Interlaminar modelling to predict composite coiled tube failure

In a field operation that uses coiled tubing in its applications, fibre-reinforced polymer matrix composite tubing is seldom used. Fibre-composite coiled tubes offer advantages, compared to steel material, through a reduction in weight and improvement in fatigue life. The stiffness of composite material degrades progressively when increasing the number of cyclic loading. The fatigue damage and failure criteria of fibre-reinforced composite coiled tubes are more complex than that of steel; hence, failure predictions are somewhat unreliable. Among the defects in composite materials, interlaminar delamination is the foremost problem in fibre-reinforced composite material, and it leads to a reduction in strength and stiffness especially in cyclic-load conditions. Delamination causes a redistribution of the load path along the composite structure, which is unpredictable; therefore, delamination in a composite coiled tube in an oil and gas field eventually leads to final failure, which could be catastrophic. A-ply-by-ply mathematical modelling and numerical simulation method was developed to predict interlaminar delamination of filament-wound composite coiled tubes under a combination of different loading scenarios with consideration to low-cycle fatigue. The objective of this paper is to explain interlaminar delamination as an initial crack and source of stress concentration in composite coiled tubes in the framework of meso-cracking progression of matrix damage modelling of composite laminates. The paper focuses on delamination failure because the largest span of the composite lifecycle is at the crack propagation phase, which manifests itself in the form of delamination. The analysis shows that the crack front tip is not uniform, and also shows that carbon fibre possesses higher stiffness values compared to glass fibre. The paper confirms that 2D modelling cannot express the real release strain energy rate at the crack front tip. Mode-I testing, however, showed that the double cantilever beam (DCB) only represents the normal stress from the release strain energy rate. The results also indicated that there were other sources contributing to the strain energy release rate, such as inter-layer frictions and normal stress in the end notched flexure (ENF) testing mode

Topological Change in Mean Convex Mean Curvature Flow

Consider the mean curvature flow of an (n+1)-dimensional, compact, mean convex region in Euclidean space (or, if n<7, in a Riemannian manifold). We prove that elements of the m-th homotopy group of the complementary region can die only if there is a shrinking S^k x R^(n-k) singularity for some k less than or equal to m. We also prove that for each m from 1 to n, there is a nonempty open set of compact, mean convex regions K in R^(n+1) with smooth boundary for which the resulting mean curvature flow has a shrinking S^m x R^(n-m) singularity.Comment: 19 pages. This version includes a new section proving that certain kinds of mean curvature flow singularities persist under arbitrary small perturbations of the initial surface. Newest update (Oct 2013) fixes some bibliographic reference

5-HT obesity medication efficacy via POMC activation is maintained during aging

Peer reviewedPublisher PD

Ionic conductivity on a wetting surface

Recent experiments measuring the electrical conductivity of DNA molecules highlight the need for a theoretical model of ion transport along a charged surface. Here we present a simple theory based on the idea of unbinding of ion pairs. The strong humidity dependence of conductivity is explained by the decrease in the electrostatic self-energy of a separated pair when a layer of water (with high dielectric constant) is adsorbed to the surface. We compare our prediction for conductivity to experiment, and discuss the limits of its applicability.Comment: 5 pages, 3 figures; one section and two illustrations added; figures updated and discussion added; typo fixe

The mononuclear metal center of type-I dihydroorotase from aquifex aeolicus

Abstract Background Dihydroorotase (DHO) is a zinc metalloenzyme, although the number of active site zinc ions has been controversial. E. coli DHO was initially thought to have a mononuclear metal center, but the subsequent X-ray structure clearly showed two zinc ions, α and β, at the catalytic site. Aquifex aeolicus DHO, is a dodecamer comprised of six DHO and six aspartate transcarbamoylase (ATC) subunits. The isolated DHO monomer, which lacks catalytic activity, has an intact α-site and conserved β-site ligands, but the geometry of the second metal binding site is completely disrupted. However, the putative β-site is restored when the complex with ATC is formed and DHO activity is regained. Nevertheless, the X-ray structure of the complex revealed a single zinc ion at the active site. The structure of DHO from the pathogenic organism, S. aureus showed that it also has a single active site metal ion. Results Zinc analysis showed that the enzyme has one zinc/DHO subunit and the addition of excess metal ion did not stimulate catalytic activity, nor alter the kinetic parameters. The metal free apoenzyme was inactive, but the full activity was restored upon the addition of one equivalent of Zn2+ or Co2+. Moreover, deletion of the β-site by replacing the His180 and His232 with alanine had no effect on catalysis in the presence or absence of excess zinc. The 2.2 Å structure of the double mutant confirmed that the β-site was eliminated but that the active site remained otherwise intact. Conclusions Thus, kinetically competent A. aeolicus DHO has a mononuclear metal center. In contrast, elimination of the putative second metal binding site in amidohydrolyases with a binuclear metal center, resulted in the abolition of catalytic activity. The number of active site metal ions may be a consideration in the design of inhibitors that selectively target either the mononuclear or binuclear enzymes

Evolution of the largest mammalian genome

The genome of the red vizcacha rat (Rodentia, Octodontidae, Tympanoctomys barrerae) is the largest of all mammals, and about double the size of their close relative, the mountain vizcacha rat Octomys mimax, even though the lineages that gave rise to these species diverged from each other only about five million years ago. The mechanism for this rapid genome expansion is controversial, and hypothesized to be a consequence of whole genome duplication or accumulation of repetitive elements. To test these alternative but nonexclusive hypotheses, we gathered and evaluated evidence from whole transcriptome and whole genome sequences of T. barrerae and O. mimax. We recovered support for genome expansion due to accumulation of a diverse assemblage of repetitive elements, which represent about one half and one fifth of the genomes of T. barrarae and O. mimax, respectively, but we found no strong signal of whole genome duplication. In both species, repetitive sequences were rare in transcribed regions as compared to the rest of the genome, and mostly had no close match to annotated repetitive sequences from other rodents. These findings raise new questions about the genomic dynamics of these repetitive elements, their connection to widespread chromosomal fissions that occurred in the T. barrerae ancestor, and their fitness effects ? including during the evolution of hypersaline dietary tolerance in T. barrerae.Fil: Evans, Ben J.. Mc Master University; CanadáFil: Upham, Nathan S.. Mc Master University; Canadá. Field Museum of Natural History; Estados Unidos. University of Yale; Estados UnidosFil: Golding, G. Brian. Mc Master University; CanadáFil: Ojeda, Ricardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Ojeda, Agustina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentin

5-HT2C Receptor Agonist Anorectic Efficacy Potentiated by 5-HT1B Receptor Agonist Coapplication: An Effect Mediated via Increased Proportion of Pro-Opiomelanocortin Neurons Activated

An essential component of the neural network regulating ingestive behavior is the brain 5-hydroxytryptamine2C receptor (5-HT2CR), agonists of which suppress food intake and were recently approved for obesity treatment by the US Food and Drug Administration. 5-HT2CR-regulated appetite is mediated primarily through activation of hypothalamic arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons, which are also disinhibited through a 5-HT1BR-mediated suppression of local inhibitory inputs. Here we investigated whether 5-HT2CR agonist anorectic potency could be significantly enhanced by coadministration of a 5-HT1BR agonist and whether this was associated with augmented POMC neuron activation on the population and/or single-cell level. The combined administration of subanorectic concentrations of 5-HT2CR and 5-HT1BR agonists produced a 45% reduction in food intake and significantly greater in vivo ARC neuron activation in mice. The chemical phenotype of activated ARC neurons was assessed by monitoring agonist-induced cellular activity via calcium imaging in mouse POMC-EGFP brain slices, which revealed that combined agonists activated significantly more POMC neurons (46%) compared with either drug alone (~25% each). Single-cell electrophysiological analysis demonstrated that 5-HT2CR/5-HT1BR agonist coadministration did not significantly potentiate the firing frequency of individual ARC POMC-EGFP cells compared with agonists alone. These data indicate a functional heterogeneity ofARCPOMCneurons by revealing distinct subpopulations of POMC cells activated by 5-HT2CRs and disinhibited by 5-HT1BRs. Therefore, coadministration of a 5-HT1BR agonist potentiates the anorectic efficacy of 5-HT2CR compounds by increasing the number, but not the magnitude, of activated ARC POMC neurons and is of therapeutic relevance to obesity treatment. © 2013 the authors

mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

Mismatch repair causes the dynamic release of an essential DNA polymerase from the replication fork

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/1/MMI_7841_sm_SuppInfor.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/2/j.1365-2958.2011.07841.x.pd

Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) trial: Study design and sample characteristics

Background Pain is the most common presenting somatic symptom in medical outpatients, and depression and anxiety are the two most common mental disorders. They frequently co-occur, are under-treated, and result in substantial disability and reduced health-related quality of life. Objectives The Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) study is a randomized comparative effectiveness trial designed to test the relative effectiveness of a lower-resource vs. a higher-resource technology-assisted intervention for the management of patients suffering from pain plus anxiety and/or depression. Methods/design CAMMPS has enrolled 294 primary care patients with chronic pain plus comorbid anxiety and/or depression and randomized them to either: 1) Assisted Symptom Management (ASM) consisting of automated symptom monitoring by interactive voice recording or Internet and prompted pain and mood self-management; or 2) Comprehensive Symptom Management (CSM) which combines ASM with optimized medication management delivered by a nurse-physician specialist team and facilitated mental health care. Outcomes are assessed at baseline, 1, 3, 6, and 12 months. The primary outcome is a composite pain-anxiety-depression (PAD) severity score. Secondary outcomes include individual pain, anxiety, and depression scores, health-related quality of life, disability, healthcare utilization, and treatment satisfaction. Discussion CAMMPS provides an integrated approach to PAD symptoms rather than fragmented care of single symptoms; coordinated symptom management in partnership with primary care clinicians and psychologists embedded in primary care; efficient use of health information technology; attention to physical and psychological symptom comorbidity; and the coupling of self-management with optimized medication management and facilitated mental health care