569 research outputs found
Anisotropy of Heat Conduction in Fibre-Reinforced Composites
Merged with duplicate record 10026.1/2749 on 27.03.2017 by CS (TIS)Fibre-reinforced composites usually exhibit anisotropy of
thermal as well as mechanical properties. For example, in
a unidirectional carbon fibre-reinforced plastic of 60%
volume fraction, the longitudinal thermal conductivity may
be greater than that in the transverse direction by a factor
of 50, and greater than that of the unreinforced polymer by
more than two orders of magnitude.
In order to evaluate the engineering applications of thermal
anisotropy, this thesis concentrates on the development and
validation of a generalised finite element model of heat
conduction in an anisotropic medium. This uses a variational
formulation of the anisotropic time-dependent heat
conduction equation, and is implemented for two and threedimensional
quadratic finite elements. The model may be
used for the solution of problems having any combination of
steady or time-dependent boundary conditions (fixed
temperature, convection, radiation, heat flux and internal
heat generation), as well as nonlinear properties. Anisotropy
is specified by the components of the two or threedimensional
thermal conductivity tensor; efficient representation
of nonhomogeneous materials is achieved by the
specification of properties at element integration points.
Theoretical validation of the model is carried out by means
of a number of mathematical solutions to orthotropic and
anisotropic problems. Experimental validation is performed
by comparison of calculations with measured steady-state
surface temperatures on a cylindrical specimen of unidirectional
carbon fibre-reinforced epoxy resin. The thermal
property data for this exercise are obtained from measurements
of principal thermal conductivities on absolute and
comparative steady-state apparatus.
The use of the finite element model in two industrial
applications is briefly described. These concern thermal
cycling during composite fabrication with reinforced
thermoplastic tape, and an analysis of heat transfer in a
composite propeller blade
Air permeability of balsa core, and its influence on defect formation in resin infused sandwich laminates
Many large composite structures are manufactured using sandwich laminates to achieve high specific bending strength and stiffness. For wind turbine blades, the self-weight becomes increasingly important as blade size increases. Resin infusion of three-dimensional sandwich laminates can result in complex flow paths, and subsequent defect formation is difficult to predict. The core material used for sandwich construction and its interaction with liquid resins may also influence the formation of defects. In the case of balsa, this effect can be used to reduce defect severity. This paper considers the effect of cored sandwich laminate construction on the formation of defects. The primary focus is the characterisation of commonly used core materials and their interaction with liquid resin under high vacuum conditions. For balsa core, experiments indicate that the available pore space can act as a sink for trapped air, which can aid the reduction of defects when multiple flow fronts converge due to the complex flow paths in sandwich laminates. Empirical data for air absorption and desorption rates in balsa core were obtained using a custom-designed experiment. Using these data, a theoretical model was developed that can indicate available pore space, which in turn informs optimum processing conditions, such as time under vacuum. The diffusion coefficients obtained for air absorption and desorption in balsa are very similar, and lie in the middle of published ranges for hard woods at around 2 × 10-7 m2/s. The methodology developed represents actual behaviour of air absorption/desorption during resin infusion, whilst other techniques do not, merely measuring diffusion of air through a sample while not allowing for finite pore space. In consequence, infusion strategies can be planned more precisely because the core/resin interaction is better understood. Knit line defect formation could be predicted with greater accuracy with suitably modified flow-modelling programs
Design, manufacture, mechanical testing and numerical modelling of an asymmetric composite crossbow limb
This paper considers the design, manufacture, mechanical testing and numerical analysis of a crossbow beam (limb). The limb should be lightweight and permit a high deflection of the beam's tip in order to achieve a good ballistic performance. Consequently, fibre-reinforced polymer matrix composites are suitable candidate materials. However, carbon fibres were considered too brittle for this application. Aramid fibres combine low density and high stiffness but are weak in compression. E-glass fibres are relatively flexible but are of high density. The optimised design developed here uses aramid fibres on the tension face with E-glass fibres on the compression side. This component was manufactured using resin infusion, modelled using a commercial finite element code (Abaqus (R)) and the model was validated by mechanical testing. A good correlation was found between the experimentally measured deflections and the numerical results. (C) 2008 Elsevier Ltd. All rights reserved
Subcellular fractionation method to study endosomal trafficking of Kaposi’s sarcoma-associated herpesvirus
Background
Virus entry involves multiple steps and is a highly orchestrated process on which successful infection collectively depends. Entry processes are commonly analyzed by monitoring internalized virus particles via Western blotting, polymerase chain reaction, and imaging techniques that allow scientist to track the intracellular location of the pathogen. Such studies have provided abundant direct evidence on how viruses interact with receptor molecules on the cell surface, induce cell signaling at the point of initial contact with the cell to facilitate internalization, and exploit existing endocytic mechanisms of the cell for their ultimate infectious agenda. However, there is dearth of knowledge in regards to trafficking of a virus via endosomes. Herein, we describe an optimized laboratory procedure to isolate individual organelles during different stages of endocytosis by performing subcellular fractionation. This methodology is established using Kaposi’s sarcoma-associated herpesvirus (KSHV) infection of human foreskin fibroblast (HFF) cells as a model. With KSHV and other herpesviruses alike, envelope glycoproteins have been widely reported to physically engage target cell surface receptors, such as integrins, in interactions leading to entry and subsequent infection.
Results
Subcellular fractionation was used to isolate early and late endosomes (EEs and LEs) by performing a series of centrifugations steps. Specifically, a centrifugation step post-homogenization was utilized to obtain the post-nuclear supernatant containing intact intracellular organelles in suspension. Successive fractionation via sucrose density gradient centrifugation was performed to isolate specific organelles including EEs and LEs. Intracellular KSHV trafficking was directly traced in the isolated endosomal fractions. Additionally, the subcellular fractionation approach demonstrates a key role for integrins in the endosomal trafficking of KSHV. The results obtained from fractionation studies corroborated those obtained by traditional imaging studies.
Conclusions
This study is the first of its kind to employ a sucrose flotation gradient assay to map intracellular KSHV trafficking in HFF cells. We are confident that such an approach will serve as a powerful tool to directly study intracellular trafficking of a virus, signaling events occurring on endosomal membranes, and dynamics of molecular events within endosomes that are crucial for uncoating and virus escape into the cytosol
Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.
One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis
E. coli NfsA: an alternative nitroreductase for prodrug activation gene therapy in combination with CB1954
Prodrug activation gene therapy is a developing approach to cancer treatment, whereby prodrug-activating enzymes are expressed in tumour cells. After administration of a non-toxic prodrug, its conversion to cytotoxic metabolites directly kills tumour cells expressing the activating enzyme, whereas the local spread of activated metabolites can kill nearby cells lacking the enzyme (bystander cell killing). One promising combination that has entered clinical trials uses the nitroreductase NfsB from Escherichia coli to activate the prodrug, CB1954, to a potent bifunctional alkylating agent. NfsA, the major E. coli nitroreductase, has greater activity with nitrofuran antibiotics, but it has not been compared in the past with NfsB for the activation of CB1954. We show superior in vitro kinetics of CB1954 activation by NfsA using the NADPH cofactor, and show that the expression of NfsA in bacterial or human cells results in a 3.5- to 8-fold greater sensitivity to CB1954, relative to NfsB. Although NfsB reduces either the 2-NO2 or 4-NO2 positions of CB1954 in an equimolar ratio, we show that NfsA preferentially reduces the 2-NO2 group, which leads to a greater bystander effect with cells expressing NfsA than with NfsB. NfsA is also more effective than NfsB for cell sensitisation to nitrofurans and to a selection of alternative, dinitrobenzamide mustard (DNBM) prodrugs
Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.
Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies
Fermi Large Area Telescope observations of PSR J1836+5925
The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly
unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments
of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic
plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8
million years, a spindown luminosity of 1.1 erg s, and a
large off-peak emission component, making it quite unusual among the known
gamma-ray pulsar population. We present an analysis of one year of LAT data,
including an updated timing solution, detailed spectral results and a long-term
light curve showing no indication of variability. No evidence for a surrounding
pulsar wind nebula is seen and the spectral characteristics of the off-peak
emission indicate it is likely magnetospheric. Analysis of recent XMM
observations of the X-ray counterpart yields a detailed characterization of its
spectrum, which, like Geminga, is consistent with that of a neutron star
showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa
Myofibrillogenesis regulator 1 induces hypertrophy by promoting sarcomere organization in neonatal rat cardiomyocytes
Human myofibrillogenesis regulator 1, a novel 17-kDa protein, is closely involved in cardiac hypertrophy. We studied the molecular mechanism that links MR-1 to hypertrophic response. Hypertrophic hallmarks such as cell size and [3H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h. However, sarcomere organization was promoted when MR-1 was transfected for 8 h. The finding that cardiac hypertrophy was induced long after increase of sarcomere organization indicates that the promoted sarcomere organization may be one of the crucial factors causing hypertrophy. Furthermore, when MR-1 was transfected into cardiomyocytes, the nuclear localization of myomesin-1 was shifted to the cytoplasm. Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1. However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level. Overexpression of MR-1 may induce cardiomyocyte hypertrophy via myomesin-1-mediated sarcomere organization
Plxdc2 Is a Mitogen for Neural Progenitors
The development of different brain regions involves the coordinated control of proliferation and cell fate specification along and across the neuraxis. Here, we identify Plxdc2 as a novel regulator of these processes, using in ovo electroporation and in vitro cultures of mammalian cells. Plxdc2 is a type I transmembrane protein with some homology to nidogen and to plexins. It is expressed in a highly discrete and dynamic pattern in the developing nervous system, with prominent expression in various patterning centres. In the chick neural tube, where Plxdc2 expression parallels that seen in the mouse, misexpression of Plxdc2 increases proliferation and alters patterns of neurogenesis, resulting in neural tube thickening at early stages. Expression of the Plxdc2 extracellular domain alone, which can be cleaved and shed in vivo, is sufficient for this activity, demonstrating a cell non-autonomous function. Induction of proliferation is also observed in cultured embryonic neuroepithelial cells (ENCs) derived from E9.5 mouse neural tube, which express a Plxdc2-binding activity. These experiments uncover a direct molecular activity of Plxdc2 in the control of proliferation, of relevance in understanding the role of this protein in various cancers, where its expression has been shown to be altered. They also implicate Plxdc2 as a novel component of the network of signalling molecules known to coordinate proliferation and differentiation in the developing nervous system
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