| 1. |
- Abolins, M., et al.
(författare)
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The ATLAS Data Acquisition and High Level Trigger system
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data acquisition and high level trigger system of the ATLAS experiment at the Large Hadron Collider at CERN, as deployed during Run 1. Data flow as well as control, configuration and monitoring aspects are addressed. An overview of the functionality of the system and of its performance is presented and design choices are discussed.
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| 2. |
- Fernandes-Cerqueira, Catia, et al.
(författare)
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Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens
- 2015
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA). Methods: The autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC (R) system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP) 2 using the CCPlus (R) ELISA kit. Results: Two peptides derived from the fibrinogen a chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen beta chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency. Conclusions: Here we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.
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| 3. |
- Granlund, David, 1979-, et al.
(författare)
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Det offentliga som konkurrent på kommersiella marknader - En samhällsekonomisk analys med exemplet konferensmarknaden
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I den här rapporten analyseras samhällsekonomiska effekter av att det offentliga konkurrerar med privata företag på kommersiella marknader. Den innehåller även en pilotstudie av marknaden för en – och tvådagarskonferenser tillämpad på Umeåregionen.Svensk konkurrenslagstiftning inkluderar regler om konkurrensbegränsande offentlig säljverksamhet. Reglerna gäller för den offentliga sektorn i sin helhet, dvs stat, primärkommuner (kommun) eller landstingskommuner (landsting) och juridiska personer vars verksamhet den offentliga sektorn har ett dominerande inflytande över. Inflytandet kan ta sig formen av ägande, finansieringsvillkor, styrelse, lag och avtal. Frågan om det offentliga som konkurrent är även samhällsekonomiskt relevant då snedvridning av konkurrens i form av exempelvis underprissättning till följd av stöd, kan innebära en samhällsekonomisk förlust.Sammantaget visar den samhällsekonomiska analysen att det inte går att dra några generella slutsatser om att konkurrens från den offentliga sektorn på marknader med en etablerad kommersiell verksamhet alltid är problematisk. Även i situationer där konkurrensen sker på olika villkor kan fördelarna med den offentliga aktörens medverkan överväga nackdelarna. Baserat på pilotstudien och olika scenarios avseende konferensmarknaden i Umeå, är det möjligt att dra slutsatsen att fördelarna med offentliga aktörer kan dominera nackdelarna under förutsättning att den offentliga aktörens produktionskostnad maximalt är en procent högre än en privat aktörs produktionskostnad för motsvarande konferens. Analysen visar att subventioner till offentliga aktörer överskridande 1,3 miljoner kronor inte kan motiveras utifrån ett samhällsekonomiskt perspektiv i något scenario. I scenariot där den offentliga aktören ägnar sig åt underprissättning överväger nackdelarna även om verksamheten klarar sig utan subvention.
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| 4. |
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| 5. |
- Rönnelid, Johan, et al.
(författare)
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Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants.
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:2, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The second generation anticycliccitrullinated peptide (anti-CCP2) assay detects the majority but not all anticitrullinated protein/peptide antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay to detect multiple specific ACPA, we have investigated the fine specificity of individual ACPA responses and the biological impact of additional ACPA reactivity among anti-CCP2-negative patients.METHODS: We investigated 2825 patients with RA and 551 healthy controls with full data on anti-CCP2, HLA-DRB1* alleles and smoking history concerning reactivity against 16 citrullinated peptides and arginine control peptides with a multiplex array.RESULTS: The prevalence of the 16 ACPA specificities ranged from 9% to 58%. When reactivity to arginine peptides was subtracted, the mean diagnostic sensitivity increased by 3.2% with maintained 98% specificity. Of the anti-CCP2-negative patients, 16% were found to be ACPA positive. All ACPA specificities associated with SE, and all but one with smoking. Correction for arginine reactivity also conveyed a stronger association with SE for 13/16 peptides. Importantly, when all ACPA specificities were analysed together, SE and smoking associated with RA in synergy among ACPA positive, but not among ACPA-negative subjects also in the anti-CCP2-negative subset.CONCLUSIONS: Multiplexing detects an enlarged group of ACPA-positive but anti-CCP2-negative patients with genetic and environmental attributes previously assigned to anti-CCP2-positive patients. The individual correction for arginine peptide reactivity confers both higher diagnostic sensitivity and stronger association to SE than gross ACPA measurement.
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| 6. |
- Terao, Chikashi, et al.
(författare)
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Distinct HLA Associations with Rheumatoid Arthritis Subsets Defined by Serological Subphenotype
- 2019
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 105:3, s. 616-624
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is the most common immune-mediated arthritis. Anti-citrullinated peptide antibodies (ACPA) are highly specific to RA and assayed with the commercial CCP2 assay. Genetic drivers of RA within the MHC are different for CCP2-positive and -negative subsets of RA, particularly at HLA-DRB1. However, aspartic acid at amino acid position 9 in HLA-B (Bpos-9) increases risk to both RA subsets. Here we explore how individual serologies associated with RA drive associations within the MHC. To define MHC differences for specific ACPA serologies, we quantified a total of 19 separate ACPAs in RA-affected case subjects from four cohorts (n = 6,805). We found a cluster of tightly co-occurring antibodies (canonical serologies, containing CCP2), along with several independently expressed antibodies (non-canonical serologies). After imputing HLA variants into 6,805 case subjects and 13,467 control subjects, we tested associations between the HLA region and RA subgroups based on the presence of canonical and/or non-canonical serologies. We examined CCP2(+) and CCP2(−) RA-affected case subjects separately. In CCP2(−) RA, we observed that the association between CCP2(−) RA and Bpos-9 was derived from individuals who were positive for non-canonical serologies (omnibus_p = 9.2 × 10−17). Similarly, we observed in CCP2(+) RA that associations between subsets of CCP2(+) RA and Bpos-9 were negatively correlated with the number of positive canonical serologies (p = 0.0096). These findings suggest unique genetic characteristics underlying fine-specific ACPAs, suggesting that RA may be further subdivided beyond simply seropositive and seronegative.
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| 7. |
- Abrahamsson, Annelie, et al.
(författare)
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Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo
- 2016
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Ingår i: Oncoimmunology. - : TAYLOR & FRANCIS INC. - 2162-4011 .- 2162-402X. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1 was decreased in dense breasts. No differences were found in levels of IL-1, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.
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| 8. |
- Anheden, Marie, et al.
(författare)
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Value chains for production of Renewable Transportation Fuels Using Intermediates
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- An increased share of renewable transportation fuels requires utilisation of new low-cost sources of bio-based raw materials other than what is currently used in the pulp and paper industry and for power and district heat generation in the bioenergy sector. Currently, proposed raw material includes forest residues (branches and tops), stumps, waste round wood and different by-products from pulp and pa-per industry and sawmills. Of these, forest residues and stumps have, by far, the largest potential for increased utilisation. However, these types of raw materials are often voluminous and heterogeneous and are difficult to handle in existing refineries for production of transportation fuels. The cost of transporting this type of raw material over large distances in order to supply a larger plant is often said to be high. This report includes an analysis of the possible advantages and disadvantages of transform-ing forest-based biomass to an intermediate product with a higher energy density that is more homo-geneous and easier to handle during transport and during final conversion to transportation fuel.Two value chains are investigated as case studies a) bio-SNG production using forest residues, bark and sawdust as raw material and b) bio-oil production from forest residues, lignin in black liquor and tall oil, which can be upgraded to transportation fuels at a refinery. In the study we have assumed that the conversion of the original biomass to an intermediate product mainly takes place at a pulp mill. The intermediate conversion technologies included for value chain a) are drying and pelletizing and for value chain b) pyrolysis and distillation. The final conversion to end product bio-SNG takes place in connection to a district heating system, and the final deoxygenation and upgrading of bio-oil to hydrodeoxygenated (HDO) oil takes place at an oil refinery. The value chains with intermediates are compared with value chains without intermediates where the entire conversion process to final product is located in connection to a district heating system in value chain a) and at a stand-alone plant near to a refinery in value chain b). The value chains are studied from a well-to-gate perspective, from extrac-tion of the forest biomass to produced bio-SNG/HDO bio-oil. A direct comparison between value chains for bio-SNG and bio-oil production should be avoided. They are based on different reference data that are not synchronized. A direct comparison between the chains should in addition be done in a well-to-wheel perspective.The results show that the initial hypothesis that local production of a more energy dense intermediate would reduce transportation costs could not be verified. The reason is primarily the introduction of a second transport step to transport the intermediate to the final conversion site in addition to the transport of the raw material. The transport costs are associated with relatively high fixed cost espe-cially for ship and train transport, so the introduction of a second relatively high fixed transport cost of the intermediate has a dominating effect. Further, it can be concluded that the transport cost make up a relatively small share of the total production cost of the final product, in the order of 10%, and in a few cases up to 20%. There is therefore a relatively small difference in total specific production cost for the final product between value chains with and without intermediates considering the level of uncer-tainty in the input data and the assumptions behind the scenarios studied.Summarizing, the results indicate that the production costs are highly sensitive to the economies of scale, oxygen content in the bio-crude oil and raw material costs (forest residues price or electricity price in the case where lignin is used as raw material). Transportation costs have, comparatively, a little effect in the total production cost.
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| 9. |
- Athron, Peter, et al.
(författare)
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GAMBIT : the global and modular beyond-the-standard-model inference tool
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:11
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Tidskriftsartikel (refereegranskat)abstract
- We describe the open-source global fitting package GAMBIT: the Global And Modular Beyond-the-Standard-Model Inference Tool. GAMBIT combines extensive calculations of observables and likelihoods in particle and astroparticle physics with a hierarchical model database, advanced tools for automatically building analyses of essentially any model, a flexible and powerful system for interfacing to external codes, a suite of different statistical methods and parameter scanning algorithms, and a host of other utilities designed to make scans faster, safer and more easily-extendible than in the past. Here we give a detailed description of the framework, its design and motivation, and the current models and other specific components presently implemented in GAMBIT. Accompanying papers deal with individual modules and present flrst GAMBIT results. GAMBIT can be downloaded from gambit.hepforge.org.
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| 10. |
- Athron, Peter, et al.
(författare)
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GAMBIT : the global and modular beyond-the-standard-model inference tool
- 2018
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 78:2
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Tidskriftsartikel (refereegranskat)abstract
- In Ref. (GAMBIT Collaboration: Athron et. al., Eur. Phys. J. C. arXiv: 1705.07908, 2017) we introduced the global-fitting framework GAMBIT. In this addendum, we describe a new minor version increment of this package. GAMBIT 1.1 includes full support for Mathematica backends, which we describe in some detail here. As an example, we backend SUSYHD (Vega and Villadoro, JHEP 07: 159, 2015), which calculates the mass of the Higgs boson in the MSSM from effective field theory. We also describe updated likelihoods in PrecisionBit and DarkBit, and updated decay data included in DecayBit.
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