6,658 research outputs found
Differential expression and MAL-dependent targeting of the L-MAG and S-MAG isoforms to myelin membranes
No full textMany degenerative diseases of the nervous system, including Multiple Sclerosis and peripheral neuropathies, are triggered by an impaired interaction between the axons and their surrounding myelin sheaths. The cause for this disturbed axon-myelin interaction, and the secondary neuronal damage that produces the clinical symptoms, lies in a primary defect of the myelin sheath. The myelin sheath itself is formed and maintained by oligodendrocytes and Schwann cells, the myelinating glial cells of the central and peripheral nervous system, respectively. The isoforms of the myelin-associated glycoprotein (MAG) are thought to be potential key elements of axon-myelin interaction, since these immunoglobulin-like cell signalling proteins are known to be localized in the periaxonal and paranodal myelin membranes. The MAG isoforms each display one of two possible intracellular C-termini as a result of alternative mRNA splicing. The C-terminus of the large isoform (L-MAG) has been shown to mediate downstream signals via the non-receptor tyrosine kinase Fyn, while the Cterminus of the short isoform (S-MAG) is thought to interact with the glial cytoskeleton. We have investigated the regulation and differential expression of L- and S-MAG in oligodendroglial cells and in transgenic mice by the use of genomic constructs that encode individually green fluorescent protein-tagged MAG isoforms. In the oligodendroglial cells LMAG was the dominant isoform prior to the stimulation of cells with cyclicAMP, whereas upon cyclicAMP stimulation, S-MAG was predominantly expressed in cells exhibiting advanced morphological differentiation. The investigation of our transgenic mice revealed that the two MAG isoforms are differentially expressed in distinct fibre tracts of the striatum and that S-MAG seems to be predominantly expressed in the long projecting fibres of the corpus callosum. Thus, the two MAG isoforms appear not only to be differentially expressed during development and in the adult, but they seem to mediate isoform-specific aspects of the axon-myelin interaction in distinct regions of the adult brain. A major question in the formation and maintenance of the myelin-axon interaction concerns the coordinated targeting of myelin signalling molecules and lipids to the different myelin compartments. Recent results suggest that glycolipid-enriched microdomains, socalled 'lipid-rafts', are involved in special sorting and trafficking mechanisms of membrane proteins and lipids. Furthermore, they are thought to serve as platforms for signal transduction processes. This makes them to interesting candidates for axon-myelin interactions, as well as for interactions between the apposed myelin membranes. The integral membrane protein 'Myelin and Lymphocyte Protein' (MAL) is suggested to be involved in lipid-raft-mediated protein targeting and signalling in myelinating cells. Our investigation of adult brain tissue of MAL-deficient mice showed that the incorporation of particular myelin components, such as MAG, into myelin membranes was significantly reduced. Thus, the targeting of L- and S-MAG to the myelin membranes appears to be dependent on the lipid-raft protein MAL. Furthermore, the MAL-deficient mice showed several ultra structural alterations comparable to those of the MAG-deficient mice and that reflect an impaired axon-myelin interaction. Our data supports the idea that-raft mediated trafficking of myelin constituents, such as MAG, to the different myelin compartments is a major task of adult oligodendrocytes in the context of maintaining the axonal contact of the myelin sheath. With the use of the isoform specific tagged MAG expressing mice, it will be possible for the first time, to investigate their differential function in axon-glia interaction as well as their dependence on MAL in vivo
Synthesis of antagonists of Myelin-associated glycoprotein (MAG) for conformational and SAR studies
No full textDamage to the central nervous system (CNS) of higher vertebrates, including humans, often results in
devastating and persistent functional deficits. The limited capacity of the adult mammalian CNS to
repair lesions by axonal regeneration is mainly caused by the inhibitory molecules in myelin: Myelinassociated
glycoprotein (MAG), Nogo, and Oligodendrocyte-myelin glycoprotein (OMgp).
Gangiosides, such as GD1a, GT1b and GQ1bα, are specific functional ligands responsible for MAGmediated
inhibition of neurite outgrowth. Based on the previous SAR studies, partial structure of
natural ligands and derivatives thereof (1, 20, 45, 54α and 54β) were chemically and chemoenzymatically
synthesized. Their biological affinities were tested in a fluorescent hapten inhibition assay; the binding epitopes
were identified by STD NMR; and the bioactive conformations were deduced by trNOEs NMR. This
led to the design of two families of novel mimics with either modifications at the C-9 position of the
α(2,3)-linked terminal sialic acid (87, 97), or substitutions of the disaccharide core by noncarbohydrate
moieties (104-107, 120-122)
Analysis of hybrid Nd:Yag laser-MAG arc welding processes.
No full textIn the hybrid laser-arc welding process, a laser beam and an electric arc are coupled in order to combine the advantages of both processes: high welding speed, low thermal load and high depth penetration thanks to the laser; less demanding on joint preparation/fit-up, typical of arc welding. So the hybrid laser-MIG/MAG (Metal Inert or Active Gas) arc welding has very interesting properties: the improvement of productivity results in higher welding speeds, thicker welded materials, joint fit-up allowance, better stability of molten pool, and improvement of joint metallurgical quality. The understanding of the main relevant involved physical processes are therefore necessary if one wants for example elaborate adequate simulations of this process. Also, for an efficient use of this process, it is necessary to precisely understand the complex physical phenomena that govern this welding technique. This paper investigates the analysis of the effect of the main operating parameters for the laser alone, MAG alone and hybrid Laser/MAG welding processes. The use of a high speed video camera allows us to precisely characterize the melt pool 3-D geometry such as the measurements of its depression and its length and the phenomena occurring inside the melt pool through keyhole-melt pool-droplet interaction. These experimental results will form a database that is used for the validation of a three-dimensional thermal model of hybrid welding process for a rather wide range of operating parameters where the 3-D geometry of the melt pool is taken into account
Soldagem MIG/MAG em transferência metálica por curto-circuito controlado aplicada ao passe de raiz
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós Graduação em Engenharia Mecânica.O presente trabalho consiste no estudo e desenvolvimento do Processo de Soldagem MIG/MAG em Transferência Metálica por Curto-circuito com Controle de Corrente (CCC), dedicado à execução do passe de raiz da solda de dutos, na construção offshore de linhas dutoviárias petrolíferas
Aplicação do processo MIG/MAG pulsado com duplo arame e potenciais isolados em soldagens de revestimentos
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Mecânica.O processo de soldagem MIG/MAG PULSADO Com Duplo Arame e com Potenciais Isolados (MIG/MAG-PDAPI) é uma das ramificações dos sistemas MIG/MAG com duplo arame e é empregado, principalmente, em aplicações que requerem alta taxa de deposição de material. Neste trabalho foram feitos estudos sobre as principais variáveis do processo em soldagens com eletrodos de aço carbono e de arames tubulares, empregando-se a corrente pulsada para a transferência de material. Foram estudados o afastamento entre os arames, a corrente média, o posicionamento dos eletrodos em relação ao sentido de deslocamento dos arcos voltaicos, o comprimento dos arcos e a defasagem entre os pulsos de corrente. O uso do arame tubular visou a aplicação do processo em operações de revestimento. Foi verificado nesse estudo que essas variáveis influenciam a rigidez dos arcos e consequentemente o perfil geométrico dos depósitos. A tecnologia que permite ao duplo arame defasar os pulsos de corrente foi investigada com auxílio de uma câmera de filmagem de alta velocidade, atentando-se para os efeitos que essa tecnologia exerce sobre as transferências metálicas e sobre o comportamento dos arcos voltaicos. Ficou constatado que, para soldagens com corrente pulsada, empregando-se eletrodos de aço carbono maciços, os efeitos dessa variável são mais significativos sobre o perfil de penetração do cordão de solda, do que, sobre a estabilidade dos arcos, para a qual esta proposta tecnológica foi concebida nos atuais sistemas de duplo arame disponíveis. Na etapa referente à aplicação do processo às operações de revestimento, constatou-se que o MIG/MAG-PDAPI pode ser empregado com sucesso, uma vez que foram obtidas altas taxas de deposição de material, conciliadas à formação de cordões largos e planos, condições desejáveis para essas aplicações. No final do trabalho, foi proposto o desenvolvimento de um programa de seleção automática das variáveis de soldagem para essa aplicação específica. As equações paramétricas que integram o programa foram testadas em ensaios de simulação e mostraram-se adequadas para a estimação das variáveis
Desenvolvimento de tecnologias no processo MIG/MAG para aumento de produtividade e melhoria da qualidade mediante o uso da polaridade negativa
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós Graduação em Engenharia Mecânica, Florianópolis. 2011Este trabalho trata do estudo feito sobre a aplicabilidade da polaridade negativa no processo MIG/MAG. Os desenvolvimentos são divididos em duas partes. A primeira parte é focada no uso em conjunto das polaridades positiva e negativa como estratégia para aumentar a produtividade e alcançar características específicas almejadas em procedimentos de revestimento por soldagem como, por exemplo, a baixa diluição. Na literatura clássica o processo MIG/MAG com polaridade negativa é definido como instável e apresenta muitos respingos. Trabalhos mais recentes mostram que para determinada faixa de corrente e gás de proteção é possível conseguir cordões sem defeitos utilizando somente a polaridade negativa no processo MIG/MAG. Entretanto, os resultados apresentados nestas literaturas são de deposito sobre chapa e cordões de alta convexidade, o que dificilmente reflete uma situação de aplicação real. A alta convexidade do cordão de solda e a conseqüente baixa penetração fazem com que os resultados não apresentem perspectiva de aplicação em soldagens de união. Nem mesmo em soldagens de revestimento onde baixa penetração é uma condição favorável é possível utilizar a polaridade negativa. Devido à convexidade da solda, a realização de cordões lado a lado resulta em falhas de fusão. Para solucionar estes problemas de soldagem foi desenvolvida uma estratégia de troca de polaridade sincronizada com a posição da tocha no movimento de tecimento. A polaridade negativa é aplicada na região central do cordão de solda enquanto que a polaridade positiva é usada nas regiões laterais. Desta maneira é possível fazer uso da polaridade negativa para aumentar a taxa de deposição e diminuir a penetração garantindo que, com a polaridade positiva, não ocorram pontos de falha de fusão nas laterais dos cordões. Na segunda parte do trabalho a polaridade negativa é aplicada na soldagem de uma peça da indústria automotiva nas mesmas condições de um posto de trabalho industrial. A velocidade de soldagem alcançada é da ordem de processos de alta produtividade como o MIG/MAG duplo arame. As soldas foram aprovadas pela norma interna da empresa que cedeu as peças para os ensaios. Neste tipo de aplicação a polaridade negativa mostrou colaborar com o aumento da velocidade de soldagem sem o aparecimento de defeitos que desqualificassem a solda. De maneira geral para algumas aplicações de revestimento e soldagem de união de chapas finas, a soldagem MIG/MAG pode ser utilizada com polaridade de eletrodo negativo mediante aplicação de técnicas que minimizem as falhasThis dissertation is a research on the applicability of negative polarity using GMAW processes. This research is divided into two parts. The first part is based on the combined use of positive and negative polarity as a strategy to achieve specific characteristics that are desired in overlay welding process, as an example the low dilution process. In classic literature the GMAW process with negative polarity is defined as unstable and as a result presents a lot of spatter. Recent studies show that, for a certain range of current and gas protection, it is possible to obtain weld seams without defects using only the negative polarity on GMAW processes. However, the results presented in these literatures are on deposit sheet and strands of high convexity, which hardly reflects a real application. The high convexity of a weld and the resulting low penetration, results in a low applicability in join welding. Not even in overlay welding, which low penetration is a favorable condition, it is possible to use negative polarity. Due to welding convexity, the realization of stands side by side results in a fusion failure. To solve the problem of this welding process it was developed a strategy of changing polarity in synchronized parameters with the torch trajectory on weaving motion. The negative polarity is applied to the central part of the weld seam while the positive polarity is applied to the borders. This way it is possible to use the negative polarity to increase the deposition rate and therefore decrease the penetration, and with positive polarity ensure that points of fusion failure will not occur on the borders of the weld bead. In the second part of this work, the negative polarity is applied to the automotive welding industry under the same terms as an industrial work station. The welding speed achieved is compared to high speed productive processes such as GMAW double wired. The welds were approved by the company's internal regulations, which also gave the parts for testing purposes. To this type of application the negative polarity showed to be efficient with an increase on welding speed without been disqualified by welding defects occurrences. However for some applications of overlay and thin metal union, the GMAW can be used with negative polarity electrode by applying techniques that minimize these types of failure
Wpływ wysokości nadlewu lica spoiny na koszty materiałów dodatkowych w procesie spawania metodą MAG (135)
No full textThis article analyzes influence of the height of the weld reinforcement on the cost of additional materials in the MAG welding process. For this purpose, a simple calculator was created based on which the welds were calculated in the quality levels B, C and D and the costs of additional materials for butt joints made of low-alloy and high-alloy steel and T-joints made of low-alloy steel. Considerations on this subject were carried out based on the PN-EN ISO 5817 standard defining quality levels according to welding nonconformities. The losses resulting from exceeding a given quality level are presented.W artykule dokonano analizy wpływu wysokości nadlewu spoin czołowych i pachwinowych na koszty materiałów dodatkowych w procesie spawania metodą MAG. W tym celu utworzono kalkulator Excel ułatwiający obliczenie mas spoin w poziomach jakości B, C i D oraz porównanie kosztów materiału dodatkowych złączy doczołowych ze stali niskostopowej i wysokostopowej a także złączy
teowych ze stali niskostopowej. Rozważania prowadzono w oparciu o wymagania PN-EN ISO 5817 określające poziomy jakości według niezgodności spawalniczych. Przedstawiono straty wynikające z niedotrzymania wymaganego poziomu jakości
Novos métodos de controle da soldagem MIG/MAG
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia Mecânica.Os processos de soldagem a arco elétrico, hoje conhecidos, já s
Improved productivity in fusion welding : executive summary
No full textThis document is an Executive Summary of individual submissions of work that the
author has submitted towards the degree of Engineering Doctorate. The work
comprises three main themes, which can be demonstrated in a broader sense as
contributing towards improved productivity in fusion welding:
i) The use of active fluxes for Tungsten Inert Gas (TIG) welding.
ii) An investigation into the reduction of porosity when Metal Active Gas (MAG)
welding galvanneal coated steel sheet used in the automotive industry.
iii) The use of high power Nd:YAG laser welding for the production of large
diameter, long distance land pipelines.
Active fluxes give improved productivity by increasing the penetration depth of the
TIG welding process by the simple addition of a flux applied to the surface.
Although the productivity benefits of the process had been proven through a joint
TWIIindustry project, the mechanism by which the fluxes produced this
improvement was not fully understood. The first theme investigated the mechanisms
at work in providing increased penetration and concluded that the primary
mechanism responsible for the action of the fluxes was not due to a change in the
flow of the molten pool but, as others had suggested, due to arc constriction. This
work contributed to a greater understanding of the welding process and,
furthermore, a greater understanding of the potential opportunities and limitations of
the process when designing new fluxes for other alloy systems.
MAG welds in coated steel sheet used in the automotive industry are prone to
porosity leading to high reject rates. The second phase of work reported here
determined welding procedures capable of delivering low porosity welds developed
through statistical experimental design. These procedures demonstrated how low
porosity welds could be made using conventional MAG welding techniques on
steels that had been galvanneal coated to provide corrosion resistance. The
procedures developed could be easily implemented at high production rates in an
industrial manufacturing environment to reduce defect levels, and thus costly repairs
or high scrap rates.
The third theme of the work demonstrated how Nd:YAG laser welding could
potentially be used to replace conventional arc welding techniques for land lay of
gas transmission pipelines. The application of a single laser fill pass, made at high
production rates, could replace the use of multiple MAG welding stations greatly
reducing the costs associated with pipeline fabrication. BP has claimed that half
pipeline cost savings of up to $300 million dollars are achievable through the
implementation of such a technique. The justification for the use of lasers in
pipelines is discussed in terms of both technical and economic suitability.
Preliminary experimental work showed that high power Nd:YAG laser welds could
achieve productivity targets, although in order to reduce defects and achieve the
necessary structural performance it would be necessary to combine laser welding
with a MAG welding process
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