Voluntary coughs are used as a diagnostic tool to detect lung diseases. Understanding the mechanics of a cough is therefore crucial to accurately interpreting the test results. A cough is characterised by a dynamic compression of the airways, resulting in large flow velocities and producing transient peak expiratory flows. Existing models for pulmonary flow have one or more of the following limitations: 1) they assume quasi-steady flows, 2) they assume low speed flows, 3) they assume a symmetrical branching airway system. The main objective of this thesis is to develop a model for a cough in the branching pulmonary airway system. First, the time-dependent one-dimensional equations for flow in a compliant tube is used to simulate a cough in a single airway. Using anatomical and physiological data, the tube law coupling the fluid and airway mechanics is constructed to accurately mimic the airway behaviour in its inflated and collapsed states. Next, a novel model for air flow in an airway bifurcation is constructed. The model is the first to capture successfully subcritical and supercritical flows across the bifurcation and allows for free time evolution from one case to another. The model is investigated by simulating a cough in both symmetric and asymmetric airway bifurcations. Finally, a cough model for the complete branching airway system is developed. The model takes into account the key factors involved in a cough; namely, the compliance of the lungs and the airways, the coughing effort and the sudden opening of the glottis. The reliability of the model is assessed by comparing the model predictions with previous experimental results. The model captures the main characteristics of forced expiatory flows; namely, the flow limitation phenomenon (the flow out of the lungs becomes independent of the applied expiratory effort) and the negative effort dependence phenomenon (the flow out of the lungs decreases with increasing expiratory effort). The model also gives a good qualitative agreement with the measured values of airway resistance. The location of the collapsed airway segment during forced expiration is, however, inconsistent with previous experimental results. The effect of changing the model parameters on the model predictions is therefore discussed.

In the first part of the submitted diploma thesis, the knowledge in the sphere of the fracture mechanics, related to the practice part of this thesis are summarized. In that the 2D parametrical numerical model of the particle composite with multiple cracks was created, using the finite elements method. Thanks to this model it is possible to find specific configurations which are showing the existance of multiple mutual interactions between these cracks, just by simple manipulation of the input data. In the calculations the influence of the residual stresses was considered which are formed during production of the material. The effect of the subcritical crack growth was taken into account as well in this thesis.

The strength of materials such as glass and ceramics can be influenced by the environment (stress corrosion). Under applied stress defects (cracks) can grow sub-critically below fracture toughness K_Ic. The aim of this work was to develop a three-dimensional finite-element model to analyze the subcritical crack growth behavior of ceramic-based particulate composites. The maximum tangential stress criterion (MTS) was used to predict the direction of the crack propagation in the framework of linear elastic fracture mechanics. The modeled material was a Low Temperature Co-fired Ceramics (LTCC), containing alumina particles embedded in a glass matrix. The main aim of this work was to develop a 3D model describing the crack growth. Conclusions from this work can contribute to a better understanding of subcritical crack propagation in particle composites.

Subcritical crack growth in composite materials plays quite an important role in determination of the service life and leads to the defects growth below the fracture toughness. The thesis presents search of the several scientific works dealing with the determination of the crack growth direction in composite materials. The aim of this diploma thesis was to create 2D and 3D finite element models to analyse crack growth in Low Temperature Co-fired Ceramics (LTCC). These models were compared based on the time calculation of the crack propagation under the subcritical growth conditions.

Cette thèse présente une étude numérique des régimes turbulents au sein d'un écoulement de Poiseuille plan forcé par un gradient de pression constant. L'effort numérique a porté principalement sur le concept d'Unité Minimale. Dans la première partie, des simulations en régime turbulent ont été conduites en géométrie périodique. Les DNS en Unité Minimale montrent que, l'activité turbulente se trouve localisée à proximité d'une des parois, et que la dynamique aux temps longs s'organise autour de renversements abrupts. Dans la seconde partie, on recherche par le calcul les états cohérents exactes en particulier les états dits frontière. Ces états frontière, obtenus par dichotomie, sont caractérisés par tourbillons longitudinaux et une paire unique de stries toujours localisées à proximité d'une seule paroi. Des représentations de la dynamique dans l'espace des phases sont reconstruites à l'aide de divers observables. La dynamique d'un renversement s'articule autour de visites transitoires vers un espace de solutions quasi-symétriques. Une onde progressive exacte, instable et quasi-symetrique a ainsi été identifiée. L'analyse de stabilité révèle que ses vecteurs propres séparent l'espace des phases en deux basins distincts. La dernière partie remet en question l'auto-similarité des différents régimes d'équilibre d'écoulement. Contrairement aux études récentes qui se concentrent sur les solutions à structure symétrique imposée, nos résultats suggèrent que les unités de parois sont également pertinentes pour les états frontière lorsqu'ils sont localisés près d'une paroi, meme si l'auto-similarité n'est pas aussi flagrante que pour les régimes turbulents. / This thesis numerically investigates the dynamics of turbulence in plane Poiseuille flow driven by a fixed pressure gradient. The focus is especially on computations carried out within the minimal flow unit (M.F.U.). In the first part, turbulent simulations are carried out in spatially periodic channels. In the M.F.U. simulations, the turbulent activity appears to be localised near one wall and the long term dynamics features abrupt reversals. In the next part, we look numerically for exact coherent states in the M.F.U. system. Edge states, which are computed using bisection exhibit streamwise vortices and a single pair of streaks localised near only wall at all times. Different state space representations and phase portraits were constructed using appropriately chosen variables. The dynamics along a turbulent reversal is organised around transient visits to a subspace of (almost) symmetric flow fields. A nearly-symmetric exact travelling wave (TW) solution was found in this subspace. Stability analysis of the TW revealed that its unstable eigenvectors separate the state space into two symmetric basins. In the last part of this thesis, the self-similarity of the different non-trivial equilibrium flow regimes computed in this work, is addressed. Contrarily to most studies focusing on symmetric solutions, the present study suggests that inner scaling is relevant for the description of edge regimes as well although the self-similarity is not as satisfactory as for the turbulent regimes.

I det här projektet extraherades värdefulla komponenter från äpple-pomace som är en restprodukt från cidertillverkning. Restprodukten var tillhandahållen av en svensk cidertillverkare. Extraktionen fokuserades mot pektin och fenolföreningar som uppvisar antioxiderande aktivitet. Extraktionsprocessen designades ur ett miljövänligt perspektiv, inga skadliga kemikalier användes. Fenolära substanser extraherades initialt från pomacen med en vattenlösning innehållande 50% etanol. Därefter studerades kompositionen och den antioxiderande aktiviteten i dessa extrakt. Fokuseringen i projektet låg främst på pektin. Pektin extraherades med subkritiskt vatten vid tre olika pH (3,5 och 7) samt vid två skilda temperaturer (120°C och 140°C) i antingen 5, 10 och 15 minuters sekvenser. Pektinet karakteriserades med avseende på extraktionsutvinningsgrad, sockerkomposition, molekylvikt och antioxiderande aktivitet. Resultaten jämfördes för att undersöka effekten av pH, temperatur och extraktionstid. Gelningsegenskapen hos olika pektin studerades som ett bevis på koncept i ett empiriskt experiment där hög-viskösa vätskor bestående av 5% pektin och 60% sackaros framställdes. Extraherade fenolföreningar har potential att fungera som naturligt utvunna antioxidanter i kosmetiska produkter och pektin kan tänkas användas som reologimodifierare i vattenbaserade formuleringar med låga pH-värden utan behov av kemiska modifieringar. / In this project, apple pomace from a Swedish cider making factory as a by-product was used as a raw material to extract valuable compounds. The extraction was focused on pectin and phenolic compounds with antioxidant activity. For the extraction procedures environmentally friendly processes were chosen without using any harsh chemicals. Phenolic compounds wereinitially extracted from the pomace using 50% aqueous ethanol and then the composition, total phenolic content and antioxidant activity were studied in these extracts. The main focus was on pectins, which were extracted by subcritical water at three different pH conditions (pH 3, 5 and 7) and two different temperatures (120°C and 140°C) in 5-, 10- and 15 minute sequences. Then the pectins were characterized in terms of extraction yield, sugar composition, molecular weight and antioxidant activity and the results were compared in terms of the effect of pH, temperatur eand extraction time. The gelling properties of the different pectins were also studied as a proof of concept in an empirical experiment, where highly viscous liquids were obtained at 5% pectinand 60% sucrose content. In summary, the extracted phenolic compounds have potential to function as naturally derived antioxidants in cosmetics and the pectin may be used as a rheology modifier in water-based formulations of low pH without any additional chemical modifications.

Enzymes and subcritical water can be used for the extraction of hemicelluloses from cereal by-products, making the processes eco-friendly. The polysaccharides extracted from cereal by-products can be used as matrices for development of materials for various applications. This includes bio-based materials such as films and hydrogels, which offer alternatives to existing materials produced from petrochemicals. The polymeric structure of cereal hemicelluloses contains functional groups which enable the modification of their structure by cross-linking, resulting in the formation of hydrogels. This project aims to use subcritical water extraction (SWE) to extract arabinoxylans (AXs) from corn and rye bran meanwhile the enzymatic treatment is done for purifying the samples during both pre- and post-treatment. AXs were further crosslinked by enzyme (laccase) for hydrogel preparation. During the whole project, the characterization included moisture and yield determination, starch and protein content which were tested using a spectrophotometer, monosaccharide content was analyzed by high performance anion exchange chromatography followed by pulsed amperometric detection (HPAEC-PAD) and phenolic acid content was quantified by high performance liquid chromatography (HPLC). The pretreatment for destarching and SWE process was successful. The result showed that arabinoxylans form corn bran were having higher content of arabino substituents, arabino toxylans ratio and ferulic acid content than rye samples. The enzymatic crosslinking could form strong gels in the condition that the AXs had high ferulic acid content. In terms of forming strong hydrogels or to improving the properties of AXs gel, the pre- and post-treatment should be optimized to increase the purity of the extracted feruloylated AX content. / Enzymer och subkritiskt vatten kan användas för extraktion av hemicellulosa från spannmålsbiprodukter, vilket gör extraktionen miljövänlig. Polysackariderna extraherade från spannmålsprodukter kan användas som matriser för utveckling av material för diverse applikationer. Detta inkluderar biobaserade material som filmer och hydrogeler, där petrokemikalier kan ersättas som råvara. Den polymera strukturen hos spannmålshemicelluloser innehåller funktionella grupper som möjliggör formation av tvärbindningar vilket resulterar i bildandet av hydrogeler. Syftet med detta projekt är extraktion av arbinoxylaner (AXs) från majs och rågkli genom att använda subkritiskt vatten-extraktion (SWE) där rening under för- och efterbehandling utförs enzymatiskt. AX modifierades därefter enzymatiskt (laccas) med tvärbindningar för hydrogelframställning. Under hela projektet karakteriserades hydrogelen utifrån fuktinnehåll, bestämmelse av utbyte, stärkelse och proteininnehåll som testades med en spektrofotometer, monosackaridhalten analyserades med högpresterande anjonsutbyteskromatografi följt avpuls-amperometrisk detektion (HPAEC-PAD), samt kvantifierades fenolsyrahalten med högupplöst vätskekromatografi (HPLC). Resultatet visade att arabinoxylaner från majskli hade högre innehåll av arabinosubstituenter, där förhållandet mellan arabino och xylans, samt arabino och ferulsyra innehållet var högre än för rågproverna. Den enzymatiska tvärbindningen kunde bilda starka geler i det tillståndet där AX hade en hög ferulsyrahalt. När det gäller att bilda starka hydrogeler eller att förbättra egenskaperna hos AXs-gel, bör för-och efterbehandlingen optimeras för att öka renheten fördet extraherade feruloylerade AX-innehållet.

Over the last two decades, there has been widespread international interest in the development of the molten salt reactor concept due to its passive safety, high coolant boiling temperature, low operational pressure, high thermal efficiency, and ease of breeding. Terrestrial Energy Incorporated (TEI) is developing a thermal-spectrum converter type molten salt reactor, called the Integral Molten Salt Reactor (IMSR-400) to be built by 2030. A physics experiment is needed in order to validate the theoretical predictions of the temperature reactivity coefficients of the IMSR-400. This thesis will determine the feasibility of conducting a subcritical experiment, utilizing a Deuterium-Deuterium Fusion Neutron Source (DD). / Thesis / Master of Science (MSc)

A lifetime prediction scheme is proposed based on the assumption that the lifetime (time to failure) of rocks under load is governed by the growth of microstructual defects (microcracks). The numerical approach is based on linear elastic fracture mechanics. The numerical calculation scheme is implemented as a cellular automat, where each cell contains a microcrack with length and orientation following certain distributions. The propagation of the microcrack is controlled by the Charles equation, based on subcritical crack growth. The zone inside the numerical model fails if the microcrack has reached the zone dimension or the stress intensity factor of the crack reached the fracture toughness. Macroscopic fractures are formed by these coalesced propagating microcracks, and finally lead to failure of the model. In the numerical approaches, elasto-plastic stress redistributions take place during the forming of the macroscopic fractures. Distinct microcrack propagation types have been programmed and applied to the proposed numerical models. These numerical models are studied under different loading conditions. Numerical results with excellent agreement with the analytical solutions are obtained with respective to predicted lifetime, important parameters for the microcracks, fracture pattern and damage evolution. Potential applications of the proposed numerical model schemes are investigated in some preliminary studies and simulation results are discussed. Finally, conclusions are drawn and possible improvements to the numerical approaches and extensions of the research work are given. / 本文认为微结构缺陷（微裂纹）的扩展决定了受力岩石的寿命（破坏时间）。基于此假设，提出了岩石寿命预测方法。利用线弹性断裂力学理论，通过FLAC进行了数值模拟。数值模型中每个单元定义一条初始裂纹，其长度与方向服从特定分布。基于亚临界裂纹扩展理论，由Charles方程决定微裂纹的扩展（速度）。如微裂纹发展至单元边界，或应力强度系数到达断裂韧度，则单元破坏。宏观裂纹由微裂纹所联合形成，并最终贯穿模型导致破坏。在形成宏观裂纹的过程中，发生弹塑性应力重分布。在数值模型中，编制了不同类型的微裂纹扩展方式，并在不同的受力条件下加以分析。数值模型的岩石寿命，裂纹形状，破坏方式以及一些重要的参数的数值模拟结果与解析解有较好的一致性。对本文所提出的数值模型的初步实际应用进行了分析，并讨论了计算结果。最后讨论了本文所提出的岩石寿命预测方法的可能改良与发展，并对进一步的研究工作给出建议。

<p>У оквиру ове докторске дисертације изведено је<br />испитивање различитих екстракционих поступака за<br />изоловање апигенина из цвета камилице, као и евалуација<br />биолошке активности добијених екстраката. Полазни<br />биљни материјал сачињавале су две групе латица<br />камилице: ферментисане и неферментисане (нативне).<br />Екстракција ферментисаних цветова је извођена применом<br />ултразвучне екстракције користећи етанол као екстрагенс,<br />а добијени екстракти су се одликовали изузетно високим<br />садржајем апигенина. Оптимизација екстракције је била<br />изведена применом методе одзивне површине. Применом<br />електрон-спин резонанце испитана је антирадикалска<br />активност екстраката. Додатно, фармаколошка вредност<br />добијених екстраката је потврђена и одређивањем њиховог<br />антимикробног и антипролиферативног потенцијала.<br />Нативни цветови камилице су екстраховани применом<br />различитих екстаркционих техника: микроталасне,<br />ултразвучне, Soxhlet екстракције као и екстракције<br />субкритичном водом. Eкстрaкција водом у субкритичном<br />стању се показала супериорнијом у односу на све остале<br />технике у погледу садржаја укупних фенола и флавоноида.<br />У циљу добијања екстраката са максималним садржајем<br />апигенина изведена је оптимизација овог екстракционог<br />процеса. Изоловање чистог апигенина је изведено из<br />екстракта добијеног под оптималним екстракцијом<br />условима (однос дрога:растварач 1:30, брзина мешања 3 Hz,<br />притисак 45 bar, температура 115&ordm;C, време 30 мин,<br />концентрација модификатора 0,001 М) применом поступка<br />колонске хроматографије на стубу полиамида. Хемијски<br />профил као и садржај појединачних полифенолних<br />компонената у екстрактима добијеним на различитим<br />притисцима, температурама и уз присуство модификатора<br />различитих концентрација одређен је применом UHPLCDAD-<br />HESI-MS/MS. У свим анализираним екстрактима<br />детектован је велики број полифенолних компонената, док<br />је апигенин у свима био доминантно једињење. Садржај<br />апигенина у екстракту добијеном под оптималним<br />екстракционим условима је износио 1.700,34 mg/kg.<br />Применом седам различитих тестова извршена је<br />евалуација антиоксидативног и антирадикалског<br />потенцијала екстраката. Антимикробни потенцијал<br />екстраката је одређен за осам различитих микробних<br />линија. in vitro тестовима испитана је способност<br />инхибиције &alpha;-амилазе, &alpha;-глукозидазе и тирозиназе.<br />Деловањем на раст три хистолошки различите ћелијске<br />линије, испитана је антипролиферативна активност<br />екстраката добијених субкритичном водом.<br />Антимотилитетна активност обе групе екстраката<br />(ферментисаних и неферментисаних цветова) одређена је у<br />in vitro условима.</p> / <p>U okviru ove doktorske disertacije izvedeno je<br />ispitivanje različitih ekstrakcionih postupaka za<br />izolovanje apigenina iz cveta kamilice, kao i evaluacija<br />biološke aktivnosti dobijenih ekstrakata. Polazni<br />biljni materijal sačinjavale su dve grupe latica<br />kamilice: fermentisane i nefermentisane (nativne).<br />Ekstrakcija fermentisanih cvetova je izvođena primenom<br />ultrazvučne ekstrakcije koristeći etanol kao ekstragens,<br />a dobijeni ekstrakti su se odlikovali izuzetno visokim<br />sadržajem apigenina. Optimizacija ekstrakcije je bila<br />izvedena primenom metode odzivne površine. Primenom<br />elektron-spin rezonance ispitana je antiradikalska<br />aktivnost ekstrakata. Dodatno, farmakološka vrednost<br />dobijenih ekstrakata je potvrđena i određivanjem njihovog<br />antimikrobnog i antiproliferativnog potencijala.<br />Nativni cvetovi kamilice su ekstrahovani primenom<br />različitih ekstarkcionih tehnika: mikrotalasne,<br />ultrazvučne, Soxhlet ekstrakcije kao i ekstrakcije<br />subkritičnom vodom. Ekstrakcija vodom u subkritičnom<br />stanju se pokazala superiornijom u odnosu na sve ostale<br />tehnike u pogledu sadržaja ukupnih fenola i flavonoida.<br />U cilju dobijanja ekstrakata sa maksimalnim sadržajem<br />apigenina izvedena je optimizacija ovog ekstrakcionog<br />procesa. Izolovanje čistog apigenina je izvedeno iz<br />ekstrakta dobijenog pod optimalnim ekstrakcijom<br />uslovima (odnos droga:rastvarač 1:30, brzina mešanja 3 Hz,<br />pritisak 45 bar, temperatura 115&ordm;C, vreme 30 min,<br />koncentracija modifikatora 0,001 M) primenom postupka<br />kolonske hromatografije na stubu poliamida. Hemijski<br />profil kao i sadržaj pojedinačnih polifenolnih<br />komponenata u ekstraktima dobijenim na različitim<br />pritiscima, temperaturama i uz prisustvo modifikatora<br />različitih koncentracija određen je primenom UHPLCDAD-<br />HESI-MS/MS. U svim analiziranim ekstraktima<br />detektovan je veliki broj polifenolnih komponenata, dok<br />je apigenin u svima bio dominantno jedinjenje. Sadržaj<br />apigenina u ekstraktu dobijenom pod optimalnim<br />ekstrakcionim uslovima je iznosio 1.700,34 mg/kg.<br />Primenom sedam različitih testova izvršena je<br />evaluacija antioksidativnog i antiradikalskog<br />potencijala ekstrakata. Antimikrobni potencijal<br />ekstrakata je određen za osam različitih mikrobnih<br />linija. in vitro testovima ispitana je sposobnost<br />inhibicije &alpha;-amilaze, &alpha;-glukozidaze i tirozinaze.<br />Delovanjem na rast tri histološki različite ćelijske<br />linije, ispitana je antiproliferativna aktivnost<br />ekstrakata dobijenih subkritičnom vodom.<br />Antimotilitetna aktivnost obe grupe ekstrakata<br />(fermentisanih i nefermentisanih cvetova) određena je u<br />in vitro uslovima.</p> / <p>In the frame of this thesis different extraction approaches for<br />apigenin isolation from chamomile ligulate flowers were<br />examined and biological activity of obtained extracts was<br />evaluated. Starting plant samples included fermented and<br />nonfermented (native) flowers.<br />Extraction of fermented flowers was performed by using<br />ultrasound-assisted extraction with ethanol. The concentration<br />of apigenin was high in obtained extracts. Optimization of the<br />extraction procedures was performed by response surface<br />methodology. Antiradical activity of observed extracts was<br />examined by electron-spin resonance spectroscopy.<br />Furthermore, pharmacological potential of obtained extracts<br />was confirmed by determining their antimicrobial and<br />antiproliferative activity.<br />Native chamomile flowers were extracted by different<br />extraction techniques: microwave, ultrasound, Soxhlet and<br />subcritical water extraction. Subcritical water extraction<br />showed to be superior in comparison to other applied techniques<br />in respect to total phenols and flavonoids content. Optimization<br />of the subcritical water extraction was directed to maximization<br />of apigenin content. Isolation of pure apigenin from extracts<br />obtained under optimal extraction conditions (sample-tosolvent<br />ratio 1:30, agitation rate 3 Hz, temperature 115&ordm;C,<br />pressure 45 bar, extraction time 30 min) was performed by<br />preparative chromatography. Chemical profiles and content of<br />individual polyphenolic components in extracts obtained at<br />different pressures, temperatures, and with different<br />concentrations of a modifier was determined by UHPLC-DADHESI-<br />MS/MS. In all analyzed extracts the great number of<br />polyphenolic components was detected while apigenin was the<br />dominant compound in all extracts. Content of apigenin in the<br />extract obtained under optimal extraction condition was<br />1,700.34 mg/kg. Antioxidant and antiradical potential of<br />extracts was evaluated according to different mechanisms.<br />Antimicrobial potential of extracts was determined against eight<br />different microbial strains. Ability of extracts to inhibit &alpha;-<br />amylase, &alpha;-glucosidase and tyrosinase was determined by in<br />vitro assays. Antiproliferative activity of subcritical water<br />extracts was defined by testing their influence on the growth of<br />three histologically different cell lines.<br />Anti-intestinal motility activity of both group of extracts (native<br />and fermented) was determined by in vivo experiments.</p>