Cathepsin B-responsive nanodrug delivery systems for precise diagnosis and targeted therapy of malignant tumors

The tumor microenvironment (TME) significantly influences cancer evolution and therapeutic efficacy. Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities. The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems (nanoDDS) to improve treatment responses and clinical outcomes. In this tutorial review, after introducing the molecular structure and physiological/pathological functions of cathepsin B, the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis, targeted therapy, and synergistic theranostics of malignant tumors are systematically described. Finally, the challenges of enzyme-substrate incompatibility, low diagnostic sensitivity, mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications     

线性时滞系统的离散最优控制

介绍了对线性时滞系统进行最优控制的设计，将具有时滞控制的线性系统离散后引入增广状态向量。获得不显含时滞的差分方程，根据时滞量的两种分类情况采用连续和离散形式的性能指标函数导出了最优控制律。控制律包含当前状态和此前若干步状态向量的叠加，最优控制律直接从时滞方程中得到，可保证系统的稳定性，此方法亦适用于大时滞的情况。数值算例验证了控制策略的有效性。     

Reachable set bounding for nonlinear perturbed time-delay systems: The smallest bound

In this letter, we propose a new approach to obtain the smallest box which bounds all reachable sets of a class of nonlinear time-delay systems with bounded disturbances. A numerical example is studied to illustrate the obtained result.     

基于波变量补偿的阻抗匹配时延双边遥操作

通信时延是遥操作系统中固有的问题,它会严重影响遥操作的性能,降低系统的稳定性和跟踪性。基于无源理论的波变量法可以保证遥操作系统在任意时延下稳定,是解决时延问题的一个重要方法。然而,波变量法带来的波反射会阻扰有用信号的传输,降低了主从端信号的跟踪性,严重时甚至会导致整个系统振荡。针对这一问题,提出了一种基于波变量补偿的阻抗匹配双边遥操作系统结构,旨在减少波反射,提高操作者的临场感和系统的跟踪性。通过仿真实验,结果表明所提方法能够保证固定时延条件下遥操作系统的稳定性,并具有较好的跟踪性。     

主副垂直腔面发射激光器动力学系统混沌输出的时延特征及带宽分析

基于垂直腔面发射激光器(VCSEL)的自旋反转模型, 数值研究了由一个光反馈VCSEL (定义为主VCSEL, M-VCSEL)输出的混沌光单向注入到另一个VCSEL (定义为副VCSLE, S-VCSEL)所构成的主副VCSELs系统的混沌动力学特性, 分析了注入强度、M-VCSEL与S-VCSEL之间的频率失谐以及M-VCSEL所受到的光反馈强度对系统混沌输出时延特征(包括强度时延特征(I-TDS) 和相位时延特征(P-TDS))以及输出带宽(BW)的影响. 结果显示: 通过调节注入强度和频率失谐, 该系统混沌输出的两个偏振分量(X-PC和Y-PC)的P-TDS和I-TDS可以同时得到抑制; 进一步分析注入强度和频率失谐对混沌BW的影响, 发现在较大负频率失谐区域, 系统可输出BW超过30 GHz 的X-PC和Y-PC混沌信号; 结合系统混沌输出信号的TDS与BW在注入强度和频率失谐参量空间下的演化特性, 可确定宽带宽、低时延特征混沌信号输出的参量空间区域. 此外, 通过合理调节M-VCSEL 所受到的光反馈强度, 可以显著优化系统的混沌输出信号质量.     

矩阵黎卡提方程的精细积分法

选择恰当的参数，将２￣Ｎ类算法用于代数与微分黎卡提方程。证明了算得的解是如此精确，几乎是计算机上的精确解。数例验证了该结论。     

CONTROLLABILITY OF A CLASS OF HYBRID DYNAMIC SYSTEMS (Ⅰ)—BASIC PROPERTIES AND PRELIMINARY RESULTS

The controllability for switched linear system with time-delay in controls was first investigated. The whole work contains three parts. This is the first part, including problem formulation and some preliminaries. Firstly, the mathematical model of switched linear systems with time-delay in control functions was presented. Secondly, the concept of column space, cyclic invariant subspace and generalized cyclic invariant subspace were introduced. And some basic properties, such as separation lemma, were presented. Finally, a basic lemma was given to reveal the relation between the solution set of a centain integral equations and the generalized cyclic invariant subspace. This lemma will play an important role in the determination of controllability. All these definitions and lemmas are necessary research tools for controllability analysis. Contributed by YE Qing-kai Foundation items: the National Natural Science Foundation of China (69925307, 60274001); the National Key Basic Reasearch and Development Program (2002CB312200); the Postdoctoral Program Foundation of China Biography: XIE Guang-ming (1972∼), Doctor (E-mail: xiegming@mech.pku.edu.cn)     

Periodic Response and Chaos in Nonlinear Systems with Parametric Excitation and Time Delay

In this paper, the periodic motions of a nonlinear system with quadratic,cubic, and parametrically excited stiffness terms and with time-delayterms are obtained by the incremental harmonic balance (IHB) method. Theelements of the Jacobian matrix and residue vector arising in the IHBformulation are derived in closed form. A mechanism model representingthe one-mode oscillation of beams and plates is considered as anexample. A path-following algorithm with an arc-length parametriccontinuation procedure is used to obtain the response diagrams. Thesystem also exhibits chaotic motion through a cascade of period-doublingbifurcations, which is characterized by phase planes, Poincaré sectionsand Lyapunov exponents. The interpolated cell mapping (ICM) procedure isused to obtain the initial condition map corresponding to multiplesteady-state solutions.     

Precise control for vibration of rigid–flexible mechanical arm

In the present paper, based on the nonlinear dynamic equation of spacial flexible mechanical arm with dual-link bar, the method of linear quadratic control is used to eliminate the remain vibration of mechanical arm. In the process of computation, the traditional differential algorithm is replaced by the time integration method. Because of taking the more precise time-intervals in the given time-interval and avoiding a lot of computational difficulties, the method of this paper has the characteristics of high precision and unconditional stable. For a typical structure, the precise control law is obtained and the advantages of the algorithm in this paper are shown.     

框架结构主动控制最优时滞研究

在结构振动主动控制中,时滞的大小对结构控制能量和响应均产生影响。在允许时滞的范围内,把结构控制能量和响应作为目标函数,数值仿真发现目标函数随着时滞的变化呈现曲线状态,这说明存在最优时滞。在目标函数处理方面,考虑到控制能量和响应数量级不一致,本文采用了无量纲化处理。同时,考虑到地震波的随机性,本文还推导了含控制力的改进的随机Newmark方法。最后给出了一个计算实例。实例表明本文所提出的方法是有效的。