Trapezoid stress fracture in an international shot-putter: a case report.

Trapezoid fractures are relatively rare upper limb fractures. The case report of a trapezoid stress fracture in the dominant hand of a 22 year old international standard shot-putter is presented.

Microstructure and high cycle fatigue fracture surface of a Ti-5Al-5Mo-5V-1Cr-1Fe titanium alloy

Because of the requirements for the damage tolerance and fatigue life of commercial aircraft components, the high cycle fatigue (HCF) properties of Ti–5Al–5Mo–5V–1Cr–1Fe titanium alloy forgings are important. The effects of microstructure types of the α+β titanium alloy on fatigue properties need to be understood. In this paper, by analysing the fracture surfaces of the titanium alloy having four types of microstructure, the effects of microstructure are investigated. The differences of initiation areas and crack propagation among different microstructures were studied. It was found that the area of the initiation region decreases in the order of coarse basketweave, fine basketweave, Widmanstätten, and bimodal microstructure.

Investigation of chip formation and fracture toughness in orthogonal cutting of UD-CFRP

Features of chip formation can inform the mechanism of a machining process. In this paper, a series of orthogonal cutting experiments were carried out on unidirectional carbon fiber reinforced polymer (UD-CFRP) under cutting speed of 0.5 m/min. The specially designed orthogonal cutting tools and high-speed camera were used in this paper. Two main factors are found to influence the chip morphology, namely the depth of cut (DOC) and the fiber orientation (angle 휃), and the latter of which plays a more dominant role. Based on the investigation of chip formation, a new approach is proposed for predicting fracture toughness of the newly machined surface and the total energy consumption during CFRP orthogonal cutting is introduced as a function of the surface energy of machined surface, the energy consumed to overcome friction, and the energy for chip fracture. The results show that the proportion of energy spent on tool-chip friction is the greatest, and the proportions of energy spent on creating new surface decrease with the increasing of fiber angle.

Measurement of fibre fracture toughness using an alternative specimen geometry

This paper presents an experimental and numerical study focused on the tensile fibre fracture toughness characterisation of hybrid plain weave composite laminates using non-standardized Overheight Compact Tension (OCT) specimens. The position as well as the strain field ahead of the crack tip in the specimens was determined using a digital speckle photogrammetry system. The limitation on the applicability of standard data reduction schemes for the determination of the intralaminar fibre fracture toughness of composites is presented and discussed. A methodology based on the numerical evaluation of the strain energy release rate using the J-integral method is proposed to derive new geometric correction functions for the determination of stress intensity factor for alternative composite specimen geometries. A comparison between different methods currently available to compute the intralaminar fracture toughness in composites is also presented and discussed. Good agreement between numerical and experimental results using the proposed methodology was obtained.

Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications

Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

CGRP-cleavage enzyme detection using a biotinylated hydroxymate affinity probe

Introduction: Neuropeptides contribute to the pathophysiology of peripheral inflammation and a neurogenic component has been described for many inflammatory diseases, including periodontitis. Neuropeptides are susceptible to cleavage by peptidases and therefore the exact location and level of expression of peptidases are major determinants of neuropeptide action. Previous studies by our research group suggested that levels of the neuropeptide calcitonin gene-related peptide (CGRP) may be regulated by peptidases present in gingival crevicular fluid (GCF). Objectives: The aim of this work was to purify and partially characterize the GCF enzyme responsible for CGRP degradation using a biotinylated hydroxymate affinity probe (based on the P1-P4 amino acid sequence of the observed cleavage site) which we previously showed to inhibit CGRP degradation. Methods: Pooled healthy and pooled periodontitis GCF samples were subject to a pre-clear step with magnetic streptavadin beads. Healthy and diseased samples were incubated with the biotinylated hydroxymate probe (20 uM) after which biotinylated proteins were purified from the sample using magnetic streptavadin beads. Bound proteins were subjected to SDS-PAGE and western blotting. Biotin incorporated proteins were disclosed using a streptavadin horse radish peroxidase conjugate. Results: A band was disclosed in the periodontitis pooled sample at a molecular weight of approximately 60 kDa. The band was absent in the pooled healthy samples. As expected, when periodontitis samples were pre-boiled to denature proteins before the addition of the hydroxymate probe, no biotin incorporated band was present. Conclusions: This work demonstrates the purification and disclosure of a protein found specifically in periodontitis which binds to the specific biotinylated hydroxymate affinity probe based on the cleavage site of CGRP only when in its native form. We intend to scale up the sample size thus allowing the identification of the putative CGRP degrading peptidase using MALDI-mass spectrometry.
Funded by an IADR/GlaxoSmithKline Innovation in Oral Care Award

Doxorubicin induces the cleavage of Poly (ADP-ribose) polymerase, a marker of programmed cell death (apoptosis) in mouse cardiomyocytes

Cancer is one of the leading causes of death in the world. Despite this, a growing number of people are surviving the disease due to medical advancements and the development of numerous new therapies. Doxorubicin, a chemotherapeutic agent, is a widely-used and successful first-line anti-tumour treatment. However, the established toxic and deleterious effects of the drug on the cardiovascular system confer increased risk of congestive heart failure, thereby necessitating the use of reduced doxorubicin doses. In order to investigate how these events are initiated, mouse cardiomyocytes (HL-1) were treated in vitro with varying concentrations of doxorubicin (0.5-4.0 µmol/L). Following treatment (24h), a marked level of cell death was observed in comparison to untreated cardiomyocytes; the level of death appeared to correlate with the concentration of the drug used. Western blotting revealed the cleavage of full length Poly (ADP-ribose) polymerase (PARP) into 89 and 24kDa fragments, a process which is instrumental in triggering programmed cell death/apoptosis. Importantly, results suggested that this event may be independent of caspase 3 cleavage and thus activation. A number of previous studies have reported a functional role for both Mitofusin-2 (Mfn2) and NADPH oxidase 2 (Nox2) in the cardiotoxic response. Given that PARP cleavage is a validated indicator of cellular apoptosis, these results clearly indicate that this marker could be used in future studies when determining if depletion of the above proteins would cause a reduction in or eradicate the pro-apoptotic action of this agent on cardiomyocytes. Such investigations may lead to significant developments in ensuring that doxorubicin can achieve its full therapeutic anti-tumour potential without causing the subsequent deleterious effects on the cardiovascular system.

Modelling the nonlinear behaviour and fracture process of AS4/PEKK thermoplastic composite under shear loading

The accurate determination of non-linear shear behaviour and fracture toughness of continuous carbon-fibre/polymer composites remains a considerable challenge. These measurements are often necessary to generate material parameters for advanced computational damage models. In particular, there is a dearth of detailed shear fracture toughness characterisation for thermoplastic composites which are increasingly generating renewed interest within the aerospace and automotive sectors. In this work, carbon fibre (AS4)/ thermoplastic Polyetherketoneketone (PEKK) composite V-notched cross-ply specimens were manufactured to investigate their non-linear response under pure shear loading. Both monotonic and cyclic loading were applied to study the shear modulus degradation and progressive failure. For the first time in the reported literature, we use the essential work of fracture approach to measure the shear fracture toughness of continuous fibre reinforced composite laminates. Excellent geometric similarity in the load-displacement curves was observed for ligament-scaled specimens. The laminate fracture toughness was determined by linear regression, of the specific work of fracture values, to zero ligament thickness, and verified with computational models. The matrix intralaminar fracture toughness (ply level fracture toughness), associated with shear loading was determined by the area method. This paper also details the numerical implementation of a new three-dimensional phenomenological model for carbon fibre thermoplastic composites using the measured values, which is able to accurately represent the full non-linear mechanical response and fracture process. The constitutive model includes a new non-linear shear profile, shear modulus degradation and load reversal. It is combined with a smeared crack model for representing ply-level damage initiation and propagation. The model is shown to accurately predict the constitutive response in terms of permanent plastic strain, degraded modulus as well as load reversal. Predictions are also shown to compare favourably with the evolution of damage leading to final fracture.