0 , k 0 ] , with k 0 being an arbitrary but fixed positive number. The asymptotic expansion is then derived by the standard regular perturbation technique. [ABSTRACT FROM AUTHOR]

[Display omitted] • IMNP precisely delivers bindarit and alendronate to their sites of action. • IMNP's spatial control of drug release promotes the synergistic effect of drugs. • IMNP effectively depletes tumor-associated macrophages. • IMNP improves the therapeutic effects of anti-PD-1 therapy. Targeting the tumor-associated macrophages (TAMs) with combinational drugs is a promising strategy to improve immune checkpoint blocking therapies. To optimize the synergetic effect of TAM-depletion, it is required for the delivery system to deliver multiple therapeutic drugs to their corresponding action-sites. Herein, we design an immune modulating nanoparticle (IMNP) that can achieve a spatial control of the release sites of the drugs to synergistically deplete TAMs. IMNP has a core–shell structure in which the shell disassembles in acidic tumor microenvironment, resulting in the release of bindarit into the intercellular space to inhibit the recruitment of monocytes and exposing the core nCS(ALN)-Man to trigger the apoptosis of TAMs. With this unique feature, systemic administration of IMNP to tumor-bearing mice effectively eliminated TAMs and altered the immunosuppressing tumor environment, which significantly improved the anti-tumor efficacy of anti-PD-1. Considering the antitumor efficacy of chemotherapy, irradiation and vascular-targeted therapies is also counteracted by TAMs, IMNP could be further developed in combination with these therapies for cancer treatment, implying the potential as a general application to improve the efficacy of cancer therapies. [ABSTRACT FROM AUTHOR]

Fast evaluation of the exact transparent boundary condition for the one-dimensional cubic nonlinear Schrödinger equation is considered in this paper. In [J. Comput. Math., 2007, 25(6): 730–745], the author proposed a fast evaluation method for the half-order time derivative operator. In this paper, we apply this method for the exact transparent boundary condition for the one-dimensional cubic nonlinear Schrödinger equation. Numerical tests demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Abstract: Based on the work of Zheng on the artificial boundary condition for the Schrödinger equation with sinusoidal potentials at infinity, an analytical impedance expression is presented for general second-order ODE problems with periodic coefficients and its validity is shown to be strongly supported by numerical evidences. This new expression for the kernel of the Dirichlet-to-Neumann mapping of the artificial boundary conditions is then used for computing the bound states of the Schrödinger operator with periodic potentials at infinity. Other potential applications are associated with the exact artificial boundary conditions for some time-dependent problems with periodic structures. As an example, a two-dimensional hyperbolic equation modeling the TM polarization of the electromagnetic field with a periodic dielectric permittivity is considered. [Copyright &y& Elsevier]

Abstract: Absorbing boundary conditions (ABCs) are generally required for simulating waves in unbounded domains. As one of those approaches for designing ABCs, perfectly matched layer (PML) has achieved great success for both linear and nonlinear wave equations. In this paper we apply PML to the nonlinear Schrödinger wave equations. The idea involved is stimulated by the good performance of PML for the linear Schrödinger equation with constant potentials, together with the time-transverse invariant property held by the nonlinear Schrödinger wave equations. Numerical tests demonstrate the effectiveness of our PML approach for both nonlinear Schrödinger equations and some Schrödinger-coupled systems in each spatial dimension. [Copyright &y& Elsevier]

Abstract: An error estimate is presented for the numerical approximation to an exterior problem of the Poisson equation when a coupled finite–infinite element method is employed in the computation. This estimate involves not only the size h and the order p of the quasiuniform finite element approximation, but also the radius R of the computational domain covered with finite elements and the number N of the radial terms of infinite elements. Numerical tests are performed, and the results partly validate the theoretical analysis. [Copyright &y& Elsevier]

Abstract: The numerical approximation of one-dimensional cubic nonlinear Schrödinger equations on the whole real axis is studied in this paper. Based on the work of A. Boutet de Monvel, A.S. Fokas and D. Shepelsky [Lett. Math. Phys., 65(3): 199–212, 2003], a kind of exact nonreflecting boundary conditions are derived on the artificially introduced boundary points. The related numerical issues are discussed in detail. Several numerical tests are performed to demonstrate the behaviour of the proposed scheme. [Copyright &y& Elsevier]

The mixed finite element method is used to solve the exterior elliptic problem with high-order local artificial boundary conditions. New unknowns are introduced to reduce the order of the derivatives to two. This leads to an equivalent mixed variational problem such that the normal finite element can be used and special finite elements are no longer needed on the adjacent layer of the artificial boundary. Error estimates are obtained for some local artificial boundary conditions with prescribed order. Numerical examples are presented and the results demonstrate the effectiveness of this method. [Copyright &y& Elsevier]

A second-order Crank-Nicolson finite difference method is designed to solve a 1D nonlocal Schrödinger equation on the whole real axis. We employ an asymptotically compatible scheme to discretize the spatially nonlocal operator, and apply the Crank-Nicolson scheme in time to achieve a fully discrete infinite system. An iterative technique for the second-order matrix difference equation is then developed to obtain Dirichlet-to-Dirichlet (DtD)-type artificial boundary conditions (ABCs) with the application of z-transform for the resulting fully discrete system. After that, with the aid of discrete nonlocal Green's first identity, we derive Dirichlet-to-Neumann (DtN)-type ABCs from DtD-type ABCs. The resulting DtN-type ABCs are available to reduce the infinite discrete system to a finite discrete system on a truncated computational domain, and make it possible to perform stability and convergence analysis for the reduced problem. Finally, numerical examples are provided to demonstrate the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

• BINE facilitated the polarization of TAMs from M2 to M1 phenotype. • A drug-free artificial nanostructure with ability to modulate cellular immunity. • A feasible and universal platform for regulating biological processes. Tumor recurrence poses a significant challenge for prognosis following tumor resection surgery. Recently, cancer immunotherapy has emerged as a promising therapeutic strategy with potential to combat tumor relapse. Current tumor immunotherapies mainly rely on antibodies to achieve immune regulation. The intrinsic issues of antibodies, such as high manufacturing costs and long development time, limit their applications in immunotherapy. Here, we present a bi-specific nanoparticle-based engager (BiNE) as an antibody alternative to regulate the cell–cell interactions for better cancer immunotherapy. BiNE is designed as a small-sized nanoparticle with two types of surface groups, mannose (Man) and phenylboronic acid (PBA), which bind to receptors on macrophages and tumor cells respectively. This enhances intercellular interactions, leading to the polarization of tumor-associated macrophages from an immunosuppressive phenotype (M2) to an inflammatory type (M1), and activates anti-tumor immune responses. Animal studies demonstrated that treatment with BiNE effectively inhibited tumor growth. Furthermore, applying BiNE at the surgical site after tumor removal reshaped the tumor microenvironment and prevented tumor recurrence, offering a promising strategy for improving surgical outcomes. In addition, by changing the functional groups on the surface, BiNE can regulate the interactions between various cells, becoming a novel platform for regulating biological processes alternative to antibodies. [ABSTRACT FROM AUTHOR]

The development of polymer‐based luminescent materials with efficient photoactivated ultralong organic phosphorescence (UOP) is of great importance but very challenging. Herein, a new class of organic phosphorescent luminogens is constructed by attaching phenyl rings and/or ethyl benzoates to the nitrogen atoms of a planar aromatic heterocycle pyrrolodiindole (PDI). The compounds show a significant elevation in phosphorescence emission capability after incorporating the ester group(s). However, they cannot produce room‐temperature phosphorescence in the crystalline state. These observations are identified to be associated with the formation of dimers and excimers and the motions of substituents within the molecules. In this context, the PDI derivatives are doped into epoxy polymers with compact and permanent 3D covalent networks. The resulting polymer films show reversible photoactivated UOP under ambient conditions, with quantum yields and lifetimes of up to 24.4% and 2.03 s, respectively, thereby enabling high‐quality and erasable light printing and multi‐level anti‐counterfeiting applications. In addition, they also exhibit excellent water and chemical resistance. This work is conducive to understanding the generation and decay mechanisms of the triplet excitons of organic luminophores with planar aromatic heterocycles in the crystalline state and provides a direction for the development of high‐performance photoactivated UOP materials. [ABSTRACT FROM AUTHOR]

Targeting the activated epidermal growth factor receptor (EGFR) via clustered regularly interspaced short palindromic repeat (CRISPR) technology is appealing to overcome the drug resistance of hepatocellular carcinoma (HCC) towards tyrosine kinase inhibitor (TKI) therapy. However, combining these two distinct drugs using traditional liposomes results in a suboptimal synergistic anti-HCC effect due to the limited CRISPR/Cas9 delivery efficiency caused by lysosomal entrapment after endocytosis. Herein, we developed a liver-targeting gene-hybridizing-TKI fusogenic liposome (LIGHTFUL) that can achieve high CRISPR/Cas9 expression to reverse the EGFR-mediated drug resistance for enhanced TKI-based HCC therapy efficiently. Coated with a galactose-modified membrane-fusogenic lipid layer, LIGHTFUL reached the targeting liver site to fuse with HCC tumor cells, directly and efficiently transporting interior CDK5- and PLK1-targeting CRISPR/Cas9 plasmids (pXG333-CPs) into the HCC cell cytoplasm and then the cell nucleus for efficient expression. Such membrane-fusion-mediated pXG333-CP delivery resulted in effective downregulation of both CDK5 and PLK1, sufficiently inactivating EGFR to improve the anti-HCC effects of the co-delivered TKI, lenvatinib. This membrane-fusion-participant codelivery strategy optimized the synergetic effect of CRISPR/Cas9 and TKI combinational therapy as indicated by the 0.35 combination index in vitro and the dramatic reduction of subcutaneous and orthotopic TKI-insensitive HCC tumor growth in mice. Therefore, the established LIGHTFUL provides a unique co-delivery platform to combine gene editing and TKI therapies for enhanced synergetic therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacterial therapy, which presents a smart platform for delivering and producing therapeutic agents, as monotherapy or in combination with other therapeutic modes, has provided a breakthrough for the treatment of a range of diseases. The integration of synthetic biology technology with bacteria enables their characteristics like chemotaxis and biomolecule secretion to outperform conventional diagnostics and therapeutics, thereby facilitating their clinical applications in a range of diseases. Compared to injection-administered bacteria, orally-delivered bacteria improve patient compliance while avoiding the risk of systemic infections. However, oral administration of microbes always leads to a substantial loss of viability due to the highly acidic environment in the stomach and bile salt in the intestine. Thus, the formulation of these bacteria into microcapsules using appropriate biomaterials is a promising approach for reducing cell death during gastrointestinal passage and controlling the release of these therapeutic cells across the intestinal tract. In this review, we reveal the basic principles of oral bacterial delivery, from internal genetic engineering approaches to external encapsulation and modification, and summarize the most recent biomedical applications. Finally, we discuss future trends in oral bacterial therapy as well as current challenges that need to be resolved to advance their clinical applications. Oral administration of bacterial therapeutics has gained attractive attention recently for the treatment of a variety of diseases according to the close associations between bacteria and the hosts. This review provides an overview of orally-administrated bacterial therapy, summarizes their most recent biomedical applications, and discusses potential future applications as well as existing challenges. Unlabelled Image • Oral administration of bacterial therapeutics is limited by their biocompatibility, stability, and efficiency in vivo. • How genetic circuits and genetic engineering technologies to enable bacterial characteristics to outperform conventional diagnostics and therapeutics will be introduced. • The choice of biomaterials and technologies for therapeutic bacteria encapsulation is closely related to the improved efficiency of oral bacterial delivery. [ABSTRACT FROM AUTHOR]

We extend the theory of global geometrical optics method, proposed originally for the linear scalar high-frequency wave-like equations in [Commun. Math. Sci., 2013, 11(1): 105-140], to the more general vector-valued Schrödinger problems in the semi-classical regime. The key ingredient in the global geometrical optics method is a moving frame technique in the phase space. The governing equation is transformed into a new equation but of the same type when expressed in any moving frame induced by the underlying Hamiltonian flow. The classical Wentzel-Kramers-Brillouin (WKB) analysis benefits from this treatment as it maintains valid for arbitrary but fixed evolutionary time. It turns out that a WKB-type function defined merely on the underlying Lagrangian submanifold can be obtained with the help of this moving frame technique, and from which a uniform first-order approximation of the wave field can be derived, even around caustics. The general theory is exemplified by two specific instances. One is the two-level Schrödinger system and the other is the periodic Schrödinger equation. Numerical tests validate the theoretical results. [ABSTRACT FROM AUTHOR]

The reconstruction of a penetrable obstacle embedded in a periodic waveguide is a challenging problem. In this paper, the inverse problem is formulated as an optimization problem. We prove some properties of the scattering operator and propose an iterative scheme to approximate the support of the obstacle. Using the limiting absorption principle and a recursive doubling technique, we implement a fast algorithm based on a carefully designed finite element method for the forward scattering problem. Numerical examples validate the effectiveness of the method. [ABSTRACT FROM AUTHOR]

The transmission eigenvalue problem arises from the inverse scattering theory for inhomogeneous media. It plays a key role in the unique determination of inhomogeneous media. Furthermore, transmission eigenvalues can be reconstructed from the scattering data and used to estimate the material properties of the unknown object. The problem is posted as a system of two second order partial differential equations and is nonlinear and non-selfadjoint. It is challenging to develop effective numerical methods. In this paper, we formulate the transmission eigenvalue problem as the eigenvalue problem of a holomorphic operator function. The Lagrange finite elements are used for the discretization and the convergence is proved using the abstract approximation theory for holomorphic Fredholm operator functions. The spectral indicator method is employed to compute the eigenvalues. Numerical examples are presented to validate the proposed method. [ABSTRACT FROM AUTHOR]

In this paper, we propose and study two time-splitting spectral methods for the generalized Zakharov system. These methods are spectrally accurate in space, second order in time, and unconditionally stable. The unconditional stability of the methods offers greater numerical efficiency than those given in previous papers, especially in the subsonic regime. Our numerical experiments confirm the accuracy and stability. In particular, we analyze their behavior in the subsonic regime. The first method, using the exact time integration in phase space for the wave equation for the nondispersive field, converges uniformly with respect to the sound speed for the dispersive wave field, while the second method, using the Crank–Nicolson method in the same step, with an initial layer fix by an L-stable time discretization, converges uniformly with respect to the sound speed for both dispersive and nondispersive fields. Using these new methods we also study the collision behavior of two solitons, in the subsonic region as well as the transsonic region. We obtain numerical results which are quantitatively different from those reported in previous papers using lower resolution numerical techniques. [Copyright &y& Elsevier]

Abstract: We present a time-splitting spectral scheme for the Maxwell–Dirac system and similar time-splitting methods for the corresponding asymptotic problems in the semi-classical and the non-relativistic regimes. The scheme for the Maxwell–Dirac system conserves the Lorentz gauge condition is unconditionally stable and highly efficient as our numerical examples show. In particular, we focus in our examples on the creation of positronic modes in the semi-classical regime and on the electron–positron interaction in the non-relativistic regime. Furthermore, in the non-relativistic regime, our numerical method exhibits uniform convergence in the small parameter δ, which is the ratio of the characteristic speed and the speed of light. [Copyright &y& Elsevier]

CRISPR/dCas9 systems can precisely control endogenous gene expression without interrupting host genomic sequence and have provided a novel and feasible strategy for the treatment of cancers at the transcriptional level. However, development of CRISPR/dCas9‐based anti‐cancer therapeutics remains challenging due to the conflicting requirements for the design of the delivery system: a cationic and membrane‐binding surface facilitates the tumor accumulation and cellular uptake of the CRISPR/dCas9 system, but hinders the circulating stability in vivo. Here, a multistage delivery nanoparticle (MDNP) that can achieve tumor‐targeted delivery of CRISPR/dCas9 systems and restore endogenous microRNA (miRNA) expression in vivo is described. MDNP is designed as a core‐shell structure in which the shell is made of a responsive polymer that endows MDNP with the capability to present different surface properties in response to its surrounding microenvironment, allowing the MNDP overcoming multiple physiological barriers and delivering the payload to tumor tissues with an optimal efficiency. Systemic administration of MDNP/dCas9‐miR‐524 to tumor‐bearing mice achieved effective upregulation of miR‐524 in tumors, leading to the simultaneous interferences of multiple signal pathways related to cancer cell proliferation and presenting remarkable tumor growth retardation, suggesting the feasibility of utilizing MDNP to achieve tumor‐targeting delivery of CRISPR/dCas9 with sufficient levels to realize its therapeutic effects. A nonviral clustered regularly interspaced short palindromic repeat (CRISPR)/nuclease‐inactivated CRISPR associated protein 9 (dCas9) delivery system based on multistage delivery nanoparticle (MDNP) is developed, with the capability to present different surface properties in response to its surrounding microenvironment, allowing the MNDP to overcome multiple physiological barriers and achieve tumor‐targeted delivery of CRISPR/dCas9 systems to suppress tumor growth in mice. [ABSTRACT FROM AUTHOR]