| 41. |
- Dawoodji, Amina, et al.
(författare)
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High Frequency of Cytolytic 21-Hydroxylase-Specific CD8(+) T Cells in Autoimmune Addison's Disease Patients
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:5, s. 2118-2126
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs <= 20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer.
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| 42. |
- De La Fuente Durán, Ana, et al.
(författare)
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Origins of hydrogen peroxide selectivity during oxygen reduction on organic mixed ionic-electronic conducting polymers
- 2023
-
Ingår i: Energy and Environmental Sciences. - 1754-5692 .- 1754-5706. ; 16:11, s. 5409-5422
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical reduction of atmospheric oxygen provides carbon emission-free pathways for the generation of electricity from chemical fuels and for the distributed production of green chemical oxidants like hydrogen peroxide. Recently, organic mixed ionic-electronic conducting polymers (OMIECs) have been reported as a new class of active electrode materials for the oxygen reduction reaction. This work sets out to identify the operative oxygen reduction mechanism of OMIECs through a multi-faceted experimental and theoretical approach. Using a combination of pH-dependent electrochemical characterization, operando UV-Vis and Raman spectroscopy, and ab initio calculations, we find that the n-type OMIEC, p(NDI-T2 P75), displays pH-dependent activity for the selective reduction of oxygen to the 2-electron hydrogen peroxide product. We use microkinetic simulations of the electrochemical behavior to rationalize our experimental observations through a polaron-mediated, non-adsorptive pathway involving chemical reduction of oxygen to the 1-electron superoxide intermediate followed by pH-dependent catalytic disproportionation to hydrogen peroxide. Finally, this pathway is applied to understand the experimental oxygen reduction reactivity across several n- and p-type OMIECs.
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| 43. |
- Debette, Stephanie, et al.
(författare)
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Identification of cis- and trans-Acting Genetic Variants Explaining Up to Half the Variation in Circulating Vascular Endothelial Growth Factor Levels
- 2011
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 109:5, s. 554-563
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Vascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings. Objective: Our aim was to identify genetic variants associated with circulating VEGF levels, using an unbiased genome-wide approach, and to explore their functional significance with gene expression and pathway analysis. Methods and Results: We undertook a genome-wide association study of serum VEGF levels in 3527 participants of the Framingham Heart Study, with preplanned replication in 1727 participants from 2 independent samples, the STANISLAS Family Study and the Prospective Investigation of the Vasculature in Uppsala Seniors study. One hundred forty single nucleotide polymorphism (SNPs) reached genome-wide significance (P<5x10(-8)). We found evidence of replication for the most significant associations in both replication datasets. In a conditional genome-wide association study, 4 SNPs mapping to 3 chromosomal regions were independently associated with circulating VEGF levels: rs6921438 and rs4416670 (6p21.1, P=6.11x10(-506) and P=1.47x10(-12)), rs6993770 (8q23.1, P=2.50x10(-16)), and rs10738760 (9p24.2, P=1.96x10(-34)). A genetic score including these 4 SNPs explained 48% of the heritability of serum VEGF levels. Six of the SNPs that reached genome-wide significance in the genome-wide association study were significantly associated with VEGF messenger RNA levels in peripheral blood mononuclear cells. Ingenuity pathway analyses showed found plausible biological links between VEGF and 2 novel genes in these loci (ZFPM2 and VLDLR). Conclusions: Genetic variants explaining up to half the heritability of serum VEGF levels were identified. These new insights provide important clues to the pathways regulating circulating VEGF levels.
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| 44. |
- Egan, Allyson C, et al.
(författare)
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The Sound of Interconnectivity; The European Vasculitis Society 2022 Report
- 2022
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:8, s. 1745-1757
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Tidskriftsartikel (refereegranskat)abstract
- The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.
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| 45. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 46. |
- Geng, Huifang, et al.
(författare)
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Controlled synthesis of highly stable lead-free bismuth halide perovskite nanocrystals : tructures and photophysics
- 2023
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Ingår i: SCIENCE CHINA Materials. - : Springer Science and Business Media LLC. - 2095-8226 .- 2199-4501. ; 66:5, s. 2079-2089
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Tidskriftsartikel (refereegranskat)abstract
- Recently, cesium bismuth halide perovskites have emerged as potential substitutes to their counterparts, cesium lead halide perovskites, owing to their low toxicity. However, the photophysics of cesium-bismuth halides nanocrystals (NCs) have not yet been fully rationalized because their structures remain highly debated. The ultraviolet-visible (UV-vis) absorption along with other photophysical properties such as the nature and lifetime of the excited states vary considerably across the previous reports. Here, we successfully synthesize pure Cs3BiBr6 and Cs3Bi2Br9 NCs via a modified hot-injection method, where the structure can be easily controlled by tuning the reaction temperature. The UV-vis absorption spectrum of the pure Cs3Bi2Br9 NCs features two characteristic peaks originating from the absorption of the first exciton and second exciton, respectively, which ultimately clarifies the debate in the previous reports. Using femtosecond transient absorption spectroscopy, we systematically investigate the excited state dynamics of the Cs3Bi2Br9 NCs and reveal that the photoexcited carriers undergo a self-trapping process within 3 ps after excitation. More intriguingly, the Cs3Bi2Br9 NCs prepared by this method show much better photostability than those prepared by the ligand-assisted reprecipitation process. Photodetectors based on these Cs3Bi2Br9 NCs show a sensitive light response, demonstrating the definite potential for breakthrough optoelectronic applications. [Figure not available: see fulltext.].
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| 47. |
- Goudzovski, Evgueni, et al.
(författare)
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New physics searches at kaon and hyperon factories
- 2023
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Ingår i: Reports on progress in physics (Print). - : Institute of Physics (IOP). - 0034-4885 .- 1361-6633. ; 86:1
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Forskningsöversikt (refereegranskat)abstract
- Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.
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| 48. |
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| 49. |
- Gramlich, Yvette, 1993-, et al.
(författare)
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Impact of Biomass Burning on Arctic Aerosol Composition
- 2024
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Ingår i: ACS Earth and Space Chemistry. - 2472-3452. ; 8:5, s. 920-936
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Tidskriftsartikel (refereegranskat)abstract
- Emissions from biomass burning (BB) occurring at midlatitudes can reach the Arctic, where they influence the remote aerosol population. By using measurements of levoglucosan and black carbon, we identify seven BB events reaching Svalbard in 2020. We find that most of the BB events are significantly different to the rest of the year (nonevents) for most of the chemical and physical properties. Aerosol mass and number concentrations are enhanced by up to 1 order of magnitude during the BB events. During BB events, the submicrometer aerosol bulk composition changes from an organic- and sulfate-dominated regime to a clearly organic-dominated regime. This results in a significantly lower hygroscopicity parameter κ for BB aerosol (0.4 ± 0.2) compared to nonevents (0.5 ± 0.2), calculated from the nonrefractory aerosol composition. The organic fraction in the BB aerosol showed no significant difference for the O:C ratios (0.9 ± 0.3) compared to the year (0.9 ± 0.6). Accumulation mode particles were present during all BB events, while in the summer an additional Aitken mode was observed, indicating a mixture of the advected air mass with locally produced particles. BB tracers (vanillic, homovanillic, and hydroxybenzoic acid, nitrophenol, methylnitrophenol, and nitrocatechol) were significantly higher when air mass back trajectories passed over active fire regions in Eastern Europe, indicating agricultural and wildfires as sources. Our results suggest that the impact of BB on the Arctic aerosol depends on the season in which they occur, and agricultural and wildfires from Eastern Europe have the potential to disturb the background conditions the most.
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| 50. |
- Grape, Sophie, 1982-, et al.
(författare)
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Partial defect verification using the DCVD : a capability evaluation approach
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The Digital Cherenkov Viewing Device (DCVD) is a non-intrusive instrument available to theInternational Atomic Energy Agency (IAEA) for verifying spent nuclear fuel in storage pools. It iscurrently used for gross-defect evaluations, i.e. to verify that an item in a storage pool is anirradiated fuel assembly and not a fresh assembly or a dummy. This is done by recording images ofthe Cherenkov light emitted in the water surrounding the fuel. Currently, the instrument’s ability toalso detect partial defects at the 50% level or even lower is under study. Here, experimental work iscomplimented by modeling and simulations due to the limited availability of assemblies with partialdefects.Ideally, an IAEA inspector should be able to use the DCVD at e.g. a fuel storage site andimmediately after scanning obtain information on (1) whether an item is an irradiated fuel assemblyor not, and (2) whether the assembly is intact or suffers from a partial defect. This paper discusses adecision-making methodology intended for the latter purpose with the objective to implement it inthe DCVD software in order to facilitate smooth inspection procedures. Inspectors will thus not berequired to possess any expertise in the decision-making methodology.The paper also describes measurements performed during spring 2011 at the CLAB interim spentfuel storage in Sweden. The measurements were carried out with the objective to optimize theequipment handling and work flow during this type of measurement campaigns and to form a basisfor the evaluation of the DCVD’s ability to detect partial defects.
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