Winona

https://digitalcommons.library.umaine.edu/mmb-me/1319/thumbnail.jp

Simultaneous optimisation of structural topology and material grading using level set method

Peer reviewedPublisher PD

ABCC6 is a basolateral plasma membrane protein

RATIONALE:: ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. OBJECTIVE:: In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. METHODS AND RESULTS:: We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. CONCLUSIONS:: Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation. © 2013 American Heart Association, Inc

Stress-based shape and topology optimization with the level set method

This paper proposes a level set method to solve minimum stress and stress-constrained shape and topology optimization problems. The method solves a sub-optimization problem every iteration to obtain optimal boundary velocities. A p-norm stress functional is used to aggregate stresses in a single constraint. The shape sensitivity function is derived and a computational procedure based on a least squares interpolation approach is devised in order to compute sensitivities at the boundaries. Adaptive constraint scaling is used to enforce exact control of stress limits. Numerical results show that the method is able to solve the problem e�ciently for single and multiple load cases obtaining solutions with smooth boundaries

Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy

Extent: 14p.OBJECTIVE: To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of advanced colorectal neoplasia and evaluating the diagnostic accuracy of faecal haemoglobin testing compared with colonoscopy in a population of kidney transplant recipients at otherwise average risk. DESIGN: Cross sectional prevalence and diagnostic accuracy study with index test of faecal haemoglobin and reference standard of colonoscopy. SETTING: Outpatient clinics in metropolitan and regional hospitals in South Australia. PARTICIPANTS: 229 kidney transplant recipients aged 50 years and over, who were at least 6 months (mean 9.0 (SD 8.4) years) post-transplant and otherwise at average risk of colorectal cancer, completed the study between June 2008 and October 2011. INTERVENTIONS: Faecal immunochemical testing (Enterix Insure) for human haemoglobin, followed by colonoscopy with histological evaluation of retrieved samples. MAIN OUTCOME MEASURES: Prevalence of advanced colorectal neoplasia, defined as an adenoma at least 10 mm in diameter, villous features, high grade dysplasia, or colorectal cancer; sensitivity, specificity, and predictive values of faecal haemoglobin testing for advanced neoplasia compared with colonoscopy. RESULTS: Advanced colorectal neoplasia was found in 29 (13%, 95% confidence interval 9% to 18%) participants, including 2% (n=4) with high grade dysplasia and 2% (n=5) with colorectal cancer. Faecal testing for haemoglobin was positive in 12% (n=28); sensitivity, specificity, and positive and negative predictive values for advanced neoplasia were 31.0% (15.3% to 50.8%), 90.5% (85.6% to 94.2%), 32.1% (15.9% to 52.4%), and 90.1% (85.1% to 93.8%). Colonoscopy was well tolerated, with no significant adverse outcomes. To identify one case of advanced neoplasia, 8 (6 to 12) colonoscopies were needed. CONCLUSIONS: Kidney transplant recipients aged over 50 years have a high prevalence of advanced colorectal neoplasia. Faecal haemoglobin screening for colorectal neoplasia has similar performance characteristics in transplant recipients to those reported in general population studies, with poor sensitivity but reasonable specificity. Surveillance colonoscopy might be a more appropriate approach in this population.Michael G. Collins, Edward Teo, Stephen R. Cole, Choy-Yoke Chan, Stephen P. McDonald, Graeme R. Russ, G.P. Young, P.A. Bampton and P. Toby Coate

A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation

A phase I study of nolatrexed, administered as a continuous 5 day intravenous infusion every 28 days, has been undertaken for children with advanced malignancy. 16 patients were treated at 3 dose levels; 420, 640 and 768 mg/m2 24 h−1. 8 patients were evaluable for toxicity. In the 6 patients treated at 768 mg/m2 24 h−1, dose-limiting oral mucositis and myelosuppression were observed. Plasma nolatrexed concentrations and systemic exposure, measured in 14 patients, were dose related, with mean AUC values of 36 mg−1 ml−1 min−1, 50 mg ml−1 min−1 and 80 mg ml−1 min−1at the 3 dose levels studied. Whereas no toxicity was encountered if the nolatrexed AUC was <45 mg ml−1 min−1, Grade 3 or 4 toxicity was observed with AUC values of >60 mg ml−1 min−1. Elevated plasma deoxyuridine levels, measured as a surrogate marker of thymidylate synthase inhibition, were seen at all of the dose levels studied. One patient with a spinal primitive neuroectodermal tumour had stable disease for 11 cycles of therapy, and in two patients with acute lymphoblastic leukaemia a short-lived 50% reduction in peripheral lymphoblast counts was observed. Nolatrexed can be safely administered to children with cancer, and there is evidence of therapeutic activity as well as antiproliferative toxicity. Phase II studies of nolatrexed in children at the maximum tolerated dose of 640 mg/m2 24 h−1are warranted. © 2001 Cancer Research Campaign http://www.bjcancer.co

Wave climate change and its impact on UK coastal management

This research report considers long-term changes in wave conditions and sea levels around the UK coast, and how these changes may affect the planning, design and management of UK coastal defences. Some new numerical techniques were developed to enhance and to help interpret the measured and simulated data used in the study. The work included a literature and data review and selective gathering and analysis of wind and wave data recorded near the UK coast

The potential use of alternatives to primary aggregates in coastal and river engineering

This paper reports on a recent CIRIA study, carried out in collaboration with HR Wallingford, to assess the potential for using recycled/re-used (secondary) aggregate and construction and demolition waste as aggregate for coastal and river engineering. The objectives were to: • Reduce the impact of river and coastal construction on natural resources by promoting the use of alternative materials in place of primary aggregate and other materials. • Enable the construction industry to provide more sustainable and cost-effective solutions for river and coastal engineering. • Raise awareness of the potential use of secondary aggregate and recycled/reused materials as aggregate. • Reassure designers and constructors of the appropriateness for use of alternatives to aggregates. • Help overcome barriers to the use of alternatives to aggregates in a strategic and co-ordinated way. • Produce a best practice guide on the above. The demand from coastal and river engineering works for primary aggregate is increasing and is expected to expand further. It is recognised that this demand will need to be met, in part, by alternatively sourced aggregate. This paper reviews the availability of secondary and waste materials for application to river and coastal engineering and how designers and engineers can apply them