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- Gisterå, A., et al.
(författare)
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Vaccination against T-cell epitopes of native ApoB100 reduces vascular inflammation and disease in a humanized mouse model of atherosclerosis
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:4, s. 383-397
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: The T-cell response to low-density lipoprotein (LDL) in the vessel wall plays a critical role in atherosclerotic plaque formation and stability. In this study, we used a new translational approach to investigate epitopes from human apolipoprotein B100 (ApoB100), the protein component of LDL, which triggers T-cell activation. We also evaluated the potential of two selected native ApoB100 epitopes to modulate atherosclerosis in human ApoB100-transgenic Ldlr-/- (HuBL) mice. Methods and Results: HuBL mice were immunized with human atherosclerotic plaque homogenate to boost cellular autoimmune response to tissue-derived ApoB100 epitopes. In vitro challenge of splenocytes from immunized mice with a library of overlapping native peptides covering human ApoB100 revealed several sequences eliciting T-cell proliferation. Of these sequences, peptide (P) 265 and P295 were predicted to bind several human leucocyte antigen (HLA) haplotypes and induced high levels of interferon (IFN)-γ. Vaccination of HuBL mice with these peptides mounted a strong adaptive immune response to native ApoB100, including high levels of epitope-specific plasma IgGs. Interestingly, P265 and P295 vaccines significantly decreased plaque size, reduced macrophage infiltration and increased IgG1 deposition in the plaques. Purified IgGs from vaccinated mice displayed anti-inflammatory properties against macrophages in vitro, reducing their response to LPS in a dose-dependent manner. Conclusion: We identified two specific epitopes from human native ApoB100 that trigger T-cell activation and protect HuBL mice against atherosclerosis when used in a vaccine. Our data suggest that vaccination-induced protective mechanisms may be mediated at least in part through specific antibody responses to LDL that inhibit macrophage activation.
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| 2. |
- Hibbard, G, et al.
(författare)
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Thermal stability of nanostructured electrodeposits
- 2002
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Ingår i: Materials Science Forum. - 1662-9752 .- 0255-5476. ; 386-388, s. 387-396
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Tidskriftsartikel (refereegranskat)abstract
- As a result of their unique, but well-behaved structure-property relationships, porosity free nanostructured electrodeposits in the form of thin and thick coatings, free-standing sheet, foil or wire, and complex shapes, are rapidly finding applications in many different areas. Because of the large driving force for grain growth in these materials, however, their thermal stability may be a critical issue for some applications. This paper reviews previous grain growth studies of nanostructured electrodeposits. Thermal stability has been evaluated using several different experimental approaches. Calorimetric studies of nanocrystalline nickel based electrodeposits have shown a general trend of increasing thermal stability by alloying with either P or Fe. There is, however, little agreement between the various studies in terms of suggested growth mechanisms. Indeed, because of the large range of annealed structures obtained from different annealing treatments, several distinct growth mechanisms have been suggested. Recent grain growth studies of nanostructured Ni electrodeposits, covering a much broader range of annealing conditions than used before, have shown that the multiple types of previously reported annealed structures are in fact the product of a multi-staged growth process.
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| 6. |
- Deckers, Tobias, et al.
(författare)
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Impact of processing gas composition on process stability and properties of PBF-LB/M processed alloy 718
- 2024
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Ingår i: Journal of Manufacturing Processes. - 1526-6125. ; 120, s. 712-718
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Tidskriftsartikel (refereegranskat)abstract
- The almost unlimited design freedom of the laser-based powder bed fusion of metals (PBF-LB/M) makes this technology very attractive for industry. However, as a developing technology, it still faces some challenges when it comes to productivity and robustness, to name some. Whereas numerous studies covered the impact of laser-based parameters on material properties and robustness, the effect of the processing gas received limited attention. The objective of this study was to evaluate the effect of processing gas composition, containing helium (He) and hydrogen (H2), compared to conventionally used argon (Ar), during PBF-LB/M processing of virgin alloy 718 powder, on printing behavior and part properties. The four gases studied were Ar, Ar +30%He, Ar +30%He +2%H2, and Ar +70%He. Optical Tomography (OT) was used to monitor process stability, which unveiled a significant decrease in process-by products (spatters) between 51 % and 89 % using He and H2-containing gases. It was also found that the process gas decreased the bulk porosity from an average value of 0.08 % when processed with Ar to 0.04 % when using Ar + 70%He. The oxygen pickup by the spatter particles was reduced from 630 ppm (Ar) to 331 ppm (Ar +70%He). EBSD analysis revealed that there were no evident changes in microstructure with the processing gas. The samples processed also had similar tensile properties with yield and ultimate tensile strength of 1180 MPa and 1395 MPa, respectively. However, there was a slight increase in ductility from 16.5 % to 17.2 %, when processed with pure Ar and Ar + 70%He, respectively. This study shows that utilizing standard Ar processing atmosphere with He addition leads to a more stable process with reduced spatter, porosity and a marginal increase in ductility for Alloy 718.
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| 7. |
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| 8. |
- Klement, G., et al.
(författare)
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A tyrosine substitution in the cavity wall of a K channel induces an inverted inactivation
- 2008
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 94:8, s. 3014-3022
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Tidskriftsartikel (refereegranskat)abstract
- Ion permeation and gating kinetics of voltage-gated K channels critically depend on the amino-acid composition of the cavity wall. Residue 470 in the Shaker K channel is an isoleucine, making the cavity volume in a closed channel insufficiently large for a hydrated K+ ion. In the cardiac human ether-a-go-go-related gene channel, which exhibits slow activation and fast inactivation, the corresponding residue is tyrosine. To explore the role of a tyrosine at this position in the Shaker channel, we studied I470Y. The activation became slower, and the inactivation faster and more complex. At +60 mV the channel inactivated with two distinct rates (t1 = 20 ms, t2 = 400 ms). Experiments with tetraethylammonium and high K + concentrations suggest that the slower component was of the P/C-type. In addition, an inactivation component with inverted voltage dependence was introduced. A step to -40 mV inactivates the channel with a time constant of 500 ms. Negative voltage steps do not cause the channel to recover from this inactivated state (t » 10 min), whereas positive voltage steps quickly do (t = 2 ms at +60 mV). The experimental findings can be explained by a simple branched kinetic model with two inactivation pathways from the open state. © 2008 by the Biophysical Society.
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| 11. |
- Strondl, A., et al.
(författare)
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Effect of Processing on Microstructure and Physical Properties of Three Nickel-Based Superalloys with Different Hardening Mechanisms
- 2012
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Ingår i: Advanced Engineering Materials. - : Wiley. - 1527-2648 .- 1438-1656. ; 14:7, s. 427-438
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Tidskriftsartikel (refereegranskat)abstract
- The nickel-based superalloys Inconel alloy 600, Udimet alloy 720, and Inconel alloy 718 were produced by electron beam melting (EBM), casting, and directional solidification (DS). The distance between dendrites and the size of the precipitates indicated the difference in solidification rates between the three processes. In this study, the solidification rate was fastest with EBM, closely followed by casting, whereas it was much slower with DS. In the directional solidified materials the direction was the fastest and thus, preferred growth direction. The EBM samples show a sharp (001)[100] texture in the building direction and in the two scanning directions of the electron beam. Macrosegregation was observed in some cast and directionally solidified samples, but not in the EBM samples. The melting temperatures are in good agreement with literature and the narrow melting interval of IN600 compare to UD720 and IN718 might reduce the risk of incipient melting during EBM processing. Porosity was observed in the EBM samples and the reasons are discussed. However, EBM seems to be a feasible process route to produce nickel-based superalloys with well-defined texture, no macrosegregation and a rapidly solidified microstructure.
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| 14. |
- Århem, P., et al.
(författare)
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Channel density regulation of firing patterns in a cortical neuron model
- 2006
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 90:12, s. 4392-4404
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Tidskriftsartikel (refereegranskat)abstract
- Modifying the density and distribution of ion channels in a neuron (by natural up- and downregulation or by pharmacological intervention or by spontaneous mutations) changes its activity pattern. In this investigation we analyzed how the impulse patterns are regulated by the density of voltage-gated channels in a neuron model based on voltage-clamp measurements of hippocampal interneurons. At least three distinct oscillatory patterns, associated with three distinct regions in the Na-K channel density plane, were found. A stability analysis showed that the different regions are characterized by saddle-node, double-orbit, and Hopf-bifurcation threshold dynamics, respectively. Single, strongly graded action potentials occur in an area outside the oscillatory regions, but less graded action potentials occur together with repetitive. ring over a considerable range of channel densities. The relationship found here between channel densities and oscillatory behavior may partly explain the difference between the principal spiking patterns previously described for crab axons (class 1 and 2) and cortical neurons ( regular. ring and fast spiking).
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