Nonlocal stress gradient formulation for damping vibration analysis of viscoelastic microbeam in thermal environment

An integral nonlocal stress gradient viscoelastic model is proposed on the basis of the integral nonlocal stress gradient model and the standard viscoelastic model,and is utilized to investigate the free damping vibration analysis of the viscoelastic BernoulliEuler microbeams in thermal environment.Hamilton's principle is used to derive the differential governing equations and corresponding boundary conditions.The integral relations between the strain and the nonlocal stress are converted into a differential form with constitutive constraints.The size-dependent axial thermal stress due to the variation of the environmental temperature is derived explicitly.The Laplace transformation is utilized to obtain the explicit expression for the bending deflection and moment.Considering the boundary conditions and constitutive constraints,one can get a nonlinear equation with complex coefficients,from which the complex characteristic frequency can be determined.A two-step numerical method is proposed to solve the elastic vibration frequency and the damping ratio.The effects of length scale parameters,viscous coefficient,thermal stress,vibration order on the vibration frequencies,and critical viscous coefficient are investigated numerically for the viscoelastic Bernoulli-Euler microbeams under different boundary conditions.

Three-Dimensional Analysis of Rolling by Twin Shear Stress Yield Criterion

Using the twin shear stress yield criterion, the surface integral of the co-line vectors, and the integration depending on upper limit, Kobayashi＇s three-dimensional velocity field of rolling was analyzed and an analytical expression of rolling torque and single force was obtained. Through redoing the same experiment of rolling pure lead as Sims, the calculated results by the above expression were compared with those of Kobayashi and Sims formulae. The results show that the twin shear stress yield criterion is available for rolling analysis and the calculated results by the new formula are a little higher than those by Kobayashi and Sims ones if the reduction ratio is less than 30%.

Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase（PERK）, eukaryotic initiation factor 2-alpha（eIF2α） and activating transcription factor 4（ATF4）. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone（0.1, 1, 10, 100 μM） treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated（p）-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

Evaluation of strongly singular domain integrals for internal stresses in functionally graded materials analyses using RIBEM

An accurate evaluation of strongly singular domain integral appearing in the stress representation formula is a crucial problem in the stress analysis of functionally graded materials using boundary element method.To solve this problem,a singularity separation technique is presented in the paper to split the singular integral into regular and singular parts by subtracting and adding a singular term.The singular domain integral is transformed into a boundary integral using the radial integration method.Analytical expressions of the radial integrals are obtained for two commonly used shear moduli varying with spatial coordinates.The regular domain integral,after expressing the displacements in terms of the radial basis functions,is also transformed to the boundary using the radial integration method.Finally,a boundary element method without internal cells is established for computing the stresses at internal nodes of the functionally graded materials with varying shear modulus.

Implicit scheme for integrating constitutive model of unsaturated soils with coupling hydraulic and mechanical behavior

A constitutive model of unsaturated soils with coupling capillary hystere- sis and skeleton deformation is developed and implemented in a fully coupled transient hydro-mechanical finite-element model （computer code U-DYSAC2）. The obtained re- sults are compared with experimental results, showing that the proposed constitutive model can simulate the main mechanical and hydraulic behavior of unsaturated soils in a unified framework. The non-lineaxity of the soil-water characteristic relation is treated in a similar way of elastoplasticity. Two constitutive relations axe integrated by an implicit return-mapping scheme similar to that developed for saturated soils. A consistent tan- gential modulus is derived to preserve the asymptotic rate of the quadratic convergence of Newton＇s iteration. Combined with the integration of the constitutive model, a complete finite-element formulation of coupling hydro-mechanical problems for unsaturated soils is presented. A number of practical problems with different given initial and boundary conditions are analyzed to illustrate the performance and capabilities of the finite-element model.

Analytic Expression of Meso-Criterion on Dynamic Fracture

This study presents a meso-criterion of dynamic fracture, on the basis of stress in integral form In such way the difficulty due to the singularity of stress distribution at the crack tip is overcome. A micro-parameter, the atom radius, is introduced into the criterion.Meanwhile a characteristic time concept is taken into account for describing the inertia effect of material. The criterion reveals The criterion reveals the effects of loading rate, defect and sample geometry,material constants including the micro-structure parameter.

Analysis of mode Ⅲ crack perpendicular to the interface between two dissimilar strips

The present work is concerned with the problem of mode Ⅲ crack perpendicular to the interface of a bi-strip composite. One of these strips is made of a functionally graded material and the other of an isotropic material, which contains an edge crack perpendicular to and terminating at the interface. Fourier transforms and asymptotic analysis are employed to reduce the problem to a singular integral equation which is numerically solved using Gauss-Chebyshev quadrature formulae. Furthermore, a parametric study is carried out to investigate the effects of elastic and geometric characteristics of the composite on the values of stress intensity factor.

Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe^(-/-)mice

Atherosclerosis is the major contributor to cardiovascular mortality worldwide.Alternate day fasting(ADF)has gained growing attention due to its metabolic benefits.However,the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models.The present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient(Apoe^(-/-))mice.Eleven-week-old male Apoe^(-/-)mice fed with Western diet(WD)were randomly grouped into ad libitum(AL)group and ADF group,and ADF aggravated both the early and advanced atherosclerotic lesion formation,which might be due to the disturbed cholesterol profiles caused by ADF intervention.ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response(ISR)in the liver.The hepatic expression of activating transcription factor 3(ATF3)was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^(-/-)mice.Moreover,the expression of ATF3 could be regulated by Krüppel-like factor 6(KLF6)and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway.In conclusion,ADF aggravates atherosclerosis progression in Apoe^(-/-)mice fed on WD.ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6,subsequently inhibiting ATF3 expression.The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^(-/-)mice.The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.

Understanding Plant Development and Stress Responses through Integrative Approaches

As the name reflects, integrative plant biology is the core topic of JIPB. In the past few years JIPB has been pursuing the development of this area, to assist the scientific community to bring together all possible research tools to understand plant growth, development and stress responses in micro- and macro-scales. As part of these efforts, JIPB and Yantai University organized the 1st International Symposium on Integrative Plant Biology in the seaside town of Yantai during August 10-12, 2009 （Figure 1） The symposium was co-sponsored by Botanical Society of China, Chinese Society for Cell Biology, Genetics Society of China, and Chinese Society for Plant Physiology.

Minimizing stress concentrations around an elliptical hole by concentrated forces acting on the uniaxially loaded plate

When concentrated forces are applied at any points of the outer region of an ellipse in an infinite plate, the complex potentials are determined using the conformal mapping method and Cauchy＇s integral formula. And then, based on the superposition principle, the analyt- ical solutions for stress around an elliptical hole in an infinite plate subjected to a uniform far-field stress and concentrated forces, are obtained. Tangential stress concentration will occur on the hole boundary when only far-field uniform loads are applied. When concen- trated forces are applied in the reversed directions of the uniform loads, tangential stress concentration on the hole boundary can be released significantly. In order to minimize the tangential stress concentration, we need to determine the optimum positions and values of the concentrated forces. Three different optimization methods are applied to achieve this aim. The results show that the tangential stress can be released significantly when the op- timized concentrated forces are applied.

Intraneuronal tau aggregation induces the integrated stress response in astrocytes

Progressive aggregation of tau protein in neurons is associated with neurodegeneration in tauopathies.Cell non-autonomous disease mechanisms in astrocytes may be important drivers of the disease process but remain largely elusive.Here,we studied cell type-specific responses to intraneuronal tau aggregation prior to neurodegeneration.To this end,we developed a fully human co-culture model of seed-independent intraneuronal tau pathology,which shows no neuron and synapse loss.Using high-content microscopy,we show that intraneuronal tau aggregation induces oxidative stress accompanied by activation of the integrated stress response specifically in astrocytes.This requires the direct co-culture with neurons and is not related to neurodegeneration or extracellular tau levels.Tau-directed antisense therapy reduced intraneuronal tau levels and aggregation and prevented the cell non-autonomous responses in astrocytes.These data identify the astrocytic integrated stress response as a novel disease mechanism activated by intraneuronal tau aggregation.In addition,our data provide the first evidence for the efficacy of tau-directed antisense therapy to target cell autonomous and cell non-autonomous disease pathways in a fully human model of tau pathology.

Mitochondrial complex Ⅰ as a therapeutic target for Alzheimer’s disease

Alzheimer’s disease(AD),the most prominent form of dementia in the elderly,has no cure.Strategies focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical trials.Novel therapeutic targets and strategies are urgently needed.Emerging data suggest that in response to environmental stress,mitochondria initiate an integrated stress response(ISR)shown to be beneficial for healthy aging and neuroprotection.Here,we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ISR.Specifically,partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions,including AD,with several small molecules being tested in clinical trials.We discuss current understanding of the molecular mechanisms involved in this counterintuitive approach.Since this strategy has also been shown to enhance health and life span,the development of safe and efficacious complex Ⅰ inhibitors could promote healthy aging,delaying the onset of age-related neurodegenerative diseases.

Homeostatic responses to amino acid insufficiency

This article provides a brief overview describing how two key signaling pathways, namely the integrated stress response and the mammalian target of rapamycin complex 1, work together to facilitate cellular adaptation to dietary amino acid insufficiency. A deeper understanding of these mechanisms is leading to identification of novel targets which aid in disease treatments, improve stress recovery and increase health span through slowed aging and enhanced metabolic fitness.

NUMERICAL SOLUTIONS FOR A NEARLY CIRCULAR CRACK WITH DEVELOPING CUSPS UNDER SHEAR LOADING

In this paper, we study the behavior of the solution at the crack edges for a nearly circular crack with developing cusps subject to shear loading. The problem of finding the resulting force can be written in the form of a hypersingular integral equation. The equation is then trans-formed into a similar equation over a circular region using conformal mapping. The equation is solved numerically for the unknown coefficients, which will later be used in finding the stress intensity factors. The sliding and tearing mode stress intensity factors are evaluated for cracks and displayed graphically. Our results seem to agree with the existing asymptotic solution.