| 1. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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| 2. |
- Burke, Sinead M., et al.
(författare)
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An experimental and modeling study of propene oxidation. Part 2: Ignition delay time and flame speed measurements
- 2015
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Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180. ; 162:2, s. 296-314
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Tidskriftsartikel (refereegranskat)abstract
- Experimental data obtained in this study (Part II) complement the speciation data presented in Part I, but also offer a basis for extensive facility cross-comparisons for both experimental ignition delay time (IDT) and laminar flame speed (LFS) observables. To improve our understanding of the ignition characteristics of propene, a series of IDT experiments were performed in six different shock tubes and two rapid compression machines (RCMs) under conditions not previously studied. This work is the first of its kind to directly compare ignition in several different shock tubes over a wide range of conditions. For common nominal reaction conditions among these facilities, cross-comparison of shock tube IDTs suggests 20-30% reproducibility (2 sigma) for the IDT observable. The combination of shock tube and RCM data greatly expands the data available for validation of propene oxidation models to higher pressures (2-40 atm) and lower temperatures (750-1750 K). Propene flames were studied at pressures from 1 to 20 atm and unburned gas temperatures of 295-398 K for a range of equivalence ratios and dilutions in different facilities. The present propene-air LFS results at 1 atm were also compared to LFS measurements from the literature. With respect to initial reaction conditions, the present experimental LFS cross-comparison is not as comprehensive as the IDT comparison; however, it still suggests reproducibility limits for the LFS observable. For the LFS results, there was agreement between certain data sets and for certain equivalence ratios (mostly in the lean region), but the remaining discrepancies highlight the need to reduce uncertainties in laminar flame speed experiments amongst different groups and different methods. Moreover, this is the first study to investigate the burning rate characteristics of propene at elevated pressures (>5 atm). IDT and LFS measurements are compared to predictions of the chemical kinetic mechanism presented in Part I and good agreement is observed. (C) 2014 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 3. |
- Zettervall, N., et al.
(författare)
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Combustion LES of a multi-burner annular aero-engine combustor using a skeletal reaction mechanism for jet- a air mixtures
- 2015
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Ingår i: 51st AIAA/SAE/ASEE Joint Propulsion Conference. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103216
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Konferensbidrag (refereegranskat)abstract
- In this study we describe combustion simulations of a single sector and a fully annular generic multi-burner aero-engine combustor. The objectives are to facilitate the understanding of the flow, mixing and combustion processes to help improve the combustor design and the design process, as well as to show that it is now feasible to perform high-fidelity reacting flow simulations of full annular gas turbine combustors with realistic combustion chemistry. For this purpose we use a carefully validated finite rate chemistry Large Eddy Simulation (LES) model together with a range of reaction mechanisms for kerosene-air combustion. The influence of the chemical reaction mechanism on the predictive capability of the LES model, and on the resulting understanding of the combustion dynamics has recently been proved very important and here we extend this for kerosene-air combustion. As part of this work a separate study of different kerosene-air reaction mechanism is comprised, and based on this evaluation the most appropriate reaction mechanisms are used in the subsequent LES computations. A generic small aircraft or helicopter aero-engine combustor is used, and modeled both as a conventional single sector configuration and more appropriately as a fully annular multi-burner configuration. The single-sector and fully annular multi-burner LES predictions are similar but with the fully annular multi-burner configuration showing different combustion dynamics and mean temperature and velocity profiles. For the fully annular multi-burner combustor azimuthal pressure fluctuations are clearly observed, resulting in successive reattachment-detachment of the flames in the azimuthal direction.
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