| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Voight, Benjamin F., et al.
(författare)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Abarenkov, Kessy, et al.
(författare)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 5. |
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| 6. |
- Afzelius, Mikael, et al.
(författare)
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Development of multipoint vibrational coherent anti-Stokes Raman spectroscopy for flame applications
- 2006
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Ingår i: Applied Optics. - 2155-3165. ; 45:6, s. 1177-1186
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Tidskriftsartikel (refereegranskat)abstract
- A novel technique for coherent anti-Stokes Raman spectroscopy (CARS) measurements in multiple points is presented. In a multipass cavity the pump and Stokes laser beams are multiply reflected and refocused into a measurement volume with an adjustable number of separated points along a line. This optical arrangement was used in a vibrational CARS setup with planar BOXCARS phase-matching configuration. The CARS spectra from spatially separated points were recorded at different heights on a CCD camera. Measurements of temperature profiles were carried out in the burned gas zone of a premixed one-dimensional flame to demonstrate the applicability of this method for temperature measurements in high-temperature regions. The ability to measure in flames with strong density gradients was demonstrated by simultaneous measurements of Q-branch spectra of N-2 and CO in a Wolfhard-Parker burner flame. Interference phenomena found in multipoint spectra are discussed, and possible solutions are proposed. Merits and limitations of the technique are discussed. (c) 2006 Optical Society of America.
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| 7. |
- Afzelius, Mikael, et al.
(författare)
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Pure rotational coherent anti-Stokes Raman spectroscopy in mixtures of CO and N-2
- 2004
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Ingår i: Applied Optics. - 2155-3165. ; 43:36, s. 6664-6672
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Tidskriftsartikel (refereegranskat)abstract
- We present a model for quantitative measurements in binary mixtures of nitrogen and carbon monoxide by the use of dual-broadband rotational coherent anti-Stokes Raman spectroscopy. The model has been compared with experimental rotational coherent anti-Stokes Raman scattering spectra recorded within the temperature range of 294-702 K. Temperatures and concentrations were evaluated by spectral fits using libraries of theoretically calculated spectra. The relative error of the temperature measurements was 1-2%, and the absolute error of the CO concentration measurements was <0.5% for temperatures less than or equal to600 K. For higher temperatures, the gas composition was not chemically stable, and we observed a conversion of CO to CO2. The influence of important spectroscopic parameters such as the anisotropic polarizability and Raman line-broadening coefficients are discussed in terms of concentration measurements. In particular, it is shown that the CO concentration measurement was more accurate if N-2-CO and CO-N-2 line-broadening coefficients were included in the calculation. The applicability of the model for quantitative flame measurements is demonstrated by measuring CO concentrations in ethylene/air flames. (C) 2004 Optical Society of America.
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| 8. |
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| 9. |
- Andersson, Arne, et al.
(författare)
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Ottenby fågelstation : Årsrapport 1999
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Decenniets, seklets och milleniets sista år blev ett år av stora förändringar vid Ottenby fågelstation. Deföregående tre-fyra åren hade präglats av mycket dålig ekonomi och därtill personalproblem. Under 1998blev situationen akut. Som ett första led i att förbättra situationen ombildades Ottenbykommittén (avSveriges Ornitologiska Förening satt att sköta fågelstationen) under hösten 1998. Den störstaförändringen blev sedan att Jan Pettersson, platschef sedan 1978, sades upp. Därtill kom uppsägning,pensionering, dödsfall (se nedan) och sedan tidigare överflyttade tjänster till OFAB, vilket innebar detatt den “fast” anställda personalstyrkan, som 1992 var 7 personer, reducerades till noll!Ottenbykommittén har nu fått en mycket mer aktiv roll i stationens arbete. Olika verksamhetsdelar haridentifierats och ledamöterna har getts olika ansvarsområden.Kommittén bestod under året av :Åke Lindström (ordförande)Christian Hjort (sekreterare, utlandsverksamheten)Dennis Kraft (ekonomi)Arne Andersson (datafrågor)Dennis Hasselquist (samordning av ansökningar)Anders Hedenström (forskningssamordnare)Niclas Jonzén (personal)Lars Lindell (SOF:s styrelse).Aktiviteterna inom dessa olika områden redovisas nedan och här skallbara de generella linjerna i arbetet läggas fram.Tvivelsutan förbättrades arbetsklimatet för den ideellt arbetandepersonalen på fågelstationen och glädjande nog var tillströmningen storav arbetsvilliga ungdomar. Stationen blev på många sätt öppnare, inteminst mot fågelskådarleden. Fler personer besökte stationen och pådetta sätt kan många fler känna sig delaktiga och trivas. Nackdelen äratt det rent praktiskt blir svårare att driva verksamheten med mångamänniskor närvarande och relativt stor omsättning på personer.Genom mycket hård åtstramning på utgiftssidan kunde ett förväntat rejält underskott i budgeten vändastill en liten vinst. Alla inblandade skall ha stor ära av detta eftersom både stora som små uppoffringarkrävts för att styra ekonomin rätt. Den lilla vinsten användes till att börja täcka det underskott somunder många år ackumulerats. Även om det nu känns som att vi har en god kontroll över den löpandeekonomin så måste vi på lång sikt hitta fler finansieringskällor till stationens verksamhet. Det är tillexempel mycket otillfredsställande att vi nu inte har någon heltidsanställd personal, något som på siktmåste lösas.Fågelstationens gamla dröm om att ha en egen filial söder om Sahara gick i uppfyllelse under 1999 meden månads försöksverksamhet i Nigeria under våren. Denna slog väl ut på alla sätt och verksamhetenskall nu intensifieras under 2000.Datahanteringen fick sig en rejäl skjuts framåt under året och kan vi bara snart förnya maskinparken finnsgrunden för en smidig och effektiv datahantering vid stationen. Detta kommer att underlätta bådeutåtriktad verksamhet (Internet) och eget analysarbete.Ottenby Försäljnings AB (OFAB), som drivit den affärsmässiga delen av stationens verksamhet sedan1995, fortsatte sin verksamhet parallellt med fågelstationens ideella verksamhet. Genom verksamheten iNaturum och restaurang Fågel Blå svarar OFAB för en viktig del av fågelstationens publika aktiviteter.Det är av stor vikt för framtiden att behålla och utveckla det goda samarbetet mellan fågelstationen ochOFAB.Figur 1. Åke LindströmFigur 2. Patrik Rhönnstad, platschef 1999Kontinuiteten i det praktiska arbetet på stationen blev naturligtvis något lidande av att den rutineradepersonalen försvunnit. Situationen hjälptes dock upp signifikant av att OFABs personal fanns på plats(Håkan och Annika Lundkvist, Gösta Friberg) samt att nye platschefen och många av de ideelltarbetande hade erfarenhet från tidigare år.
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| 10. |
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| 11. |
- Barredo, José I., et al.
(författare)
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Mapping and assessment of forest ecosystems and their services : Applications and guidance for decision making in the framework of MAES
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this report is to illustrate by means of a series of case studies the implementation of mapping and assessment of forest ecosystem services in different contexts and geographical levels. Methodological aspects, data issues, approaches, limitations, gaps and further steps for improvement are analysed for providing good practices and decision making guidance. The EU initiative on Mappingand Assessment of Ecosystems and their Services (MAES), with the support of all Member States, contributes to improve the knowledge on ecosystem services. MAES is one of the building-block initiatives supporting the EU Biodiversity Strategy to 2020.
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| 12. |
- Beck, Astrid L, et al.
(författare)
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Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring : A prospective nested case-control study
- 2024
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Ingår i: International Journal of Cancer. - 0020-7136. ; 154:1, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.
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| 13. |
- Belmeguenai, Amor, et al.
(författare)
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Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells
- 2010
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 30:41, s. 13630-13643
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinaseA (PKA) and case in kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.
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| 14. |
- Bengtsson, Anders A., et al.
(författare)
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Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
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| 15. |
- Bengtsson, Anders A., et al.
(författare)
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Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus
- 2020
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW. Methods: Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability on the neutrophil cell surface by flow cytometry, whereas the commercial ELISA measures IC binding to C1q. Results: Using IC-FLOW, 90% of SLE patients with active disease had elevated levels of circulating ICs (p < 0.0001). Using the commercial assay, only 17% of SLE patients had elevated levels of circulating ICs. For both assays, levels of ICs reflected active disease as determined by SLEDAI (r = 0.45, p < 0.0001) and were associated with type I IFN activity (r = 0.37, p = 0.001), and complement consumption (p = 0.0002). Levels of ICs measured with IC-FLOW, but not with the commercial ELISA, were associated with active lupus nephritis (p = 0.004). Conclusions: This novel FcγRIIA-IC assay can detect levels of circulating ICs in patients with SLE. Analyzing IC levels may facilitate monitoring of disease activity, as well as identify patients at risk of lupus nephritis, allowing for early preventive interventions.
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| 16. |
- Bengtsson, Anders A, et al.
(författare)
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Pharmacokinetics, tolerability, and preliminary efficacy of ABR-215757, a new quinoline-3-carboxamide derivative, in murine and human SLE
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:5, s. 1579-1588
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the efficacy of ABR-215757, a new immunomodulatory small molecule in a murine SLE model, to evaluate the pharmacokinetics and tolerability in SLE patients at doses predicted to be efficacious and safe, and to determine the maximum tolerated dose (MTD). METHODS: The efficacy of ABR-215757 was studied in lupus prone MRLlpr/lpr mice and compared with established SLE treatments. Dose response data of ABR-215757 were together with pharmacokinetic data used to calculate effective and safe clinical doses. The pharmacokinetics and tolerance of ABR-215757 were evaluated in a Phase Ib double-blind, placebo controlled, dose-escalation study where cohorts of SLE patients received daily oral treatment for 12 weeks. RESULTS: Disease inhibition in MRLlpr/lpr mice, comparable to that of prednisolone and mycophenolate mofetil, was obtained with ABR-215757. Prominent effects on disease manifestations, serological markers and a steroid sparing effect were seen for ABR-215757. The pharmacokinetic properties in SLE patients were linear and well suitable for once daily oral treatment. The majority of the adverse events (AEs) were mild or moderate and transient. The most frequent AEs were arthralgia and myalgia, reported at the highest (4.5 and 6 mg/day) dose levels. At 4.5 mg and higher some AEs of severe intensity and serious adverse events (SAEs) were reported. CONCLUSION: ABR-215757 effectively inhibited disease and had a steroid sparing effect in experimental lupus. Clinical doses up to 3 mg/day, dose levels predicted from pre-clinical studies to be efficacious and safe, were well tolerated in the SLE patients. The MTD was concluded to be 4.5 mg/day.
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| 17. |
- Bengtsson, Anton, 1979, et al.
(författare)
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Effects of thermal processing on the in vitro bioaccessibility and microstructure of beta-carotene in orange-fleshed sweet potato
- 2010
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 58:20, s. 11090-11096
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Tidskriftsartikel (refereegranskat)abstract
- The effects of different preparation methods on the bioaccessibility of beta-carotene in orange-fleshed sweet potato (OFSP), an important food crop in sub-Saharan Africa, have been evaluated using an in vitro digestion procedure. The preparation methods included, on fresh roots, boiling followed by pureeing and oil addition (BOL) and homogenization followed by boiling and oil addition (HOM); on milled flour from freeze-dried fresh roots, cooking of porridge followed by oil addition (POA) and oil addition to flour followed by cooking of porridge (POB). The retention of all-trans-beta-carotene ranged from 58% (POB) to 72% (BOL). The presence of oil during heating resulted in a significantly higher formation of 13-cis-beta-carotene for the POB-treated samples than for the other samples. The efficiency of micellarization of all-trans-beta-carotene after in vitro digestion was 50% (HOM), 48% (POB), 31% (POA), and 16% (BOL). Brightfield microscopy of the cell structure after processing and in vitro digestion showed a high degree of cell-wall rupture for the HOM-treated samples, whereas cells appeared intact for the BOL samples. Also, coherent anti-Stokes Raman scattering (CARS) microscopy showed smaller beta-carotene bodies residing in the HOM samples than in the BOL samples after digestion. These results suggest that the in vitro bioaccessibility of beta-carotene in an OFSP meal can be improved by processing methods that promote cell-wall rupture.
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| 18. |
- Bengtsson, Anders, 1954, et al.
(författare)
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Extracorporeal ("ex vivo") connection of pig kidneys to humans. III. Studies of plasma complement activation and complement deposition in the kidney tissue.
- 1998
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Ingår i: Xenotransplantation. - 0908-665X. ; 5:3, s. 176-83
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is one of the important factors involved in the hyperacute rejection of xenografts. This report deals with the activation of the complement system in a clinical trial where pig kidneys were extracorporeally connected to two volunteer dialysis patients who were pretreated with plasmapheresis in order to substantially reduce anti-pig xenoantibodies. The clinical data of the perfusion experiments and the patients humoral immune response to pig xenoantigens have been reported in detail (Xenotransplantation 1996; 3:328-339, 340-353). Three consecutive daily plasmapheresis treatments of the patients reduced the plasma complement protein (C3, C4, and C5) concentrations to 8-27% of the baseline values. The perfusion of the pig kidney connected to patient 1 was terminated at 65 min due to graft rejection and this patient was not hemodynamically affected by the experiment. The second experiment was terminated at 15 min due to an anaphylactic like reaction of the patient. In patient 1 a slight reduction of plasma C3, C4, and C5 and an increase of C5a and SC5b-9 occurred, while C3a decreased during the perfusion. Patient 2 had an increase of all complement parameters, most prominent for C4d and SC5b-9, which occurred concomitant with the appearance of the anaphylactic like side effects. In general, plasma levels of PMN elastase, IL6 and IL8 increased in both patients during the perfusion. Immunohistochemical investigation of the kidney tissues revealed deposition of human complement factors C1q, C4c, and C3c in a congruent pattern with the vasculature of the kidney in patient 1. In kidney 2 only trace amounts of C1q and C3c were found. Both kidneys were negative for properdin. Therefore, in this experimental set up with extracorporeal connection of pig kidneys to the human circulation the human complement cascade is activated mainly through the classical pathway.
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| 19. |
- Bengtsson, Andreas, 1991, et al.
(författare)
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Improved Success Probability with Greater Circuit Depth for the Quantum Approximate Optimization Algorithm
- 2020
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Ingår i: Physical Review Applied. - 2331-7019. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Present-day, noisy, small or intermediate-scale quantum processors-although far from fault tolerant-support the execution of heuristic quantum algorithms, which might enable a quantum advantage, for example, when applied to combinatorial optimization problems. On small-scale quantum processors, validations of such algorithms serve as important technology demonstrators. We implement the quantum approximate optimization algorithm on our hardware platform, consisting of two superconducting transmon qubits and one parametrically modulated coupler. We solve small instances of the NP (nondeterministic polynomial time)-complete exact-cover problem, with 96.6% success probability, by iterating the algorithm up to level two.
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| 20. |
- Bengtsson, Anders, et al.
(författare)
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Pharmacokinetics, tolerability, and preliminary efficacy of paquinimod (ABR-215757), a new quinoline-3-carboxamide derivative: Studies in lupus-prone mice and a multicenter, randomized, double-blind, placebo-controlled, repeat-dose, dose-ranging study in patients with systemic lupus erythematosus
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:5, s. 1579-1588
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the efficacy of paquinimod, a new immunomodulatory small molecule, in a murine lupus model, and to evaluate its pharmacokinetics and tolerability in systemic lupus erythematosus (SLE) patients at doses predicted to be efficacious and safe and determine the maximum tolerated dose. Methods The efficacy of paquinimod was studied in lupus-prone MRL-lpr/lpr mice and compared with that of established SLE treatments. Dose-response data and pharmacokinetic data were used to calculate effective and safe clinical doses of paquinimod. The pharmacokinetics and tolerability of paquinimod were evaluated in a phase Ib double-blind, placebo controlled, dose-ranging study in which cohorts of SLE patients received daily oral treatment for 12 weeks. Results Paquinimod treatment resulted in disease inhibition in MRL-lpr/lpr mice, comparable to that obtained with prednisolone and mycophenolate mofetil; prominent effects on disease manifestations and serologic markers and a steroid-sparing effect were observed. In patients with SLE, the pharmacokinetic properties of paquinimod were linear and well suitable for once-daily oral treatment. The majority of the adverse events (AEs) were mild or moderate, and transient. The most frequent AEs were arthralgia and myalgia, reported with the highest dose levels of paquinimod (4.5 mg/day and 6.0 mg/day). At the 4.5 mg/day dose level and higher, some AEs of severe intensity and serious adverse events were reported. Conclusion Paquinimod effectively inhibited disease and had a steroid-sparing effect in experimental lupus. Results from preclinical models together with pharmacokinetic data were successfully translated into a safe clinical dose range, and doses of up to 3.0 mg/day were well tolerated in the SLE patients. Taken together, the promising combined data from a murine model and human SLE support the future clinical development of paquinimod.
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| 21. |
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| 22. |
- Bengtsson, Christian, et al.
(författare)
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Association of genomically enhanced and parent average breeding values with cow performance in Nordic dairy cattle
- 2020
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Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 103, s. 6383-6391
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Tidskriftsartikel (refereegranskat)abstract
- This study compared the abilities of virgin heifer genomically enhanced breeding values (GEBV) and parent average breeding values (PA) to predict future cow performance. To increase confidence in genomic technology among farmers, a clear demonstration of the relationship between genomic predictions and future phenotypes is needed. We analyzed 12 different traits in first parity, including production, conformation, fer-tility, and other functional traits. Phenotype data were obtained from national milk recording schemes and breeding values from the Nordic Cattle Genetic Evalu-ation. Direct genomic breeding values were calculated using genomic BLUP and combined with traditional breeding values, using bivariate blending. The data covered 14,862 Red Dairy Cattle, 17,145 Holstein, and 7,330 Jersey genotyped virgin heifers born between 2013 and 2015 in Denmark, Finland, and Sweden. Phe-notypes adjusted for systematic environmental effects were used as measures of cow performance. Two meth-ods were used to compared virgin heifer GEBV and PA regarding their ability to predict future cow per-formance: (1) correlations between breeding values and adjusted phenotypes, (2) ranking cows into 4 quartiles for their virgin heifer GEBV or PA, and calculating actual cow performance for each quartile. We showed that virgin heifer GEBV predicted cow performance significantly better than PA for the vast majority of analyzed traits. The correlations with adjusted pheno-types were 38 to 136% higher for GEBV than for PA in Red Dairy Cattle, 42 to 194% higher for GEBV in Holstein, and 11 to 78% higher for GEBV in Jersey. The relative change between GEBV bottom and top quartiles compared with that between PA bottom and top quartiles ranged from 9 to 261% for RDC, 42 to 138% for Holstein, and 4 to 90% for Jersey. Hence, farmers in Denmark, Finland, and Sweden can have confidence in using genomic technology on their herds.
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| 23. |
- Bengtsson, Christian
(författare)
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Dairy cattle mating plans at herd level using genomic information
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genotyping of dairy cattle can benefit farmers by increasing the accuracy of breeding values and improving mating plans at herd level. Validation studies on breeding values in this thesis revealed that for the vast majority of traits analysed in Holstein, Jersey and Nordic Red Dairy Cattle, genomically enhanced breeding values for virgin heifers were able to predict cow performance significantly more accurately than parent average breeding values. Linear programming was used to optimise matings based on economic scores for Red Dairy Cattle and Holstein, considering genetic level, semen cost, recessive genetic defects, and genetic relationship. For Holstein, we also studied polledness and beta-casein genotype. The mating results for Red Dairy Cattle showed that it was possible to reduce genetic relatedness between parents and eliminate expression of genetic defects with minimal effect on genetic level. Similar results were achieved for Holstein cattle, in which it was also possible to increase the frequency of polled and beta-casein genotype A2A2 offspring without negatively impacting other comparison criteria. Evaluation of the long-term impact of genomic mating allocations in a simulation study revealed that planning matings with genomic information at herd level involves important risk management decisions, e.g. a trade-off between using fewer bulls to increase the polled allele frequency more quickly and using more bulls to reduce the rate of inbreeding and the variation in carrier frequency for genetic defects.
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| 24. |
- Bengtsson, Christian, et al.
(författare)
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Mating allocations in Holstein combining genomic information and linear programming optimization at the herd level
- 2023
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Ingår i: Journal of Dairy Science. - 0022-0302 .- 1525-3198. ; 106, s. 3359-3375
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explored mating allocation in Hol-stein using genomic information for 24,333 Holstein fe-males born in Denmark, Finland, and Sweden. We used 2 data sets of bulls: the top 50 genotyped bulls and the top 25 polled genotyped bulls on the Nordic total merit scale. We used linear programming to optimize economic scores within each herd, considering genetic level, genetic relationship, semen cost, the economic impact of genetic defects, polledness, and 0-casein. We found that it was possible to reduce genetic relation-ships and eliminate expression of genetic defects with minimal effect on the genetic level in total merit index. Compared with maximizing only Nordic total merit in-dex, the relative frequency of polled offspring increased from 13.5 to 22.5%, and that of offspring homozygous for 0-casein (A2A2) from 66.7 to 75.0% in one genera-tion, without any substantial negative impact on other comparison criteria. Using only semen from polled bulls, which might become necessary if dehorning is banned, considerably reduced the genetic level. We also found that animals carrying the polled allele were less likely to be homozygous for 0-casein (A2A2) and more likely to be carriers of the genetic defect HH1. Hence, adding economic value to a monogenic trait in the economic score used for mating allocation sometimes negatively affected another monogenetic trait. We rec-ommend that the comparison criteria used in this study be monitored in a modern genomic mating program.
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| 25. |
- Bengtsson, Christian, et al.
(författare)
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Mating allocations in Nordic Red Dairy Cattle using genomic information
- 2022
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Konferensbidrag (refereegranskat)abstract
- In this study, we compared mating allocations in Nordic Red Dairy Cattle using genomic or pedigree information. We used linear programming to optimise different economic scores within each herd, considering genetic level, semen cost, the economic impact of recessive genetic defects, and genetic relationships. We found high correlations (≥0.83) between the pedigree and genomic relationship measures. The mating results showed that it was possible to reduce the different genetic relationships between parents with minimal effect on genetic level. Including the cost of known recessive genetic defects eliminated expression of genetic defects. It was possible to reduce genomic relationships between parents with pedigree information, but it was best done with genomic measures. Linear programming maximised the economic score for all herds studied within seconds, which means that it is suitable for implementation in mating software to be used by advisors and farmers.
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