Size-dependent Analysis Research Articles

HMGB1 Accelerates Regeneration of Multiple Tissues By Transitioning Stem Cells to GAlert

Chemotherapy induced leucopoenia and neutropaenia results in an increased risk of infection, with febrile neutropaenia being associated with bacteraemia, sepsis and death. Haematopoietic regeneration is reliant on endogenous stem cells and the acceleration of this process would reduce the length of time (nadir) of clinical neutropaenia, thereby reducing the risk of infection and the treatment associated morbidity and mortality associated with chemotherapy. The haematopoietic stem cell injury-niche has not been extensively explored for potential novel in vivo regenerative targets. Our objective was to assess if alarmins, endogenous molecules which are released upon tissue damage and widely considered to only be triggers of the immune response, may potentiate stem-cell mediated repair and regeneration. Here we show that the alarmin HMGB1 transitions endogenous quiescent G0 stem cells to the recently described GAlert phase, thereby enhancing regeneration in multiple tissues, including blood, bone, and muscle.Utilising complete diaphyseal fractures as a model of massive HSC-niche injury, we found that alarmins were elevated post-fracture in both human and murine blood samples. Next, we administered exogenous HMGB1 systemically to wild type C57BL6/J mice and serial peripheral blood counts showed they displayed accelerated haematopoietic recovery following 5-fluouracil (5-FU) induced myeloablation. The nadirs of leucopoenia and neutropaenia were reduced by approximately 28% and 23% respectively. Analysis of cell cycle kinetics, cell size, ATP levels, mitochondrial DNA, and mTORC1 dependency revealed that the underlying mechanism was that HMGB1 transitioned the murine haematopoietic stem cell to the dynamic GAlert phase. We confirmed these findings by generating conditional Hmgb1-/- mice and performed rescue experiments. Additionally we showed these cellular effects extended to CD34+ human haematopoietic stem and progenitor cells.Hybrid ELISAs and small molecule inhibitors showed that the molecular pathway through which HMGB1 exerted these regenerative effects was by forming a heterocomplex with CXCL12 and acting via CXCR4. Subsequently we showed that other CXCR4+ stem and progenitor cells, including murine skeletal and muscle stem cells, and human mesenchymal stromal cells, also transitioned to GAlert following administration of exogenous HMGB1. HMGB1 also accelerated fracture repair and muscle regeneration, and accelerated recovery in all three murine models when administered 2 weeks before injury. In summary, we have identified a molecular and cellular pathway that accelerates the physiological regenerative response in a dynamic and adaptive manner to current or future injuries. We propose a model in which a highly-conserved injury signal, HMGB1, acts via a well-established maintenance signalling pathway, CXC12-CXCR4, to ultimately promote tissue regeneration. As a therapeutic target with broad clinical applications, such as in chemotherapy, trauma, or elective surgery, FR or 3S-HMGB1 could be administered as a single dose either locally or systemically at the time of injury or even up to 2 weeks beforehand. Most importantly this pathway has wide potential therapeutic benefit, as it could conceivably accelerate healing in any tissue that relies on repair from cells that express CXCR4 and can transition to GAlert. [Display omitted] DisclosuresVenereau:HMGBiotech: Employment, Patents & Royalties: HMGBiotech. Bianchi:HMGBiotech: Employment, Patents & Royalties: HMGBiotech.

Influence of initial geometric imperfection on static and free vibration analyses of porous FG nanoplate using an isogeometric approach

In this paper, the size-dependent analysis of geometrically imperfect porous functionally graded (FG) nanoplates is studied by an isogeometric approach based on a new refined plate theory. Simultaneous effects of initial geometric imperfection and porosity on the natural frequency and deflection of the FG nanoplates are investigated. The initial geometric imperfection is considered as an initial curvature and modeled by an analytical function in the governing equations of the nanoplate. Material properties of porous FG nanoplate are defined by a modified power-law function, and two types of distribution for porosity are used. A four-variable refined plate theory with a new polynomial shape function is proposed. Based on Hamilton’s principle, a weak form of static and free vibration problem for nonlocal plate is derived. The discrete system of equations is solved by an isogeometric approach based on NURBS basis functions, and the accuracy of the present study is verified by comparing the results with solutions given in published papers. Present results indicate the importance of porosity parameter, porosity distributions, nonlocal parameter, material index, plate geometrical parameters, and specially imperfection amplitude on the static and free vibration behavior of FG nanoplates.

A comprehensive study on the size-dependent analysis of strain gradient multi-directional functionally graded microplates via finite element model

This paper presents a comprehensive study on bending, vibration and buckling behaviours of the multi-directional FG microplates. The material properties vary continuously both in-plane and through-thickness directions. Based on a quasi-3D shear and normal deformation plate theory and the modified strain gradient theory, a finite element model is proposed and employed to solve the problems of the multi-directional FG microplates with various boundary conditions. The verification is performed by comparing the numerical results with those from the previous studies. A number of numerical examples on the multi-directional FG microplates with nine boundary conditions and power-law index have been carried out. The effects of three material length scale parameters, aspect ratio, gradient indexes in spatial directions and boundary conditions on the displacements, natural frequencies and buckling loads of 1D, 2D and 3D-FG microplates are investigated in details. Some new results, which are not available in open literature, are provided as references for the future studies.

Generalized conforming Trefftz element for size-dependent analysis of thin microplates based on the modified couple stress theory

In this work, a new displacement-based Trefftz plate element is developed for size-dependent bending analysis of the thin plate structures in the context of the modified couple stress theory. This is achieved via two steps. First, the Trefftz functions, that are derived by introducing the thin plate bending assumptions into the three-dimensional governing equations of the modified couple stress elasticity, are adopted as the basis functions for designing the element's displacement interpolations. Second, the generalized conforming theory is employed to meet the interelement compatibility requirements in weak sense for ensuring the convergence property. The resulting 4-node displacement-based plate element performs like nonconforming models on coarse meshes and gradually converges into a conforming one with the mesh refinement. Numerical tests reveal that the new element can efficiently capture the size-dependent mechanical responses of thin microplates and exhibits satisfactory numerical accuracy and distortion tolerance. Moreover, as the element has only three degrees of freedom (DOF) per node, it can be easily incorporated into the commonly available finite element programs.

Applying nonlocal strain gradient theory to size-dependent analysis of functionally graded carbon nanotube-reinforced composite nanoplates

In this research paper, as initial endeavors, the vibrational responses of functionally graded carbon nanotube-reinforced composite (FG-CNTRC) nanoplates taking into account the effect of nonlocal parameter and strain gradient coefficient are investigated. The study aims at developing mathematical modeling via an analytical solution to FG-CNTRC nanoplate structure with allowance for the nonlocal strain gradient effect. The four types of CNT distribution are used and compared in the context of the vibration of nanoplate in the presence of the small length scale effects, namely the (a) UD, (b) FG-V, (c) FG-O, and (d) FG-X. Some theoretical equations based on the first-order shear deformation plate theory (FSDT) are presented to provide a lucid understanding of how the small length-scale influences the FG-CNTRC nanoplate. For the vibrational analysis of a nanoplate, which is simply supported boundary condition, Navier solutions are obtained. Also, in contrast to earlier studies, an analytical approach is used to establish the governing equations of the FG-CNTRC nanoplate. Some specific numerical examples are given and compared with the results presented in the literature. In the section of numerical results, the influence of the nonlocal parameter, strain gradient coefficient, geometric parameters and vibrational modes on the non-dimensional natural frequency are investigated and discussed in detail. These could be useful to analysts and designers to estimate the fundamental natural frequencies in each of the four CNT distributions that the FG-CNTRC nanoplate possesses.

Thermo-electro-mechanical buckling of FGP nano shell with considering thickness stretching effect based on size dependent analysis

Buckling analysis of functionally graded piezoelectric nanoshell is studied in this paper based on the higher-order shear and normal deformation theory and accounting thickness stretching effect. The nanoshell is subjected to axial load, applied electric potential and thermal loads. Thickness stretching effect is accounted in the analysis based on higher-order shear and normal deformation theory. Small scale effects are accounted based on the Eringen nonlocal elasticity theory. The Navier solution is used for the buckling analysis of the cylindrical nanoshell with simply-supported boundary conditions. The accuracy and trueness of the present paper is justified using comparison with literature. The importance of the present analysis and corresponding results is justified using presentation of results with and without thickness stretching effect. A large parametric analysis is presented to investigate the influence of significant parameters such as dimensionless small scale parameter, length to radius ratio, thickness to radius ratio, temperature rising and applied electric voltage on critical buckling axial loads. One can conclude that the critical buckling axial loads are decreased with increase of small scale parameters and applied electric potential.

Size Dependent Buckling Analysis of Hybrid Organic/Inorganic Nano-Sized I-Beam

In the paper, the size dependent buckling analysis of hybrid organic/inorganic nanobeam with I cross section is investigated. Eringen’s nonlocal elasticity theory is used to take the size effect into consideration. Comparative buckling loads of nanobeams for first ten modes is plotted in figure using Euler-Bernoulli theory and Eringen’s nonlocal elasticity theory. Two different size parameter is used. It is clearly demonstrated that the size effect can be neglected for first modes while it is unneglectable for higher modes. Simply supported case in investigated. The advantages of I-cross section are discussed.

Isogeometric nonlinear oscillations of nonlocal strain gradient PFGM micro/nano-plates via NURBS-based formulation

The present investigation deals with the size-dependent analysis of the geometrically nonlinear vibration response of micro/nano-plates with and without a central cutout made of a porous functionally graded material (PFGM) in the presence of nonlocality and strain gradient size dependencies. In accordance with this purpose, a modified porosity-dependent power-law function is put to use to estimate the effective mechanical properties of PFGM micro/nano-plates with various porosity distribution patterns. To solve the constructed nonlinear nonlocal strain gradient problem, the non-uniform rational B-spline (NURBS)-based isogeometric analysis is utilized as an efficient discretization technique having the capability to satisfy C−1 continuity. It is seen that for specific values of the material property gradient index, porosity index and the plate deflection, the enhancement in the nonlinear frequency due to the strain gradient size effect is more than the reduction caused by the nonlocality. Furthermore, it is found that there is a specific value of the length to thickness ratio, corresponding to which the nonlocal strain gradient frequency ratio becomes minimum. This minimum value enhances by increasing the value of the porosity index of PFGM micro/nano-plates. Also, by increasing the value of the material property gradient index, the minimum point of the nonlocal strain gradient frequency ratio shifts to a higher ratio of the length to width ratio.

Size-dependent analysis of a functionally graded piezoelectric micro-cylinder based on the strain gradient theory with the consideration of flexoelectric effect: plane strain problem

In this study, a size-dependent analysis of functionally graded piezoelectric (FGP) micro-rotating cylinder is presented based on the plane strain condition and strain gradient theory, which is a non-classical theory capable of capturing the size effect in microscaled structures. The present model is used to analyze the FGP micro-rotating cylinder with the consideration of flexoelectric effects exposed to a symmetric magneto-electro-mechanical loading. All mechanical and electrical properties are assumed to be graded in the thickness direction according to a power-law distribution. With respect to the fifth-order strain gradient coefficient and electromechanical coupling, the constitutive equations are obtained from electric Gibbs free energy density, which is a function of strain, second-order deformation gradient and electric field. By substituting the constitutive equations in electric and mechanical equilibrium equations, two coupled electromechanical governing differential equations in terms of radial displacement and electric potential are derived considering centrifugal force and Lorentz magnetic force obtained from Maxwell’s relations. The generalized differential quadrature method is proposed to solve the coupled governing differential equations. Numerical results attained from the strain gradient elasticity reveal the effects of flexoelectric, microstructural length scale, non-homogeneity constant, rotation and magnetic field on the response of the FGP micro-rotating cylinder.

Size-dependent mechanical-diffusion responses of multilayered composite nanoplates

ABSTRACT Multi-cell storage devices (e.g. lithium-ion batteries (LIBs)) stand as one of the most important components which are widely used in battery energy storage technology for renewable energy power system, hybrid electric vehicles and portable electronic devices due to its high energy density and low manufacturing cost. In recent years, there has been an explosion of developing new and multifunctional nanomaterials with particular interest to electrode nanomaterials (nano-MnO2, nano-LiMn2O4, etc.). In such case, size-dependent mechanical-diffusion responses analysis of multilayered composite nanostructure under non-uniform concentration in-service environment will become significantly important. To address the problem, a multilayered composite nanoplates account for diffusion impedance and elastic wave impedance at the interface is considered in this research. Governing equations involving with size-dependent characteristic lengths and material constant ratio of each two adjacent layers are formulated, and then, a semi-analytical approach via the Laplace transformation is applied. Then, the obtained solutions are applied to bilayered composite nanoplates, and the influences of size effects and material constants ratio on structural responses are emphatically discussed to provide guidelines on and new insights into the optimal design and management of mechanical responses and vibration control of nano-sized multi-cell storage devices under non-uniform concentration environment, especially for the nano-coating.

Analysis of size dependency on Love-type wave propagation in a functionally graded piezoelectric smart material

This study investigates Love-type wave propagation in a layered structure consisting of a functionally graded piezoelectric material (FGPEM) stratum followed by a semi-infinite couple-stress substrate exhibiting microstructural properties. Dispersion relations are obtained for electrically open and short conditions. Possible particular cases are discussed. The dispersion relation is reduced to the classical Love wave equation to validate the results. The influence of microstructural parameters, electromechanical coupling factor, thickness, functional gradedness and material parameters of the FGPEM stratum on the phase velocity of the Love-type wave has been scrutinized and illustrated graphically for electrically open and short conditions. The findings have meaningful practical application in the enhancement of efficiency and performance of sensors and transducers.

Static analysis of functionally graded composite shells on elastic foundations with nonlocal elasticity theory

The aim of this present work is to study the higher-order modelling of a cylindrical nano-shell resting on Pasternak’s foundation based on nonlocal elasticity theory. Third-order shear deformation theory is developed for modelling the kinematic relations, and nonlocal elasticity theory is developed for size-dependent analysis. The principle of virtual work is applied to derive static governing equations. The solution is presented for simply supported boundary conditions in terms of various important parameters. The numerical results including lower- and higher-order longitudinal and radial displacements are presented in terms of nonlocal parameter, two parameters of Pasternak’s foundation and some dimensionless geometric parameters such as length-to-radius ratio and length-to-thickness ratio.

On the isogeometric analysis of geometrically nonlinear shell structures with the consideration of surface energies

Presented in this article is a size-dependent analysis which is aimed to discover the surface stress effects on the large deformation characteristics of small-scaled shell structures. Consideration of surface energies in the micro/nanodimensions, and also in the cases of structures with high ratios of surface to volume like shells, significantly affects the predicted responses. To take the surface stress effects into account, it is assumed that the body is surrounded by thin surface layers at the top and bottom. The first-order shear deformation shell theory with seven parameters is adopted in the Lagrangian configuration system for the bulk part of structure. Also, the effects of surface stresses are captured based on the surface elasticity theory. Because of its unique features, IGA (isogeometric analysis) solution methodology is implemented to solve the governing equations. In this regard, the matrix–vector form of nonlinear relations, including the constitutive equations and energy functionals, is presented to directly utilize IGA for the problem. As case studies and also to show the main contribution of present investigation, i.e., studying the effects of surface energies on the mechanical behavior of geometrically nonlinear shells, the well-known benchmarks in the literature are studied in micro/nanodimensions with the consideration of surface influences.

A GN-based modified model for size-dependent coupled thermoelasticity analysis in nano scale, considering nonlocality in heat conduction and elasticity: An analytical solution for a nano beam with energy dissipation

This investigation deals with a size-dependent coupled thermoelasticity analysis based on Green-Naghdi (GN) theory in nano scale using a new modified nonlocal model of heat conduction, which is based on the GN theory and nonlocal Eringen theory of elasticity. In the analysis based on the proposed model, the nonlocality is taken into account in both heat conduction and elasticity. The governing equations including the equations of motion and the energy balance equation are derived using the proposed model in a nano beam resonator. An analytical solution is proposed for the problem using the Laplace transform technique and Talbot technique for inversion to time domain. It is assumed that the nano beam is subjected to sinusoidal thermal shock loading, which is applied on the one of beam ends. The transient behaviors of fields\' quantities such as lateral deflection and temperature are studied in detail. Also, the effects of small scale parameter on the dynamic behaviors of lateral deflection and temperature are obtained and assessed for the problem. The proposed GN-based model, analytical solution and data are verified and also compared with reported data obtained from GN coupled thermoelasticity analysis without considering the nonlocality in heat conduction in a nano beam.

3-D magneto-electro-thermal analysis of layered nanoplate including porous core nanoplate and piezomagnetic face-sheets

In the present article, three-dimensional size dependent thermal analysis of three-layered nanoplate with porous graded core and two piezomagnetic face-sheets is studied based on nonlocal strain gradient theory considering thickness stretching effect. The sandwich nanoplate standing on an elastic foundation and face layers are exposed to electric/magnetic potentials. Porosity is evenly and unevenly repartitioned thorough thickness of the core. To predict both reduction and enhancement of stiffness in small scales, a nonlocal parameter and a strain gradient parameter is used for analysis. The governing equations are derived using the principle of virtual works based on sinusoidal shear and normal deformation theory. The small size effect is obtained exploiting Eringen’s nonlocal elasticity theory. The influences of the porosity coefficient, temperature parameters, electric/magnetic potential, boundary conditions (simply supported and clamped) and parameters of foundation on bending, electrical, and magnetic behaviors of the sandwich nanoplate are presented and discussed.

Analysis of Prediction Results and Grid Size Dependence According to Changes in Fire Area

건축물의 í™”ìž¬ì•ˆì „ì„±í‰ê°€ë¥¼ 위한 í™”ìž¬ì‹œë®¬ë ˆì´ì ˜ì—ì„œ í™”ì›ë©´ì  및 격자크기의 변화는 예측결과에 큰 영향을 ë¯¸ì¹ ìˆ˜ 있다. 따라서 동일한 최대 ì—´ë°œìƒë¥ ì„ 갖는 화원의 ë©´ì  변화가 구획화재의 예측결과에 미치는 영향이 ê²€í† ë˜ì—ˆìœ¼ë©°, 동일한 í™”ì›ë©´ì ì˜ 조건에서 격자크기에 대한 예측결과의 의존도가 동시에 ê²€í† ë˜ì—ˆë‹¤. 주요 결과로서, 특성화재직경을 기준으로 6개 이상의 격자가 ì‚½ìž ë˜ë©´ í™”ì›ë©´ì ì´ 변화되더라도 격자크기는 화재의 열 및 í™”í•™ì  특성에 큰 영향을 미치지 않았다. 또한 í™”ì›ë©´ì ì˜ 변화는 구획 내부에서 허용피난시간(ASET)ê³¼ ê´€ë ¨ëœ 주요 물리량의 예측결과에 상당한 차이를 야기하였다. 그러나 개구부를 기준으로 ì¼ì • 거리 이상의 구획외부에서는 í™”ì›ë©´ì ì˜ 변화가 ì „ë°˜ì  화재특성에 미치는 영향이 크지 않음이 확인되었다.

Third-order electro-elastic analysis of sandwich doubly curved piezoelectric micro shells

The present paper studies size dependent electro-elastic analysis of sandwich doubly curved piezoelectric micro shells. The structure is composed of a micro elastic core and two piezoelectric micro layers as sensor and actuator. The kinematic relations are developed based on third-order shear deformation theory proposed by Reddy. The principle of virtual work is used to derive governing equations in terms of primary displacements, rotation components, and electric potential. The sandwich doubly curved micro shell is resting on Pasternak’s foundation. After verification of numerical results, the analytical results are presented in terms of important parameters such as micro length scale parameter, applied electric potential, and some geometric parameters of the problem. The numerical results indicate that the in-plane deformation and out of plane displacement are decreased with increase of micro length scale parameter and decrease of applied electric potential.

Nonlinear size dependent analysis and effectiveness of nanocrystalline micro/nanogyroscopes

Vibratory micro/nanogyroscopes made of nanocrystalline silicon have a complex microstructure consisting of grains, voids, and interface material phases. Given that the length scale of such inertial sensors is close to the size of the grains themselves, classical continuum mechanics theories are no longer adequate to accurately model the dynamic behaviors of these sensors. In this work, the couple stress and surface elasticity are incorporated to the governing equations of an electrically-actuated, amplitude-based, capacitive sensing cantilever gyroscope to obtain a comprehensive model of the nano-system. Then, the impact of the size dependent effects on the nonlinear dynamic behavior of the gyroscope is investigated by studying its performance for gyroscopes ranging in size from the micro-to the nano-scale. The present numerical study shows that the additional stiffness contributions from the couple stress and surface elasticity and changes in scale cause significant changes in the frequency response, nonlinear behaviors, and sensitivity of the gyroscope to the rotation rates. This numerical analysis demonstrates the importance of accounting for size dependent effects for micro/nanogyroscopes in order to avoid any deterioration of the effectiveness of the gyroscope operability. • Differential quadrature method is utilized to discretize the governing equations of micro/nanogyroscopes. • Impact of the size dependent effects on the nonlinear dynamic behavior of the gyroscope is investigated. • Couple stress and surface elasticity cause significant changes in the gyroscope's performance. • Size dependent effects must be considered to avoid any deterioration of the gyroscope operability.

Size dependent analysis of tapered FG micro-bridge based on a 3D beam theory

In the current study, an analytical solution based on the modified couple stress theory for a nonlinear model describing the couple 3D motion of a functionally graded tapered micro-bridge is presented. The small scale effects and the nonlinearity arising from the mid-plane stretching are taken into consideration. Governing equations of motions are derived utilizing the modified couple stress theory and applying Hamilton principle. Dynamic and static analyses to determine the effects of lateral distributed forces and mid-plane stretching are investigated. To this aim, analytical Homotopy-pade technique is employed to capture the nonlinear natural frequencies in high amplitude vibrations of tapered micro-bridges with different types of geometries and material compositions. The obtained results of frequencies propose that there is a good agreement between the present analytical results and the numerical ones in opposed to well-known multiple-scale method. Furthermore, comparing the results in 2D and 3D analyses shows that in 2D analysis, the stiffness and natural frequency of the micro-beam is underestimated and it is found that increasing the tapered ratio has different impacts on natural frequencies for micro-beams with different slender ratios.

Accuracy of standard clinical 3T prostate MRI for pelvic lymph node staging: Comparison to68Ga-PSMA PET-CT

The aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1–88.9%), 98.6% (CI 97.6–99.2%), 73.5% (CI 52.1–87.6%) and 99.5% (CI 98.8–99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT.