| 1. |
- Berglund, Eva Caroline, et al.
(författare)
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A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias
- 2022
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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care. Clinical Trial Registration: [https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].
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| 2. |
- Salmasi, Armin, 1983-
(författare)
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ICME guided study of mass transport in production and application of cemented carbides
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cemented carbides are metallic composites consisting of a WC hard phase and a ductile binder, usually Co-based, produced by powder metallurgy and sintering. Cemented carbides are an essential part of modern material and manufacturing processes. However, Co powder is classified as a carcinogenic material with serious health hazards, and most virgin Co reservoirs are located in conflict regions. In addition, there are monopolies in the market for pure tungsten. Therefore, reducing the consumption of cobalt or replacing it with other non-hazardous elements would increase the sustainability of cemented carbide production. Furthermore, advances in production technology can help overcome raw material limitations. One such advancement is non-homogeneous structures and properties for optimization of microstructure which is the topic of this thesis. Integrated computational materials engineering (ICME) and its complementary tools, calculation of phase diagram (CALPHAD), and ab-initio modeling are strong tools that bridge experimentation and modeling. In this thesis, a framework for the material design of non-homogeneous cemented carbides is proposed and tested using these computational tools. The workflow of the material design of non-homogeneous microstructure and properties were studied on different length scales. Atomistic modeling with density functional theory (DFT), ab-initio molecular dynamics (AIMD), and generalized hydrodynamics (GHD) were used to model the viscosity of liquid Co binder. In addition, the mobility of Ti and Fe in disordered BCC TiFe alloy was assessed using new experimental data from the diffusion couple experiments and an electron probe micro-analyzer (EPMA). These two studies were conducted to complete the data necessary to study cemented carbides’ processing and performance. The other studied phenomenon studied by experimentation and modeling is the formation of the gradient zone and the γ cone structure. In addition, a phenomenological model for liquid phase migration (LPM) was created and implemented using the homogenization approach. The LPM pro- cess was studied experimentally and modeled with the YAPFI software. A study of these performers was necessary to link processing and microstructure. On the performance side, the chemical interaction between cutting tools and Ti alloys was studied in detail through experimentation and modeling of diffusion. In addition, hardness and toughness models were applied to predict the longevity of studied cemented carbides. Finally, by applying ICME and material design, a high entropy alloy (HEA) alternative to Co binder was designed, produced, and tested. The research presented in this dissertation attempts to fill the gaps in the material design workflow of cemented carbides by developing new tools and methods based on ICME and CALPHAD paradigms. This goal is achieved by studying different length scales, processing methods, microstructure, properties, and performance of cemented carbides.
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| 3. |
- Höglund, Martin
(författare)
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Optical Functionalization of Transparent Wood Biocomposites
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transparent wood (TW) biocomposites combines load-bearing properties with high transmittance of light. TW consists of a reinforcing wood substrate that has been infiltrated with a polymer matrix. TW can be combined with additives so that new multifunctional materials are obtained. Functional additives are, however, sensitive to aggregation and the wood structure limits particle infiltration. Dispersion and distribution of additives as well as optical properties were controlled by chemical treatment of the wood substrate. The structure and chemistry of the wood substrate was influenced by delignification or bleaching.With a thiol-ene polymer matrix, wood was tailored to produce TW with high or low optical scattering. It was possible to dope a delignified wood substrate with a high content of a fluorescent dye to produce TW solid-state dye lasers. Optical scattering enhanced the spectral brightness of the lasers and wave-guiding in TW partially directed the emission, producing a quasi-random laser.Favourable distribution of nanoparticles (NPs) was obtained by two routes: in-situ synthesis and charge-regulated NP diffusion. With in-situ synthesis, mobile precursors infiltrated the substrate. With charge-regulated diffusion, cationic NPs were dispersed by negative charges in the wood substrate. Structurally coloured TW with wavelength-specific polarization was produced by in-situ synthesis of plasmonic NPs (PNPs). Utilization of wood compounds as reagents and stabilizing ligands produced TW with well-dispersed PNPs. Flame-retardant and self-extinguishing TW with preserved optical transmittance was prepared by charge-regulated diffusion of cationic silica NPs.In conclusion, functionalization of wood substrates promoted controlled dispersion of additives for TW with new functionalities, such as laser performance, fluorescence, fire-retardant properties and structural colours.
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