| 1. |
- Michelsen, B., et al.
(författare)
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Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration
- 2020
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries. METHODS: Real-life data from 13 European registries participating in the European Spondyloarthritis Research Collaboration Network were pooled. Kaplan-Meier with log-rank test, Cox regression, χ² and logistic regression analyses were performed to assess 6-month and 12-month secukinumab retention, inactive disease/low-disease-activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <2/<4, Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3/<2.1) and response rates (BASDAI50, Assessment of Spondyloarthritis International Society (ASAS) 20/40, ASDAS clinically important improvement (ASDAS-CII) and ASDAS major improvement (ASDAS-MI)). RESULTS: We included 1860 patients initiating secukinumab as part of routine care. Overall 6-month/12-month secukinumab retention rates were 82%/72%, with significant (p<0.001) differences between the registries (6-month: 70-93%, 12-month: 53-86%) and across number of previous b/tsDMARDs (b/tsDMARD-naïve: 90%/73%, 1 prior b/tsDMARD: 83%/73%, ≥2 prior b/tsDMARDs: 78%/66%). Overall 6-month/12-month BASDAI<4 were observed in 51%/51%, ASDAS<1.3 in 9%/11%, BASDAI50 in 53%/47%, ASAS40 in 28%/22%, ASDAS-CII in 49%/46% and ASDAS-MI in 25%/26% of the patients. All rates differed significantly across number of previous b/tsDMARDs, were numerically higher for b/tsDMARD-naïve patients and varied significantly across registries. Overall, time since diagnosis was not associated with secukinumab effectiveness. CONCLUSIONS: In this study of 1860 patients from 13 European countries, we present the first comprehensive real-life data on effectiveness of secukinumab in patients with axSpA. Overall, secukinumab retention rates after 6 and 12months of treatment were high. Secukinumab effectiveness was consistently better for bionaïve patients, independent of time since diagnosis and differed across the European countries. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 2. |
- Abramsson, Mia L., et al.
(författare)
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Charge Engineering Reveals the Roles of Ionizable Side Chains in Electrospray Ionization Mass Spectrometry
- 2021
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Ingår i: JACS Au. - : American Chemical Society (ACS). - 2691-3704. ; 1:12, s. 2385-2393
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Tidskriftsartikel (refereegranskat)abstract
- In solution, the charge of a protein is intricately linked to its stability, but electrospray ionization distorts this connection, potentially limiting the ability of native mass spectrometry to inform about protein structure and dynamics. How the behavior of intact proteins in the gas phase depends on the presence and distribution of ionizable surface residues has been difficult to answer because multiple chargeable sites are present in virtually all proteins. Turning to protein engineering, we show that ionizable side chains are completely dispensable for charging under native conditions, but if present, they are preferential protonation sites. The absence of ionizable side chains results in identical charge state distributions under native-like and denaturing conditions, while coexisting conformers can be distinguished using ion mobility separation. An excess of ionizable side chains, on the other hand, effectively modulates protein ion stability. In fact, moving a single ionizable group can dramatically alter the gas-phase conformation of a protein ion. We conclude that although the sum of the charges is governed solely by Coulombic terms, their locations affect the stability of the protein in the gas phase.
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| 3. |
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| 4. |
- Sidstedt, Maja, et al.
(författare)
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Ultrasensitive sequencing of STR markers utilizing unique molecular identifiers and the SiMSen-Seq method
- 2024
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Ingår i: Forensic Science International: Genetics. - : Elsevier Ireland Ltd. - 1872-4973 .- 1878-0326. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- Massively parallel sequencing (MPS) is increasingly applied in forensic short tandem repeat (STR) analysis. The presence of stutter artefacts and other PCR or sequencing errors in the MPS-STR data partly limits the detection of low DNA amounts, e.g., in complex mixtures. Unique molecular identifiers (UMIs) have been applied in several scientific fields to reduce noise in sequencing. UMIs consist of a stretch of random nucleotides, a unique barcode for each starting DNA molecule, that is incorporated in the DNA template using either ligation or PCR. The barcode is used to generate consensus reads, thus removing errors. The SiMSen-Seq (Simple, multiplexed, PCR-based barcoding of DNA for sensitive mutation detection using sequencing) method relies on PCR-based introduction of UMIs and includes a sophisticated hairpin design to reduce unspecific primer binding as well as PCR protocol adjustments to further optimize the reaction. In this study, SiMSen-Seq is applied to develop a proof-of-concept seven STR multiplex for MPS library preparation and an associated bioinformatics pipeline. Additionally, machine learning (ML) models were evaluated to further improve UMI allele calling. Overall, the seven STR multiplex resulted in complete detection and concordant alleles for 47 single-source samples at 1 ng input DNA as well as for low-template samples at 62.5 pg input DNA. For twelve challenging mixtures with minor contributions of 10 pg to 150 pg and ratios of 1–15% relative to the major donor, 99.2% of the expected alleles were detected by applying the UMIs in combination with an ML filter. The main impact of UMIs was a substantially lowered number of artefacts as well as reduced stutter ratios, which were generally below 5% of the parental allele. In conclusion, UMI-based STR sequencing opens new means for improved analysis of challenging crime scene samples including complex mixtures.
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| 7. |
- Galfi, Helen
(författare)
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Assessment of stormwater and snowmelt quality based on water management priorities and the consequent water quality parameters
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stormwater and snowmelt pollution contributes to degradation of quality of the receiving waters. For assessing such impacts, it is effective to focus on specific causes of degradation, as done in this study of the quality of stormwater and snowmelt discharges into the receiving waters serving for supply of raw drinking water and water-based recreation. While the main priority were faecal indicator bacteria (FIBs), the understanding of their occurrence, and of other potential effects on the receiving waters, required addressing additional water quality parameters as well. Exports of FIBs in stormwater and snowmelt discharged from four urban catchments yielded the following findings: (a) E.coli, with mean concentration of all stormwater data Cmean = 430 cfu (colony forming units)/100 mL, and enterococci (Cmean=1380 cfu/100 mL) were the best indicators of faecal pollution of stormwater, but total coliform (Cmean=3130 cfu/100 mL) and C. perfringens (Cmean=150 cfu/100 mL) were much less effective: the former indicator includes non-faecal bacteria and the latter one barely varied; (b) Among the different catchments, the central catchment with mixed land use produced the highest concentrations of FIBs; (c) FIB concentrations in snowmelt were significant only in the case of enterococci (400 cfu/100 mL); and, (d) Baseflows in two catchments were practically devoid of FIBs, with Cmean=10 cfu/100 mL for both E.coli and enterococci. Hence, there were no contributions of sanitary sewage to the storm sewer baseflows.FIB concentrations varied with stormwater or snowmelt quality, described by associated parameters, which were identified by cluster analysis as: temperature, conductivity, TSS, flow rate, and TP. Such findings were used in statistical regressions indicating that E. coli and enterococci could be statistically modelled in three of the four catchments, with determination coefficients R2 ranging from 38-66%. In spite of uncertainties, such modelling would be useful for future FIB monitoring, or for comparing remediation alternatives. Estimation of FIBs by microbial partitioning to settleable solids (represented by gully pot sediments) was infeasible, because these highly mineral sediments contained little FIBs.Storm sewer outfall effluents were also analyzed for mineral (Al, Ca, Fe, K, Mg, Na) and anthropogenic indicator trace metal (TM) inorganics (Cd, Cr, Cu, Ni, Pb, Zn). The total mass of inorganics exported from the catchments by runoff or snowmelt was dominated by mineral inorganics, which were particularly high in baseflows. TM concentrations were compared to the tentative guidance limits suggested in Sweden as annual mean, or maximum event mean, total TM concentrations. Effluents from the catchments studied clearly exceeded the recommended values 5 times in the case of Zn.Field studies drew attention to uncertainties in measured FIBs and solids. Automated sampling of greatly varying FIB concentrations was affected by sampling line water residuals, which can be minimized by short sampling lines and avoidance of sags in the sampling line. Stormwater and snowmelt solids were underestimated by the conventional TSS method requiring withdrawal of aliquots from total samples. This bias can be eliminated by using whole-sample methods; either the existing SSC (suspended sediment concentration) method, or the newly proposed (and easier to use) multiple filter procedure (MFP), filtering whole samples through progressively finer filters (pore sizes 25, 1.6 and 0.45 µm). The MFP produced data equivalent to those obtained with SSC, as confirmed by the Limits of Agreement (LoA) statistical procedure.
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| 8. |
- Sahin, Cagla, et al.
(författare)
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Ion mobility-mass spectrometry shows stepwise protein unfolding under alkaline conditions
- 2021
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Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 57:12, s. 1450-1453
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Tidskriftsartikel (refereegranskat)abstract
- Although native mass spectrometry is widely applied to monitor chemical or thermal protein denaturation, it is not clear to what extent it can inform about alkali-induced unfolding. Here, we probe the relationship between solution- and gas-phase structures of proteins under alkaline conditions. Native ion mobility-mass spectrometry reveals that globular proteins are destabilized rather than globally unfolded, which is supported by solution studies, providing detailed insights into alkali-induced unfolding events. Our results pave the way for new applications of MS to monitor structures and interactions of proteins at high pH.
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| 9. |
- Sahin, Cagla, et al.
(författare)
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Ion mobility-mass spectrometry shows stepwise protein unfolding under alkaline conditions
- 2021
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 57:12, s. 1450-1453
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Tidskriftsartikel (refereegranskat)abstract
- Although native mass spectrometry is widely applied to monitor chemical or thermal protein denaturation, it is not clear to what extent it can inform about alkali-induced unfolding. Here, we probe the relationship between solution- and gas-phase structures of proteins under alkaline conditions. Native ion mobility-mass spectrometry reveals that globular proteins are destabilized rather than globally unfolded, which is supported by solution studies, providing detailed insights into alkali-induced unfolding events. Our results pave the way for new applications of MS to monitor structures and interactions of proteins at high pH.
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| 10. |
- Smulko, J., et al.
(författare)
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Low-frequency noise in Au-decorated graphene-Si Schottky barrier diode at selected ambient gases
- 2023
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 122:21
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Tidskriftsartikel (refereegranskat)abstract
- We report results of the current-voltage characteristics and low-frequency noise in Au nanoparticle (AuNP)-decorated graphene-Si Schottky barrier diodes. Measurements were conducted in ambient air with addition of either of two organic vapors, tetrahydrofuran [(CH2)(4)O; THF] and chloroform (CHCl3), as also during yellow light illumination (592 nm), close to the measured particle plasmon polariton frequency of the Au nanoparticle layer. We observed a shift of the DC characteristics at forward voltages (forward resistance region) when tetrahydrofuran vapor was admitted (in a Au-decorated graphene-Si Schottky diode), and a tiny shift under yellow irradiation when chloroform was added (in not decorated graphene-Si Schottky diode). Significantly larger difference in the low-frequency noise was observed for the two gases during yellow light irradiation, compared with no illumination. The noise intensity was suppressed by AuNPs when compared with noise in graphene-Si Schottky diode without an AuNP layer. We conclude that flicker noise generated in the investigated Au-decorated Schottky diodes can be utilized for gas detection.
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