Additive manufacturing processes such as 3D printing are booming in the industry due to their high degree of freedom in terms of geometric shapes and available materials. Focusing on patient-specific medicine, 3D printing has also proven useful in the Life Sciences, where it exploits the shape fidelity for individualized tissues in the field of bioprinting. In parallel, the current systems of bioreactor technology have adapted to the new manufacturing technology as well and 3D-printed bioreactors are increasingly being developed. For the first time, this work combines the manufacturing of the tissue and a tailored bioreactor, significantly streamlining the overall process and optimally merging the two processes. This way the production of the tissues can be individualized by customizing the reactor to the tissue and the patient-specific wound geometry. For this reason, a common basis and guideline for the cross-device and cross-material use of 3D printers was created initially. Their applicability was demonstrated by the iterative development of a perfusable bioreactor system, made from polydimethylsiloxane (PDMS) and a lignin-based filament, into which a biological tissue of flexible shape can be bioprinted. Cost-effective bioink-replacements and in silico computational fluid dynamics simulations were used for material sustainability and shape development. Also, nutrient distribution and shear stress could be predicted in this way pre-experimentally. As a proof of functionality and adaptability of the reactor, tissues made from a nanocellulose-based Cellink® Bioink, as well as an alginate-based ink mixed with Me-PMeOx100-b-PnPrOzi100-EIP (POx) (Alginate-POx bioink) were successfully cultured dynamically in the bioreactor together with C2C12 cell line. Tissue maturation was further demonstrated using hMSC which were successfully induced to adipocyte differentiation. For further standardization, a mobile electrical device for automated media exchange was developed, improving handling in the laboratory and thus reduces the probability of contamination. / Additive Fertigungsverfahren wie der 3D-Druck boomen in der Industrie aufgrund ihres hohen Freiheitsgrads in Bezug auf geometrische Formen und verfügbare Materialien. Mit Blick auf die patientenspezifische Medizin hat sich der 3D-Druck auch in den Biowissenschaften bewährt, wo er die Formtreue für individualisierte Gewebe im Bereich des Bioprinting nutzt. Parallel dazu haben sich auch die derzeitigen Systeme der Bioreaktortechnologie an die neue Fertigungstechnologie angepasst, und es werden zunehmend 3D-gedruckte Bioreaktoren entwickelt. In dieser Arbeit werden erstmals die Herstellung des Gewebes und ein maßgeschneiderter Bioreaktor kombiniert, wodurch der Gesamtprozess erheblich gestrafft und beide Verfahren optimal zusammengeführt werden. Auf diese Weise kann die Herstellung der Gewebe individualisiert werden, indem der Reaktor an das Gewebe und die patientenspezifische Wundgeometrie angepasst wird. Aus diesem Grund wurde zunächst eine gemeinsame Basis und Leitlinie für den Geräte- und Materialübergreifenden Einsatz von 3D-Druckern geschaffen. Deren Anwendbarkeit wurde durch die iterative Entwicklung eines perfundierbaren Bioreaktorsystems aus Polydimethylsiloxan (PDMS) und einem Lignin-basierten Filament demonstriert, in das ein biologisches Gewebe mit flexibler Form gedruckt werden kann. Kostengünstige Biotintenalternativen und emph in silico Computational Fluid Dynamics Simulationen wurden für eine materialschonende Formentwicklung verwendet. Nährstoffverteilung und Scherspannung konnten auf diese Weise präexperimentell vorhergesagt werden. Als Beweis für die Funktionalität und Anpassbarkeit des Reaktors wurden Gewebe aus einer Cellink® Bioink auf Nanocellulosebasis sowie einer Tinte auf Alginatbasis, welche mit Me-PMeOx100-b-PnPrOzi100-EIP (POx) gemischt wurde (Alginat-POx-Bioink), erfolgreich zusammen mit C2C12-Zelllinie dynamisch im Reaktor kultiviert. Die Gewebereifung wurde außerdem mit hMSC demonstriert, die erfolgreich zur adipozyten Differenzierung induziert wurden. Zur weiteren Standardisierung wurde ein mobiles elektrisches Gerät für den automatischen Medienwechsel entwickelt, welches die Handhabung im Labor verbessert und damit die Wahrscheinlichkeit einer Kontamination deutlich verringert.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Vårt samhälle och våra värderingar är starkt påverkade av vår historia. För att elever ska få en djupare förståelse av samhället behöver de få en överblick över hur det har utvecklats genom tiderna, vilket innebär att de måste få ett historiemedvetande. Syftet med den här studien är att undersöka hur lärare skapar en inkluderande och engagerande historieundervisning. Erfarenheter från fem legitimerade lärare i historia har samlats in med hjälp av semistrukturerade intervjuer och därefter analyserat via meningskoncentration. Resultatet visar på att ett varierande arbetssätt, med olika metoder där bildstöd och diskussioner är viktiga för förståelsen hos eleverna. De svårigheter som framkommer handlar om tidsbrist, kompetensbrist och utmaningar i hur lärarna kan hjälpa alla elever till en historiemedvetenhet. Behov av kompetensutveckling, statlig styrning och tidsanvändning diskuteras. Förslag på vidare forskning är elevernas perspektiv på en engagerande historieundervisning samt hur lärare ska utforma sin undervisning i historia med fokus på elever med annat modersmål.

No description available.

No description available.

No description available.

No description available.

Lim klassificeras som ett ämne som kan hålla ihop två ytor så att de motstår separation. Dagens lim kan anpassas efter vilken applikation de ska användas till och kan ha ett stort antal olika egenskaper. De fysikaliska och kemiska egenskaperna av limmet är de viktigaste faktorerna för att bilda en bra limbindning. I stort sett alla syntetiska lim består idag av polymerer, varav de flesta är petroleumbaserade. För att skapa ett mer miljövänligt alternativ undersökte denna studie tillämpningen av poly(3-hydroxibutyrat- co-3-hydroxivalerat), PHBV med 36 eller 56 vikt% HV, som huvudkomponent i ett lim. Huvudfokus ligger på hur väl PHBV är lämpligt för användning som lim och hur olika tillsatser kan förbättra dess egenskaperna. Flera olika limblandningar innehållande PHBV, mjukgörare (sebacinsyra, dimetylsebacat, etylbutanoat eller tributylcitrat) och förtjockningsmedel (Abalyn eller Foralyn) skapades och undersöktes. Ett single lap skjuvtest utfördes med kopieringspapper, filterpapper och träpinnar som vidhäftningsmaterialet, medan ett avskalningstest undersökte användningen av kopieringspappersetiketter och plastetiketter på en glasflaska samt frukt.  Båda testen visar att kopieringspapper har de mest lovande egenskaperna som en adherent för användningen av ett PHBV-baserat lim, både för PHBV innehållande 36 vikts% och 56 vikts% HV. Denna slutsats kunde dras då kopieringspapperet påvisade den starkaste bindningen med limmet. Ren PHBV uppvisade lovande häftstyrka och vidhäftning som ett smältlim. Tillsatsen av sebacinsyra tillsammans med Abalyn eller dimetylsebacat med Foralyn ökade limmets häftstyrka ytterligare. Vi fann också att lim som skapats med PHBV med 36 vikt% HV ger bättre hållfasthetsegenskaper. Framtida arbete innefattar mer exakta mätmetoder för att bestämma egenskaperna hos limblandningarna. / An adhesive is classified as a substance that holds two surfaces together and resists separation. Today’s adhesives can be modified according to various application demands, obtaining a large variety of properties. The most important factors of forming a good adhesive bond are the physical and chemical properties. Essentially all synthetic adhesives consist of polymers, most of them being petroleum-based. To obtain a more environmentally friendly option, this study investigated the use of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV with 36 or 56 wt% HV, as the main component in an adhesive. The main focus was to investigate on how well PHBV is suited for use as an adhesive and how different additives can improve the adhesive properties. Several different adhesive formulations containing PHBV, plasticizers (sebacic acid, dimethyl sebacate, ethyl butyrate, or tributyl citrate) and tackifiers (Abalyn or Foralyn) were created and investigated using various tests, such as single lap shear test, peel test, tackiness determination, optical analysis, and application testing. Single lap shear tests were performed using printing paper, filter paper, and wooden sticks as adherents, while peel tests explored the use of printing paper labels and plastic labels on a glass bottle and on fruit. It was determined that two PHBV adhesives, containing 36 wt% and 56 wt% of HV, performed best using printing paper as adherent. This conclusion could be drawn based on the good interaction between the adherent and the adhesive, thereby creating a strong bond. Pure PHBV with 36 or 56 wt% showed promising strength and tackiness properties as a hot-melt adhesive. The addition of sebacic acid together with Abalyn or dimethyl sebacate with Foralyn further increased the adhesive’s strength. It was also found that adhesive formulations created using a PHBV with a lower amount of HV (around 36 wt% of HV) yields better strength properties when used as an adhesive for paper labels. Future work involves more precise measurement methods to determine the properties of the adhesive formulations.

The emergence of antibiotic resistance to current treatments of bacterial infection represents a major challenge that needs to be addressed with the development of new generations of inhibitors. The enzyme 5-enolpyruvylshikimate 3- phosphate synthase (EPSPS) catalyses the sixth step in the shikimate biosynthetic pathway, which is essential for the synthesis of aromatic compounds such as the aromatic amino acids phenylalanine, tryptophan and tyrosine. It occurs in plants, bacteria and some parasites. Since the pathway is absent in mammals but essential for the pathogenicity of a number of organisms, EPSPS is considered a prospective target for new inhibiter design. A number of EPSPS inhibitors have been reported in the literature. What we are lacking is an understanding of the features that are important for binding EPSPS. We have synthesized compounds to probe the active site of the enzyme based on the knowledge of an enzyme-catalyzed intermediate with a high cationic character. This will include assembling bipartite/tripartite inhibitors to discover what interactions or structural motifs are important for binding. Once the features important for binding to EPSPS are understood, the possibility of elaborating them to create potent inhibitors of EPSPS will be investigated. In addition, the synthesis of two shikimate analogs [5-^(18)O] shikimic acid and 4-deoxyshikimic acid were completed for further experiments to probe the enzyme mechanism in detail, and for transition state structure by transition state analysis. Transition state analysis using kinetic isotopic effects (KIE) will elucidate the transition state structure of the enzyme-catalyzed EPSP reaction, and provide a detailed starting point for designing EPSPS inhibitors. / Thesis / Master of Science (MSc)

Supplementary Information Video attached / <p> Machado-Joseph disease (MJD), also known as Spinocerebellar ataxia type 3 (SCA3) is one of nine poly glutamine neurodegenerative diseases caused by an expansion of CAG DNA triplets in the genes resulting in an expanded poly glutamine tract in the expressed proteins. These proteins are unrelated in function yet all manifest as specific neurological diseases. The Truant lab and others have previously shown that six of the nine polyglutamine proteins display nucleocytoplasmic shuttling capabilities and that this shuttling is affected by polyglutamine expansion. It is believed that deciphering the mechanism of nucleocytoplasmic transport may be important in understanding the normal function of these proteins, which in turn may lead to a better understanding of the pathogenesis of disease. Studies that looked at the subcellular localization of the MJD/SCA3 protein, ataxin-3, have shown that the normal protein is variably distributed between the nucleus and the cytoplasm, whereas mutant ataxin-3 is localized primarily in the nucleus. Using fluorescent protein technology and fluorescence microscopy, this thesis project attempts to analyze the nucleocytoplasmic shuttling capabilities of ataxin-3 and to evaluate the potential mechanisms that govern its translocation into and out of the nucleus. </p> <p> It was revealed that ataxin-3 is able to shuttle into and out of the nucleus and that the shuttling dynamics are dependent on the length of the poly glutamine tract. As well, two putative, CRMl dependent nuclear export signals and a putative, importin-a/~1 dependent, classical, nuclear localization signal were tested and shown to be nonfunctional as transport signals. It was then discovered that ataxin-3 is marginally leptomycin B (an inhibitor ofCRMl dependent nuclear export) sensitive in NIH3T3 and MCF7 cells, more sensitive to the drug in STHdhQ71Q7 cells and even more so in HEK 293 cells. This suggests that an exogenous factor mediates the nuclear import of ataxin-3 through the CRMl pathway. Subsequently, four known binding partners, hHDACl, hHDAC2, hHDAC6 and hHRAD23b, were tested for their potential ability to shuttle ataxin-3. It was concluded that although hHDAC6 had the greatest effect on ataxin-3 subcellular localization, we believe that it does not mediate its nuclear import or export. Future studies would involve an investigation as to how and why different polyglutamine lengths affect the nucleocytoplasmic shuttling of ataxin-3 and to identify the factor(s) that cause ataxin-3 to be more sensitive to LMB treatments in HEK 293 cells. </p> / Thesis / Master of Science (MSc)