| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
- Aartsen, M. G., et al.
(författare)
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PINGU : a vision for neutrino and particle physics at the South Pole
- 2017
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 44:5
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Tidskriftsartikel (refereegranskat)abstract
- The Precision IceCube Next Generation Upgrade (PINGU) is a proposed low-energy in-fill extension to the IceCube Neutrino Observatory. With detection technology modeled closely on the successful IceCube example, PINGU will provide a 6 Mton effective mass for neutrino detection with an energy threshold of a few GeV. With an unprecedented sample of over 60 000 atmospheric neutrinos per year in this energy range, PINGU will make highly competitive measurements of neutrino oscillation parameters in an energy range over an order of magnitude higher than long-baseline neutrino beam experiments. PINGU will measure the mixing parameters theta(23) and Delta m(32)(2), including the octant of theta(23) for a wide range of values, and determine the neutrino mass ordering at 3 sigma median significance within five years of operation. PINGU's high precision measurement of the rate of nu(T) appearance will provide essential tests of the unitarity of the 3 x 3 PMNS neutrino mixing matrix. PINGU will also improve the sensitivity of searches for low mass dark matter in the Sun, use neutrino tomography to directly probe the composition of the Earth's core, and improve IceCube's sensitivity to neutrinos from Galactic supernovae. Reoptimization of the PINGU design has permitted substantial reduction in both cost and logistical requirements while delivering performance nearly identical to configurations previously studied.
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| 6. |
- Aartsen, M. G., et al.
(författare)
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Development of an analysis to probe the neutrino mass ordering with atmospheric neutrinos using three years of IceCube DeepCore data IceCube Collaboration
- 2020
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Ingår i: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- The Neutrino Mass Ordering (NMO) remains one of the outstanding questions in the field of neutrino physics. One strategy to measure the NMO is to observe matter effects in the oscillation pattern of atmospheric neutrinos above similar to 1GeV, as proposed for several next-generation neutrino experiments. Moreover, the existing IceCube DeepCore detector can already explore this type of measurement. We present the development and application of two independent analyses to search for the signature of the NMO with three years of DeepCore data. These analyses include a full treatment of systematic uncertainties and a statistically-rigorous method to determine the significance for the NMO from a fit to the data. Both analyses show that the dataset is fully compatible with both mass orderings. For the more sensitive analysis, we observe a preference for normal ordering with a p-value of pIO=15.3% and CLs=53.3% for the inverted ordering hypothesis, while the experimental results from both analyses are consistent within their uncertainties. Since the result is independent of the value of delta CP and obtained from energies E nu greater than or similar to 5GeV, it is complementary to recent results from long-baseline experiments. These analyses set the groundwork for the future of this measurement with more capable detectors, such as the IceCube Upgrade and the proposed PINGU detector.
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| 7. |
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| 8. |
- White, H, et al.
(författare)
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A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real time quantitative PCR.
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 29:2, s. 369-376
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Tidskriftsartikel (refereegranskat)abstract
- Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukemia, but there is substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10(6), 1.08±0.11 × 10(5), 1.03±0.10 × 10(4), 1.02±0.09 × 10(3), 1.04±0.10 × 10(2) and 10.0±1.5 copies/μL. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise the numbers of measured transcripts of e14a2 BCR-ABL1 and three control genes; ABL1, BCR and GUSB. The set of 6 plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (http://irmm.jrc.ec.europa.eu; CRM code ERM-AD623a-f).Leukemia accepted article preview online, 18 July 2014; doi:10.1038/leu.2014.217.
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| 9. |
- Abbatt, J. P. D., et al.
(författare)
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Halogen activation via interactions with environmental ice and snow in the polar lower troposphere and other regions
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:14, s. 6237-6271
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Tidskriftsartikel (refereegranskat)abstract
- The role of ice in the formation of chemically active halogens in the environment requires a full understanding because of its role in atmospheric chemistry, including controlling the regional atmospheric oxidizing capacity in specific situations. In particular, ice and snow are important for facilitating multiphase oxidative chemistry and as media upon which marine algae live. This paper reviews the nature of environmental ice substrates that participate in halogen chemistry, describes the reactions that occur on such substrates, presents the field evidence for ice-mediated halogen activation, summarizes our best understanding of ice-halogen activation mechanisms, and describes the current state of modeling these processes at different scales. Given the rapid pace of developments in the field, this paper largely addresses advances made in the past five years, with emphasis given to the polar boundary layer. The integrative nature of this field is highlighted in the presentation of work from the molecular to the regional scale, with a focus on understanding fundamental processes. This is essential for developing realistic parameterizations and descriptions of these processes for inclusion in larger scale models that are used to determine their regional and global impacts.
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| 10. |
- Lessard, Christopher J., et al.
(författare)
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Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome
- 2013
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA. - 1061-4036 .- 1546-1718. ; 45:11, s. 1284-
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Tidskriftsartikel (refereegranskat)abstract
- Sjogrens syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta andlt; 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogrens syndrome.
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| 11. |
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| 12. |
- Kumar, Nitin, et al.
(författare)
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Adaptation of host transmission cycle during Clostridium difficile speciation
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:9, s. 1315-1320
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming, healthcare-associated enteropathogen Clostridium difficile is actively undergoing speciation. Through large-scale genomic analysis of 906 strains, we demonstrate that the ongoing speciation process is linked to positive selection on core genes in the newly forming species that are involved in sporulation and the metabolism of simple dietary sugars. Functional validation shows that the new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels of resistant spores, that is adapted for healthcare-mediated transmission.
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| 13. |
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| 14. |
- Webb, Ryan, et al.
(författare)
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Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1076-1084
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype. METHODS: We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus-associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus-associated MECP2 risk haplotype. RESULTS: We confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 x 10(-11)). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease-associated MECP2 haplotype; most ( approximately 81%) were up-regulated. Genes that were up-regulated had significantly more CpG islands in their promoter regions compared with genes that were down-regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up-regulated genes are regulated by interferon. The disease-risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1. CONCLUSION: Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.
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| 15. |
- Delgado-Vega, Angélica M., et al.
(författare)
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Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:7, s. 1219-1226
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE).MethodsGenotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was done using PLINK and conditional analyses using GENABEL's test score. Transfections of BLK constructs on HEK293 cells containing the novel mutation or the wild type form were analysed for their effect on protein half-life using a protein stability assay, cycloheximide and western blot. CHiP-qPCR for detection of nuclear factor. B (NFkB) binding.ResultsFine mapping of BLK identified two independent genetic effects with functional consequences: one represented by two tightly linked associated haplotype blocks significantly enriched for NF kappa B-binding sites and numerous putative regulatory variants whose risk alleles correlated with low BLK mRNA levels. Binding of NFkBp50 and p65 to an associated 1.2 Kb haplotype segment was confirmed. A second independent genetic effect was represented by an Ala71Thr, low-frequency missense substitution with an OR = 2.31 (95% CI 1.38 to 3.86). The 71Thr decreased BLK protein half-life.ConclusionsThese results show that rare and common regulatory variants in BLK are involved in disease susceptibility and both, albeit independently, lead to reduced levels of BLK protein.
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| 16. |
- Johansson, Johannes D., et al.
(författare)
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Comparison between a detailed and a simplified finite element model of radio-frequency lesioning in the brain
- 2004
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Ingår i: 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, San Fransisco, USA. ; , s. 2510-2513
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Konferensbidrag (refereegranskat)abstract
- A detailed and a simplified model of a lesioning electrode was made using the finite element method. 15 simulations of the lesioning procedure were performed for each model and the resulting lesion volumes were compared in order to investigate if the simplified model is adequate. The simplified model resulted in a very slight overestimation of the volume compared to the detailed model. It was thus concluded that the simplified model is adequate for simulations.
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| 17. |
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| 18. |
- Johansson, Johannes D., 1977-, et al.
(författare)
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Impact of cysts during radio frequency (RF) lesioning in deep brain structures : a simulation and in-vitro study
- 2007
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Ingår i: Journal of Neural Engineering. - : Institute of Physics Publishing (IOPP). - 1741-2560 .- 1741-2552. ; 4:2, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- Radiofrequency lesioning of nuclei in the thalamus or the basal ganglia can be used to reduce symptoms caused by e.g. movement disorders such as Parkinson's disease. Enlarged cavities containing cerebrospinal fluid (CSF) are commonly present in the basal ganglia and tend to increase in size and number with age. Since the cavities have different electrical and thermal properties compared with brain tissue, it is likely that they can affect the lesioning process and thereby the treatment outcome. Computer simulations using the finite element method and in vitro experiments have been used to investigate the impact of cysts on lesions' size and shape. Simulations of the electric current and temperature distributions as well as convective movements have been conducted for various sizes, shapes and locations of the cysts as well as different target temperatures. Circulation of the CSF caused by the heating was found to spread heat effectively and the higher electric conductivity of the CSF increased heating of the cyst. These two effects were together able to greatly alter the resulting lesion size and shape when the cyst was in contact with the electrode tip. Similar results were obtained for the experiments.
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| 19. |
- Johansson, Johannes D, 1977-, et al.
(författare)
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Radio-frequency lesioning in brain tissue with coagulation-dependent thermal conductivity : modelling, simulation and analysis of parameter influence and interaction
- 2006
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Ingår i: Medical and Biological Engineering and Computing. - Heidleberg : Springer. - 0140-0118 .- 1741-0444. ; 44:9, s. 757-766
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Tidskriftsartikel (refereegranskat)abstract
- Radio-frequency brain lesioning is a method for reducing e.g. symptoms of movement disorders. A small electrode is used to thermally coagulate malfunctioning tissue. Influence on lesion size from thermal and electric conductivity of the tissue, microvascular perfusion and preset electrode temperature was investigated using a finite-element model. Perfusion was modelled as an increased thermal conductivity in non-coagulated tissue. The parameters were analysed using a 24-factorial design (n = 16) and quadratic regression analysis (n = 47). Increased thermal conductivity of the tissue increased lesion volume, while increased perfusion decreased it since coagulation creates a thermally insulating layer due to the cessation of blood perfusion. These effects were strengthened with increased preset temperature. The electric conductivity had negligible effect. Simulations were found realistic compared to in vivo experimental lesions.
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| 20. |
- Johansson, Johannes D., et al.
(författare)
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Simulations of radio-frequency lesions with varying brain electrode dimensions
- 2005
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Ingår i: 13th Nordic Baltic conference biomedical engineering and medical physics, Umeå, Sweden. ; , s. 62-63
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Konferensbidrag (refereegranskat)abstract
- Radio-frequency (RF) lesioning in thebrain was simulated using the finite element method(FEM). Heating for 60 s with temperature control inorder to keep the tip at 80 °C was simulated. Length,L, (2 – 4 mm) and diameter, D, (0.5 – 2.5 mm) of theelectrode tip were varied and the resulting lesionvolumes were used to calculate a regression model:Lesion Volume = – 13.1D + 15.7L⋅D + 13.1D2 mm3.The results can be useful for electrode design andprediction of lesion size.
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| 21. |
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| 22. |
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| 23. |
- Ortiz-Fernandez, Lourdes, et al.
(författare)
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Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study
- 2021
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Ingår i: American Journal of Human Genetics. - CAMBRIDGE, MA USA : Cell Press. - 0002-9297 .- 1537-6605. ; 108:1, s. 84-99
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Tidskriftsartikel (refereegranskat)abstract
- Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
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