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 et al. (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

Effects of hydrogen on 4130 steel microstructure during tensile loading

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Microbial dynamics in a High Arctic glacier forefield: A combined field, laboratory, and modelling approach

Modelling the development of soils in glacier forefields is necessary in order to assess how microbial and geochemical processes interact and shape soil development in response to glacier retreat. Furthermore, such models can help us predict microbial growth and the fate of Arctic soils in an increasingly ice-free future. Here, for the first time, we combined field sampling with laboratory analyses and numerical modelling to investigate microbial community dynamics in oligotrophic proglacial soils in Svalbard. We measured low bacterial growth rates and growth efficiencies (relative to estimates from Alpine glacier forefields) and high sensitivity of bacterial growth rates to soil temperature (relative to temperate soils). We used these laboratory measurements to inform parameter values in a new numerical model and significantly refined predictions of microbial and biogeochemical dynamics of soil development over a period of roughly 120 years. The model predicted the observed accumulation of autotrophic and heterotrophic biomass. Genomic data indicated that initial microbial communities were dominated by bacteria derived from the glacial environment, whereas older soils hosted a mixed community of autotrophic and heterotrophic bacteria. This finding was simulated by the numerical model, which showed that active microbial communities play key roles in fixing and recycling carbon and nutrients. We also demonstrated the role of allochthonous carbon and microbial necromass in sustaining a pool of organic material, despite high heterotrophic activity in older soils. This combined field, laboratory, and modelling approach demonstrates the value of integrated model-data studies to understand and quantify the functioning of the microbial community in an emerging High Arctic soil ecosystem

Cell transplantation preserves matrix homeostasis: A novel paracrine mechanism

ObjectivesCell transplantation prevents chamber dilatation, but the underlying molecular mechanisms remain undefined. Structural cardiac remodeling involves matrix degradation from an imbalance of matrix metalloproteinases (MMP) relative to endogenous tissue inhibitors of metalloproteinases (TIMP). We aimed to determine the capacity of cell transplantation to alter extracellular matrix in the failing heart and, in so doing, identify novel paracrine molecular mediators underlying the beneficial effects of cell transplantation on chamber dilatation.MethodsSmooth muscle cells were transplanted to the dilating left ventricle of cardiomyopathic hamsters (CTX, n = 15) compared with age-matched media-injected cardiomyopathic (CON, n = 15) and normal hamsters (n = 7). After 5 weeks, left ventricular volume was measured by computerized planimetry. Fibrillar collagen was examined by confocal microscopy. Matrix homeostasis was quantified by measuring MMP/TIMP expression/activity relative to myocardial collagen synthesis (14C-proline uptake).ResultsLeft ventricular dilatation was attenuated in CTX hearts (P = .02). CTX restored perimysial collagen fiber content and architecture to normal levels. TIMP-2 and TIMP-3 expression were enhanced in CTX (TIMP-2, 195% ± 42% of CON, P = .02; TIMP-3, 118% ± 3% of CON, P = .002), and correspondingly, gelatinase MMP-2 activity was reduced (P < .05). The TIMP:MMP ratio was increased in CTX hearts (TIMP-2 to MMP-2, 410% ± 134% of CON, P = .04, and TIMP-3 to MMP-9, 205% ± 47% of CON, P = .03), reflecting a reduced capacity for matrix degradation. Collagen synthesis was equivalent (CTX vs CON), suggesting that restored matrix architecture was a function of attenuated matrix degradation.ConclusionsThese data provide the first evidence that cell transplantation limits ventricular dilatation in the failing heart through a paracrine-mediated mechanism that preserves extracellular matrix homeostasis

Identification of complex health interventions suitable for evaluation: development and validation of the 8-step scoping framework

Background: There is extensive literature on the methodology of evaluation research and the development and evaluation of complex interventions but little guidance on the formative stages before evaluation and how to work with partner organizations that wish to have their provision evaluated. It is important to be able to identify suitable projects for evaluation from a range of provision and describe the steps required, often with academic institutions working in partnership with external organizations, in order to set up an evaluation. However, research evaluating programs or interventions rarely discusses these stages. Objective: This study aimed to extend work on evaluability assessment and pre-evaluation planning by proposing an 8-Step Scoping Framework to enable the appraisal of multiple programs in order to identify interventions suitable for evaluation. We aimed to add to the literature on evaluability assessment and more recent evaluation guidance by describing the processes involved in working with partner organizations. Methods: This paper documents the steps required to identify multiple complex interventions suitable for process and outcome evaluation. The steps were developed using an iterative approach by working alongside staff in a local government organization, to build an evidence base to demonstrate which interventions improve children’s outcomes. The process of identifying suitable programs for evaluation, thereby establishing the pre-evaluation steps, was tested using all Flying Start provision. Results: The 8-Step Scoping Framework was described using the example of the local government organization Flying Start to illustrate how each step contributes to finding projects suitable for process and outcome evaluation: (1) formulating overarching key questions that encompass all programs offered by an organization, (2) gaining an in-depth understanding of the work and provision of an organization and engaging staff, (3) completing a data template per project/program offered, (4) assessing the robustness/validity of data across all programs, (5) deciding on projects suitable for evaluation and those requiring additional data, (6) negotiating with chosen project leads, both within and outside the organization, (7) developing individual project evaluation protocols, and (8) applying for ethical approval from the university and partner organization. Conclusions: This paper describes the processes involved in identifying suitable projects for evaluation. It adds to the existing literature on the assessment of specific programs suitable for evaluation and guidance for conducting evaluations by establishing the formative steps required to identify suitable programs from a range of provision. This scoping framework particularly relates to academic partners and organizations tasked with delivering evidence-based services designed to meet local needs. The steps identified have been described in the context of early years provision but can be applied to a range of community-based evaluations, or more generally, to cases where an academic partner is working with external stakeholders to identify projects suitable for academic evaluation

Macroscopic and Microstructural Aspects of the Transformation Behavior in a Polycrystalline NiTi Shape Memory Alloy

The mechanical and microstructural behavior of a polycrystalline Ni(49.9)Ti(50.1) (at.%) shape memory alloy was investigated as a function of temperature around the transformation regime. The bulk macroscopic responses, measured using ex situ tensile deformation and impulse excitation tests, were compared to the microstructural evolution captured using in situ neutron diffraction. The onset stress for inelastic deformation and dynamic Young's modulus were found to decrease with temperature, in the martensite regime, reaching a significant minimum at approximately 80 C followed by an increase in both properties, attributed to the martensite to austenite transformation. The initial decrease in material compliance during heating affected the ease with which martensite reorientation and detwinning could occur, ultimately impacting the stress for inelastic deformation prior to the start of the reverse transformation

Reducing bias and improving transparency in medical research: A critical overview of the problems, progress so far and suggested next steps

In recent years there has been increasing awareness of problems that have undermined trust in medical research. This review outlines some of the most important issues including research culture, reporting biases, and statistical and methodological issues. It examines measures that have been instituted to address these problems and explores the success and limitations of these measures. The paper concludes by proposing three achievable actions which could be implemented to deliver significantly improved transparency and mitigation of bias. These measures are as follows: (1) mandatory registration of interests by those involved in research; (2) that journals support the ‘registered reports’ publication format; and (3) that comprehensive study documentation for all publicly funded research be made available on a World Health Organization research repository. We suggest that achieving such measures requires a broad-based campaign which mobilises public opinion. We invite readers to feedback on the proposed actions and to join us in calling for their implementation

Effect of Selenium Nanoparticle Size on IL-6 Detection Sensitivity in a Lateral Flow Device

Sepsis is the body’s response to an infection. Existing diagnostic testing equipment is not available in primary care settings and requires long waiting times. Lateral flow devices (LFDs) could be employed in point-of-care (POC) settings for sepsis detection; however, they currently lack the required sensitivity. Herein, LFDs are constructed using 150–310 nm sized selenium nanoparticles (SeNPs) and are compared to commercial 40 nm gold nanoparticles (AuNPs) for the detection of the sepsis biomarker interleukin-6 (IL-6). Both 310 and 150 nm SeNPs reported a lower limit of detection (LOD) than 40 nm AuNPs (0.1 ng/mL compared to 1 ng/mL), although at the cost of test line visual intensity. This is to our knowledge the first use of larger SeNPs (>100 nm) in LFDs and the first comparison of the effect of the size of SeNPs on assay sensitivity in this context. The results herein demonstrate that large SeNPs are viable alternatives to existing commercial labels, with the potential for higher sensitivity than standard 40 nm AuNPs

Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus

© 2013 Al-Mahdawi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, which induces epigenetic changes and FXN gene silencing. Bisulfite sequencing studies have identified 5-methylcytosine (5 mC) DNA methylation as one of the epigenetic changes that may be involved in this process. However, analysis of samples by bisulfite sequencing is a time-consuming procedure. In addition, it has recently been shown that 5-hydroxymethylcytosine (5 hmC) is also present in mammalian DNA, and bisulfite sequencing cannot distinguish between 5 hmC and 5 mC.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242193/EFACTS (CS), the Wellcome Trust [089757] (SA) and Ataxia UK (RMP) to MAP