Creep crack-growth: A new path-independent integral (T sub c), and computational studies

The development of valid creep fracture criteria is considered. Two path-independent integral parameters which show some degree of promise are the C* and (Delta T)sub c integrals. The mathematical aspects of these parameters are reviewed by deriving generalized vector forms of the parameters using conservation laws which are valid for arbitrary, three dimensional, cracked bodies with crack surface tractions (or applied displacements), body forces, inertial effects, and large deformations. Two principal conclusions are that (Delta T)sub c has an energy rate interpretation whereas C* does not. The development and application of fracture criteria often involves the solution of boundary/initial value problems associated with deformation and stresses. The finite element method is used for this purpose. An efficient, small displacement, infinitesimal strain, displacement based finite element model is specialized to two dimensional plane stress and plane strain and to power law creep constitutive relations. A mesh shifting/remeshing procedure is used for simulating crack growth. The model is implemented with the quartz-point node technique and also with specially developed, conforming, crack-tip singularity elements which provide for the r to the n-(1+n) power strain singularity associated with the HRR crack-tip field. Comparisons are made with a variety of analytical solutions and alternate numerical solutions for a number of problems

Creep crack-growth: A new path-independent T sub o and computational studies

Two path independent integral parameters which show some degree of promise as fracture criteria are the C* and delta T sub c integrals. The mathematical aspects of these parameters are reviewed. This is accomplished by deriving generalized vector forms of the parameters using conservation laws which are valid for arbitrary, three dimensional, cracked bodies with crack surface tractions (or applied displacements), body forces, inertial effects and large deformations. Two principal conclusions are that delta T sub c is a valid crack tip parameter during nonsteady as well as steady state creep and that delta T sub c has an energy rate interpretation whereas C* does not. An efficient, small displacement, infinitestimal strain, displacement based finite element model is developed for general elastic/plastic material behavior. For the numerical studies, this model is specialized to two dimensional plane stress and plane strain and to power law creep constitutive relations

Stress and Fracture Analyses Under Elastic-plastic and Creep Conditions: Some Basic Developments and Computational Approaches

A new hybrid-stress finite element algorith, suitable for analyses of large quasi-static deformations of inelastic solids, is presented. Principal variables in the formulation are the nominal stress-rate and spin. A such, a consistent reformulation of the constitutive equation is necessary, and is discussed. The finite element equations give rise to an initial value problem. Time integration has been accomplished by Euler and Runge-Kutta schemes and the superior accuracy of the higher order schemes is noted. In the course of integration of stress in time, it has been demonstrated that classical schemes such as Euler's and Runge-Kutta may lead to strong frame-dependence. As a remedy, modified integration schemes are proposed and the potential of the new schemes for suppressing frame dependence of numerically integrated stress is demonstrated. The topic of the development of valid creep fracture criteria is also addressed

HIV and Cocaine Impact Glial Metabolism: Energy Sensor AMP-activated protein kinase Role in Mitochondrial Biogenesis and Epigenetic Remodeling

HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF. Results showed that cocaine exposure during HIV infection significantly increased the level of p24, reactive oxygen species (ROS), ATP-utilization and upregulated energy sensor AMPKs, CDC25B/C, MAP/Tau and Wee1 protein expression. Increased ROS production subsequently inhibits OCR/ECAR ratio and OXPHOS, and eventually upregulate epigenetics remodeling complex SWI/SNF in CHME-5 cells. These results suggest that HIV infection induced energy deficit and metabolic dysfunction is accelerated by cocaine inducing energy sensor AMPKs, mitochondrial biogenesis and chromatin remodeling complex SWI/SNF activation, which may lead to neuroAIDS disease progression

An explicit total Lagrangian Fragile Points Method for finite deformation of hyperelastic materials

This research explored a novel explicit total Lagrangian Fragile Points Method (FPM) for finite deformation of hyperelastic materials. In contrast to mesh-based methods, where mesh distortion may pose numerical challenges, meshless methods are more suitable for large deformation modelling since they use enriched shape functions for the approximation of displacements. However, this comes at the expense of extra computational overhead and higher-order quadrature is required to obtain accurate results. In this work, the novel meshless method FPM was used to derive an explicit total Lagrangian algorithm for finite deformation. FPM uses simple one-point integration for exact integration of the Galerkin weak form since it employs simple discontinuous polynomials as trial and test functions, leading to accurate results even with single-point quadrature. The proposed method was evaluated by comparing it with FEM in several case studies considering both the extension and compression of a hyperelastic material. It was demonstrated that FPM maintained good accuracy even for large deformations where FEM failed to converge

Brucella abortus Infection of Placental Trophoblasts Triggers Endoplasmic Reticulum Stress-Mediated Cell Death and Fetal Loss via Type IV Secretion System-Dependent Activation of CHOP.

Subversion of endoplasmic reticulum (ER) function is a feature shared by multiple intracellular bacteria and viruses, and in many cases this disruption of cellular function activates pathways of the unfolded protein response (UPR). In the case of infection with Brucella abortus, the etiologic agent of brucellosis, the unfolded protein response in the infected placenta contributes to placentitis and abortion, leading to pathogen transmission. Here we show that B. abortus infection of pregnant mice led to death of infected placental trophoblasts in a manner that depended on the VirB type IV secretion system (T4SS) and its effector VceC. The trophoblast death program required the ER stress-induced transcription factor CHOP. While NOD1/NOD2 expression in macrophages contributed to ER stress-induced inflammation, these receptors did not play a role in trophoblast death. Both placentitis and abortion were independent of apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain (ASC). These studies show that B. abortus uses its T4SS to induce cell-type-specific responses to ER stress in trophoblasts that trigger placental inflammation and abortion. Our results suggest further that in B. abortus the T4SS and its effectors are under selection as bacterial transmission factors.IMPORTANCE Brucella abortus infects the placenta of pregnant cows, where it replicates to high levels and triggers abortion of the calf. The aborted material is highly infectious and transmits infection to both cows and humans, but very little is known about how B. abortus causes abortion. By studying this infection in pregnant mice, we discovered that B. abortus kills trophoblasts, which are important cells for maintaining pregnancy. This killing required an injected bacterial protein (VceC) that triggered an endoplasmic reticulum (ER) stress response in the trophoblast. By inhibiting ER stress or infecting mice that lack CHOP, a protein induced by ER stress, we could prevent death of trophoblasts, reduce inflammation, and increase the viability of the pups. Our results suggest that B. abortus injects VceC into placental trophoblasts to promote its transmission by abortion

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: Insights from the canadian biomarker integration network in depression

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We presentthe insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND). CAN-BIND is a multi-site, multi-investigator, and multiproject network supported by the Ontario Brain Institute with access to Brain-CODE, an informatics platform that hosts a multitude of biological data across a growing list of brain pathologies. We describe our approaches and insights on documenting and standardizing parameters across the study design, data collection, monitoring, analysis, integration, knowledge-translation, and data archiving phases of CAN-BIND projects. We introduce a custom-built EEG toolbox to track data preprocessing with open-access for the scientific community. We also evaluate the impact of variation in equipment setup on the accuracy of acquired data. Collectively, this work is intended to inspire establishing comprehensive and standardized guidelines for multi-site studies

Short-term oral administration of non-porous and mesoporous silica did not induce local or systemic toxicity in mice

In this study, two sets of methyl-coated non-porous and mesoporous amorphous silica materials of two target sizes (100 and 300 nm; 10–844 m2/g) were used to investigate the potential role of specific surface area (SSA) and porosity on the oral toxicity in mice. Female Swiss mice were administered by oral gavage for 5 consecutive days. Two silica dose levels (100 and 1000 mg/kg b.w.) were tested for all four materials. All dispersions were characterized by transmission electron microscopy (TEM) and Nanoparticle tracking analysis (NTA). Batch dispersions of porous silica were rather unstable due to agglomeration. Animals were sacrificed one day after the last administration or after a three-week recovery period. No relevant toxicological effects were induced by any of the silica materials tested, as evaluated by body weight, gross pathology, relative organ weights (liver, spleen, kidneys), hematology, blood biochemistry, genotoxicity (Comet assay in jejunum cells and micronucleus test in peripheral blood erythrocytes), liver and small intestine histopathology, and intestinal inflammation. The presence of silica particles in the intestine was evaluated by a hyperspectral imaging microscopy system (CytoViva) using histological samples of jejunum tissue. Silica spectral signatures were found in jejunum samples with all the treatments, but only statistically significant in one of the treatment groups

Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack

AbstractNeuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics