| 1. |
|
|
| 2. |
- van Hoof, M., et al.
(author)
-
Clinical Outcomes of Soft Tissue Preservation Surgery With Hydroxyapatite-Coated Abutments Compared to Traditional Percutaneous Bone Conduction Hearing Implant Surgery-A Pragmatic Multi-Center Randomized Controlled Trial
- 2020
-
In: Frontiers in Surgery. - : Frontiers Media SA. - 2296-875X. ; 7
-
Journal article (peer-reviewed)abstract
- Background: Soft tissue preservation using a hydroxyapatite-coated abutment in bone conduction hearing implant surgery may lead to improved clinical outcomes over the short (1 year) and long term (3 years). Methods: In this open multi-center, randomized (1:1), controlled clinical trial, subjects with conductive, mixed hearing loss or single-sided sensorineural deafness were randomly assigned to receive the conventional intervention, a titanium abutment with soft tissue reduction surgery (control), or a new intervention, a hydroxyapatite-coated abutment with soft tissue preservation surgery (test). The primary efficacy outcome was the combined endpoint of numbness, pain, peri-abutment dermatitis, and soft tissue thickening/overgrowth after 1 and 3 years. Results: The Intention-to-treat (ITT) population consisted of 52 control subjects and 51 test subjects. The difference between the groups after 1 year of follow-up as measured by the primary efficacy outcome was not statistically significant (p = 0.12) in the ITT population (n = 103), but did reach statistical significance (p = 0.03) in the per-protocol (PP) population (n = 96). It showed an advantage for the test group, with over twice as many subjects (29%) without these medical events during the first year compared to the control group (13%). After 3 years, the difference between the two groups had declined and did not reach statistical significance (24 vs. 10%, ITT p = 0.45). Secondary outcome measures which showed a statistical significant difference during the first year, such as surgical time (15 vs. 25 minutes, p < 0.0001), numbness (90 vs. 69% of subjects experienced no numbness at 1 year, p < 0.01), neuropathic pain at 3 months (p = 0.0087) and the overall opinion of the esthetic outcome (observer POSAS scale at 3 months, p < 0.01) were favorable for the test group. More soft tissue thickening/overgrowth was observed at 3 weeks for the test group (p = 0.016). Similar results were achieved for the long term follow up. Conclusions: Soft tissue preservation with a hydroxyapatite-coated abutment leads to a reduction in the combined occurrence of complications over the first year which is not statistically significant in the ITT population but is in the PP population. This effect decreased for the long-term study follow up of 3 years and did also not reach statistical significance.
|
|
| 3. |
|
|
| 4. |
- Björkbacka, H, et al.
(author)
-
Plasma stem cell factor levels are associated with risk of cardiovascular disease and death
- 2017
-
In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 282:6, s. 508-521
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Stem cell factor (SCF) is a key growth factor for several types of stem and progenitor cells. There is experimental evidence that such cells are of importance for maintaining the integrity of the cardiovascular system. We investigated the association between circulating levels of SCF and risk for development of cardiovascular events and death.METHODS: SCF was analysed by the proximity extension assay technique in plasma from 4742 subjects participating in the Malmö Diet and Cancer Study. Cardiovascular events and death were monitored through national registers with a mean follow-up time of 19.2 years.RESULTS: Subjects with high baseline levels of SCF had lower cardiovascular (n = 340) and all-cause mortality (n = 1159) as well as a lower risk of heart failure (n = 177), stroke (n = 318) and myocardial infarction (n = 452). Smoking, diabetes and high alcohol consumption were associated with lower levels of SCF. Single nucleotide polymorphisms in the gene region encoding PDX1 C-terminal inhibiting factor 1 (PCIF1) and matrix metalloproteinase-9 were associated with plasma SCF levels. The highest SCF quartile remained independently associated with a lower risk of a lower risk of cardiovascular [hazard ratio and 95% confidence interval 0.59 (0.43-0.81)] and all-cause mortality [0.68 (0.57-0.81)], heart failure [0.50 (0.31-0.80)] and stroke [0.66 (0.47-0.92)], but not with MI [0.96 (0.72-1.27)] as compared with the lowest quartile when adjusting for traditional cardiovascular risk factors in Cox proportional hazard regression models.CONCLUSIONS: This prospective population-based study demonstrates that subjects with high levels of SCF have a lower risk of cardiovascular events and death. The findings provide clinical support for a protective role of SCF in maintaining cardiovascular integrity.
|
|
| 5. |
- Choquet, Isabelle, 1965-, et al.
(author)
-
New powder port holder geometry to avoid lump formation in APS
- 2005
-
In: 17th international symposium on plasma chemistry (ISPC 17). ; , s. OP7. 1-6
-
Conference paper (other academic/artistic)abstract
- A new geometry of the powder port ring holder used in atmospheric plasma spraying has recently been designed to avoid lump formation, and successfully tested for a set of process parameters associated with Ni-5Al powder used in production to form bond coat [1]. But with ZrO 2 powder used to made top coat, improvements were not enough satisfactory. Here, we investigate numerically the cause of the remaining defects, and further improve the ring geometry to prevent lump from forming in any part of the coating.
|
|
| 6. |
|
|
| 7. |
- Notarnicola, A., et al.
(author)
-
Serum and balf-derived anti-JO1 autoantibodies exhibit high reactivity to distinct HISRS domains and associate with lung and joint involvement in patients with IIM/ASS
- 2020
-
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1109-1110
-
Journal article (other academic/artistic)abstract
- Autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS) represent the serological marker of the anti-synthetase syndrome (ASS), a major subgroup of the idiopathic inflammatory myopathies (IIM) (1). Among the anti-aaRS, anti-histidyl tRNA synthetase (HisRS) autoantibodies (anti-Jo1) are the most common. Up to 90% of IIM/ASS patients diagnosed with interstitial lung disease (ILD) harbor anti-Jo1 autoantibodies (2).Objectives:Reactivity and affinity of anti-Jo1 autoantibodies from serum and broncheoalveolar lavage fluid (BALF) were investigated against HisRS autoantigen. Associations with clinical data from patients IIM/ASS were addressed.Methods:Total IgGs were purified by affinity chromatography. Samples and clinical data were obtained from: i) 26 anti-Jo1+patients (19 at diagnosis, 16/19 at follow-up, 7 BALF/matching serum at baseline; ii) 29 anti-Jo1-(25 serum at diagnosis, 4 BALF/matching serum at baseline); iii) 24 age/gender matched healthy controls. Anti-Jo1 IgG and IgA response against HisRS was evaluated by ELISA and western blot. Affinity was measured by surface plasmon resonance. HisRS full-length (HisRS-FL), two HisRS domains (ABD and CD), and two HisRS splice variants (WHEP and WHEP + ABD splice variant (SV)) were tested. Correlations between autoantibody reactivity and clinical data, at baseline and over disease course, were evaluated.Results:Anti-Jo1 autoantibodies from serum and lung bound HisRS-FL, WHEP and SV with high reactivity and affinity already at diagnosis and recognized both conformational and linear HisRS epitopes (Fig. 1). Levels of autoantibodies (against HisRS-FL, -domains and -splice variants) varied among patients and overtime. Patients with ILD, arthritis and less skin involvement presented higher anti-Jo1 titers compared to those with lower anti-Jo1 titers and to the anti-Jo1 negative group (Fig. 2). Anti-WHEP reactivity in BALF strongly correlated with poor pulmonary function.Conclusion:High reactivity and affinity at time of diagnosis indicates that autoimmunity against HisRS is most likely initiated before IIM/ASS diagnosis. Reactivity to specific splice variants of HisRS may be employed as diagnostic and prognostic markers.References:[1]Marguerie C, Bunn CC, Beynon HL, Bernstein RM, Hughes JM, So AK, Walport MJ: Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. Q J Med 1990, 77(282):1019-1038[2]Richards TJ, Eggebeen A, Gibson K, Yousem S, Fuhrman C, Gochuico BR, Fertig N, Oddis CV, Kaminski N, Rosas IO et al: Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum 2009, 60(7):2183-2192.Fig. 1.Anti-Jo1 reactivity in total IgG purified from the first available serum sampleFig. 2.Reactivity of total anti-Jo1+ IgG purified from the first available serum close to IIM/ASS diagnosis in relation to clinical dataDisclosure of Interests:Antonella Notarnicola: None declared, Charlotta Preger: None declared, Susanna Lundström: None declared, Nuria Renard: None declared, Edvard Wigren: None declared, Eveline Van Gompel: None declared, Angeles Shunashy Galindo-Feria: None declared, Helena Persson: None declared, Maryam Fathi: None declared, Johan Grunewald: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,, Susanne Gräslund: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Catia Cerqueira: None declared
|
|
| 8. |
- Preger, C., et al.
(author)
-
Generation and validation of recombinant antibodies to study human aminoacyl-tRNA synthetases
- 2020
-
In: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 295:41, s. 13981-13993
-
Journal article (peer-reviewed)abstract
- Aminoacyl-tRNA synthetases (aaRSs) have long been viewed as mere housekeeping proteins and have therefore often been overlooked in drug discovery. However, recent findings have revealed that many aaRSs have noncanonical functions, and several of the aaRSs have been linked to autoimmune diseases, cancer, and neurological disorders. Deciphering these roles has been challenging because of a lack of tools to enable their study. To help solve this problem, we have generated recombinant high-affinity antibodies for a collection of thirteen cytoplasmic and one mitochondrial aaRSs. Selected domains of these proteins were produced recombinantly in Escherichia coli and used as antigens in phage display selections using a synthetic human single-chain fragment variable library. All targets yielded large sets of antibody candidates that were validated through a panel of binding assays against the purified antigen. Furthermore, the top-performing binders were tested in immunoprecipitation followed by MS for their ability to capture the endogenous protein from mammalian cell lysates. For antibodies targeting individual members of the multi-tRNA synthetase complex, we were able to detect all members of the complex, co-immunoprecipitating with the target, in several cell types. The functionality of a subset of binders for each target was also confirmed using immunofluorescence. The sequences of these proteins have been deposited in publicly available databases and repositories. We anticipate that this open source resource, in the form of high-quality recombinant proteins and antibodies, will accelerate and empower future research of the role of aaRSs in health and disease.
|
|
| 9. |
- Szykowska, Aleksandra, et al.
(author)
-
Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain
- 2021
-
In: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 29:11, s. 1241-
-
Journal article (peer-reviewed)abstract
- Mutations in TREM2, a receptor expressed by microglia in the brain, are associated with an increased risk of neurodegeneration, including Alzheimer's disease. Numerous studies support a role for TREM2 in sensing damaging stimuli and triggering signaling cascades necessary for neuroprotection. Despite its significant role, ligands and regulators of TREM2 activation, and the mechanisms governing TREM2-dependent responses and its cleavage from the membrane, remain poorly characterized. Here, we present phage display generated antibody single-chain variable fragments (scFvs) to human TREM2 immunoglobulin-like domain. Co-crystal structures revealed the binding of two scFvs to an epitope on the TREM2 domain distal to the putative ligand-binding site. Enhanced functional activity was observed for oligomeric scFv species, which inhibited the production of soluble TREM2 in a HEK293 cell model. We hope that detailed characterization of their epitopes and properties will facilitate the use of these renewable binders as structural and functional biology tools for TREM2 research.
|
|
| 10. |
- Andersen, J. N., et al.
(author)
-
Surface core-level shifts as a probe of the local overlayer structure : CO on Pd(100)
- 1991
-
In: Physical Review Letters. - 0031-9007. ; 67:20, s. 2822-2825
-
Journal article (peer-reviewed)abstract
- The bonding energies of the Pd 3d and the C 1s core levels have been studied for the p(2 S 2 × 2) R45°, p(3 s2 × S2) R45°, and p(4 S 2 × S 2) R45°structures of CO on Pd(100). Adsorption of CO shifts the Pd 3d surface emission to higher binding energies with the magnitude of the shift depending almost linearly on the number of Pd to CO bonds; the measured shift per bond is close to 0.5 eV. A direct relation is established between the detailed geometry of the CO overlayer and the changes in the Pd 3d spectra.
|
|
| 11. |
|
|
| 12. |
- Björneholm, O., et al.
(author)
-
Resonant photoemission at core-level shake-up thresholds : Valence-band satellites in nickel
- 1990
-
In: Physical Review B (Condensed Matter). - 0163-1829. ; 41:15, s. 10408-10412
-
Journal article (peer-reviewed)abstract
- Three-hole satellites (3d7 final-state configuration) in the nickel valence-band photoelectron spectrum have been identified at 13 and 18 eV binding energy with use of synchrotron radiation from the MAX storage ring. The three-hole satellites show resonances at photon energies close to the threshold for excitation of 3p53d9 core-hole shake-up states. The 13-eV satellite also shows a resonance directly at the 3p threshold. This is interpreted as an interference between the direct three-hole ionization and a shake-up transition in the Auger decay of the 3p hole. This shake-up process is also identified directly in the M2,3M4,5M4,5 Auger spectrum.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- den Besten, C. A., et al.
(author)
-
Stability, Survival, and Tolerability of an Auditory Osseointegrated Implant for Bone Conduction Hearing: Long-Term Follow-Up of a Randomized Controlled Trial
- 2016
-
In: Otology & Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129. ; 37:8, s. 1077-1083
-
Journal article (peer-reviewed)abstract
- Objective: To compare implant stability, survival, and soft tissue reactions for a novel (test) and previous generation (control) percutaneous auditory osseointegrated implant for bone conduction hearing at long-term follow-up of 5 years. Study Design: Single follow-up visit of a previously completed multicenter, randomized, controlled trial. Patients: Fifty-seven of the 77 participants of a completed randomized controlled trial on a new auditory osseointegrated implant underwent a single follow-up visit 5 years after implantation, which comprised implant stability measurements and collection of Holgers scores. Additionally, implant survival was recorded for all 77 patients from the original trial. Results: The test implant showed significantly higher implant stability quotient (ISQ) values compared with the control implant throughout the 5-year follow-up. Mean area under the curve of ISQ high from baseline to 5 years was 71.6 (standard deviation [SD] +/-2.0) and 66.7 (SD +/-3.4) for the test and control implant, respectively (p < 0.0001). For both implants, the mean ISQ value recorded at 5 years was higher compared with implantation (test group +2.03 [SD +/-2.55, within group p < 0.0001] and control group +2.25 [SD +/-4.95, within group p = 0.12]). No difference was noticed in increase from baseline between groups (p = 0.64). Furthermore, evaluation of soft tissue reactions continued to show superiority of the test implant. At the 5-year follow-up visit, one patient (2.5%) presented with a Holgers grade 2 in the test group, compared with four patients (23.5%) in the control group (p = 0.048); no patient presented with more severe soft tissue reactions. Excluding explantations, the survival rate was 95.8% for the test group and 95.0% for the control group. The corresponding rates including explantations were 93.9 and 90.0%. Conclusion: The test implant showed superiority in terms of higher mean ISQ values and less adverse soft tissue reactions, both at the single 5-year follow-up visit and during the complete follow-up. In addition, both implants showed an equally high implant survival.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Ilver, L, et al.
(author)
-
Quantum size effects in epitaxial ErAs on GaAs(001)
- 1996
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 77:24, s. 4946-4949
-
Journal article (peer-reviewed)abstract
- The electronic structure of very thin epitaxial ErAs layers on GaAs(100) is studied with angle resolved photoelectron spectroscopy. Clear evidence is found for confinement induced quantization of states around the Fermi level. From the dispersive properties of the quantum well states effective masses are obtained, representing electron motion parallel to the surface layers and orthogonal to the layers. We find, for the first time, that effective masses along equivalent bulk directions (XW) are significantly different in the thin layers. Furthermore, the bottom of the highest occupied band shifts towards the Fermi level when going from very thin to thick ErAs layers.
|
|
| 20. |
- Lagerqvist, Nina, et al.
(author)
-
Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers
- 2021
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.
|
|
| 21. |
- Liu, Yan, et al.
(author)
-
Experimental and numerical life prediction of thermally cycled thermal barrier coatings
- 2004
-
In: Journal of Thermal Spray Technology. - : Springer Science and Business Media LLC. - 1544-1016 .- 1059-9630 .- 0000-0000. ; 13:3, s. 415-424
-
Research review (peer-reviewed)abstract
- This article addresses the predominant degradation modes and life prediction of a plasma-sprayed thermal barrier coating (TBC). The studied TBC system consists of an air-plasm a-sprayed bond coat and an air-plasma-sprayed, yttria partially stabilized zirconia top layer on a conventional Hastelloy X substrate. Thermal shock tests of air-sprayed TBC and pre-oxidized TBC specimens were conducted under different burner flame conditions at Volvo Aero Corporation (Trollhiittan, Sweden). Finite element models were used to simulate the thermal shock tests. Transient temperature distributions and thermal mismatch stresses in different layers of the coatings during thermal cycling were calculated. The roughness of the interface between the ceramic top coat and the bond coat was modeled through an ideally sinusoidal wavy surface. Bond coat oxidation was simulated through adding an aluminum oxide layer between the ceramic top coat and the bond coat. The calculated stresses indicated that interfacial delamination cracks, initiated in the ceramic top coat at the peak of the asperity of the interface, together with surface cracking, are the main reasons for coating failure. A phenomenological life prediction model for the coating was proposed. This model is accurate within a factor of
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Nyholm, R., et al.
(author)
-
The surface core-level shift of the Pd(100) single-crystal surface
- 1992
-
In: Journal of Physics: Condensed Matter. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 4:1, s. 277-283
-
Journal article (peer-reviewed)abstract
- The surface core-level shift of the Pd(100) single-crystal surface has been measured from high-resolution Pd 3d core-level spectra. The surface atoms are found to have 0.44+or-0.03 eV lower binding energy than the bulk atoms. The result is compared with theoretical estimates.
|
|
| 28. |
|
|
| 29. |
- Preger, C., et al.
(author)
-
Abundant autoantibody isotypes in idiopathic inflammatory myopathies
- 2022
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:Suppl 1, s. 242.2-243
-
Journal article (other academic/artistic)abstract
- Anti-synthetase syndrome (ASSD), a sub-group of idiopathic inflammatory myopathies (IIM) is characterized by the presence of autoantibodies targeting aminoacyl tRNA synthetases (aaRS) and specific clinical manifestations such as myositis and interstitial lung disease (ILD) [1]. Some of the most common anti-aaRS autoantibodies in ASSD are anti-Jo1, -PL7, -PL12 and-EJ. In addition, many anti-aaRS positive patients are also positive for anti-Ro52. Having the combination of anti-Jo1 and anti-Ro52 increases the risk of developing ILD [2]. The presence of autoantibodies is an important part of the classification of ASSD, however only autoantibodies of IgG isotype are usually analyzed in the clinical setting. In rheumatoid arthritis there is evidence that anti-citrullinated protein/peptide antibodies (ACPA) can be found as IgG, IgA and IgM, and importantly, specific isotypes might correlate with disease activity [3, 4].ObjectivesTo verify if other autoantibody isotypes, besides IgG, might be present in sera of patients with IIM/ASSD and to compare with the corresponding frequencies in population controls (PC).MethodsStored sera collected from consecutive 366 IIM patients and 156 age/gender matched PC at Karolinska University Hospital were retrospectively selected. The serum samples were screened for the presence of autoantibodies of isotypes IgG, IgA and IgM, against a panel of 20 antigens representing Jo1 (HisRS), PL7 (ThrRS), PL12 (AlaRS), EJ (GlyRS), and Ro52 (TRIM21) using a multiplex bead array assay.ResultsWe identified IIM patients with autoantibodies of different isotypes, and a low frequency in PC (Figure 1). For anti-Jo1 autoantibodies we could detect IIM patients with only IgG (n=13), only IgM (n=8) and only IgA (n=4), but the majority had a combination of two (n=32) or three isotypes (n=16). For the other anti-aaRS autoantibodies the distribution was more equal to each of the three isotypes with anti-PL12 and anti-PL7 being represented by a slightly higher frequency of IgG and only a few patients had antibodies of more than one isotype targeting PL12, PL7 or EJ. The majority of anti-Ro52 positive IIM patients (n=52) only harbored IgG isotype. The combination of anti-Ro52 and anti-aaRS autoantibodies was identified in 28 patients (anti-Jo1 (n=19), -PL12 (n=2), -PL7 (n=3), and -EJ (n=4)). Most patients with such combination had anti-Ro52 IgG together with anti-aaRS IgG or IgG in combination with IgA and/or IgM. The exception was observed for three anti-Jo1 positive patients who had the combination anti-Ro52 IgG with only anti-Jo1 IgM and one anti-PL7 positive patient who had anti-Ro52 IgA together with anti-PL7 IgA and IgG.Figure 1.Venn diagrams showing reactivity in idiopathic inflammatory myopathies (IIM) (top) and population controls (PC) (bottom) for the three autoantibody isotypes IgG, IgA and IgM against five myositis antigens: Jo1 (HisRS), PL12 (AlaRS), ThrRS (PL7), EJ (GlyRS) and Ro52 (TRIM21).ConclusionThe frequency of the different autoantibody isotypes seems to be autoantigen dependent. Our results suggest that for anti-aaRS autoantibodies it could be important to investigate additional autoantibody isotypes, as some patients only harbor autoantibodies of IgM or IgA isotypes but not IgG. The clinical relevance of the different antibody isotypes still needs to be determined.References[1]Mahler, M., et al., Rev, 2014. 13(4-5): p. 367-71.[2]Huang, H.L., et al., J Clin Neurosci, 2020.[3]Arlestig, L., et al., Ann Rheum Dis, 2012. 71(6): p. 825-9.[4]Roos Ljungberg, K., et al., Arthritis Res Ther, 2020. 22(1): p. 274.Table 1.Total number of individuals and percentage (n (%)) in each group for each of the isotypes and antigens.anti-Jo1anti-PL12anti-PL7anti-EJanti-Ro52IIMPCIIMPCIIMPCIIMPCIIMPCIgG61 (16.7)1 (0.6)7 (1.9)0 (0.0)7 (1.9)0 (0.0)3 (0.8)0 (0.0)54 (14.8)5 (3.2)IgA20 (5.5)0 (0.0)2 (1.2)1 (0.6)3 (0.8)2 (1.3)1 (0.3)1 (0.6)3 (0.8)1 (0.6)IgM56 (15.3)1 (0.6)1 (0.3)2 (1.3)7 (1.9)0 (0.0)1 (0.3)0 (0.0)3 (0.8)2 (1.3)AcknowledgementsSciLifeLab facilities Autoimmunity and Serology Profiling and Human Antibody Therapeutics (Drug Discovery and Development). IMI project EUbOPEN, This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875510. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Ontario Institute for Cancer Research, Royal Institution for the Advancement of Learning McGill University, Kungliga Tekniska Hoegskolan, Diamond Light Source Limited.Disclosure of InterestsCharlotta Preger Grant/research support from: IMI project EUbOPEN, Grant no 875510, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren Grant/research support from: IMI project EUbOPEN, Grant no 875510, Ingrid E. Lundberg Shareholder of: Roche and Novartis, Consultant of: Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Astra Zeneca, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Consultant of: UCB, Grant/research support from: Gesynta Pharma, Helena Persson Employee of: Affibody AB, Susanne Gräslund Grant/research support from: IMI project EUbOPEN, Grant no 875510
|
|
| 30. |
|
|
| 31. |
- Preger, C., et al.
(author)
-
Characterization of anti-aminoacyl TRNA synthetase autoantibodies in patients with idiopathic inflammatory myopathies
- 2020
-
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1084-1085
-
Journal article (other academic/artistic)abstract
- Idiopathic inflammatory myopathies (IIM) are rare chronic inflammatory diseases associated with high mortality and morbidity [1]. One sub-group of IIM, anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS), together with specific clinical manifestations such as myositis, interstitial lung disease (ILD), arthritis, mechanic’s hand, Raynaud’s syndrome and fever [2]. The most common anti-aaRS autoantibody, anti-Jo1 targeting histidyl tRNA synthetase (HisRS), is present in up to 20-30% of patients with IIM, and up to 90% of patients with myositis and ILD [3, 4]. Besides Jo1, there are today seven other identified autoantigens within the aaRS family.Objectives:A large part of patients with IIM, including individuals with clinical manifestations indicating ASS, test seronegative to all known myositis specific autoantibodies. However, these patients could potentially harbor autoantibodies against targets not tested for in clinic. In this study, we aimed at extending the detection of autoantibodies by including all cytoplasmic aaRS in the analysis of patients with IIM. We hypothesized the existence of new potential autoantigens within this protein family.Methods:The presence of anti-aaRS autoantibodies was determined using a multiplex suspension bead array assay on 242 IIM patients from the Karolinska University Hospital myositis cohort. A panel of 186 recombinant constructs, representing 57 proteins that included full-length or partial sequence overlaps between constructs of all cytoplasmic aaRS as well as other myositis related proteins, were coupled to magnetic color-coded beads and each plasma sample was tested against the complete antigen panel.Results:By the use of this multiplex method we identified patients with autoantibodies against many of the tested aaRS. Autoantibodies binding to HisRS have previously been shown to bind with higher reactivity to the WHEP domain of HisRS and this was also confirmed in this study. We confirmed reactivity against three of the other aaRS tested for in the clinic (PL-12, PL-7, and EJ). In addition, we identified patients positive for anti-Zo, -KS and -HA, autoantibodies usually not screened for in routine. Finally, our data indicates that there are autoantibodies binding to other aaRS than the previously known eight autoantigens, which will be presented.Conclusion:In this study, we could detect autoantibodies in plasma from patients with IIM, both against the most common aaRS autoantigens, but also against other aaRS that are usually not tested for in clinic. We conclude that it is important to continue the studies of anti-aaRS autoantibodies, and their correlation to clinical manifestations, and in the long run also include more aaRS autoantigens in clinical practice.References:[1]Dobloug, G.C., et al., Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis, 2018. 77(1): p. 40-47.[2]Barsotti, S. and I.E. Lundberg, Myositis an evolving spectrum of disease. Immunol Med, 2018. 41(2): p. 46-54.[3]Vencovsky, J., H. Alexanderson, and I.E. Lundberg, Idiopathic Inflammatory Myopathies. Rheum Dis Clin North Am, 2019. 45(4): p. 569-581.[4]Richards, T.J., et al., Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum, 2009. 60(7): p. 2183-92.Disclosure of Interests:Charlotta Preger: None declared, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren: None declared, Catia Cerqueira: None declared, Peter Nilsson: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helena Persson: None declared, Susanne Gräslund: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,
|
|
| 32. |
- Storey, David J., et al.
(author)
-
Per Davidsson : recipient of the 2023 Global Award for Entrepreneurship Research
- 2023
-
In: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 61:4, s. 1381-1390
-
Journal article (other academic/artistic)abstract
- Professor Per Davidsson is the recipient of the 2023 Global Award for Entrepreneurship Research. Throughout an extraordinarily productive career, he has made invaluable contributions in building the field of entrepreneurship. His early studies on entrepreneurship and culture and his studies on the growth of small businesses played an important role in the emergence and development of entrepreneurship as a scholarly field of research. He has also, continuously, made more conceptual contributions by critically probing the development of the field, and engaged in writing foundational books that have been used extensively in higher education institutes. By probing and challenging traditional assumptions throughout his career, he has contributed to the refinement and renewal of the field.
|
|
| 33. |
- Storey, David J., et al.
(author)
-
Per Davidsson : recipient of the 2023 Global Award for Entrepreneurship Research
- 2023
-
In: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 61:4, s. 1381-1390
-
Journal article (pop. science, debate, etc.)abstract
- Professor Per Davidsson is the recipient of the 2023 Global Award for Entrepreneurship Research. Throughout an extraordinarily productive career, he has made invaluable contributions in building the field of entrepreneurship. His early studies on entrepreneurship and culture and his studies on the growth of small businesses played an important role in the emergence and development of entrepreneurship as a scholarly field of research. He has also, continuously, made more conceptual contributions by critically probing the development of the field, and engaged in writing foundational books that have been used extensively in higher education institutes. By probing and challenging traditional assumptions throughout his career, he has contributed to the refinement and renewal of the field.
|
|
| 34. |
- Vikström, Linnea, et al.
(author)
-
Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern : an observational study
- 2023
-
In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 30
-
Journal article (peer-reviewed)abstract
- BACKGROUND: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents.METHODS: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Sweden. We analyzed immunological and registry data from 16 September 2021 to 31 August 2022 with follow-up of deaths to 30 September 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves.FINDINGS: A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG in blood and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the associated 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The death risk plateaued at population average above the lower 35th percentile of S-binding IgG.INTERPRETATION: In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.FUNDING: Swedish Research Council, SciLifeLab via Knut and Alice Wallenberg Foundation, VINNOVA. Swedish Healthcare Regions, and Erling Persson Foundation.
|
|
| 35. |
- Wigren, C., et al.
(author)
-
Sm- and Yb-induced reconstructions of the Si(111) surface
- 1993
-
In: Physical Review B. - 0163-1829. ; 48:15, s. 11014-11019
-
Journal article (peer-reviewed)abstract
- Low-energy electron diffraction, scanning tunneling microscopy, and photoelectron spectroscopy results from the submonolayer Sm- and Yb-induced surface structures are presented. Several similar metal-induced surface reconstructions are found to exist for Yb and Sm on Si(111) for low submonolayer coverages: 3×2, 5×1, and 7×1. At higher submonolayer coverage, Yb induces a 2×1 reconstruction while Sm induces a (3 × 3) R30°-like reconstruction. Yb is found to be divalent in all structures, whereas the Sm valence increases with increasing coverage. In the 3×2 structure only divalent Sm is present, in the 5×1 and 7×1 structures a small amount of trivalent Sm appears, and, finally, in the (3 × 3) R30°structure approximately half of the Sm atoms are trivalent. The surface Fermi-level position in the band gap for the different Sm and Yb reconstructions has been measured. The difference in valence stability between Sm and Yb is suggested to be the cause of the difference in the high-coverage structures found and the differences in pinning level for the two elements observed for the 5×1 and 7×1 structures. © 1993 The American Physical Society.
|
|
| 36. |
- Wigren, J., et al.
(author)
-
Thermal conductivity and heat capacity of adamantane and hexamethylenetetramine under pressure
- 1980
-
In: Molecular Crystals and Liquid Crystals. - : Taylor & Francis. - 1542-1406 .- 1563-5287 .- 0026-8941. ; 59:1-2, s. 137-148
-
Journal article (peer-reviewed)abstract
- We have used the transient hot-wire technique to measure simultaneously the thermal conductivity and the heat capacity per unit volume of solid adamantane and hexamethylenetetramine. Data were obtained over the temperature range 115 K to 445 K, and at pressures up to 2.5 GPa. The thermal conductivity of plastic crystalline adamantane is much less temperature dependent than those of normal crystalline adamantane and hexamethylenetetramine. The volume dependence of the thermal conductivity of plastic crystalline adamantane is considerably smaller than those of the normal crystalline phases, and thus more similar to that of a liquid. The molar heat capacities for the different phases and substances were found to change very little with pressure. We discuss the temperature and volume dependences of the thermal properties in relation to available theoretical models.
|
|
| 37. |
|
|
| 38. |
- Wigren, Maria, et al.
(author)
-
Pathogenic immunity in systemic lupus erythematous and atherosclerosis: common mechanisms and possible targets for intervention.
- 2015
-
In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 278:5, s. 494-506
-
Research review (peer-reviewed)abstract
- Systemic lupus erythematous (SLE) is an autoimmune disorder that primarily affects young women and is characterized by inflammation in several organs including the kidneys, skin, joints, blood, and nervous system. Abnormal immune cellular and humoral responses play important roles in the development of the disease process. Impaired clearance of apoptotic material is a key factor contributing to activation of self-reactive immune cells. The incidence of atherosclerotic cardiovascular disease (CVD) is increased up to 50-fold in SLE patients compared to age- and gender-matched control subjects and this can only partly be explained by traditional risk factors for CVD. Currently, there is no effective treatment to prevent CVD complications in SLE. Traditional preventive CVD therapies have not been found to significantly lower the incidence of CVD in SLE; therefore, there is a need for novel treatment strategies and increased understanding of the mechanisms involved in the pathogenesis of CVD complications in SLE. The pathogenic immune responses in SLE and development of atherosclerotic plaques share some characteristics, such as impaired efferocytosis and skewed T cell activation, suggesting the possibility of identifying novel targets for intervention. As novel immune-based therapies for CVD are being developed, it is possible that some of these may be effective for the prevention of CVD and for immunomodulation in SLE. However, further understanding of the mechanisms leading to an increased prevalence of cardiovascular events in SLE is critical for the development of such therapies. This article is protected by copyright. All rights reserved.
|
|
