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| 12. |
- Rando, Halie M, et al.
(författare)
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Molecular and Serologic Diagnostic Technologies for SARS-CoV-2
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The COVID-19 pandemic has presented many challenges that have spurred biotechnological research to address specific problems. Diagnostics is one area where biotechnology has been critical. Diagnostic tests play a vital role in managing a viral threat by facilitating the detection of infected and/or recovered individuals. From the perspective of what information is provided, these tests fall into two major categories, molecular and serological. Molecular diagnostic techniques assay whether a virus is present in a biological sample, thus making it possible to identify individuals who are currently infected. Additionally, when the immune system is exposed to a virus, it responds by producing antibodies specific to the virus. Serological tests make it possible to identify individuals who have mounted an immune response to a virus of interest and therefore facilitate the identification of individuals who have previously encountered the virus. These two categories of tests provide different perspectives valuable to understanding the spread of SARS-CoV-2. Within these categories, different biotechnological approaches offer specific advantages and disadvantages. Here we review the categories of tests developed for the detection of the SARS-CoV-2 virus or antibodies against SARS-CoV-2 and discuss the role of diagnostics in the COVID-19 pandemic.
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| 14. |
- Strollo, Rocky, et al.
(författare)
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Autoantibody and T cell responses to oxidative post-translationally modified insulin neoantigenic peptides in type 1 diabetes
- 2023
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:1, s. 132-146
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Antibodies specific to oxidative post-translational modifications (oxPTM) of insulin (oxPTM-INS) are present in most individuals with type 1 diabetes, even before the clinical onset. However, the antigenic determinants of such response are still unknown. In this study, we investigated the antibody response to oxPTM-INS neoepitope peptides (oxPTM-INSPs) and evaluated their ability to stimulate humoral and T cell responses in type 1 diabetes. We also assessed the concordance between antibody and T cell responses to the oxPTM-INS neoantigenic peptides. Methods oxPTM-INS was generated by exposing insulin to various reactive oxidants. The insulin fragments resulting from oxPTM were fractionated by size-exclusion chromatography further to ELISA and LC-MS/MS analysis to identify the oxidised peptide neoepitopes. Immunogenic peptide candidates were produced and then modified in house or designed to incorporate in silico-oxidised amino acids during synthesis. Autoantibodies to the oxPTM-INSPs were tested by ELISA using sera from 63 participants with new-onset type 1 diabetes and 30 control participants. An additional 18 fresh blood samples from participants with recently diagnosed type 1 diabetes, five with established disease, and from 11 control participants were used to evaluate, in parallel, CD4(+) and CD8(+) T cell activation by oxPTM-INSPs. Results We observed antibody and T cell responses to three out of six LC-MS/MS-identified insulin peptide candidates: A:12-21 (SLYQLENYCN, native insulin peptide 3 [Nt-INSP-3]), B:11-30 (LVEALYLVCGERGFFYTPKT, Nt-INSP-4) and B:21-30 (ERGFFYTPKT, Nt-INSP-6). For Nt-INSP-4 and Nt-INSP-6, serum antibody binding was stronger in type 1 diabetes compared with healthy control participants (p <= 0.02), with oxidised forms of ERGFFYTPKT, oxPTM-INSP-6 conferring the highest antibody binding (83% binders to peptide modified in house by hydroxyl radical [(OH)-O-?] and >88% to in silico-oxidised peptide; p <= 0.001 vs control participants). Nt-INSP-4 induced the strongest T cell stimulation in type 1 diabetes compared with control participants for both CD4(+) (p<0.001) and CD8(+) (p=0.049). CD4(+) response to oxPTM-INSP-6 was also commoner in type 1 diabetes than in control participants (66.7% vs 27.3%; p=0.039). Among individuals with type 1 diabetes, the CD4(+) response to oxPTM-INSP-6 was more frequent than to Nt-INSP-6 (66.7% vs 27.8%; p=0.045). Overall, 44.4% of patients showed a concordant autoimmune response to oxPTM-INSP involving simultaneously CD4(+) and CD8(+) T cells and autoantibodies. Conclusions/interpretation Our findings support the concept that oxidative stress, and neoantigenic epitopes of insulin, may be involved in the immunopathogenesis of type 1 diabetes.
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| 15. |
- Vincent, F. H., et al.
(författare)
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Geometric modeling of M87*as a Kerr black hole or a non-Kerr compact object
- 2021
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 646
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Event Horizon Telescope (EHT) collaboration recently obtained the first images of the surroundings of the supermassive compact object M87* at the center of the galaxy M87. This provides a fascinating probe of the properties of matter and radiation in strong gravitational fields. It is important to determine from the analysis of these results what can and cannot be inferred about the nature of spacetime around M87*Aims. We want to develop a simple analytic disk model for the accretion flow of M87*. Compared to general-relativistic magnetohydrodynamic models, this new approach has the advantage that it is independent of the turbulent character of the flow and is controlled by only a few easy-to-interpret, physically meaningful parameters. We want to use this model to predict the image of M87*, assuming that it is either a Kerr black hole or an alternative compact object.Methods. We computed the synchrotron emission from the disk model and propagate the resulting light rays to the far-away observer by means of relativistic ray tracing. Such computations were performed assuming different spacetimes, such as Kerr, Minkowski, nonrotating ultracompact star, rotating boson star, or Lamy spinning wormhole. We performed numerical fits of these models to the EHT data.Results. We discuss the highly lensed features of Kerr images and show that they are intrinsically linked to the accretion-flow properties and not only to gravitation. This fact is illustrated by the notion of the secondary ring, which we introduce. Our model of a spinning Kerr black hole predicts mass and orientation consistent with the EHT interpretation. The non-Kerr images result in a similar quality of numerical fits and may appear very similar to Kerr images, once blurred to the EHT resolution. This implies that a strong test of the Kerr spacetime may be out of reach with the current data. We note that future developments of the EHT could alter this situation.Conclusions. Our results show the importance of studying alternatives to the Kerr spacetime to be able to test the Kerr paradigm unambiguously. More sophisticated treatments of non-Kerr spacetimes and more advanced observations are needed to proceed further in this direction.
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