| 1. |
|
|
| 2. |
- Lindström, Per, 1967-, et al.
(författare)
-
Materials and Fabrication Technology : Committee v.3
- 2015. - 1
-
Ingår i: Proceedings of the 19th International Ship and Offshore Structures Congress, Volume 2. - EH Leiden, Nederlands : CRC Press. - 9781138028975 - 9781138028968 ; , s. 619-698
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Due to the past crises, the shipbuilding and offshore industry has realised that new innovative designs and design and production methods are necessary to decrease operational costs, production costs and emissions,while meeting the changing rules and regulations. This ISSC-V.3 report is discussing recent developmentin materials and fabrication technology applied to ship and offshore structures.Chapter 2 focuses on worldwide trends in materials and fabrication methods. Developments in metallicand non-metallic structural materials are dealt in Chapter 3. Advances in fabrication and joining technologiessuch as welding are increasing. Some main areas of applications and research in those areas aredescribed in Chapter 4. Innovative development about corrosion protection systems are presented inChapter 5 while Chapter 6 give an overview about the application of production simulation and virtualreality to improve the production management of ship and offshore structures.The ISSC-V.3 technical committee has performed a benchmark to define a Best Practice Guideline touse Computational Welding Mechanics tools (CWM) in shipbuilding and offshore industry. To achievethis objective various experimental welding tests have been performed in order to give a reference point.Both the residual welding distortions and residual stresses have been compared between numerical simulationsand welding experiments for a common “T” welded assembly used in the shipbuilding industry.However, it has been decided to publish the results of this study in a separate document. Nevertheless, Chapter 7 of this report presents the state of the art as well as the experimental test case that has been analysed.
|
|
| 3. |
- Blanch, Ewan W, et al.
(författare)
-
Is polyproline II helix the killer conformation? A Raman optical activity study of the amyloidogenic prefibrillar intermediate of human lysozyme.
- 2000
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 301:2, s. 553-563
-
Tidskriftsartikel (refereegranskat)abstract
- The amyloidogenic prefibrillar partially denatured intermediate of human lysozyme, prepared by heating the native protein to 57 degrees C at pH 2.0, was studied using Raman optical activity (ROA). A positive band in the room temperature ROA spectrum of the native protein at approximately 1345 cm(-1), assigned to a hydrated form of alpha-helix, is not present in that of the prefibrillar intermediate, where a new strong positive band at approximately 1318 cm(-1) appears instead that is assigned to the poly(l-proline) II (PPII)-helical conformation. A sharp negative band at approximately 1241 cm(-1) in the native protein, assigned to beta-strand, shows little change in the ROA spectrum of the prefibrillar intermediate. The disappearance of a positive ROA band at approximately 1551 cm(-1) assigned to vibrations of tryptophan side-chains indicates that major conformational changes have occurred among the five tryptophan residues present in human lysozyme, four of which are located in the alpha-domain. The various ROA data suggest that a substantial loss of tertiary structure has occurred in the prefibrillar intermediate and that this is located more in the alpha-domain than in the beta-domain. There is no evidence for any increase in beta-structure. The ROA spectrum of hen lysozyme, which does not form amyloid fibrils so readily, remains much more native-like on heating to 57 degrees C at pH 2.0. The thermal behaviour of the alanine-rich alpha-helical peptide AK21 in aqueous solution was found to be similar to that of human lysozyme. Hydrated alpha-helix therefore appears to readily undergo a conformational change to PPII structure on heating, which may be a key step in the conversion of alpha-helix into beta-sheet in the formation of amyloid fibrils in human lysozyme. Since it is extended, flexible, lacks intrachain hydrogen bonds and is fully hydrated in aqueous solution, PPII helix has the appropriate characteristics to be implicated as a critical conformational element in many conformational diseases. Disorder of the PPII type may be a sine qua non for the formation of regular fibrils; whereas the more dynamic disorder of the random coil may lead only to amorphous aggregates.
|
|
| 4. |
|
|
| 5. |
- Hammitzsch, A, et al.
(författare)
-
Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 15645-
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, cultured in-vitro under Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFNγ were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow. In-vitro inhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing of JAK1-3 and Tyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS.
|
|
| 6. |
|
|
