| 1. |
- Ahlen, Maria Therese, et al.
(författare)
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The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes
- 2012
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Ingår i: Clinical & Developmental Immunology. - : Hindawi Limited. - 1740-2530 .- 1740-2522.
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Tidskriftsartikel (refereegranskat)abstract
- Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995-2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25-0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.
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| 2. |
- Ayoglu, Burcu, et al.
(författare)
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Anoctamin 2 identified as an autoimmune target in multiple sclerosis
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences of the USA. - 0027-8424 .- 1091-6490. ; 113:8, s. 2188-2193
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.
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| 3. |
- Backofen, Rolf, et al.
(författare)
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Requirements and specification of bioinformatics use cases
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This deliverable specifies use cases based on bioinformatics research carried out by members ofA2. The use cases involve the use of rules to reason over ontologies and pathways (Dresden,Edinburgh, Paris, Linköping) and rules to specify workflows to integrate bioinformatics data (Lisbon, Skövde, Jena, Bucharest). The use cases are designed as a reference point to foster the take up of A2 use cases by I-work packages. Most notably, many of the use cases specify the need for querying and reactivity with languages like Xcerpt (I4), Erus (I5) and Prova (I5). The use cases range from basic research applications to fully deployed software with an international user base.
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| 4. |
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| 5. |
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| 6. |
- Flygt, Hjalmar, et al.
(författare)
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Long-term tolerability and efficacy after initial PegIFN-alpha addition to dasatinib in CML-CP : Five-year follow-up of the NordCML007 study
- 2021
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Ingår i: European Journal of Haematology. - : Wiley-Blackwell. - 0902-4441 .- 1600-0609. ; 107:6, s. 617-623
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Treatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-alpha in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-alpha (PegIFN-alpha) in combination with dasatinib (DAS) in CML-CP. Methods Forty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 mu g/wk of PegIFN-alpha was added and increased to 25 mu g/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data. Results After 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study. Conclusion Initial addition of PegIFN-alpha to DAS shows good long-term efficacy without increased toxicity.
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| 7. |
- Gavali, Hamid, et al.
(författare)
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Semi-Conservative Treatment Versus Surgery in Abdominal Aortic Graft and Endograft Infections
- 2023
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 66:3, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft-preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort.METHODS: Patients with abdominal AGI-related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for definition of AGI. Multivariable regression was performed to identify factors associated with mortality.RESULTS: A total of 169 patients with surgically treated abdominal AGI were identified, comprising 43 SC [14 endografts; 53% with a graft-enteric fistula (GEF) in total] and 126 RS [26 endografts; 50% with a GEF in total]. The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated 5-year survival for SC versus RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated 5-year survival for SC patients with a GEF versus without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC versus RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in 5-year survival comparing SC versus RS (HR 1.0, 95% CI 0.6 - 1.5).CONCLUSION: In this national AGI cohort, we could not identify any mortality difference comparing SC versus RS for AGI when adjusting for comorbidities. Presence of GEF likely negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC-treated patients.
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| 8. |
- Geelen, Inge G. P., et al.
(författare)
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Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response : clinical and immunological effects
- 2023
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Ingår i: Annals of Hematology. - : Springer. - 0939-5555 .- 1432-0584. ; 102:6, s. 1395-1408
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Tidskriftsartikel (refereegranskat)abstract
- In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.
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| 9. |
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| 10. |
- Hjorth-Hansen, Henrik, et al.
(författare)
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Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)
- 2015
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 94:3, s. 243-250
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Tidskriftsartikel (refereegranskat)abstract
- We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100mg QD or imatinib 400mg QD and report outcome as an intention-to-treat analysis with 36months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3months in 36% vs. 8% (P=0.02), at 12months in 81% vs. 46% (P=0.02) and at 18months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6months onwards, reaching 61% vs. 21% (P<0.05) at 36months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.
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| 11. |
- Mork, Bjorn E., et al.
(författare)
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Changing practice through boundary organizing :
- 2012
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Ingår i: Human Relations. - : SAGE Publications. - 0018-7267 .- 1741-282X. ; 65:2, s. 263-288
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Tidskriftsartikel (refereegranskat)abstract
- This article contributes to our understanding of practices in innovating organizations. Previous studies have demonstrated how breakthroughs in knowledge may fail to be translated into practices if they are not aligned with existing practices, or if they cut across established boundaries and power structures. By drawing upon an ethnographic study of a medical R&D department that has been highly successful in developing new medical practices, this article investigates how such challenges can be overcome. To date, much of the literature has focused on coordination across single, well-defined boundaries. We here extend this focus and introduce the notion of 'boundary organizing' to analyse highly political and contingent processes of innovation and change within and across different practices. We add to existing literature by highlighting how the handling of multiple boundaries, the indirect effects of boundary work, the negotiation of mutual benefits and interests, and mutual adaptation are key aspects of boundary organizing.
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| 12. |
- Munappy, Aiswarya Raj, 1990, et al.
(författare)
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Data Management Challenges for Deep Learning
- 2019
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Ingår i: Proceedings - 45th Euromicro Conference on Software Engineering and Advanced Applications, SEAA 2019. - : IEEE. ; , s. 140-147
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Konferensbidrag (refereegranskat)abstract
- © 2019 IEEE. Deep learning is one of the most exciting and fast-growing techniques in Artificial Intelligence. The unique capacity of deep learning models to automatically learn patterns from the data differentiates it from other machine learning techniques. Deep learning is responsible for a significant number of recent breakthroughs in AI. However, deep learning models are highly dependent on the underlying data. So, consistency, accuracy, and completeness of data is essential for a deep learning model. Thus, data management principles and practices need to be adopted throughout the development process of deep learning models. The objective of this study is to identify and categorise data management challenges faced by practitioners in different stages of end-to-end development. In this paper, a case study approach is employed to explore the data management issues faced by practitioners across various domains when they use real-world data for training and deploying deep learning models. Our case study is intended to provide valuable insights to the deep learning community as well as for data scientists to guide discussion and future research in applied deep learning with real-world data.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Nilsson, Jonas, 1970, et al.
(författare)
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Expression of influenza A virus glycan receptor candidates in mallard, chicken, and tufted duck
- 2024
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Ingår i: GLYCOBIOLOGY. - 0959-6658 .- 1460-2423. ; 34:3
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) pandemics result from interspecies transmission events within the avian reservoir and further into mammals including humans. Receptor incompatibility due to differently expressed glycan structures between species has been suggested to limit zoonotic IAV transmission from the wild bird reservoir as well as between different bird species. Using glycoproteomics, we have studied the repertoires of expressed glycan structures with focus on putative sialic acid-containing glycan receptors for IAV in mallard, chicken and tufted duck; three bird species with different roles in the zoonotic ecology of IAV. The methodology used pinpoints specific glycan structures to specific glycosylation sites of identified glycoproteins and was also used to successfully discriminate alpha 2-3- from alpha 2-6-linked terminal sialic acids by careful analysis of oxonium ions released from glycopeptides in tandem MS/MS (MS2), and MS/MS/MS (MS3). Our analysis clearly demonstrated that all three bird species can produce complex N-glycans including alpha 2-3-linked sialyl Lewis structures, as well as both N- and O- glycans terminated with both alpha 2-3- and alpha 2-6-linked Neu5Ac. We also found the recently identified putative IAV receptor structures, Man-6P N-glycopeptides, in all tissues of the three bird species. Furthermore, we found many similarities in the repertoires of expressed receptors both between the bird species investigated and to previously published data from pigs and humans. Our findings of sialylated glycan structures, previously anticipated to be mammalian specific, in all three bird species may have major implications for our understanding of the role of receptor incompatibility in interspecies transmission of IAV.
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| 17. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 18. |
- Olafsson, S, et al.
(författare)
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Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
- 2017
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
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| 19. |
- Rajala, Hanna L. M., et al.
(författare)
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Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia
- 2017
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : SPRINGER. - 0171-5216 .- 1432-1335. ; 143:8, s. 1543-1554
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. Methods We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. Results Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of patients with IgA, IgG, and IgM levels below the lower limit of normal (LLN) was 0, 11, and 6% of all CML patients, respectively, whereas at 12 months timepoint the proportions were 6% (p = 0.13), 31% (p = 0.042) and 28% (p = 0.0078). Lower initial Ig levels predisposed to the development of hypogammaglobulinemia during TKI therapy. Decreased Ig levels in imatinibtreated patients were associated with higher percentages of immature BM B cells. The patients, who had low Ig levels during the TKI therapy, had significantly more frequent minor infections during the follow-up compared with the patients with normal Ig values (33% vs. 3%, p = 0.0016). No severe infections were reported, except recurrent upper respiratory tract infections in one imatinib-treated patient, who developed severe hypogammaglobulinemia. Conclusions TKI treatment decreases plasma Ig levels, which should be measured in patients with recurrent infections.
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| 20. |
- Sinha, Rajib, 1983-, et al.
(författare)
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Sustainable Personal Transport Modes in a Life Cycle Perspective-Public or Private?
- 2019
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 11:24
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Tidskriftsartikel (refereegranskat)abstract
- Life cycle-based studies endorse public transport to cause lower environmental pressures compared to a private car. However, a private car can cause lower environmental pressure when a public vehicle (bus or train) runs on a lower occupancy during an off-peak hour. This fact should be the basis for a more profound debate regarding public versus private transport. Many transport interventions are striving to reduce the number of car transports. To reach this goal, passengers need attractive alternatives to their reduced number of car travels (i.e., attractive public transport). This study aimed to develop a model allowing us to estimate potential environmental gains by changing travel behavior. A passenger travel model was developed based on life cycle inventories (LCI) of different travel modes to calculate environmental footprints. The model was applied in an intervention of public transport through temporary free public transport. The intervention was successful in significantly reducing the number of car transports (12%). However, total passenger kilometer travelled (PKT) increased substantially more, mainly by bus, but also train, bicycle and walking. The total energy, carbon and nitrogen oxide footprints were slightly increased after the intervention. If the commuters were assumed to travel during peak hours or the number of public transports were not affected by the increased number of commuters, the overall environmental footprints decreased. Our conclusions are that transport interventions are very complex. They may result in desired changes, but also in altered travel behavior, increasing overall impact. Thus, a very broad evaluation of all transport modes as well as potential positive social influences of the transport intervention will be necessary.
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| 21. |
- Suarez Corredor, Andres Felipe, 1988, et al.
(författare)
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Characterization Method for Gas Flow Reactor Experiments-NH3 Adsorption on Vanadium-Based SCR Catalysts
- 2021
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Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 60:30, s. 11399-11411
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Tidskriftsartikel (refereegranskat)abstract
- In this study, NH3 adsorption isotherms for a commercial vanadium-based SCR catalyst coated on a monolith substrate were obtained using a gas flow reactor over a wide range of parameters which have not been performed before in a single study. The isotherms were obtained under different conditions, where adsorption temperature, NH3 concentration, water concentration, washcoat loading, and catalyst oxidation state were varied. For this purpose, a systematic data processing method was developed, which characterizes the dispersion and delay effects in the experimental setup using a residence time distribution model, and artifacts such as NH3 adsorbed in the experimental setup and uncertainties in the washcoat loading were removed. As a result, data from different catalyst samples were integrated, and adsorption isotherms with low data spread and well-defined regions were obtained. This allows the identification of the complex nature of the catalyst and dynamics, where multiple types of adsorption sites are present. For instance, the oxidized catalyst has 50% higher NH3 storage capacity compared to the reduced state of the sample. Moreover, water reduces the NH3 storage capacity at high concentrations (5.0%), whereas at low concentration (0.5%), water increases the NH3 adsorption capacity for an oxidized catalyst. The proposed data processing method can be extended for the analysis of further phenomena in catalysts studied using gas flow reactors, complementing current methods and providing information for models with extended validity and lower parameter correlations.
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| 22. |
- Suarez Corredor, Andres Felipe, 1988, et al.
(författare)
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Understanding the NH3 adsorption mechanism on a vanadium-based SCR catalyst : A data-driven modeling approach
- 2022
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Ingår i: Chemical Engineering Science. - : Elsevier BV. - 0009-2509 .- 1873-4405. ; 262
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Tidskriftsartikel (refereegranskat)abstract
- Ammonia adsorption is a precondition for the selective catalytic reduction (SCR) of nitrogen oxides (NOx) to take place and it influences catalyst performance under transient conditions. For a vanadium-based SCR catalyst NH3 adsorption takes place on multiple adsorption sites over the catalyst surface with different behaviours depending on temperature, gas concentration and catalyst oxidation state. In this study, a mechanistic NH3 adsorption model within the framework of Langmuir adsorption models was developed for describing the NH3 adsorption isotherms obtained with a gas flow reactor for a vanadium-based SCR. The model was created by a data-driven modeling process, which involves different steps. First, a large set of candidate models was created systematically by combining multiple feasible adsorption mechanisms. Then, a parameter estimation workflow was performed using three different objective functions with increased complexity. Finally, a model reconciliation step was executed and a quality assessment was done for creating a unified robust model with a high degree of validity. As a result of this method, an NH3 adsorption model with five adsorption sites with different mechanisms was obtained that captures the main features from the experimental data. Furthermore, the model parameters have physical significance and relate to the adsorption strength and spatial arrangement for NH3 and water molecules. The proposed model can be used in the development of transient models with increased validity over a wide experimental region.
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| 23. |
- Wixner, Jonas, et al.
(författare)
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Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis
- 2017
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 24:1, s. 78-79
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Tidskriftsartikel (refereegranskat)abstract
- Doxycycline has been shown to disrupt transthyretin amyloid (ATTR) fibrils [1] and tauro-ursodeoxycholic acid (TUDCA) has been shown to reduce TTR toxic aggregates in mice [2]. Further, in 2010 Cardoso et al. showed that a combined doxycycline/TUDCA treatment had a synergistic effect, decreasing ATTR deposition. Ursodeoxycholic acid (UDCA) is a bile acid used for the treatment of certain cholestatic syndromes with an efficacy similar to that of TUDCA. Based on this knowledge, we wanted to explore if treatment with doxycycline and UDCA (Dox/Urso) would prevent disease progression in ATTR amyloidosis. UDCA was selected since TUDCA is not available in Sweden.
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