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- Kreins, AY, et al.
(författare)
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Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome
- 2015
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:10, s. 1641-1662
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
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| 2. |
- Rachmeler, L. A., et al.
(författare)
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Quiet Sun Center to Limb Variation of the Linear Polarization Observed by CLASP2 Across the Mg ıı h and k Lines
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 936:1
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Tidskriftsartikel (refereegranskat)abstract
- The CLASP2 (Chromospheric LAyer Spectro-Polarimeter 2) sounding rocket mission was launched on 2019 April 11. CLASP2 measured the four Stokes parameters of the Mg ıı h and k spectral region around 2800 Å along a 200'' slit at three locations on the solar disk, achieving the first spatially and spectrally resolved observations of the solar polarization in this near-ultraviolet region. The focus of the work presented here is the center-to-limb variation of the linear polarization across these resonance lines, which is produced by the scattering of anisotropic radiation in the solar atmosphere. The linear polarization signals of the Mg ıı h and k lines are sensitive to the magnetic field from the low to the upper chromosphere through the Hanle and magneto-optical effects. We compare the observations to theoretical predictions from radiative transfer calculations in unmagnetized semiempirical models, arguing that magnetic fields and horizontal inhomogeneities are needed to explain the observed polarization signals and spatial variations. This comparison is an important step in both validating and refining our understanding of the physical origin of these polarization signatures, and also in paving the way toward future space telescopes for probing the magnetic fields of the solar upper atmosphere via ultraviolet spectropolarimetry.
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| 3. |
- Egg, David, et al.
(författare)
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Therapeutic options for CTLA-4 insufficiency
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 149:2, s. 736-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. Objective: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. Methods: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. Results: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. Conclusion: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
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| 4. |
- Jeppsson, Ulf, et al.
(författare)
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Benchmark simulation models, quo vadis?
- 2013
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Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 68:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- As the work of the IWA Task Group on Benchmarking of Control Strategies for wastewater treatment plants (WWTPs) is coming to an end, it is essential to disseminate the knowledge gained. For this reason, all authors of the IWA Scientific and Technical Report on benchmarking have come together to provide their insights, highlighting areas where knowledge may still be deficient and where new opportunities are emerging, and to propose potential avenues for future development and application of the general benchmarking framework and its associated tools. The paper focuses on the topics of temporal and spatial extension, process modifications within the WWTP, the realism of models, control strategy extensions and the potential for new evaluation tools within the existing benchmark system. We find that there are major opportunities for application within all of these areas, either from existing work already being done within the context of the benchmarking simulation models (BSMs) or applicable work in the wider literature. Of key importance is increasing capability, usability and transparency of the BSM package while avoiding unnecessary complexity.
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| 9. |
- Solon, K., et al.
(författare)
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Plant-wide modelling of phosphorus transformations in wastewater treatment systems : Impacts of control and operational strategies
- 2017
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354. ; 113, s. 97-110
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this paper is to report the effects that control/operational strategies may have on plant-wide phosphorus (P) transformations in wastewater treatment plants (WWTP). The development of a new set of biological (activated sludge, anaerobic digestion), physico-chemical (aqueous phase, precipitation, mass transfer) process models and model interfaces (between water and sludge line) were required to describe the required tri-phasic (gas, liquid, solid) compound transformations and the close interlinks between the P and the sulfur (S) and iron (Fe) cycles. A modified version of the Benchmark Simulation Model No. 2 (BSM2) (open loop) is used as test platform upon which three different operational alternatives (A1, A2, A3) are evaluated. Rigorous sensor and actuator models are also included in order to reproduce realistic control actions. Model-based analysis shows that the combination of an ammonium (SNHX ) and total suspended solids (XTSS) control strategy (A1) better adapts the system to influent dynamics, improves phosphate (SPO4 ) accumulation by phosphorus accumulating organisms (XPAO) (41%), increases nitrification/denitrification efficiency (18%) and reduces aeration energy (Eaeration) (21%). The addition of iron XFeCl3 ) for chemical P removal (A2) promotes the formation of ferric oxides (XHFO−H, XHFO−L), phosphate adsorption (XHFO−H,P, XHFO−L,P), co-precipitation (XHFO−H,P,old, XHFO−L,P,old) and consequently reduces the P levels in the effluent (from 2.8 to 0.9 g P.m−3). This also has an impact on the sludge line, with hydrogen sulfide production (GH2S) reduced (36%) due to iron sulfide (XFeS) precipitation. As a consequence, there is also a slightly higher energy production (Eproduction) from biogas. Lastly, the inclusion of a stripping and crystallization unit (A3) for P recovery reduces the quantity of P in the anaerobic digester supernatant returning to the water line and allows potential struvite (XMgNH4PO4 ) recovery ranging from 69 to 227 kg.day−1 depending on: (1) airflow (Qstripping); and, (2) magnesium (QMg(OH)2 ) addition. All the proposed alternatives are evaluated from an environmental and economical point of view using appropriate performance indices. Finally, some deficiencies and opportunities of the proposed approach when performing (plant-wide) wastewater treatment modelling/engineering projects are discussed.
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