Microscopy of glazed layers formed during high temperature sliding wear at 750C

The evolution of microstructures in the glazed layer formed during high temperature sliding wear of Nimonic 80A against Stellite 6 at 750 ◦C using a speed of 0.314ms−1 under a load of 7N has been investigated using scanning electron microscopy (SEM), energy dispersive analysis by X-ray (EDX), X-ray diffraction (XRD) analysis, scanning tunnelling microscopy (STM) and transmission electron microscopy (TEM). The results indicate the formation of a wear resistant nano-structured glazed layer. The mechanisms responsible for the formation of the nano-polycrystalline glazed layer are discussed

Challenges in the delivery of e-government through kiosks

Kiosks are increasingly being heralded as a technology through which governments, government departments and local authorities or municipalities can engage with citizens. In particular, they have attractions in their potential to bridge the digital divide. There is some evidence to suggest that the citizen uptake of kiosks and indeed other channels for e-government, such as web sites, is slow, although studies on the use of kiosks for health information provision offer some interesting perspectives on user behaviour with kiosk technology. This article argues that the delivery of e-government through kiosks presents a number of strategic challenges, which will need to be negotiated over the next few years in order that kiosk applications are successful in enhancing accessibility to and engagement with e-government. The article suggests that this involves consideration of: the applications to be delivered through a kiosk; one stop shop service and knowledge architectures; mechanisms for citizen identification; and, the integration of kiosks within the total interface between public bodies and their communities. The article concludes by outlining development and research agendas in each of these areas.</p

Differential expression of secreted factors SOSTDC1 and ADAMTS8 cause pro-fibrotic changes in linear morphoea fibroblasts

This is the peer reviewed version of the following article: Badshah, I. I., et al. "Differential expression of secreted factors SOSTDC1 and ADAMTS8 cause pro-fibrotic changes in linear morphoea fibroblasts." British Journal of Dermatology 0(ja)., which has been published in final form at https://doi.org/10.1111/bjd.17352. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsFunding: RO, IB and SB are funded by the Great Ormond Street Children's Charity. This research was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centr

Studies of high temperature sliding wear of metallic dissimilar interfaces

The evolution of microstructures in the glaze layer formed during limited debris retention sliding wear of Nimonic 80A against Stellite 6 at 750 8C and a sliding speed of 0.314 m sK1 (7 N applied load, 4522 m sliding distance) was investigated using scanning electron microscopy (SEM), energy dispersive analysis by X-ray (EDX), X-ray diffraction (XRD), scanning tunnelling microscopy (STM) and transmission electron microscopy (TEM). The collected data indicate the development of a wear resistant nano-structured glaze layer. The process of ‘fragmentation’ involving deformation, generation of dislocations, formation of sub-grains and their increasing refinement causing increasing misorientation was responsible for the formation of nano-structured grains. The rapid formation of this glaze layer from primarily cobalt–chromium debris transferred from (and also back to) the surface of the Stellite 6, kept wear of both the Nimonic 80A and Stellite 6 to very low levels. However, increasing the sliding speed to 0.905 m sK1 (750 8C) suppressed glaze formation with only a patchy, unstable glaze forming on the Stellite 6 counterface and an absence of glaze development on the Nimonic 80A sample (the Nimonic 80A surface was covered with at most, a very thinly smeared layer of oxide). The high levels of oxide debris generated at 0.905 m sK1 instead acted as a loose abrasive assisting wear of especially the Nimonic 80A. This behaviour was attributed to a change in oxide chemistry (due to the dominance of nickel and chromium oxides generated from the Nimonic 80A) resulting in poor oxide sintering characteristics, in combination with increased mobility and reduced residency of the oxide debris at 0.905 m sK1

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Comparing Cosmic Microwave Background Datasets

To extract reliable cosmic parameters from cosmic microwave background datasets, it is essential to show that the data are not contaminated by residual non-cosmological signals. We describe general statistical approaches to this problem, with an emphasis on the case in which there are two datasets that can be checked for consistency. A first visual step is the Wiener filter mapping from one set of data onto the pixel basis of another. For more quantitative analyses we develop and apply both Bayesian and frequentist techniques. We define the ``contamination parameter'' and advocate the calculation of its probability distribution as a means of examining the consistency of two datasets. The closely related ``probability enhancement factor'' is shown to be a useful statistic for comparison; it is significantly better than a number of chi-squared quantities we consider. Our methods can be used: internally (between different subsets of a dataset) or externally (between different experiments); for observing regions that completely overlap, partially overlap or overlap not at all; and for observing strategies that differ greatly. We apply the methods to check the consistency (internal and external) of the MSAM92, MSAM94 and Saskatoon Ring datasets. From comparing the two MSAM datasets, we find that the most probable level of contamination is 12%, with no contamination only 1.05 times less probable, and 100% contamination strongly ruled out at over 2 X 10^5 times less probable. From comparing the 1992 MSAM flight with the Saskatoon data we find the most probable level of contamination to be 50%, with no contamination only 1.6 times less probable and 100% contamination 13 times less probable. [Truncated]Comment: LaTeX, 16 pages which include 16 figures, submitted to Phys. Rev.

Universities and community-based research in developing countries: community voice and educational provision in rural Tanzania

The main focus of recent research on the community engagement role of universities has been in developed countries, generally in towns and cities and usually conducted from the perspectives of universities rather than the communities with which they engage. The purpose of this paper is to investigate the community engagement role of universities in the rural areas of developing countries, and its potential for strengthening the voice of rural communities. The particular focus is on the provision of primary and secondary education. The paper is based on the assumption that in order for community members to have both the capacity and the confidence to engage in political discourse for improving educational capacity and quality, they need the opportunity to become involved and well-versed in the options available, beyond their own experience. Particular attention is given in the paper to community-based research (CBR). CBR is explored from the perspectives of community members and local leaders in the government-community partnerships which have responsibility for the provision of primary and secondary education in rural Tanzania. The historical and policy background of the partnerships, together with findings from two case studies, provide the context for the paper

An i2b2-based, generalizable, open source, self-scaling chronic disease registry

Objective: Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Materials and methods Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. Results: The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. Discussion We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. Conclusions: The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases

Constraint-Based Modeling and Kinetic Analysis of the Smad Dependent TGF-β Signaling Pathway

Background Investigation of dynamics and regulation of the TGF-β signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. Methodology/Principal Findings We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-β signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-β pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-β. Conclusions/Significance The simulation results indicate that the signal response to TGF-β is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways