The idea underlying the present study was to apply twisting in order to introduce different levels of transverse pressure. The modified structure affected both the bonding level and the evolution of the damage in the yarn. In order to isolate this effect in a broader context, additional parameters were included in the experiment design, namely effects of loading rate, specimen length and filament diameter (directly linked to the fineness of the yarn). These factors have been studied in various contexts by several authors. Some related studies on involved factors will be briefly reviewed.

<div>The work discussed in this document seeks to integrate conductive additives with energetic material systems to offer an alternative source of ignition for the energetic material. By utilizing the conductive properties of the additives, ohmic heating may serve as a method for preheating and igniting an energetic material. This would allow for controlled ignition of the energetic material without the use of a traditional ignition source, and could also result in easier system fabrication.</div><div>For ohmic heating to be a viable method of preheating or igniting these conductive energetic materials, there cannot be significant impact on the energetic properties of the energetic materials. Various mass solids loadings of graphene nanoplatelets (GNPs) were mixed with a reactive mixture of aluminum (Al)/polyvinylidene fluoride (PVDF) to test if ohmic heating ignition was feasible and to inspect the impact that these loadings had on the energetic properties of the Al/PVDF. Results showed that while ohmic heating was a plausible method for igniting the conductive energetic samples, the addition of GNPs degraded the energetic properties of the Al/PVDF. The severity of this degradation was minimized at lower solids loadings of GNPs, but this consequently resulted in larger voltage input requirements to ignite the conductive energetic material. This was attributable to the decreased conductivities of the samples at lower solids loading of GNPs.</div><div>In hopes of conserving the energetic properties of the Al/PVDF while integrating the conductive additives, additive manufacturing techniques, more specifically fused filament fabrication, was used to print two distinct materials, Al/PVDF and a conductive composite, into singular parts. A CraftBot 3 was used to selectively deposit Conductive Graphene PLA (Black Magic) filament with a reactive filament comprised of a PVDF binder with 20% mass solids loadings of aluminum. Various amounts of voltage were applied to these conductive energetic samples to quantify the time to ignition of the Al/PVDF as the applied voltage increased. A negative correlation was discovered between the applied voltage and time to ignition. This result was imperative for demonstrating that the reaction rate could be influenced with the application of higher applied voltages.</div><div>Fused filament fabrication was also used to demonstrate the scalability of the dual printed conductive energetic materials. A flexural test specimen made of the Al/PVDF was printed with an embedded strain gauge made of the Black Magic filament. This printed strain gauge was tested for dual purposes: as an igniter and as a strain sensor, demonstrating the multi-functional use of integrating conductive additives with energetic materials.</div><div>In all, the experiments in this document lay a foundation for utilizing conductive additives with energetic materials to offer an alternative form of ignition. Going forward, ohmic heating ignition may serve as a replacement to current, outdated methods of ignition for heat sensitive energetic materials.</div>

In this bachelor thesis, I examine how automation of fused filament fabrication (FFF) can be implemented, and what the limitations are for different kinds of automation solutions for FFF. Fused filament fabrication is a 3D-printing technology where a material is extruded through a nozzle, layer by layer, to create a print. The thesis also provides a calculation for the commercial feasibility of small batch rapid production with the implementation of an automation solution for FFF. The approach was a qualitative study containing five interviews, combined with empirical knowledge and data from the additive manufacturing company Svensson 3D. This was complemented with an analysis of which criteria to use when evaluating FFF automation solutions, and a framework for looking at FFF from an operator perspective. To calculate commercial feasibility of automation solutions for FFF, Internal Rate of Return and Payback Time were used. This resulted in six criteria to evaluate solutions for automation of FFF, three evaluations of problems within three solutions for automation of FFF, and a finding showing that small batch rapid production is commercially feasible with automated FFF. Lastly, the thesis contains a discussion regarding what the future is for FFF, and the limitations of the framework presented for evaluating automated FFF systems. Possible promising solutions for automated FFF are presented, together with ideas for how design for additive manufacturing can help shape the future of automated FFF. / I det här kandidatarbetet undersöker jag hur automatisering inom fused filament fabrication (FFF) kan implementeras, och vad begränsningarna är för olika sorters automatiseringslösningar för FFF. Det läggs även fram en uträkning för den kommersiella gångbarheten för small batch rapid production med implementeringen av ett automatiskt FFF-system. Tillvägagångsättet bestod av en kvalitativ studie baserad på fem intervjuer, kombinerad med empirisk kunskap och data från additiva tillverkningsföretaget Svensson 3D. Det här kompletterades med en analys av vilka parametrar som bör användas för att utvärdera lösningar för FFF-automatisering, och ett ramverk där automatiseringslösningarna betraktas ur ett operatörs-perspektiv. För att räkna ut den kommersiella gångbarheten för automatiseringslösningar av FFF användes internränta och återbetalningstid. Det här resulterade i sex parametrar för att utvärdera automatiseringslösningar för FFF, tre utvärderingar av vilka problem som finns i tre existerande automatiseringslösningar, och slutsatsen att small batch rapid production är kommersiellt gångbart för automatiserad FFF. Slutligen innehåller arbetet en diskussion gällande framtiden för FFF och begränsningarna hos det ramverk som presenterades för att utvärdera automatiserade FFF system. Möjliga lovande lösningar för automatiserad FFF presenteras och hur design för additiv tillverkning kan hjälpa till att forma framtiden för automatiserad FFF.

Detta examensarbete handlar om framställandet av en dokumentation för konstruktörer inom området 3D-skrivning. Arbetet är ett uppdrag från elbilstillverkaren Ecoist i syftet att underlätta för företag med begränsad kunskap och erfarenhet inom 3D-utskrifter att utnyttja tillverkningsmetoden för sina produkter. Dokumentationen skall innehålla riktlinjer för materialval, konstruktionsprinciper, och inställningar för 3D-utskrifter. För att begränsa arbetet till tidsramen läggs fokus på en typ av skrivare. Den valda typen är FDM eftersom det är den bedöms vara mest tillgängliga, både i pris och utbud. De material och dess egenskaper som betonas i dokumentationen är ASA, PETG, PLA, PP och TPU. Det huvudsakliga arbetet kommer främst innefatta faktainsamling och sammanställning från befintliga information, men även laborationer med 3D-skrivare. Kapitelindelningen i dokumentationen är strukturerad för att följa konstruktörens arbetsprocess. Den inleds med materialval, fortsätter med konstruktion och avslutas med inställningar för 3D-skrivare. I materialegenskaper behandlas de grundläggande egenskaperna hos olika material som används inom 3D-utskrift, med särskilt fokus på deras hållfasthet, miljöpåverkan, användningsområde samt för- och nackdelar. Konstruktionsriktlinjer handlar om utformning av detaljer, inklusive minsta detaljtjocklek, hantering av överhäng, fasning, efterbearbetning, integrering av fästelement samt toleranser mellan närliggande delar. Fokus ligger på att säkerställa att detaljerna är konstruerade för att vara hållbara och funktionella efter tillverkning med 3D-skrivare. Inställningar för 3D-skrivare handlar om STL-filer, olika typer av ifyllnadsmönster samt vanliga defekter och åtgärder för att motverka dem. Vidare behandlas materialspecifika inställningar för optimal justering av 3D-skrivaren. Vid utformningen av dokumentet läggs mest fokus på utseende och läsbarhet, samt ordning och struktur genom färgval, text/tabellspresentation och anpassandet av dokumentet för både fysiskt och digitalt exemplar. Hela dokumentationen finns i bilaga 1. / This thesis focuses on creating documentation for designers in the field of 3D printing. The project is commissioned by the electric car manufacturer Ecoist with the aim of helping companies with limited knowledge and experience in 3D printing to utilize this manufacturing method for their products. The documentation will include guidelines for material selection, design principles, and 3D printing settings. To fit the project within the given timeframe, the focus is limited to one type of printer. The selected type is FDM, as it is considered the most accessible in terms of price and availability. The materials and their properties emphasized in the documentation are ASA, PETG, PLA, PP, and TPU. The main work will primarily involve gathering and compiling information from existing sources, but also conducting experiments with 3D printers. The chapters in the documentation are structured to follow the designer's workflow. It begins with material selection, continues with design, and concludes with 3D printer settings. In material properties, the basic characteristics of different materials used in 3D printing are covered, with a particular focus on their strength, environmental impact, areas of use, as well as their advantages and disadvantages. Design guidelines involve the configuration of details, including minimum detail thickness, handling of overhangs, chamfering, post-processing, integration of fasteners, and tolerances between adjacent parts. The focus is on ensuring that the details are designed to be durable and functional after manufacturing with a 3D printer. 3D printer settings cover STL files, different types of infill patterns, and common defects along with countermeasures to avoid them. Furthermore, material-specific settings for optimal adjustment of the 3D printer are presented. In the design of the document, the emphasis is on appearance and readability, as well as order and structure through the choice of colors, text/table presentation, and adapting the document for both physical and digital copies. The entire documentation is included in Appendix 1.

Background. Head and neck cancers (HNC) are among the most common malignancies worldwide, and about 90–92% of oral neoplasias are oral squamous cell carcinomas (OSCC). Alcohol and tobacco consumption have been recognized as the main risk factors for OSCC development. Oncogenic viruses, such as human papillomavirus (HPV) or Epstein-Barr virus (EBV), as well as genetic alterations may also contribute to tumour formation.  Aims. To study the prevalence of HPV, EBV, Herpes simplex type-1 (HSV-1), and HPV-16 and their integration status as well as the molecular mechanisms that can serve as a basis for the development of OSCC. Results. In Paper I we reported a statistically significant increase in the prevalence of HPV-16 in oral epithelial dysplasia (OED) and OSCC samples compared to controls. A statistically significant increase was also seen in integrated HPV-16 compared to episomal viral forms when comparing OED and OSCC samples. Paper II reported the detection of HSV-1 in 54% of healthy samples, in 36% of oral leukoplakia samples, and 52% of OSCC samples. However, these differences were not statistically significant. In Paper III we reported a statistically significant increase in the detection of HPV-positive samples when comparing nested polymerase chain reaction (PCR) with single-PCR results in OSCC and fresh oral mucosa. Paper IV reported that the highest prevalence of HPV (65%) was seen in Sudan, while an HSV-1 prevalence of 55% and an EBV prevalence of 80% were seen in the UK. Finally, Paper V reported that the mRNA levels of Bcl-2, keratin 1, keratin 13, and p53 were significantly lower and that the level of survivin was significantly higher in the OSCC samples of the toombak users than in their paired control samples. Significant downregulation in keratin 1 and keratin 13 expression levels was found in the OSCC samples of the non-toombak users relative to their normal control samples. Conclusion. HPV-16 integration was increased in oral epithelial dysplasia and OSCC compared to normal oral mucosa. Nested PCR is a more accurate method of establishing HPV prevalence in samples containing low copy numbers of HPV DNA. HPV and EBV may be a risk factor in OSCC development. Our findings confirmed the role of survivin in OSCC carcinogenesis and survivin might be interesting as a biomarker to be monitored. The results presented here provide both clinical and biological insights that will bring us closer to the goal of managing this disease and improving treatment and outcomes for future patients.

Le but du travail est de montrer la faisabilité du tissage de filament de très faible diamètre (de l'ordre de 10 à 25 -tm) et de matières différentes (cuivre, or, polyester...). Les essais du comportement mécanique (traction, fatigue) du micro filament de cuivre ont montré la possibilité du tissage de ce type du filament à cette échelle. A partir de ces résultats, il est possible d'entrevoir des solutions techniques de tissage pour réaliser des tissus à partir de ces filaments. Ce travail a permis donc de concevoir les différentes parties de la machine de micro tissage : système d'alimentation des fils de chame, système de formation de la foule, système d'insertion du fil de trame, système de mouvement du peigne, système d'appel et de stockage du tissu. Le système de formation de la foule de type Jacquard représente le cœur de la machine à tisser. Il lève un verrou technologique persistant depuis de très nombreuses années. Les résultats prometteurs des micros actionneurs fluidiques ont permis de montrer la faisabilité du micro tissage. Ils ont permis également de valider le procédé de la fabrication d'un bloc des plusieurs actionneurs capable de séparer les filaments de chaîne pour former la foule. Le logiciel de contrôle et de dessin conçu permet à la fois de réaliser des armures et de les compiler en format convenable pour pouvoir les transmettre à la carte de contrôle. Cette dernière permet de contrôler les différentes parties de la machine à tisser.

Cardiac myosin binding protein-C (cMyBP-C) is a structural and regulatory component of cardiac thick filaments. It is observed in electron micrographs as seven to nine transverse stripes in the central portion of each half of the A band. Its C-terminus binds tightly to the myosin rod and contributes to thick filament structure, while the N-terminus can bind both myosin S2 and actin, influencing their structure and function. Mutations in the MYBPC3 gene (encoding cMyBP-C) are commonly associated with hypertrophic cardiomyopathy (HCM). In cardiac cells there exists a population of myosin heads in the super-relaxed (SRX) state, which are bound to the thick filament core with a highly inhibited ATPase activity. This report examines the role cMyBP-C plays in regulating the population of the SRX state of cardiac myosin by using an assay that measures single ATP turnover of myosin. We report a significant decrease in the proportion of myosin heads in the SRX state in homozygous cMyBP-C knockout mice, however heterozygous cMyBP-C knockout mice do not significantly differ from the wild type. A smaller, non-significant decrease is observed when thoracic aortic constriction is used to induce cardiac hypertrophy in mutation negative mice. These results support the proposal that cMyBP-C stabilises the thick filament and that the loss of cMyBP-C results in an untethering of myosin heads. This results in an increased myosin ATP turnover, further consolidating the relationship between thick filament structure and the myosin ATPase. Crown Copyright (C) 2016 Published by Elsevier Ltd. All rights reserved.

Die Anpassung des Aktinzytoskeletts an extrazelluläre Gewebsstrukturen ist Voraussetzung für die Interaktion mit der extrazellulären Matrix und für die Zellbewegung, einschließlich der Invasion und Metastasierung von Tumorzellen. Wir untersuchten bei invasiven B16/F1 GFP-Aktin Mausmelanomzellen, ob und wie sich Zellform, Art und Effizienz der Bewegung an physikalisch unterschiedlich beschaffene kollagenöse Umgebungen anpassen: 1) mit Kollagen-Monomeren beschichtete 2D Objektträger, 2) 2D Oberfläche einer fibrillären Kollagenmatrix und 3) Zellen, die in einer 3D Kollagenmatrix eingebettet waren. Zur Darstellung des Aktinzytoskeletts wurden Zellen eingesetzt, die GFP-Aktin Fusionsprotein exprimierten, und mittels Zeitraffer-Videomikroskopie und Konfokalmikroskopie untersucht. Im direkten Vergleich waren Struktur und Dynamik des Aktinzytoskelett wie auch Zellform und Art der Migration unterschiedlich in den verschiedenen Umgebungen. Auf 2D planer Oberfläche erfolgte eine rasche Adhäsion und Abflachung der Zellen (Spreading) mit nachfolgender Migration mit Bildung fokaler Adhäsionszonen, in die kabelartige Aktinstrukturen (Stress fibers) einstrahlten. Dagegen entwickelte sich in 3D Kollagenmatrices eine spindelförmige, fibroblastenähnliche Zellform (mesenchymal) mit zylindrischen fingerförmigen vorderen Pseudopodien, die Zug der Zelle nach vorne bewirken und hochdynamisches polymeres Aktin, nicht jedoch Stress Fibers enthielten. Eine ähnliche Zellform und Struktur des Zytoskeletts entwickelte sich in Zellen auf 2D fibrillärem Kollagen. Die Kontaktfindung und Migrationseffizienz auf oder in fibrillären Matrices war im Vergleich zu 2D kollagenbeschichteter Oberfläche erschwert, die Migrationseffizienz verringert. In Kontrollversuchen wurden Migration und polarisierte Bildung von Aktindynamik durch Inhibitoren des Aktinzytoskeletts (Cytochalasin D, Latrunculin B, Jasplakinolide) stark gehemmt. Diese Befunde zeigen , dass die Struktur und Dynamik des Aktinzytoskeletts sowie die Art der Migration in Tumorzellen stärker als bisher angenommen durch die umgebende Kollagenstruktur bestimmt wird. Während 3D Kollagenmatrices in vivo ähnliche bipolare Zytoskelettstruktur fördern, müssen Abflachung der Zellen mit Bildung von Stress Fibers als spezifische Charakteristika von 2D Modellen angesehen werden. / The dynamics and the adaptation of the actin cytoskeleton in response to extracellular matrix structures is the prerequisite for cell polarisation, shape change, and migration, including the invasion and metastasis of tumor cells. In invasive B16-mouse melanoma cells expressing GFP-actin fusion protein we directly imaged cytoskeletal dynamics, adaptation and movement in response to physically different collagen substrata using time-lapse videomicroscopy and confocal microscopy: 1) cells on 2D surfaces coated with monomeric collagen, 2) 2D surfaces composed of fibrilliar collagen, and 3) cells which were embedded in 3D collagen matrices. In directly comparision the structure and dynamic of the actin cytoskeleton, cell shape and migration efficiency were different between the different collagen substrata. On 2D monomeric collagen quick cell adhesion, spreading, and cell flattening were followed by migration driven by focal contacts in which cable like actin structures (stress fibres) inserted. In 3D collagen matrices however, cells developed a spindle like (mesenchymal) shape with cylindrical finger-like pseudopods which generated the forward-driving force towards collagen fibres. These pseudopods contained dynamic polymerized actin yet lacked stress fibres. A similar mesenchymal cell shape and structure of the actin cytosceleton that lacked stringent focal contacts and stress fibres developed on 2D fibrilliar collagen matrices. The migration efficiency in 3D collagen was significantly lower, compared to 2D substrata, suggesting an impact of matrix barriers on the migration velocity. Both, actin polymerization and migration were severely impaired by inhibitors of the actin cytoskeleton (Cytochalasin D, Latrunculin B, Jasplakinolide), causing cell rounding and oscillatory “running on the spot”. These findings show the dynamics of the actin cytoskeleton in living melanoma cells critically dependent on and respond to the physical structure of the ECM. 3D collagen matrices hence favour in vivo-like cell shape and cytoskeletal organization while flat cell spreading and formation of stress fibres are specific cell characteristics of cells on 2D.

[pt] Tubos de material compósito - matriz polimérica reforçada por fibra de vidro - fabricados pela técnica de enrolamento filamentar, foram caracterizados através de microscopia eletrônica digital e processamento de imagens. Três tubos foram fabricados em equipamento próprio seguindo parâmetros de enrolamento similar. Um tubo comercial fabricado por empresa especializada, com parâmetros de enrolamento mais complexos, também foi caracterizado. Para tal, seções circunferenciais foram observadas em um microscópio eletrônico de varredura com captura digital de imagem. Mosaicos de imagens foram gerados, permitindo obter informação com boa resolução local e, simultaneamente, grande abrangência espacial. Assim, foi possível realizar uma caracterização que abrangia desde o tamanho e forma de fibras individuais até a distribuição espacial de milhares de fibras em uma vasta área da amostra. Foram cridas rotinas de processamento e análise de imagens para medir dados como diâmetro, fator de forma, fração volumétrica e ângulo de enrolamento de fibras. Além disso, uma rotina específica foi desenvolvida para a identificação automática das várias camadas de fibras presentes no tubo comercial. / [en] Pipes made from composite material - polymer matrix reinforced with glass fibers - manufactured by filament winding, were characterized by scanning electron microscopy and image analysis. Three pipes were manufactured with equipment owned by the research group, following similar winding parameters. A commercial tube made by a specialized company, with more complex winding conditions, was also characterized. Circumferential sections were observed in a scanning electron microscope with digital image acquisition. Image mosaics were created, providing information with good spatial resolution and, at the same time, wide spatial coverage. Thus, it was possible to characterize size and shape of individual fibers and, simultaneously, obtain the spatial distribution of thousands of fibers within a large sample area. Image processing and analysis routines were created to measure fiber diameter, shape factor, area fraction and winding angle. A specific routine was developed for the automatic identification of the several fiber layers present in the commercial pipe.

O complexo troponina-tropomiosina regula a contração muscular esquelética e cardíaca. A ligação do cálcio nos sítios regulatórios localizados no domínio N-terminal da troponina C (TnC) induz uma mudança conformacional que remove a ação inibitória da troponina I (TnI) e inicia a contração muscular. Nós usamos fragmentos recombinantes da TnI e uma série de mutantes da TnC para estudar as interações estruturais e regulatórias das diferentes regiões da TnI com os domínios da TnC, TnT e actina-tropomiosina. Nossos resultados indicam que a TnI é organizada em regiões que apresentam funções estruturais e regulatórias e que se ligam de modo antiparalelo com os correspondentes domínios estruturais e regulatórios da TnC. Estudos funcionais mostram que a região inibitória (aminoácidos 103-116) em combinação com a região C-terminal da TnI (TnI103-182) pode regular a atividade ATPásica da acto-miosina de maneira dependente de Ca2+. A regulação não é observada com a região inibitória em combinação com a região N-terminal (TnI116) Estudos de ligação mostram que a região N-terminal da TnI (TnI1-98) interage com o domínio C-terminal da TnC na presença e na ausência de Ca2+ e também interage com a TnT. A região inibitória/C-terminal da TnI (TnI103-182) interage com o domínio N-terminal da TnC de maneira dependente de Ca2+. Baseados nestes resultados, propomos um modelo para a mudança conformacional induzida pelo Ca2+. Neste modelo, a região N-terminal da TnI está ligada fortemente com o domínio C-terminal da TnC na presença ou na ausência de Ca2+. As regiões inibitórias e C-terminal da TnI ligam-se à actina-tropomiosina na ausência de Ca2+ e nos domínios N-terminal e C-terminal da TnC na presença de Ca2+. / The troponin-tropomyosin complex regulates skeletal and cardiac muscle contraction. Calcium binding to the regulatory sites in the N-terminal domain of troponin C (TnC). induces a conformational change which removes the inhibitory action of troponin I (TnI) and initiates muscular contraction. We used recombinant TnI fragments and a series of TnC mutants to study the structural and regulatory interactions between different TnI regions and the domains of TnC, TnT and actin-tropomyosin. Our results indicate that TnI is organized into regions with distinct structural and regulatory functions which bind, in an antiparallel manner, with the corresponding structural and regulatory domains of TnC. Functional studies show that a fragment containing the inhibitory and C-terminal regions of TnI (TnIl03-182) can regulate the actomyosin ATPase in a Ca2+- dependent manner. Regulation was not observed with a fragment containing the N-terminal and inhibitory regions (TnIl-116). Binding studies show that the N-terminal region of TnI (TnI1-98) interacts with the C-terminal domain of TnC in the presence of Ca2+ or Mg2+. The inhibitory/C-terminal region of TnI (TnI103-182) binds to the N-terminal domain of TnC in a Ca2+-dependent manner. Based on these results, we propose a model for the Ca2+ -induced conformational change. In this model the N-terminal region of TnI is bound strongly to the C-terminal domain of TnC in the presence or absence of Ca2+. The inhibitory and C-terminal regions of TnI bind to actin-tropomyosin in the absence of Ca2+ and to tne N- and C-terminal domains of TnC in the presence of Ca2+.