| 1. |
- Fieblinger, Tim, et al.
(författare)
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Mechanisms of Dopamine D1 Receptor-Mediated ERK1/2 Activation in the Parkinsonian Striatum and Their Modulation by Metabotropic Glutamate Receptor Type 5
- 2014
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 34:13, s. 4728-4740
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Tidskriftsartikel (refereegranskat)abstract
- In animal models of Parkinsons disease, striatal overactivation of ERK1/2 via dopamine (DA) D1 receptors is the hallmark of a supersensitive molecular response associated with dyskinetic behaviors. Here we investigate the pathways involved in D1 receptor-dependent ERK1/2 activation using acute striatal slices from rodents with unilateral 6-hydroxydopamine (6-OHDA) lesions. Application of the dopamine D1-like receptor agonist SKF38393 induced ERK1/2 phosphorylation and downstream signaling in the DA-denervated but not the intact striatum. This response was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent of ionotropic glutamate receptors but blocked by antagonists of L-type calcium channels. Coapplication of an antagonist of metabotropic glutamate receptor type 5 (mGluR5) or its downstream signaling molecules (PLC, PKC, IP3 receptors) markedly attenuated SKF38393-induced ERK1/2 activation. The role of striatal mGluR5 in D1-dependent ERK1/2 activation was confirmed in vivo in 6-OHDA-lesioned animals treated systemically with SKF38393. In one experiment, local infusion of the mGluR5 antagonistMTEPin the DA-denervated rat striatum attenuated the activation of ERK1/2 signaling by SKF38393. In another experiment, 6-OHDA lesions were applied to transgenic mice with a cell-specific knockdown of mGluR5 in D1 receptor-expressing neurons. These mice showed a blunted striatal ERK1/2 activation in response to SFK38393 treatment. Our results reveal that D1-dependent ERK1/2 activation in the DA-denervated striatum depends on a complex interaction between PKA-and Ca2+ -dependent signaling pathways that is critically modulated by striatal mGluR5.
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| 2. |
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| 3. |
- Rebeggiani, Sabina, et al.
(författare)
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A quantitative method to estimate high gloss polished tool steel surfaces
- 2011
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Ingår i: Journal of Physics, Conference Series. - Bristol : Institute of Physics Publishing (IOPP). - 1742-6588 .- 1742-6596. ; 311:1, s. 35-39
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Tidskriftsartikel (refereegranskat)abstract
- Visual estimations are today the most common way to assess the surface quality of moulds and dies; a method that are both subjective and, with today’s high demands on surfaces, hardly usable to distinguish between the finest surface qualities. Instead a method based on non-contact 3D-surface texture analysis is suggested. Several types of tool steel samples, manually as well as machine polished, were analysed to study different types of surface defects such as pitting, orange peel and outwardly features. The classification of the defect structures serves as a catalogue where known defects are described. Suggestions of different levels of ‘high surface quality’ defined in numerical values adapted to high gloss polished tool steel surfaces are presented. The final goal is to develop a new manual that can work as a ‘standard’ for estimations of tool steel surfaces for steel producers, mould makers, polishers etc.
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| 4. |
- Rebeggiani, Sabina, et al.
(författare)
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Polished injection moulds’ and surface defects’ influence on the quality of plastic components
- 2009
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Ingår i: Proceedings of the 12th International Conference on Metrology and Properties of Engineering Surfaces. - Rzeszów : Rzeszów University of Technology. ; , s. 396-397
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Konferensbidrag (refereegranskat)abstract
- The quality of injection mould surfaces is important as it has a major influence on tool performance. In the specific field of plastic moulding, many products require defect free, glossy, and very smooth mould surfaces (roughness parameters in the nm-range) to achieve a satisfactory surface appearance. The surface quality is also crucial for the mould to function properly in the actual tooling application; too rough surfaces might disturb the flow of the polymer melt and increase wear, while too smooth surfaces give rise to sticking problems. A key factor towards improved tool performance is the development of a metrology framework to characterise the polished surfaces. This paper summarises a study based on a non-contact 3D-surface texture analysis, where tool steel moulds and injection moulded plastic components are characterised in terms of surface quality. Different types of defects, such as non-metallic inclusions and carbides, are studied in more detail to better understand their effect on final plastic component surfaces. Critical defect size?, Types of defects? and Defect distribution? are typical questions at issue. A test mould with intentional manufactured pores and scratches in different sizes and distributions will be designed and verified in order to enable injection mould industry to optimize selection of polymer and process variables with respect to plastic component surface quality and tool material selection.
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| 5. |
- Rebeggiani, Sabina, 1980-, et al.
(författare)
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Surface characterisation of high gloss polished tool steels
- 2009
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Ingår i: Proceedings of the 8th International Tooling Conference. - Aachen : Mainz. - 3861307014 - 9783861307013 ; , s. 953-963
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Konferensbidrag (refereegranskat)abstract
- It is well known that high quality tool steels, i.e. steels possessing low contents of defect structures, and the adoption of well developed polishing techniques are required to get satisfactory mould surfaces for plastic forming. However, there is still a lack of knowledge concerning how different defect structures on mould surfaces affect final plastic components, and how tool steel surfaces can be measured and analysed in convenient ways.Based on non-contact 3D-surface texture analysis, three test moulds and corresponding injection moulded plastic plaques were characterised with the objective to study how defect structures on the mould surfaces were transferred into the final plastic components.Surface structures, remaining scratches and to a certain extent pin-holes originated from the mould surface were all detected on the surface of the plastic components. However, more extensive studies need to be performed in order to understand why different defect structures on tool steels occur, how they can be avoided and, for different plastic products, which the critical limits are (in terms of amount, shape and size of the defects).
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| 6. |
- Rebeggiani, Sabina, 1980-, et al.
(författare)
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Tool steel polishing and topography characterization
- 2007
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Ingår i: The Swedish Production Symposium in Göteborg 28-30 August 2007.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Manual polishing is a common method to accomplish a mirror-like mould surface, although it is a cumbersome and time-consuming process. It is, thus, of great interest within the industry to find faster and better polishing techniques to decrease the costs and lead times. A key factor towards improved polishing techniques is to find ways to characterize polished surfaces; which parameters and instruments can be used and what is the definition of polishability? This paper summarises a study where three steel grades were analysed with five different measuring devices. The results showed that mechanical stylus instrumentations are not enough to describe very smooth surfaces, but measurement devices with better resolution are needed, such as interferometers.
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| 7. |
- Sarwar, Martuza, et al.
(författare)
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Protein kinase A (PKA) pathway is functionally linked to androgen receptor (AR) in the progression of prostate cancer
- 2014
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 32:1, s. 25.e1-25.e12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In the present study, we investigated whether the cyclic adenosine monophosphate (cAMP)-activated protein kinase A (PKA) pathway may regulate the expression of AR and prostate-specific antigen (PSA) and whether there is a correlation between the expression of cAMP/PKA-associated genes and androgen receptor (AR) in patients with prostate cancer (CaP).MATERIALS AND METHODS: The functional studies were performed in LNCaP and PC3 cell lines. Data on the mRNA expression of sets of genes in human clinical samples, including prostate tissues from organ donors, prostate primary cancer, and metastatic cancer, were extracted from the National Center for Biotechnology Informations Gene Expression Omnibus (GEO) database. Statistical tests were applied.RESULTS: We showed that elevated levels of cAMP/PKA pathways induced an increased expression of AR and PSA proteins in LNCaP cells in the absence of androgen. A cAMP-associated phosphodiesterase-4 (PDE4) inhibitor, rolipram induced an up-regulation in AR expression, whereas a cAMP enhancer, forskolin increased PSA level without affecting AR expression. Forskolin treatment increased the level of PKA R1α in LNCaP cells, but remarkably inhibited R1α expression in aggressive PC3 cells. In patients with CaP, we found that the expression of genes encoding R1α and phosphodiesterase-4B was statistically significantly lower in the metastatic specimens than that in the primary CaP specimens or in the normal prostate tissues (P<0.01) and was reversely correlated with AR expression. Conversely, AR and PRKAR2B mRNA expressions were significantly higher in metastatic lesions than those in the primary CaP specimens or in the normal prostate tissues (P<0.01).CONCLUSION: Our study revealed a novel mechanism to precisely define the functional and clinical interrelationship between the cAMP/PKA pathway and AR signaling in the development of androgen-independent growth of CaPs and metastasis progression.
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