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Real-world data study evidence, as an important part of evaluating the safety and effectiveness of drugs and devices, has attracted increasing attention from regulatory agencies and scholars both at home and abroad, and has become an essential source of evidence to support the development and review of drugs and devices. This paper systematically discusses the process and mode of real-world data system construction based on the preliminary practical study of real-world data according to the guidelines/technical specifications issued by regulatory agencies and academic research results. This study result provides not only reference for the generation of clinical evaluation evidence to meet the regulatory requirements for innovative drugs and devices, but also reference for researchers, sponsors and regulators to carry out real-world data studies successfully.真实世界数据研究证据作为评价药物和医疗器械（药械）安全性和有效性的重要组成部分，日益受到国内外监管机构和学者的关注，已成为支持药械研发与审评的关键证据来源。本文在真实世界数据的前期实际研究基础上，结合国内外监管机构所发布的指导原则/技术规范和学术研究成果，系统探讨了真实世界数据体系的构建流程和模式探索。以期为特许药械产生满足监管要求的临床评价证据提供参考，而且为研究者、申办方及监管部门顺利开展真实世界数据研究提供借鉴。.

By calculating the zenith troposphere information from 11 reference stations of the CORS network in Guilin City, Guangxi Province in 2018 by GAMIT10.6 as the reference values, analyzing the relationship between the zenith troposphere and the elevation, as well as the latitude in the Guilin Region, building a model for the zenith tropospheric delay (ZTD) suitable for the Guilin Region, uniformly selecting 8 CORS reference stations in the Guilin Region to build a new model, comparing with the ZTD estimated by GAMIT10.6 and studying the applicability of the new model in the Guilin Region, the results showed that: 1) In the Guilin Region, the ZTD presented linear negative correlation with the station elevation; 2) the ZTD estimated by the new model was well consistent with the reference value, with high precision, and increased with the elevation.

Melatonin receptor type 1 (MTNR1A or MT1) is known to play an important role in cancer progression; however, its prognostic value for resected gastric adenocarcinoma (RGA) is unknown. In this study, we examined the potential of MT1 as a prognostic biomarker for RGA. The expression of the MT1 was evaluated in 67 patients with RGA by immunohistochemistry, and the relationship between MT1 levels and RGA prognosis was analyzed by Chi-square test, multivariate Cox regression, Kaplan-Meier method, and log-rank test. High MT1 expression was associated with a poor survival rate (29.0%, p=0.002) and the occurrence of metastasis (62.9%, p=0.004). Kaplan-Meier survival analysis and log rank tests revealed that patients with high expression of the MT1 had significantly shorter median overall survival compared to those with low expression (33.0 vs. 65.0 months, respectively; p=0.02). Multivariate Cox analysis indicated that the calculated death risk (hazard ratio [HR]) in patients with high expression levels of the MT1 increased to 2.68 (95% confidence interval [CI] 1.21-5.94, p=0.015), which was higher compared to those with low levels. HR of death was also high in patients with advanced T stage (2.51; 95 % CI 1.00-6.26, p=0.049) and metastasis (5.02; 95% CI 1.94-13.03, p=0.001). Our results showed that high MT1 expression in primary gastric adenocarcinoma tissues was associated with the occurrence of metastasis and poor prognosis. It may have prognostic significance as a potential biomarker in patients with RGA.

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.博鳌乐城国际医疗旅游先行区是全国唯一的真实世界数据应用试点地区，基于博鳌乐城特许医疗政策，开展真实世界数据研究，形成支持创新药械临床评价和审评审批的真实世界证据，已成为我国药品审评审批制度改革的重要领域，真实世界证据的产生不仅依靠高质量的真实世界数据，还需要合理可靠的研究设计。本文在国内外相关学术研究和监管部门所发布的真实世界数据研究指导原则或规范的基础上，结合博鳌乐城特殊政策环境和前期实践经验，总结了博鳌乐城真实世界数据研究的设计类型，并探讨了各设计类型在博鳌乐城特殊医疗政策环境中的关键考虑，旨在为进一步实施和开展真实世界数据研究提供借鉴。.

In this study, we investigate the targeted energy transfer (TET) from a simply supported beam that is subjected to thermal variations and external excitations to a local nonlinear energy sink (NES). We derive the governing equation of motion for the beam with an NES device and study the influences of NES parameters on the vibration-suppressing effect. We obtain the optimized parameters of the NES under constant-amplitude harmonic excitation at room temperature. The optimized NES gradually loses its vibration absorption efficiency as the excitation amplitude and temperature increase. We change the nonlinear stiffness of the NES to mitigate the influence of temperature variation and show that NES efficiency can be enhanced by reducing the nonlinear stiffness. We propose a variable-stiffness NES, and the results demonstrate this NES is best for maintaining efficiency over the whole temperature range. We also analyze the transient responses of the system under impulse loads. Results indicate that, like the performance of the system subjected to harmonic excitation, an NES with relatively low stiffness can better suppress vibration with increasing impulse amplitude and temperature.

In this paper, the optical and electrical characteristics of ultra-thin GaAs solar cell with front-surface pyramid array are investigated systematically. The results show that the cell with pyramid array could significantly improve the photon absorption efficiency due to synergistic effects of antireflection and diffraction compared with reference solar cells with single and double anti-reflective coating (ARC), and the maximal integrated quantum efficiency of 0.88 is obtained for pyramid cells, much higher than that of 0.75 and 0.71 for double and single ARC solar cells, respectively. Electric simulation demonstrates the total recombination rate of solar cell with pyramid array is higher than that of reference solar cells due to higher carrier concentration. The radiative recombination dominated in the base and emitter region, while the Shockely-Read-Hall recombination becomes the primary recombination mechanism in the space charge region, both which are much higher than Auger recombination. Surface recombination has little impact on the photovoltaic performance due to the presence of wide bandgap window layer. For pyramid cell, the J s c , V o c , η of 22.65 mA cm−2, 1.120 V and 21.84% are obtained when considering photon recycling effect, respectively, are higher than those of 19.52 mA cm−2, 1.106 V and 18.72% for double ARC solar cell, and those of 18.32 mA cm−2, 1.106 V and 17.60% for single ARC solar cell.

In this study, nonlinear forced vibrations of a functionally graded material circular conical panel under the transverse excitation and the in-plane excitation are discussed. The temperature field of the system is considered as a steady-state temperature. Material properties of temperature-dependence for the system vary along the thickness direction in the light of a power law. The nonlinear geometric partial differential equations expressed by general displacements are derived by the first-order shear deformation theory and Hamilton’s principle. Furthermore, the ordinary differential equations of the system are acquired by the Galerkin method. The nonlinear dynamic behaviors of the system are fully analyzed. Based on numerical simulations, time history records, Poincare maps, phase portraits and bifurcation diagrams are depicted to clarify the existence of complex nonlinear dynamic behaviors of the system.

The effects of nonlinear energy sink (NES) on vibration suppression of a simply supported beam are investigated in this work. The slow flow equations of the system are derived by using complexification–averaging method, and the validity of the derivation is verified. By comparing the vibration absorption of single and parallel NESs of equal mass, it is found that the latter exhibits superior vibration absorption performance. In addition, the parallel NES can eliminate higher branch responses of the system under the harmonic load. Furthermore, it is found that parallel NES can eliminate the higher branches of the system more effectively by tuning nonlinear stiffness and damping. Moreover, the thermal effect on natural frequencies of the simply supported beam is considered, and the influences of the parallel NES’s parameters on the energy dissipation rate under shock load are investigated. The nonlinear responses of the simply supported beam with parallel NES under harmonic load and with the increase of temperature are described.

Supersonic flutter behaviors of functionally graded material (FGM) shallow conical panel with steady thermal stress are investigated. It is assumed that temperature dependent material properties are graded along the radial direction following power law form. The shallow conical panel is formulated with the aid of first-order shear deformation theory and von-Karman geometrical nonlinearity. The aerodynamic loads are evaluated by using the first-order piston theory. The equations of motion in the form of nonlinear partial differential are derived by applying the Hamilton’s principle. In order to get a high dimensional dynamic discrete system, the Galerkin’s method is utilized and this system includes the effect of steady thermal stress due to considering the thermal stress. Newton–Raphson method and continuation method are applied to obtain the equilibrium points, and flutter boundaries are analyzed by solving the eigenvalue problem. The influences of damping, ratio of length to thickness and volume fraction index on the flutter characteristics of the simply supported FGM shallow conical shell panel are studied.

The free vibration of composite truss core sandwich plates is investigated. The natural frequencies of the sandwich plate are calculated by using the classic laminated plate theory, the first-order shear deformation theory, Reddy's third-order shear deformation theory, and a Zig-Zag theory. The differences between the natural frequencies, obtained from the four theories, are compared. The influences of structural parameters on the natural frequencies and the ratios of natural frequency to equivalent density of the sandwich plates with pyramidal core, tetrahedral core, and 3D-Kagome core are studied with the aid of the Zig-Zag theory.

This article explores the subharmonic orbits of a four-dimensional degenerate resonance non-autonomous system. The well-known subharmonic Melnikov method is improved in this paper. Suppose the unperturbed system is a two-degree-of-freedom decoupled Hamiltonian system and possesses a family of periodic orbits. The important issue is the persistence of the periodic orbits after periodic perturbations. In order to solve this problem, we propose a four-dimensional subharmonic Melnikov function based on periodic transformations and Poincare map. Then, a main theorem, which can be used to check the existence of the periodic orbits for the four-dimensional degenerate resonance system, is presented and proved by using the implicit function theorem. In order to verify the validity and applicability of the improved subharmonic Melnikov method, we apply it to investigate the subharmonic orbits of a honeycomb sandwich plate. The theoretical result shows that the subharmonic orbits of period 2T can exist under certain conditions. Numerical simulations are carried out to verify the analytical predictions. It is found that the subharmonic orbits for the honeycomb sandwich plate do exist based on the results of numerical simulations.

The nonlinear flutters of a truncated conical shell, which is subjected to aerodynamic pressure and aerodynamic heating, are researched. Material properties with gradient features along the radial direction depend on the temperature. The supersonic aerodynamic force is obtained by applying the first-order piston theory, including the correction factor for curvature. The temperature in the external surface of the functionally graded material truncated conical shell rises as a result of viscous aerodynamic heating, and the temperature distribution along the thickness can be described by polynomial series. Hamilton's principle is utilized to obtain the nonlinear partial differential equilibrium equation of the system. Using Galerkin's method, a high-dimensional nonlinear system can be derived. Without considering the parts of nonlinear terms and the external forcing excitation, the flutter boundaries are obtained by solving the eigenvalues problem. The influences of ratios of top radius to thickness,...

Due to the limits of size and weight of probes, analysis and design of the low-energy escaping orbit play a significant role in saving the energy in space exploration. In this paper, we research the mechanism of the evolution of the probe orbital energy and develop a design method for the low-energy escaping orbits in the Earth–Moon system. A dynamic model accounting for the Sun–Earth–Moon-probe elliptical four-body problem is presented by considering Moon’s eccentricity and Sun’s direct gravitational influence. Considering the influences from phase of Earth, Moon and Sun, the equations of the probe orbital energy and its variation are derived and theoretical analysis is implemented based on corresponding energy expressions. Then, the Poincare mapping technique is utilized to search two types of low-energy families of escaping orbits and the results of numerical simulation confirm the theoretical predictions. The dynamic model proposed in this paper is more accurate and has practical value comparing with the circular restricted three-body problem, and the escaping strategy can save over 25 % of energy relative to the hyperbolic escaping.

Nonlinear dynamic behaviors of a simply supported honeycomb sandwich plate subjected to the transverse excitations are investigated in this paper. Based on the classical thin plate theory and Von Karman large deformation theory, the governing equation of motion for the honeycomb sandwich plate is established by using the Hamilton principle. The nonlinear governing partial differential equation is discretized to the ordinary differential equations by differential quadrature method and then solved by Runge-Kutta-Fehlberg method. Based on the numerical simulations, combined with nonlinear dynamic theory, the influences of the frequency and amplitude of the transverse excitation are investigated respectively by using the bifurcation diagrams, Poincare maps and phase portraits. The results exhibit the existence of the period-1, period-2 and chaotic responses with the variation of the excitations, which demonstrate that those motions appear alternately.

In this paper, the Nth-order rogue waves are investigated for an inhomogeneous higher-order nonlinear Schrodinger equation. Based on the Heisenberg ferromagnetic spin system, the higher-order nonlinear Schrodinger equation is generated. The generalized Darboux transformation is constructed by the Darboux matrix. The solutions of the Nth-order rogue waves are given in terms of a recursive formula. There are complex nonlinear phenomena in the rogue waves, add the first-order to the fourth-order rogue waves are discussed in some figures obtained by analytical solutions. It is shown that the general Nth-order rogue waves contain $$2n-1$$ free parameters. The free parameters play a crucial role to affect the dynamic distributions of the rogue waves. The results obtained in this paper will be useful to understand the generation mechanism of the rogue wave.

The existence and bifurcations of the subharmonic orbits for four-dimensional non-autonomous nonlinear systems are investigated in this paper. The improved subharmonic Melnikov method is presented by using the periodic transformations and Poincare map. The theoretical results and the formulas are obtained, which can be used to analyze the subharmonic dynamic responses of four-dimensional non-autonomous nonlinear systems. The improved subharmonic Melnikov method is used to investigate the subharmonic orbits of a simply supported rectangular thin plate under combined parametric and external excitations for verifying the validity and applicability of the method. The theoretical results indicate that the subharmonic orbits can occur in the rectangular thin plate with 1:1 and 1:2 internal resonances. The results of numerical simulation also indicate the existence of the subharmonic orbits for the rectangular thin plate, which can verify the analytical predictions.

In this paper, a Fourier expansion-based differential quadrature (FDQ) method is developed to analyze numerically the transverse nonlinear vibrations of an axially accelerating viscoelastic beam. The partial differential nonlinear governing equation is discretized in space region and in time domain using FDQ and Runge–Kutta–Fehlberg methods, respectively. The accuracy of the proposed method is represented by two numerical examples. The nonlinear dynamical behaviors, such as the bifurcations and chaotic motions of the axially accelerating viscoelastic beam, are investigated using the bifurcation diagrams, Lyapunov exponents, Poincare maps, and three-dimensional phase portraits. The bifurcation diagrams for the in-plane responses to the mean axial velocity, the amplitude of velocity fluctuation, and the frequency of velocity fluctuation are, respectively, presented when other parameters are fixed. The Lyapunov exponents are calculated to further identify the existence of the periodic and chaotic motions in the transverse nonlinear vibrations of the axially accelerating viscoelastic beam. The conclusion is drawn from numerical simulation results that the FDQ method is a simple and efficient method for the analysis of the nonlinear dynamics of the axially accelerating viscoelastic beam.

Alumina matrix ceramic composites were fabricated by pressureless sintering. The effect of temperature and holding time, two of the most important pressureless sintering parameters, on the microstructures and grain growth of undoped and diopside doped alumina was researched. Experiments were performed at the temperature of 1420, 1520 and 1620°C, and with four holding times, i.e. 100, 140, 180 and 220 min. The results showed that temperature and holding time had different impacts on grain growth and microstructures. Grain growth was found to be strongly dependent on sintering temperature. The apparent activation energies of 19–20·5 kJ mol−1 for alumina matrix ceramic composites were calculated by the least squares. The sintering kinetic equations were deduced. It was concluded that the sintering of pure alumina was controlled by volume diffusion, while that of alumina matrix ceramic composites doped with diopside was controlled by grain boundary diffusion and volume diffusion.

In the present work, mixed rare earth and diopside were simultaneously introduced in alumina matrix ceramic materials. Composites were fabricated by hot press sintering, during which liquid phase, leading to interface reactions between alumina matrix and additives, was formed. Hardness, fracture toughness and bending strength of the composites were measured. Microstructure observations on fracture surfaces of alumina matrix ceramic materials were analysed. Results showed that diopside, as a sintering assistant, could prompt the formation of transient liquid phase as well as carbides and nitrides of rare earth elements and thus contributed to improve the mechanical properties of alumina matrix ceramic materials.

In this paper, we investigate the vibration characteristics of a Z-shaped beam with variable folding angles which is used to model a folding wing of a morphing aircraft under the condition of a fixed structure. The governing equations of motions for the Z-shaped beam are formulated. For a specific set of material and geometrical parameters, the first three in-plane and the first two out-of-plane linear frequencies of the Z-shaped beam are theoretically calculated, and validated by the experiments and numerical simulations. Additionally, the theoretical mode shapes at a fixed folding angle are compared to the experimental results and the finite element simulations. The theoretical results agree well with numerical simulations and experiments. The results obtained in this paper are helpful for designing and controlling Z-shaped beam structures, and can also be used as a basis to study the nonlinear dynamics of these structures.

This paper investigates the multi-pulse global bifurcations and chaotic dynamics for the nonlinear, non-planar oscillations of the parametrically excited viscoelastic moving belt using an extended Melnikov method in the resonant case. Using the Kelvin-type viscoelastic constitutive law and Hamilton's principle, the equations of motion are derived for the viscoelastic moving belt with the external damping and parametric excitation. Applying the method of multiple scales and Galerkin's approach to the partial differential governing equation, the four-dimensional averaged equation is obtained for the case of 1:1 internal resonance and primary parametric resonance. From the averaged equations obtained, the theory of normal form is used to derive the explicit expressions of normal form with a double zero and a pair of pure imaginary eigenvalues. Based on the explicit expressions of normal form, the extended Melnikov method is used for the first time to investigate the Shilnikov-type multi-pulse homoclinic bifurcations and chaotic dynamics. The paper demonstrates how to employ the extended Melnikov method to analyze the Shilnikov-type multi-pulse homoclinic bifurcations and chaotic dynamics of high-dimensional nonlinear systems in engineering applications. Numerical simulations show that for the nonlinear non-planar oscillations of the viscoelastic moving belt, the Shilnikov-type multi-pulse chaotic motions can occur. Overall, both theoretical and numerical studies suggest that the chaos for the Smale horseshoe sense in motion exists.

The mathematical models of multi-degree-of-freedom (MDOF) strongly nonlinear dynamical systems are described by coupled second-order differential equations. In general, the exact solutions of MDOF strongly nonlinear dynamical systems are frequently unavailable. Therefore, efforts have been mainly concentrated on the approximate analytical solutions. The homotopy analysis method (HAM) is a useful analytic tool for solving strongly nonlinear dynamical systems, and it provides a simple way to ensure the convergence of solution series by means of a convergence-control parameter $${\hbar}$$ . Unlike the classical perturbation techniques, this method is independent of the presence of small parameters in the governing equations of motion. In this paper, the HAM is applied to formulate the analytical approximate periodic solutions of MDOF strongly nonlinear coupled van der Pol oscillators. Within this research framework, the frequency and the displacements of two-degree-of-freedom (2-DOF) strongly nonlinear systems can be explicitly obtained. For authentication, comparisons are carried out between the results obtained by the homotopy analysis and numerical integration methods. It is shown that the fourth-order or eighth-order solutions of the present method provide excellent accuracy. Illustrative examples of three-degree-of-freedom (3-DOF) strongly nonlinear coupled van der Pol oscillators are also presented and discussed. Finally, the optimal HAM approach is used to accelerate the convergence of the solutions.

The global bifurcations and multi-pulse chaotic dynamics of a simply supported laminated composite piezoelectric rectangular thin plate under combined parametric and transverse excitations are investigated in this paper for the first time. The formulas of the laminated composite piezoelectric rectangular plate are derived by using the von Karman-type equation, the Reddy’s third-order shear deformation plate theory and the Galerkin’s approach. The extended Melnikov method is improved to enable us to analyze directly the non-autonomous nonlinear dynamical system, which is applied to the non-autonomous governing equations of motion for the laminated composite piezoelectric rectangular thin plate. The results obtained here indicate that multi-pulse chaotic motions can occur in the laminated composite piezoelectric rectangular thin plate. Numerical simulation is also employed to find the multi-pulse chaotic motions of the laminated composite piezoelectric rectangular thin plate.

The aim of this survey paper is to illustrate the perspectives on the theories of the single- and multi-pulse global bifurcations and chaotic dynamics of high-dimensional nonlinear systems and applications to several engineering problems in the past two decades. Two main methods for studying the Shilnikov type multi-pulse homoclinic and heteroclinic orbits in high-dimensional nonlinear systems, which are the energy-phase method and generalized Melnikov method, are briefly demonstrated in the theoretical frame. In addition, the theory of normal form and an improved adjoint operator method for high-dimensional nonlinear systems is also applied to describe a reducing procedure to high-dimensional nonlinear systems. The aforementioned methods are utilized to investigate the Shilnikov type multi-pulse homoclinic bifurcations and chaotic dynamics for the nonlinear nonplanar oscillations of the cantilever beam subjected to a harmonic axial excitation and two transverse excitations at the free end. How to employ these methods to analyze the Shilnikov type multi-pulse homoclinic and heteroclinic bifurcations and chaotic dynamics of high-dimensional nonlinear systems in engineering applications is demonstrated through this example.

The Shilnikov-type multipulse orbits and chaotic dynamics for a simply supported rectangular thin plate under combined parametric and external excitations are studied in this paper for the first time. The rectangular thin plate is subjected to spatially and temporally varying transversal and in-plane excitations, simultaneously. The formulas of the rectangular thin plate are derived from the von Kármán equation and Galerkin's method. The method of multiple scales is used to find the averaged equation in the case of 1:2 internal resonance. Based on the averaged equation, the theory of normal form is used to obtain the explicit expressions of normal form associated with a double zero and a pair of purely imaginary eigenvalues using the Maple program. The dissipative version of the energy-phase method is utilized to analyze the multipulse global bifurcations and chaotic dynamics of a parametrically and externally excited rectangular thin plate. The global dynamical analysis indicates that there exist the multipulse jumping orbits in the perturbed phase space of the averaged equation for a parametrically and externally excited rectangular thin plate. These results show that the chaotic motions of the multipulse Shilnikov-type can occur for a parametrically and externally excited rectangular thin plate. Numerical simulation results are presented to verify the analytical predictions. It is also found from the results of numerical simulation that the Shilnikov-type multipulse orbits exist for a parametrically and externally excited thin plate.

In this paper, a new homotopy analysis technique which is applying to solve initial boundary value problems of partial differential equations by admitted both the initial and boundary conditions in the recursive relation to obtain a good approximate solution for the problem is proposed. The proposed iterative scheme finds the solution without any discretization, linearization, or restrictive assumptions. Furthermore, we can easily control and adjust the convergence domain and rate of series solutions by the convergence control parameter. The effectiveness of the approach is verified by several examples.

In this paper, the two-dimensional nonlinear dynamics are investigated for the nonplanar nonlinear vibrations of an axially accelerating moving viscoelastic beam with in-plane and out-of-plane vibrations by the differential quadrature method (DQM). The coupled nonlinear partial differential equations for the two-dimensional nonplanar nonlinear vibrations are discretized in space and time domains using DQ and Runge-Kutta-Fehlberg methods respectively. Based on the numerical solutions, the nonlinear dynamical behaviors such as bifurcations and chaotic motions of the nonlinear system are investigated by use of the Poincare map, the three-dimensional phase portrait and the bifurcation diagrams. The bifurcation diagrams for the in-plane and out-of-plane displacements via the mean axial velocity and the amplitude of velocity fluctuation are respectively presented while other parameters are fixed.

The objective of this study was to explore the trend and the epidemiological characteristics of malaria in Ningbo from 2000 through 2011 and provide scientific evidence for the prevention and control. Using the retrospective study, data relating to malaria epidemics during 2000-2011 in Ningbo were collected through the questionnaires of the cases and other important surveillance data. Adult mosquitoes were collected using CDC light traps baited with CO2. Results showed that Plasmodium vivax was the main species, and Anopheles sinensis was the only vector species of malaria. The annual incidence rates (per 100000) ranged from 0.156 to 3.224, and about 95.41% of the cases were imported. The cases occurred mainly between May and November and the incidence showed two peaks, and the local transmission of malaria was determined by vector density. Considering the vast majority of these infections were imported vivax malaria cases from domestic endemic areas (particularly Anhui province), and may lead to limited local transmission, strengthening the routine monitoring of imported malaria, ensuring timely diagnosis, improving case detection rate, giving a standardized treatment to patients and intensifying public health education on malaria prevention are extremely important to malaria prevention and control activities.

Harvesting vibration energy using piezoelectric materials has gained considerable attention over the past few years. Typically, a piezoelectric energy harvester is a unimorph or bimorph cantilevered beam which undergoes base vibration. The focus of this paper is to compare the Euler-Bernoulli model and the Timoshenko model, which are both used for modeling the vibration-based energy harvester. Procedures of deriving the electro-mechanical equation of motion are provided, following exact expressions for the electrical output in two models. Parametric case studies are carried out in order to compare the frequency response of two models. Simulation results show that there is a great difference between Euler-Bernoulli model and Timoshenko model at low length-to-thickness aspect ratio. Such difference diminishes and becomes negligible as aspect ratio increases. It is shown that for the design of piezoelectric energy harvester with small aspect ratio, Timoshenko model can be more accurate than Euler-Bernoulli model in predicting the system behavior.Copyright © 2011 by ASME

In reality, the behavior and nature of nonlinear dynamical systems are ubiquitous in many practical engineering problems. The mathematical models of such problems are often governed by a set of coupled second-order differential equations to form multi-degree-of-freedom (MDOF) nonlinear dynamical systems. It is extremely difficult to find the exact and analytical solutions in general. In this paper, the homotopy analysis method is presented to derive the analytical approximation solutions for MDOF dynamical systems. Four illustrative examples are used to show the validity and accuracy of the homotopy analysis and modified homotopy analysis methods in solving MDOF dynamical systems. Comparisons are conducted between the analytical approximation and exact solutions. The results demonstrate that the HAM is an effective and robust technique for linear and nonlinear MDOF dynamical systems. The proof of convergence theorems for the present method is elucidated as well.Copyright © 2010 by ASME

The multi‐pulse orbits and chaotic dynamics of the cantilevered pipe conveying pulsating fluid with harmonic external force are studied in detail. The nonlinear geometric deformation of the pipe and the Kelvin constitutive relation of the pipe material are considered. The nonlinear governing equations of motion for the cantilevered pipe conveying pulsating fluid are determined by using Hamilton principle. The four‐dimensional averaged equation under the case of principle parameter resonance, 1/2 subharmonic resonance and 1:2 internal resonance and primary parametric resonance is obtained by directly using the method of multiple scales and Galerkin approach to the partial differential governing equation of motion for the cantilevered pipe. The system is transformed to the averaged equation. From the averaged equation, the theory of normal form is used to find the explicit formulas of normal form. Based on normal form obtained, the extended Melnikov method is utilized to analyze the multi‐pulse global homoclinic bifurcations and chaotic dynamics for the cantilevered pipe conveying pulsating fluid. The analysis of global dynamics indicates that there exist the multi‐pulse jumping orbits in the perturbed phase space of the averaged equation. From the averaged equations obtained, the chaotic motions and the Shilnikov type multi‐pulse orbits of the cantilevered pipe are found by using numerical simulation. The results obtained above mean the existence of the chaos for the Smale horseshoe sense for the pulsating fluid conveying cantilevered pipe.

Tethered satellite systems (TSSs) are becoming more widely used in space exploration and exploitation. In this analytical investigation, the criteria on the existence and uniqueness of periodic solutions for the TSSs are presented based on Mawhin’s continuation theorem. In addition, the conditions on the global asymptotic stability for the equilibrium states of the TSSs are also addressed in accordance with the Lyapunov stability theorem.

To understand mutation of isoniazid-resistant genes in M. tuberculosis clinical isolates, and to develop the method for rapid detection of drug resistance.Analyzing the katG genes in 30 M. tuberculosis clinical isolates with PCR-SSCP(single stranded conformation polymorphism) and PCR-DS (direct sequencing) techinques.With the reference of M. tuberculosis strain H37 Rv was used as control, all isoniazid-sensitive isolates and 4 isoniazid-resistant isolates displayed ab normal PCR-SSCP and PCR-DS patterns. But of 12 isoniazid-resistant isolates, 4(33.4%) isolates displayed abnormal katG PCR-SSCP pattern, 8 (46.7%) isolates displayed abnormal katG PCR-SSCP pattern, 5(41.7%) isolates were missense mutation at codon 94, 3(25%) isolates were cosense mutation at codon 96.Resistance to isoniazid in most M. tuberculosis isolates is due to the mutations on katG genes. PCR-SSCP techniques could be used as a method for rapid detection of isoniazid-resistance in M. tuberculosis.

This paper studies the global bifurcations and multipulse chaotic dynamics of a four-edge simply supported honeycomb sandwich rectangular plate under combined in-plane and transverse excitations. Based on the von Karman type equation for the geometric nonlinearity and Reddy's third-order shear deformation theory, the governing equations of motion are derived for the four-edge simply supported honeycomb sandwich rectangular plate. The Galerkin method is employed to discretize the partial differential equations of motion to a three-degree-of-freedom nonlinear system. The six-dimensional nonautonomous nonlinear system is simplified to a three-order standard form by using the normal form method. The extended Melnikov method is improved to investigate the six-dimensional nonautonomous nonlinear dynamical system in a mixed coordinate. The global bifurcations and multipulse chaotic dynamics of the four-edge simply supported honeycomb sandwich rectangular plate are studied by using the improved extended Melnikov method. The multipulse chaotic motions of the system are found by using numerical simulation, which further verifies the result of theoretical analysis.

This paper investigates the multi-pulse global heteroclinic bifurcations and chaotic dynamics for nonlinear, nonplanar oscillations of the parametrically excited viscoelastic moving belts by using an extended Melnikov method in the resonant case. Applying the method of multiple scales, the Galerkin's approach and the theory of normal form, the explicit normal form is obtained for the case of 1:1 internal resonance and primary parametric resonance. Studies are performed for the heteroclinic bifurcations of the unperturbed system and for the characteristics of the hyperbolic dynamics of the dissipative system, respectively. The extended Melnikov method is used to investigate the Shilnikov type multi-pulse bifurcations and chaotic dynamics of the viscoelastic moving belt. Based on the investigation, the geometric structure of the multi-pulse orbits is described in the four-dimensional phase space. Numerical simulations show that the Shilnikov type multi-pulse chaotic motions can occur. Furthermore, numerical simulations lead to the discovery of the new shapes of chaotic motion. Overall, both theoretical and numerical studies suggest that chaos for the Smale horseshoe sense in motion exists.

To study the effects of toquipidine (1-p-methyl-phenyl-2-(alpha-piperidinoacetyl)-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride, Toq), a new anti-arrhythmic agent first synthesized in China, on ionic channels.Ionic channel currents were recorded by whole-cell patch clamp technique in cultured embryonic Xenopus laevis myoblasts and neurons.Toq (0.1, 1, 10, and 100 mumol L-1) caused a concentration-dependent inhibition of the Na+ currents with IC50 7.2 mumol L-1 (5.3-9.8 mumol L-1). Toq (10 mumol L-1) also suppressed the high-voltage-activated Ca2+ currents in neurons. But the steady-state outward K+ currents in myoblasts were activated by Toq (10 mumol L-1).Toq blocked the Na+ and Ca2+ channels and opened the steady-state outward K+ channels.

To evaluate whether there might be some difference in the action modes of nimodipine (Nim) and felodipine (Fel).Compare the inhibitory effects of Nim and Fel with that of verapamil (Ver) as a representative of phenylalklamine on norepinephrine (NE)- and CaCl2-evoked contractions of human arteries.In Ca(2+)-free and high K+ depolarized solution, inhibitory effects of Nim, Fel, and Ver were more potent on CaCl2-induced contractions on isolated human arteries than those on NE-induced contractions. In CaCl2-induced contraction, the pD2 values for Nim, Fel, and Ver were 7.5, 7.42, 6.35 on uterine arteries; 7.38, 7.65, 7.20 on mesenteric arteries and 7.87, 9.10, 7.32 on renal arteries, respectively. Ver inhibited 2 components of NE-evoked contraction, while Nim and Fel only inhibited extracellular Ca(2+)-dependent contractions.The result indicates that Fel has a selective action on human renal arteries.