Design,optimization and evaluation of poly-ɛ-caprolactone (PCL) based polymeric nanoparticles for oral delivery of lopinavir

Lopinavir (LPV)-loaded poly-ε-caprolactone (PCL) nanoparticles (NPs) were prepared by emulsion solvent evaporation technique. Effects of various critical factors in preparation of loaded NPs were investigated. Box–Behnken design (BBD) was employed to optimize particle size and entrapment efficiency (EE) of loaded NPs. Optimized LPV NPs exhibited nanometeric size (195.3?nm) with high EE (93.9%). In vitro drug release study showed bi-phasic sustained release behavior of LPV from NPs. Pharmacokinetic study results in male Wistar rats indicated an increase in oral bioavailability of LPV by 4-folds after incorporation into PCL NPs. From tissue distribution studies, significant accumulation of loaded NPs in tissues like liver and spleen indicated possible involvement of lymphatic route in absorption of NPs. Mechanistic studies using rat everted gut sac model revealed endocytosis as a principal mechanism of NPs uptake. In vitro rat microsomal metabolism studies demonstrated noticeable advantage of LPV NPs by affording metabolic protection to LPV. These studies indicate usefulness of PCL NPs in enhancing oral bioavailability and improving pharmacokinetic profile of LPV.     

Mesenchymal Stem Cells Functionalized Sonodynamic Treatment for Improving Therapeutic Efficacy and Compliance of Orthotopic Oral Cancer

Despite multiple treatment options being available, many critical challenges are still ongoing in the treatment of oral squamous cell carcinoma (OSCC). Particularly, the major hurdle is to avoid facial disfigurement and oral function disability during treatment. Herein, nanoengineered mesenchymal stem cells (MSCs) are developed as a supersonosensitizer, named M/LPV/O₂, for improving nondestructive sonodynamic therapy (SDT) against OSCC along with good therapeutic compliance. M/LPV/O₂ is composed of an MSCs membrane functionalized liposomal formulation of oxygen-loading perfluorocarbon and sonosensitizer verteporfin (M/LPV/O₂), which can not only increase circulation and targeting efficacy but also supply oxygen to overcome tumor-hypoxia-associated resistance in SDT, resulting in enhanced therapeutic outcomes in vitro and in vivo. It is identified that M/LPV/O₂ effectively stimulates the generation of reactive oxygen species even in hypoxic conditions, and consequently tremendously induces cancer cell death. In addition, M/LPV/O₂ displays good tumor accumulation and penetration under ultrasound stimulation, and efficiently induces tumor inhibition and even abrogation, leading to prolonged survival of tumor-bearing mice. Importantly, M/LPV/O₂-based SDT exhibits minimal systemic adverse effects and successfully maintains oral functions with no facial tissue damage. Therefore, these studies provide a promising therapeutic strategy for OSCC, which has a potential to enhance life quality and compliance after treatment.     

Model reduction for LPV systems based on approximate modal decomposition

The paper presents a novel model order reduction technique for large‐scale linear parameter‐varying (LPV) systems. The approach is based on decoupling the original dynamics into smaller dimensional LPV subsystems that can be independently reduced by parameter‐varying reduction methods. The decomposition starts with the construction of a modal transformation that separates the modal subsystems. Hierarchical clustering is applied then to collect the dynamically similar modal subsystems into larger groups. The resulting parameter‐varying subsystems are then independently reduced. This approach substantially differs from most of the previously proposed LPV model reduction techniques, since it performs manipulations on the LPV model itself, instead of on a set of linear time‐invariant models defined at fixed scheduling parameter values. Therefore, the interpolation, which is often a challenging part in reduction techniques, is inherently solved. The applicability of the developed algorithm is thoroughly investigated and demonstrated by numerical case studies.     

风力发电机自适应鲁棒保性能控制器设计

本文针对变速变桨距风力发电机系统对于风能利用率、动态稳定性要求高的特点,建立了风能转换系统的线性参数变化（LPV）模型,给出了设计一个具有自适应机制的鲁棒保性能控制器的充分条件,进而设计出了一种新的自适应鲁棒保性能控制器。首先,运用自适应方法估计出系统的不确定参数,然后利用参数估计和鲁棒保性能控制方法设计系统的状态反馈控制器,其反馈增益阵是通过求解一组线性矩阵不等式（LMI）的约束而得到,并且满足某二次型性能指标。仿真表明,无论在低风速下还是在高风速下,控制器不仅使系统具有良好的动态特性和鲁棒性,而且使系统具有抑制外界干扰能力。     

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%–2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5–9) versus 11 d (IQR: 8–13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.     

Complex Gaussian functions expansion method applied to truncated Gaussian beams

An analytical expression for the beam propagation factor (M ² factor) of truncated Gaussian beams was derived by using the complex Gaussian functions expansion method. The reasonability of the approximation of complex Gaussian functions expansion method is studied, and a comparison of this method with the generalised truncated second-order moments method and the asymptotic analysis method is also made. In general, an easy analytical expression for the M ² factor of truncated laser beams can be derived by using the complex Gaussian functions expansion method. The M ² factor obtained by using the complex Gaussian functions expansion method is more consistent with that in practice than that obtained by using two other methods. The analytical results obtained by using the complex Gaussian functions expansion method can be reduced to that for the non-truncated case when the truncation parameter is sufficiently large. Therefore, the complex Gaussian functions expansion method is a suitable approximation method for studying the M ² factor of truncated laser beams.     

Determination of the relaxation modulus of a linearly viscoelastic material

In this paper, a numerical method for computing the relaxation modulus of a linearly viscoelastic material is presented. The method is valid for relaxation tests where a constant strain rate is followed by a constant strain. The method is similar to the procedure suggested by Zapas and Phillips. Unlike Zapas-Phillips approach, this new method can be also applied for times shorter than t ₁/2, where t ₁ denotes time when the maximum strain is achieved. Therefore this method is very suitable for materials that experiences fast relaxation. The method is verified with numerical simulations. Results from the simulations are compared with analytical solution and Zapas-Phillips method. Results indicate that the presented approach is suitable for estimating the relaxation modulus.     

On the accuracy of direct integration methods for structural dynamics

Abstract

This paper presents a method of eigen analysis to evaluate the accuracy of the time integration method in the structural dynamic analysis of both transient and steady state responses. Accuracy measure for transient response is evaluated by period elongation and amplitude decay after a complete cycle of response of an undamped system. The proposed method is a unique measure, independent of the initial conditions. Accuracy measure for steady state response is evaluated by the amplitude decay and phase angle of a frequency response. The accuracy measure proposed by this method can be applied to all ranges of ?t/T. The significance of the large range ?t/T is discussed. The proposed method is used to evaluate the accuracy of three commonly used time integration methods: the Wilson method, the Newmark method and the Houbolt method.     

Creep analysis of surface-cracked plates by a creep line-spring method

The creep line-spring method proposed in this paper is based on the solutions for the following two problems: a creep crack under non-steady creep condition; an elastic-plastic surface-cracked plate. For the problem of a non-steady creep crack, an engineering approach for estimating the load-line displacement, crack-tip J and C integrals is presented by extending the engineering approach for elastic-plastic fracture analysis to creep analysis. For solving the elastic-plastic surface crack, a simplified elastic-plastic line-spring method is applied. These two approximate solutions are checked by the finite element method. On the basis of the above two approximate methods, a creep line-spring method is proposed and the corresponding fundamental equations are established. The creep line-spring method is used to estimate creep fracture parameters for three-dimensional cracks. In order to check its accuracy, several surface-cracked plates under uniform tension are analyzed by the creep line-spring method and by the three-dimensional finite-element method. The numerical results show that the creep line-spring method is in good agreement with the finite-element method and has the same accuracy as the common elastic-plastic line-spring method.     

磷酸钾镁水泥水化产物六水磷酸钾镁(K-Struvite)定量分析

磷酸钾镁水泥的各项性能与其中水化产物六水磷酸钾镁(K-Struvite)的含量息息相关。使用基于X射线衍射的绝热法、Rietveld法分析了不同配比磷酸钾镁水泥中K-Struvite和MgO的相对含量,并提出了将相对含量转化为绝对含量的公式。之后使用热重分析法确定了K-Struvite的脱水温度和绝对含量,并和绝热法、Rietveld法所得结果进行了比较,发现三种方法所得结果较为一致。绝热法和Rietveld法在分析K-Struvite相对含量时简便快速,但换算为绝对含量时比热重分析法需要的相关信息要多,可操作性弱于热重分析法。     

Quick Solution of Scattering Problems,from Very Short to Long Wavelengths

Abstract

An approximate method for the solution of scattering problems is presented: the plane approximation delta function boundary operator (PDBO) method. Numerical results based on the use of the fast Fourier transform show that this method, which takes into account the vector character of the light, is able to give reliable results both for short and for long wavelengths, provided the radius of curvature is large enough. The method is applied to diffraction gratings and to non-periodic rough surfaces. Comparison with rigorous results shows that the new method is much better than the classical Beckmann method.     

A review on nano-TiO<Subscript>2</Subscript> sol–gel type syntheses and its applications

Nanomaterials, defined as particles ranging from 1 to 100 nm diameter, have become widely utilized because of their unique physicochemical properties. Among those nanoparticles, titanium dioxide (TiO₂) is frequently used in the production of paints, paper, plastics, welding rod-coating material, cosmetics, etc. TiO₂ is the most commonly used semiconductor photocatalyst. Among the different nanomaterials, it is the most studied. Activated by UV-A irradiation, its photocatalytic properties have been utilized in various applications. A wealth of information on TiO₂ photocatalytic in activation of bacteria has been acquired over the last 20 years. Hence, in this review article we have described synthesis methods mainly sol–gel type method like sol–gel method, ultrasonic-assisted sol–gel method, microemulsion method, colloidal synthesis, and also other method are discussed like solvo-thermal method, thermal plasma process, supersonically expanded plasma jet method, induction plasma torch, reactive plasma processing, plasma electrolytic oxidation, hydrolysis method, thermohydrolysis method, coprecipitation method, citrate–nitrate autocombustion method, etc. Also applications of TiO₂ like medical applications, environmental application, sensor application, photocatalytic applications, and also its health impact for long-term exposure are discussed.     

Direct-iterative solution of ill-conditioned finite element stiffness matrices

In this paper we discuss and expand the direct-iterative method proposed originally by Wilson.¹ First we introduce several simple numerical examples to illustrate the basic idea of this method before we proceed to prove the convergence of the direct-iterative method. We then discuss the methods for selecting the transformative matrix (Q) to be used in transforming an ill-conditioned matrix into a well-conditioned matrix in the direct-iterative method. There are two methods used to choose the matrix Q, namely the rigid body movement method and the imaginary element method. From examples 1-3 we can see that the imaginary element mesh is optional, and the finite element mesh is not necessary. The imaginary element method is a generalization of the mesh refinement method development in Reference 3. Because instead of local rotation angle we only choose displacements of nodes to represent rigid body movement, the rigid body movement method is an improvement of the method in Reference 2. The advantage of these two methods is that, in order to obtain well-conditioned matrices, only a few changes in the stiffness matrices are required even with general ill-conditioned stiffness matrices, and then convergency is achieved rapidly under SOR iteration. Finally, the examples for computing each type of the ill-conditioned matrix in three-dimensional finite element analysis are presented to demonstrate the effectiveness of the direct-iterative method in solving the large bandwidth problems.     

Backward simulation of the probability of a trace particle reaching a given region

This paper describes the solution of the backward-type Kolmogorov equation (backward method) as an alternative to the forward method to determine the probability (P) of a trace particle reaching a given region within a time τ, which is of interest in groundwater contamination investigation, such as pollution monitoring and controlling. The backward-type Kolmogorov equation describing P was theoretically derived under the assumption that the divergence of the velocity field is zero. We here verify that this assumption is unnecessary and therefore the equation can be used in general cases when various recharge/discharge sources in the flow equation are considered. The backward method is validated by comparing its results with that from the forward method. We find that boundary conditions must be properly imposed in the backward method in order to obtain the same results as from the forward method. The backward method is much more efficient than the forward method.     

基于静力衡量法和光学法的超微容量测量方法对比分析

分别使用静力衡量法和光学法对超微容量进行测量。光学法测量中,按照分光原理分别设计了以时域分光和空域分光为基础的测量系统。2套光学测量系统在1μL和10μL的容量测量数据分别为0.967μL和0.929μL以及9.976μL和9.729μL;时域分光测量系统在1μL和10μL测量点重复性为3.2%和2.54%,空域分光测量系统为3.6%和2.02%。2套光学系统相比,时域分光系统的探测器灵敏度更好,在低浓度超微容量测量中能检测到更多光强信息。光学法与静力衡量法获得了相同的结论,证明了光学法在超微容量测量领域的可行性。光学法与静力衡量法相比,光学法针对液体蒸发的处理方法更加简单,光学元件的设计可以有效减小蒸发的影响。     

Velocity-Free MS/AE Source Location Method for Three-Dimensional Hole-Containing Structures

Microseismic/acoustic emission (MS/AE) source localization method is crucial for predicting and controlling of potentially dangerous sources of complex structures. However, the locating errors induced by both the irregular structure and pre-measured velocity are poorly understood in existing methods. To meet the high-accuracy locating requirements in complex three-dimensional hole-containing structures, a velocity-free MS/AE source location method is developed in this paper. It avoids manual repetitive training by using equidistant grid points to search the path, which introduces A* search algorithm and uses grid points to accommodate complex structures with irregular holes. It also takes advantage of the velocity-free source location method. To verify the validity of the proposed method, lead-breaking tests were performed on a cubic concrete test specimen with a size of 10 cm × 10 cm × 10 cm. It was cut out into a cylindrical empty space with a size of ϕ6 cm × 10 cm. Based on the arrivals, the classical Geiger method and the proposed method are used to locate lead-breaking sources. Results show that the locating error of the proposed method is 1.20 cm, which is less than 2.02 cm of the Geiger method. Hence, the proposed method can effectively locate sources in the complex three-dimensional structure with holes and achieve higher precision requirements.     

稳健统计与格拉布斯准则在能力验证结果分析中的应用

分别运用稳健统计（四分位和迭代）法、格拉布斯准则剔除离群值后用经典统计法对热轧带肋钢筋的6组数据进行了统计分析。结果表明:数据组中Z比分值大于5的数据,为离群值。数据组总体服从正态分布或接近正态分布的,3种统计方法结果基本吻合;不存在离群数据的情况下,建议采用稳健统计（四分位或迭代）法进行统计;存在离群数据的情况下,应采用格拉布斯准则剔除离群值后用经典统计法进行统计。对于数据明显偏离正态分布的,不存在离群数据的情况下,建议采用迭代稳健统计法进行统计;存在离群数据的情况下,应采用格拉布斯准则剔除离群值后用经典统计法进行统计。     

A novel method to measure the porosity of porous materials

ABSTRACT

Porosity is the single most important feature of porous materials. On the basis of the research work, a new method to measure the porosity of porous materials is proposed in this paper. This method is a system of equations composed of six formulas, so it is called model equation method. It is not only applicable to space holder technique but also applicable to metal prepared by pure powder metallurgy. Compared with mass volume method and immersion medium method, our new method is more simple and efficient. More importantly, it can be used as a standard measure. This study provides a fundamental basis for the measurement of porosity in porous materials.     

Relationship between contact stiffness ratio and structural stiffness coefficient of a rectangular granular sample: a numerical analysis

In this study, the relationship between contact stiffness ratio and stiffness coefficient of a rectangular sample of granular material is investigated using the granular element method (GEM). Randomly packed granular samples are studied with different contact force models and particle size distributions in numerical simulation using the GEM. Initial arrangements of particles in the granular samples are generated using different algorithms such as inwards packing method, iterative growth method and compression method. It is demonstrated that the relationship between the stiffness coefficient of the granular sample and the contact stiffness ratio is basically logarithmic (Eq. 6). For granular samples generated by inwards packing method, the deviation for logarithmic relationship is relatively small. For granular samples generated by iterative growth method and compressive method, the deviation for logarithmic relationship is relatively large.