9,220 research outputs found

    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    Studies on human cancer variant and mycobacterial isocitrate dehydrogenases

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    Mutations in human IDH genes occur in cancer and result in active site IDH variants with a gain-of-function ability to reduce the normal 2-oxoglutarate (2-OG) product of IDH catalysis to 2-hydroxyglutarate (2-HG). As reviewed in Chapter 1, elevated 2-HG levels are proposed to promote tumorigenesis via chromatin remodelling. Efficient IDH1 variant inhibitors bind in an allosteric manner at the dimer-interface and hinder binding of 2-OG and Mg2+. Ivosidenib is an IDH1 variant inhibitor that is approved for acute myeloid leukaemia (AML) treatment; however, acquired second-site S280F mutations to IDH1 render cancer cells resistant to ivosidenib treatment. The research described in this thesis investigated the mechanism of action of the second site IDH1 mutation and how to overcome resistance due to it. Kinetic analyses show that the IDH1 S280F substitution not only leads to resistance against ivosidenib but results in a higher affinity for 2-OG and Mg2+, and consequently, more efficient turnover of 2-OG to 2-HG. 1H Nuclear magnetic resonance (NMR) studies reveal that IDH1 cancer variants can turn over D-isocitrate to 2-HG. The rate of conversion of D-isocitrate to 2-HG by S280F substituted variants is more efficient than for IDH1 wildtype or active site variants without the S280F substitution. Mechanistic studies on IDH1 variants provide insights into the influence of various R132 substitutions and the role of the dimer-interface in IDH1 catalysis. In addition to resistance enabled by more efficient 2-HG production, ivosidenib binding is hindered by the loss of a hydrogen bond to S280, steric hindrance due to the S280F substitution, formation of a new hydrophobic pocket at the dimer-interface, and higher enzymatic affinity for 2-OG and Mg2+. Certain IDH1 variant inhibitors were shown to retain activity against isolated IDH1 R132C S280F and R132H S280F, some with high potency. Non-denaturing mass spectrometry (MS) reveals that inhibitors retaining activity bind with a stoichiometry of two inhibitors per IDH1 variant dimer, in contrast to ivosidenib, which binds with a stoichiometry of one inhibitor per dimer. Several inhibitors reduce 2-HG levels in cell lines overexpressing IDH1 R132C S280F or R132H S280F. Some of these inhibitors are in phase 2 clinical studies (FT-2102, DS-1001B) indicating that S280F-mediated ivosidenib resistance can be overcome by using alternative inhibitors. Targeting metabolism has also been of long-standing interest in the antibacterial field, including for Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Msm). After establishing production strategies and an activity assay for Mtb IDH1/IDH2 and Msm IDH, kinetic studies support the proposal that Mtb IDH2 is likely the essential IDH isoform for oxidative decarboxylation of isocitrate in Mtb metabolism. Mtb IDH2 activity is enhanced by several reactive carbonyl group containing metabolites. Most Hs IDH1 cancer variant inhibitors are not active against Mtb IDH1/IDH2 and Msm IDH but some exhibit weak activity. The overall results provide mechanistic insights into resistance to Hs IDH1 variant inhibitors and show how this can be overcome. The studies suggest that targeting IDH may be a viable strategy for mycobacterial treatment

    New Building Blocks for Cancer Phototherapeutics: 5d Metallocorroles

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    Corroles are ring-contracted, triprotic analogues of porphyrins. This PhD study expands earlier knowledge in particular on ReO corroles. Early on, it became apparent that ReO corroles exhibit the highest phosphorescence quantum yields among all metallocorroles. They also sensitize singlet oxygen formation and serve as oxygen sensors and as triplet-triplet annihilation upconverters. I accordingly wanted to synthesize new classes of functionalized 5d corroles as well as to examine ReO corroles as photosensitizers in in vitro photodynamic therapy experiments. I found that amphiphilic meta/para-carboxyl-appended ReO triphenylcorroles exhibit high photocytotoxicity against multiple cancer cell lines. In the synthetic realm, one study examined electrophilic chlorination and bromination of ReO corroles. X-ray structures of ReO octachloro- and octabromocorroles yielded a host of insights into the conformational preferences of sterically hindered corrole derivatives. Another synthetic study afforded an innovative approach to water-soluble iridium corroles, involving the use of water-soluble axial ligands. I also undertook extensive studies of formylation of ReO and Au triarylcorroles, arriving at the rather elegant conclusion that whereas the former largely afford 3-monoformyl products, the latter preferentially yield 3,17-diformylproducts, presumably reflecting the higher nucleophilicity of the Au complexes. The formylcorrole products could be readily postfunctionalized, such as via the Knoevenagel reaction. The 5d formylcorroles should serve as valuable starting materials for bio- and nanoconjugated 5d metallocorroles for advanced, targeted cancer therapies. I feel privileged to have developed a new class of triplet photosensitizers – the ReO corroles – that to this day remain unique to our Tromsø laboratory. I am confident, however, that we shall soon see exciting applications of these compounds as advanced photodynamic, photothermal and multimodal cancer therapeutics

    Knowledge-based Modelling of Additive Manufacturing for Sustainability Performance Analysis and Decision Making

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    Additiivista valmistusta on pidetty käyttökelpoisena monimutkaisissa geometrioissa, topologisesti optimoiduissa kappaleissa ja kappaleissa joita on muuten vaikea valmistaa perinteisillä valmistusprosesseilla. Eduista huolimatta, yksi additiivisen valmistuksen vallitsevista haasteista on ollut heikko kyky tuottaa toimivia osia kilpailukykyisillä tuotantomäärillä perinteisen valmistuksen kanssa. Mallintaminen ja simulointi ovat tehokkaita työkaluja, jotka voivat auttaa lyhentämään suunnittelun, rakentamisen ja testauksen sykliä mahdollistamalla erilaisten tuotesuunnitelmien ja prosessiskenaarioiden nopean analyysin. Perinteisten ja edistyneiden valmistusteknologioiden mahdollisuudet ja rajoitukset määrittelevät kuitenkin rajat uusille tuotekehityksille. Siksi on tärkeää, että suunnittelijoilla on käytettävissään menetelmät ja työkalut, joiden avulla he voivat mallintaa ja simuloida tuotteen suorituskykyä ja siihen liittyvän valmistusprosessin suorituskykyä, toimivien korkea arvoisten tuotteiden toteuttamiseksi. Motivaation tämän väitöstutkimuksen tekemiselle on, meneillään oleva kehitystyö uudenlaisen korkean lämpötilan suprajohtavan (high temperature superconducting (HTS)) magneettikokoonpanon kehittämisessä, joka toimii kryogeenisissä lämpötiloissa. Sen monimutkaisuus edellyttää monitieteisen asiantuntemuksen lähentymistä suunnittelun ja prototyyppien valmistuksen aikana. Tutkimus hyödyntää tietopohjaista mallinnusta valmistusprosessin analysoinnin ja päätöksenteon apuna HTS-magneettien mekaanisten komponenttien suunnittelussa. Tämän lisäksi, tutkimus etsii mahdollisuuksia additiivisen valmistuksen toteutettavuuteen HTS-magneettikokoonpanon tuotannossa. Kehitetty lähestymistapa käyttää fysikaalisiin kokeisiin perustuvaa tuote-prosessi-integroitua mallinnusta tuottamaan kvantitatiivista ja laadullista tietoa, joka määrittelee prosessi-rakenne-ominaisuus-suorituskyky-vuorovaikutuksia tietyille materiaali-prosessi-yhdistelmille. Tuloksina saadut vuorovaikutukset integroidaan kaaviopohjaiseen malliin, joka voi auttaa suunnittelutilan tutkimisessa ja täten auttaa varhaisessa suunnittelu- ja valmistuspäätöksenteossa. Tätä varten testikomponentit valmistetaan käyttämällä kahta metallin additiivista valmistus prosessia: lankakaarihitsaus additiivista valmistusta (wire arc additive manufacturing) ja selektiivistä lasersulatusta (selective laser melting). Rakenteellisissa sovelluksissa yleisesti käytetyistä metalliseoksista (ruostumaton teräs, pehmeä teräs, luja niukkaseosteinen teräs, alumiini ja kupariseokset) testataan niiden mekaaniset, lämpö- ja sähköiset ominaisuudet. Lisäksi tehdään metalliseosten mikrorakenteen karakterisointi, jotta voidaan ymmärtää paremmin valmistusprosessin parametrien vaikutusta materiaalin ominaisuuksiin. Integroitu mallinnustapa yhdistää kerätyn kokeellisen tiedon, olemassa olevat analyyttiset ja empiiriset vuorovaikutus suhteet, sekä muut tietopohjaiset mallit (esim. elementtimallit, koneoppimismallit) päätöksenteon tukijärjestelmän muodossa, joka mahdollistaa optimaalisen materiaalin, valmistustekniikan, prosessiparametrien ja muitten ohjausmuuttujien valinnan, lopullisen 3d-tulosteun komponentin halutun rakenteen, ominaisuuksien ja suorituskyvyn saavuttamiseksi. Valmistuspäätöksenteko tapahtuu todennäköisyysmallin, eli Bayesin verkkomallin toteuttamisen kautta, joka on vankka, modulaarinen ja sovellettavissa muihin valmistusjärjestelmiin ja tuotesuunnitelmiin. Väitöstyössä esitetyn mallin kyky parantaa additiivisien valmistusprosessien suorituskykyä ja laatua, täten edistää kestävän tuotannon tavoitteita.Additive manufacturing (AM) has been considered viable for complex geometries, topology optimized parts, and parts that are otherwise difficult to produce using conventional manufacturing processes. Despite the advantages, one of the prevalent challenges in AM has been the poor capability of producing functional parts at production volumes that are competitive with traditional manufacturing. Modelling and simulation are powerful tools that can help shorten the design-build-test cycle by enabling rapid analysis of various product designs and process scenarios. Nevertheless, the capabilities and limitations of traditional and advanced manufacturing technologies do define the bounds for new product development. Thus, it is important that the designers have access to methods and tools that enable them to model and simulate product performance and associated manufacturing process performance to realize functional high value products. The motivation for this dissertation research stems from ongoing development of a novel high temperature superconducting (HTS) magnet assembly, which operates in cryogenic environment. Its complexity requires the convergence of multidisciplinary expertise during design and prototyping. The research applies knowledge-based modelling to aid manufacturing process analysis and decision making in the design of mechanical components of the HTS magnet. Further, it explores the feasibility of using AM in the production of the HTS magnet assembly. The developed approach uses product-process integrated modelling based on physical experiments to generate quantitative and qualitative information that define process-structure-property-performance interactions for given material-process combinations. The resulting interactions are then integrated into a graph-based model that can aid in design space exploration to assist early design and manufacturing decision-making. To do so, test components are fabricated using two metal AM processes: wire and arc additive manufacturing and selective laser melting. Metal alloys (stainless steel, mild steel, high-strength low-alloyed steel, aluminium, and copper alloys) commonly used in structural applications are tested for their mechanical-, thermal-, and electrical properties. In addition, microstructural characterization of the alloys is performed to further understand the impact of manufacturing process parameters on material properties. The integrated modelling approach combines the collected experimental data, existing analytical and empirical relationships, and other data-driven models (e.g., finite element models, machine learning models) in the form of a decision support system that enables optimal selection of material, manufacturing technology, process parameters, and other control variables for attaining desired structure, property, and performance characteristics of the final printed component. The manufacturing decision making is performed through implementation of a probabilistic model i.e., a Bayesian network model, which is robust, modular, and can be adapted for other manufacturing systems and product designs. The ability of the model to improve throughput and quality of additive manufacturing processes will boost sustainable manufacturing goals

    Proceedings of FORM 2022. Construction The Formation of Living Environment

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    This study examines the integration of building information modelling (BIM) technologies in operation & maintenance stage in the system of managing real estate that helps to reduce transaction costs. The approach and method are based on Digital Twin technology and Model Based System Engineering (MBSE) approach. The results of the development of a service for digital facility management and digital expertise are presented. The connection between physical and digital objects is conceptualized

    Optimisation of Triboelectric Nanogenerator performance in vertical contact-separation mode

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    Triboelectric nanogenerator (TENG) is one of the most promising energy harvesters – a technology that uses repeated or reciprocating contact of suitably chosen materials to generate charge via the triboelectric effect (TE) and utilizes this as usable voltage and current. TENGs are attractive as they can continuously generate charge over a wide range of operating conditions and have several valuable advantages such as light weight, simple structure, low cost and high efficiency. Therefore, TENGs have been explored in a wide range of applications, including self-powered wearable electronics, powering electronics and even for harvesting ocean wave/wind energy. One of the major limitations of TENGs is their low power output (usually <500 W/m2). This thesis focuses of a few specific approaches to optimising TENG output performance. This thesis begins by presenting a solution to this challenge by optimizing a low permittivity substrate beneath the tribo-contact layer. The open circuit voltage is found to increase by a factor of 1.3 in moving from PET to the lower permittivity PTFE. TENG performance is also believed to depend on contact force, but the origin of the dependence had not previously been explored. Herein, we show that this behaviour results from a contact force dependent real contact area Ar as governed by surface roughness. The open circuit voltage Voc, short circuit current Isc and Ar for a TENG were found to increase with contact force/pressure. Critically, Voc and Isc saturate at the same contact pressure as Ar suggesting that electrical output follows the same evolution as Ar. Assuming that tribo charges can only transfer across the interface at areas of real contact, it follows that an increasing Ar with contact pressure should produce a corresponding increase in the electrical output. These results underline the importance of accounting for real contact area in TENG design, as well as the distinction between real and nominal contact area in tribo-charge density definition. High-performance ferroelectricassisted TENGs (Fe-TENGs) are developed using electrospun fibrous surfaces based on P(VDFTrFE) with dispersed BaTiO3 (BTO) nanofillers in either cubic (CBTO) or tetragonal (TBTO) form in this thesis. TENGs with three types of tribo-negative surface were investigated and output increased progressively. Critically, P(VDF-TrFE)/TBTO produced higher output than P(VDFTrFE)/ CBTO even though permittivity is nearly identical. Thus, it is shown that BTO fillers boost output, not just by increasing permittivity, but also by enhancing the crystallinity and amount of the β-phase (as TBTO produced a more crystalline β-phase present in greater amounts)

    CITIES: Energetic Efficiency, Sustainability; Infrastructures, Energy and the Environment; Mobility and IoT; Governance and Citizenship

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    This book collects important contributions on smart cities. This book was created in collaboration with the ICSC-CITIES2020, held in San José (Costa Rica) in 2020. This book collects articles on: energetic efficiency and sustainability; infrastructures, energy and the environment; mobility and IoT; governance and citizenship

    Modeling, Simulation and Data Processing for Additive Manufacturing

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    Additive manufacturing (AM) or, more commonly, 3D printing is one of the fundamental elements of Industry 4.0. and the fourth industrial revolution. It has shown its potential example in the medical, automotive, aerospace, and spare part sectors. Personal manufacturing, complex and optimized parts, short series manufacturing and local on-demand manufacturing are some of the current benefits. Businesses based on AM have experienced double-digit growth in recent years. Accordingly, we have witnessed considerable efforts in developing processes and materials in terms of speed, costs, and availability. These open up new applications and business case possibilities all the time, which were not previously in existence. Most research has focused on material and AM process development or effort to utilize existing materials and processes for industrial applications. However, improving the understanding and simulation of materials and AM process and understanding the effect of different steps in the AM workflow can increase the performance even more. The best way of benefit of AM is to understand all the steps related to that—from the design and simulation to additive manufacturing and post-processing ending the actual application.The objective of this Special Issue was to provide a forum for researchers and practitioners to exchange their latest achievements and identify critical issues and challenges for future investigations on “Modeling, Simulation and Data Processing for Additive Manufacturing”. The Special Issue consists of 10 original full-length articles on the topic
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