| 11. |
- Maccari, Maria Elena, et al.
(författare)
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.
- 2023
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825. ; 152:4
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Tidskriftsartikel (refereegranskat)abstract
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
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| 12. |
- Qiu, Chunjing, et al.
(författare)
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ORCHIDEE-PEAT (revision 4596), a model for northern peatland CO2, water, and energy fluxes on daily to annual scales
- 2018
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 11:2, s. 497-519
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Tidskriftsartikel (refereegranskat)abstract
- Peatlands store substantial amounts of carbon and are vulnerable to climate change. We present a modified version of the Organising Carbon and Hydrology In Dynamic Ecosystems (ORCHIDEE) land surface model for simulating the hydrology, surface energy, and CO2 fluxes of peatlands on daily to annual timescales. The model includes a separate soil tile in each 0.5° grid cell, defined from a global peatland map and identified with peat-specific soil hydraulic properties. Runoff from non-peat vegetation within a grid cell containing a fraction of peat is routed to this peat soil tile, which maintains shallow water tables. The water table position separates oxic from anoxic decomposition. The model was evaluated against eddy-covariance (EC) observations from 30 northern peatland sites, with the maximum rate of carboxylation (Vcmax) being optimized at each site. Regarding short-term day-to-day variations, the model performance was good for gross primary production (GPP) (r2 Combining double low line 0.76; Nash-Sutcliffe modeling efficiency, MEF Combining double low line 0.76) and ecosystem respiration (ER, r2 Combining double low line 0.78, MEF Combining double low line 0.75), with lesser accuracy for latent heat fluxes (LE, r2 Combining double low line 0.42, MEF Combining double low line 0.14) and and net ecosystem CO2 exchange (NEE, r2 Combining double low line 0.38, MEF Combining double low line 0.26). Seasonal variations in GPP, ER, NEE, and energy fluxes on monthly scales showed moderate to high r2 values (0.57-0.86). For spatial across-site gradients of annual mean GPP, ER, NEE, and LE, r2 values of 0.93, 0.89, 0.27, and 0.71 were achieved, respectively. Water table (WT) variation was not well predicted (r2<0.1), likely due to the uncertain water input to the peat from surrounding areas. However, the poor performance of WT simulation did not greatly affect predictions of ER and NEE. We found a significant relationship between optimized Vcmax and latitude (temperature), which better reflects the spatial gradients of annual NEE than using an average Vcmax value.
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| 13. |
- Schmid, F., et al.
(författare)
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In situ tensile testing of human aortas by time-resolved small-angle X-ray scattering
- 2005
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 12, s. 727-733
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Tidskriftsartikel (refereegranskat)abstract
- The collagen diffraction patterns of human aortas under uniaxial tensile test conditions have been investigated by synchrotron small- angle X- ray scattering. Using a recently designed tensile testing device the orientation and d- spacing of the collagen fibers in the adventitial layer have been measured in situ with the macroscopic force and sample stretching under physiological conditions. The results show a direct relation between the orientation and extension of the collagen fibers on the nanoscopic level and the macroscopic stress and strain. This is attributed first to a straightening, second to a reorientation of the collagen fibers, and third to an uptake of the increasing loads by the collagen fibers.
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| 14. |
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| 15. |
- Szendroedi, Julia, et al.
(författare)
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Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes
- 2009
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 32:4, s. 677-679
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE - Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective beta-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS - We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using P-31/H-1 magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS(myopathy,encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects. RESULTS - The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 +/- 0.5 mg . kg(-1) . min(-1)) and suppression of EGP (69 vs. 94 +/- 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 +/- 1.0 and 12.8 +/- 1.3 mu mol . l(-1) . min(-1)) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects. CONCLUSIONS - Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome.
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| 16. |
- Zhang, Yafan, et al.
(författare)
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Simulation-driven development of a novel SiC embedded power module design concept
- 2017
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Ingår i: 2017 18th International Conference on Thermal, Mechanical and Multi-Physics Simulation and Experiments in Microelectronics and Microsystems, EuroSimE 2017. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509043446
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Konferensbidrag (refereegranskat)abstract
- Silicon carbide embedded power modules enable a compact and cost competitive packaging solution for high-switching frequency and high-temperature operation applications. Power module packaging technologies span several engineering domains. At the early design stage, simulation-driven development is necessary to shorten the design period and reduce the design cost. This paper presents a novel design concept of a three-phase embedded power module (1200 V, 20 A, 55 mm × 36 mm × 0.808 mm) including silicon carbide metal-oxide-semiconductor field-effect transistor and antiparallel diode dies. Based on the E/CAD design data different layer built-up designs have been tested against thermal, mechanical, and electrical behavior. The obtained simulation data then have been evaluated against a commercial available power module (Motion Smart Power Module SMP33) which utilizes over mold direct bonded copper substrates with soldered semiconductor dies and bond wire contacts. Compared to the conventional module, the loop conductive interconnection parasitic inductance and resistance of the design concept (Vdc+ to Vdc-) reduces approximately by 88 % and 72 %, respectively. The average junction to case thermal resistance has been improved by approximately more than 10 % even though the total package size reduces by approximately 88 %. Furthermore, the contours of deformation and stresses have been investigated for the design concept in the thermomechanical simulation.
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