803 research outputs found

    Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

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    It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies

    Chronic Oedema and the older person: The effects of ageing upon treatment outcomes

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    Chronic oedema (CO) and lymphoedema (LO) are long-term conditions that can become more complicated or are more likely to develop with age. The ageing process can involve alterations in the structures that support the normal function of the lymphatic system or put it at greater risk of damage. The main three components (skin care, exercise and compression therapy) within the management of CO/LO can become more difficult to apply with age. This is because of reduced healing rates, decreased cardiovascular capacity and deterioration in vascular and arterial structures. The impact of ageing and how this can affect patients and treatment outcomes requires careful consideration

    Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line

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    This article is made available through the Brunel Open Access Publishing Fund. Copyright: © 2013 Mahajan 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.Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and timedependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2) showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SPD in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host’s immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.Department of Biotechnology, Indi

    Algebraic conformal quantum field theory in perspective

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    Conformal quantum field theory is reviewed in the perspective of Axiomatic, notably Algebraic QFT. This theory is particularly developped in two spacetime dimensions, where many rigorous constructions are possible, as well as some complete classifications. The structural insights, analytical methods and constructive tools are expected to be useful also for four-dimensional QFT.Comment: Review paper, 40 pages. v2: minor changes and references added, so as to match published versio

    On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

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    In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MSn experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine-1-carbonyl]-3aH-indol-3-yl}-2-morpholinoethane-1,2-dione resulted in eight products, three of which showed bioaffinity in the continuous-flow p38α bioaffinity assay used. Electrochemical conversion of BIRB796 resulted, amongst others, in the formation of the reactive quinoneimine structure and its corresponding hydroquinone. Both products were detected in the p38α bioaffinity assay, which indicates binding to the p38α kinase

    Pulmonary intravascular lymphoma diagnosed by 18-fluorodeoxyglucose positron emission tomography-guided transbronchial lung biopsy in a man with long-term survival: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>18-Fluorodeoxyglucose positron emission tomography can detect the pulmonary involvement of intravascular lymphoma that presents no abnormality in a computed tomography scan.</p> <p>Case presentation</p> <p>We report the case of a 61-year-old Japanese man who had pulmonary intravascular lymphoma and no computed tomography abnormality. We were able to make an antemortem diagnosis of pulmonary intravascular lymphoma by transbronchial lung biopsy according to 18-fluorodeoxyglucose positron emission tomography findings. He is free of recurrent disease 24 months after chemotherapy.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first reported case of a long-term survivor of pulmonary intravascular lymphoma diagnosed by transbronchial lung biopsy under the guide of 18-fluorodeoxyglucose positron emission tomography.</p

    Wet Granular Materials

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    Most studies on granular physics have focused on dry granular media, with no liquids between the grains. However, in geology and many real world applications (e.g., food processing, pharmaceuticals, ceramics, civil engineering, constructions, and many industrial applications), liquid is present between the grains. This produces inter-grain cohesion and drastically modifies the mechanical properties of the granular media (e.g., the surface angle can be larger than 90 degrees). Here we present a review of the mechanical properties of wet granular media, with particular emphasis on the effect of cohesion. We also list several open problems that might motivate future studies in this exciting but mostly unexplored field.Comment: review article, accepted for publication in Advances in Physics; tex-style change

    Steps to improve gender diversity in the fields of coastal geosciences and engineering

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    Robust data are the base of effective gender diversity policy. Evidence shows that gender inequality is still pervasive in science, technology, engineering and mathematics (STEM). Coastal geoscience and engineering (CGE) encompasses professionals working on coastal processes, integrating expertise across physics, geomorphology, engineering, planning and management. The article presents novel results of gender inequality and experiences of gender bias in CGE, and proposes practical steps to address it. It analyses the gender representation in 9 societies, 25 journals, and 10 conferences in CGE and establishes that women represent 30% of the international CGE community, yet there is under-representation in prestige roles such as journal editorial board members (15% women) and conference organisers (18% women). The data show that female underrepresentation is less prominent when the path to prestige roles is clearly outlined and candidates can self-nominate or volunteer instead of the traditional invitation-only pathway. By analysing the views of 314 survey respondents (34% male, 65% female, and 1% ‘‘other’’), we show that 81% perceive the lack of female role models as a key hurdle for gender equity, and a significantly larger proportion of females (47%) felt held back in their careers due to their gender in comparison with males (9%). The lack of women in prestige roles and senior positions contributes to 81% of survey respondents perceiving the lack of female role models in CGE as a key hurdle for gender equality. While it is clear that having more women as role models is important, this is not enough to effect change. Here seven practical steps towards achieving gender equity in CGE are presented: (1) Advocate for more women in prestige roles; (2) Promote high-achieving females; (3) Create awareness of gender bias; (4) Speak up; (5) Get better support for return to work; (6) Redefine success; and, (7) Encourage more women to enter the discipline at a young age. Some of these steps can be successfully implemented immediately (steps 1–4), while others need institutional engagement and represent major societal overhauls. In any case, these seven practical steps require actions that can start immediately
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