Modelling adhesive contact problems involving a layered elastic solid and cylindrical indenter using Lennard Jones potential

This paper presents an iterative algorithm that solves for the displacement and sub-surface stresses induced within a layered elastic solid adhering to a rigid cylindrical indenter under lightly loaded conditions. The solid is assumed to comprise a functionally graded coating of finite thickness bonded to a homogeneous substrate of infinite extent and is assumed to be in a state of plane strain which allows a two-dimensional analysis to be performed. The Lennard–Jones potential is used to model the adhesive force acting between the indenter and solid whilst the effects of surface adhesion are characterised using Tabor’s parameter. A selection of numerical results for the adhesive contact problem are presented which indicate that the maximum pressure and induced sub-surface stresses increase dramatically as Tabor’s parameter increases. It is also found that the shear modulus and thickness of the coating have a significant effect on material behaviour with harder coatings experiencing significantly larger tensile stresses but smaller surface displacement than softer coatings. The present investigation allows us to deduce that at smaller scales, surface adhesion can be instrumental in causing wear or potential material failure if coatings are improperly designed

Analysing the effects of sliding, adhesive contact on the deformation and stresses induced within a multi-layered elastic solid

This paper presents a mathematical model of sliding, adhering contact between a rigid parabolic indenter and a multi-layered elastic solid, which is assumed to comprise of a homogeneous coating bonded through a functionally-graded transitional layer to a homogeneous substrate. The adhesive forces in this investigation are modelled using Lennard-Jones potential and an iterative algorithm is proposed that solves for the contact pressure, surface displacement and sub-surface stresses resultant within the layered solid. The effects of surface adhesion and different material properties such as varying coating/transition layer thickness and coating hardness on the solution of the contact problem are subsequently investigated in detail. The numerical approach presented in this paper demonstrates the significance of having a suitable mathematical representation for the traction distribution along the sliding, adhering contact. It is found that under weakly adhering conditions, the assumption of only Coulombic traction suffices to determine the displacements and subsurface stresses within the multi-layered solid. However, it is noted that stress concentrations within the material begin to propagate through all three layers of the elastic solid with increased surface adhesion, which could potentially induce plasticity and lead to material ploughing under sliding. The proposed model allows us to further investigate and improve our understanding of the combined effects of traction and boundary adhesion in sliding contacts, which can be used to inform the design of materials needed in such conditions

On the two-dimensional solution of both adhesive and non-adhesive contact problems involving functionally graded materials

This paper presents a semi-analytical algorithm for the determination of the contact half width and surface pressure which results from both adhesive and non-adhesive contact problems involving functionally graded materials (FGM). The inhomogeneously elastic solid comprises a graded elastic coating whose shear modulus depends exponentially on the vertical coordinate and a homogeneously elastic substrate. The solid is assumed to be in a state of plane strain and thus a two-dimensional analysis is performed within this work.Using the work of Chidlow etal. (2011a) as a starting point, we derive a pair of integral equations which may be used to determine approximations to the contact pressure when either the surface deflection or the deflection gradient is known over the contact region. As these integral equations are non-singular, we use Galerkin's method to approximate the contact pressure and it is found that relatively small trial spaces allow accurate computation of the pressure. Information about the prescribed load is then used to formulate an iterative algorithm to determine the contact half width.A selection of numerical results are presented using this method and it is found that the solutions computed here compare favourably with those of other authors. A further investigation is then conducted into the solution of adhesive contact problems using the assumptions of Maugis (1992) and Johnson and Greenwood (2008) to inform the nature of the adhesive stresses outside of the contact. It is found that both JKR-like and DMT-like behaviour can be observed in contact problems involving FGMs

A solution method for the sub-surface stresses and local deflection of a semi-infinite inhomogeneous elastic medium

This paper proposes analytical Fourier series solutions (based on the Airy stress function) for the local deflection and subsurface stress field of a two-dimensional graded elastic solid loaded by a pre-determined pressure distribution. We present a selection of numerical results for a simple sinusoidal pressure which indicates how the inhomogeneity of the solid affects its behaviour. The model is then adapted and used to derive an iterative algorithm which may be used to solve for the contact half width and pressure induced from contact with a rigid punch. Finally, the contact of a rigid cylindrical stamp is studied and our results compared to those predicted by Hertzian theory. It is found that solids with a slowly varying elastic modulus produce results in good agreement with those of Hertz whilst more quickly varying elastic moduli which correspond to solids that become stiffer below the surface give rise to larger maximum pressures and stresses whilst the contact pressure is found to act over a smaller area

Modelling the effects of glucagon during glucose tolerance testing

Background Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. Results Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). Conclusions The models are used to investigate how different degrees of pax‘tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted

The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma

The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas

Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

Cancer-like metabolism of the mammalian retina

The retina, like many cancers, produces energy from glycolysis even in the presence of oxygen. This phenomenon is known as aerobic glycolysis and eponymously as the Warburg effect. In recent years, the Warburg effect has become an explosive area of study within the cancer research community. The expanding knowledge about the molecular mechanisms underpinning the Warburg effect in cancer promises to provide a greater understanding of mammalian retinal metabolism and has motivated cancer researchers to target the Warburg effect as a novel treatment strategy for cancer. However, if the molecular mechanisms underlying the Warburg effect are shared by the retina and cancer, treatments targeting the Warburg effect may have serious adverse effects on retinal metabolism. Herein, we provide an updated understanding of the Warburg effect in mammalian retina.Soo Khai Ng, John PM Wood, Glyn Chidlow, Guoge Han, Thaksaon Kittipassorn, Daniel J Peet and Robert J Casso

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Modelling the effects of glucagon during glucose tolerance testing.

From Europe PMC via Jisc Publications RouterHistory: ppub 2019-12-01, epub 2019-12-12Publication status: PublishedBACKGROUND:Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. RESULTS:Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). CONCLUSIONS:The models are used to investigate how different degrees of pax'tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted