<p>Aminoglycoside antibiotics are commonly used to treat bacterial infections but are highly susceptible to chemical modification, leading to resistance. Chemical modification can be hindered through the use of small molecule inhibitors that target bacterial enzymes involved in resistance, most notably kinases. Current methods for the discovery of small molecule inhibitors of kinases and related “kinase-like” enzymes are limited in throughput and utilize slow, tedious, and expensive assays. This thesis is focused on the development of highly versatile and scaleable kinase and “kinase-like” screening platforms for the discovery of small molecule inhibitors of these drug targets. The work begins with the validation of a matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) platform utilizing phosphorylation of kanamycin, an aminoglycoside antibiotic, by aminoglycoside phosphotransferase 3ʹIIIa (APH 3ʹIIIa) as a model system. Using a product-to-substrate signal ratio as an internal standard, the assay was used to functionally screen over 200 compounds, combined into mixtures to enhance assay throughput. Moreover, the assay was used to determine inhibitory dissocation constants for newly discovered modulators. Throughput was further increased to a novel dual-kinase assay targeting a bacterial enzyme, APH 3ʹIIIa and a human kinase, protein kinase A (PKA), which was validated using the previous small molecule library. Alternative assay development platforms were also studied using imaging mass spectrometry of reaction microarrays and the fabrication of sol-gel derived bioaffinity chromatography columns. The MS-based kinase assays developed herein are highly amenable to high throughput screening, and have the potential to be extended to other important therapeutic targets.</p> / Doctor of Philosophy (PhD)

Cellulose Nano Fibrils (CNFs) can be extracted from wood and other plants. These CNFs are expected to play a large roll in future materials owing to their interesting properties and biobased nature. In this project, dewatering of gels made from CNF by non-confined mechanical pressing has been studied. A CNF suspension was gelled by the addition of HCl at pH 2 to form gel cakes and then pressed mechanically. The goal was to find the pressure limits of the gel cakes for different starting concentrations, in weight percentage [wt%], of CNF to optimize the pressure used when dewatering CNF gels. The non-confined pressing was achieved via the useof a Zwick/Roell Torsion multi-axis testing system. Gel cakes were pressed until a pressing equilibrium was reached. Equilibrium was reached when compression was less than 0.01 mm per 100 seconds. Gel cakes were frozen with liquid N2, freeze-dried, and analysed with Scanning Electron Microscopy (SEM). The results observed from the pressing data showed that gel cakes with higher CNF starting concentrations could survive higher pressures. Using the highest pressure available, at the pressure limit, yielded both the shortest run time and the highest dryness content. SEM imaging showed that the compression of the gel cakes starts at the surfaces and continuous inwards through the bulk. The mechanical pressure creates sheets of CNF both vertically and horizontally. By plotting the starting concentrations vs applied pressure a limit map with pressure regions could be created. From the limit map further optimization can be achieved to shorten the dewatering process of the CNF gels.

The aim of this thesis is to determine the mechanical properties of copper, titanium and carbon thin films deposited on foil substrates, and identify how the properties are affected by the deposition process. This is important when such coated foils are subjected to mechanical deformation during applications. Three coating materials, Cu, Ti, and C, were evaluated on PET and Al foils. The materials were deposited by direct current magnetron sputtering (DCMS) and high-power impulse magnetron sputtering (HiPIMS). The crack initiation and propagation during tensile tests were investigated in-situ by a SEM. The coatings’ crack onset strain (COS), cohesive strength, interfacial shear strength (IFSS), and Weibull shape and scale parameters were successfully determined from the experimental data. The results showed the Cu coatings had similar cohesive strengths and IFSS, independent of the deposition process. The main difference was the COS, where thin films deposited with ion assistance displayed a higher value. The coatings also displayed different morphologies that clearly influenced the crack propagation. Larger grains hindered the crack propagation and resulted in a more ductile fragmentation, with coatings displaying short and tortuous cracks. All Ti films displayed similar fragmentation and thus mechanical properties, despite small differences in morphology. However, the surface roughness of the Al foil influences the results. Localized stresses arise in the rolling tracks from the foil production and facilitates the crack propagation, thus affecting the fragmentation of the coatings. Lastly, it could be shown that the addition of a thin Ti adhesion layer resulted in a fully adherent C film.

På senare år har efterfrågan på stålmaterial av låg vikt ökat, speciellt inom transportsektorn. Genom att addera Al till stål sänks densiteten vilket gör att FeAl-legeringar är ett lovande material för fordonskonstruktion. Vätskekorrosionsegenskaper undersöktes av 3D – printade FeAl prover som innehöll 0 – 10 vikt% Al och 0,1 vikt% Zr för att bestämma hur korrosionsegenskaperna förändrades med avseende på Al – innehållet. Korrosionsresistansen var i stor utsträckning beroende av huruvida en passiv film av Al2O3 bildades på ytan eller ej. Korrosionshastigheten bestämdes genom EIS – och PDP – analyser utförda i 3,5 vikt% NaCl-lösning samt genom viktförlusttester i 1 M HCl respektive 0,5 M H2SO4. Vidare karaktäriserades proverna genom XRF, XRD, EDS, SEM och optisk mikroskopi vilket bland annat visade på att samtliga prover var enfassystem samt att den kemiska sammansättningen var enligt förväntan. Vidare indikerade optisk mikroskopi och SEM att ett högre Al – innehåll resulterar i att proverna blir mer porösa. Elektrokemiska tester antyder att ett Al – innehåll om 10 vikt% förbättrade korrosionsresistansen. Detta antyder möjligen, men kan inte definitivt fastslås från de utförda experimenten, att det krävs 10 vikt% Al för att en passiv film som täcker hela materialytan ska bildas. Korrosionshastigheten var 7 – 10 gånger högre vid viktförlusttest jämfört med elektrokemiska test. Detta förklaras genom att den skyddande passiva filmen bröts ned under de sura förhållanden som viktförlusttesten utfördes i medan den passiva Al2O3 filmen kunde bestå i de pH – neutrala förhållanden som elektrokemiska test utfördes vid. Detta speglar att bildandet och stabiliteten av Al2O3-filmen är vitalt för att sänka korrosionshastigheten. / In recent years the demand for lightweight ferritic steels has increased, particularly for transport applications. The addition of Al lowers the density, hence making FeAl alloys promising materials for such constructions. Aqueous corrosion properties of 3D – printed FeAl samples ranging from 0 – 10 wt% Al and containing 0.1 wt% Zr were investigated to determine how the Al content affects the corrosion resistance. The corrosion rate was found to greatly depend on the formation and stability of a protective passive film of Al2O3 forming on the material surface. A corrosion rate was obtained via EIS and PDP in 3.5 wt% NaCl as well as via weight loss testing in 1 M HCl and 0.5 M H2SO4. Additionally, XRF, XRD, EDS, SEM and optical microscopy tests were carried out to characterize the samples. XRF and EDS confirmed that the elemental composition of the samples was as expected and XRD indicated that all samples were single phase systems. Furthermore, optical microscopy and SEM indicated that higher Al content makes the samples more porous. Electrochemical testing indicated that addition of 10 wt% Al greatly improves the corrosion properties suggesting that it may require 10 wt% Al to form a passive film that covers the whole surface, although this cannot be said for certain from these experiments. Moreover, the corrosion rate was 7 – 70 times lower during electrochemical testing compared to weight loss testing, in which the passive film breaks down due to the acidic conditions. This emphasizes that the stability of the Al2O3 film is vital for slowing down the corrosion rate of FeAl alloys.

Fluffmassa är, i ordets rätta bemärkelse, ett fluffigt material som i de allra flesta fall tillverkas av fibrer ifrån trä, den utgör en viktig del i blöjor, hygienprodukter, näsdukar och ett flertal andra produkter. Syftet med fluffmassa i absorptionsprodukter är framförallt att sprida vätskan, öka absorbtionshastigheten och behålla superabsorberande polymerer på plats i nätverket. Två viktiga kvalitetsparametrar hos fluffmassan är defibreringsenergi och knuthalt. Dessa är korrelerade till hur enkelt fibrerna kan separeras ifrån varandra i torr eller fuktad luft. Denna separation av fibrer är ett högst avgörande steg för att skapa den fluffiga massan ifrån torkade massaark.  Målet med arbetet har varit att reducera defibreringsenergin och knuthalten genom att behandla massa med oorganiska partiklar genom att använda den sk. lager-på-lager (LbL) – metoden där en konsekutiv behandling av fibrerna med motsatt laddade polyelektrolyter och nanopartilkar. Genom att belägga fiberytan med tunna skikt av ett oorganiskt material var avsikten att reducera fiber-fiber-interaktionerna för att slutligen minska defiberingsenergin och knuthalten. Studien visade att en viss effekt kunde uppnås med LbL-skikt av pDADMAC (diallyldimetylammonium klorid) och MMT (montmorillonit) vilket noterades som en minskning av knuthalten från 35% till ungefär 20%, medan defibreringsenergin däremot var oförändrad jämfört med ett obehandlat referensprov. De bildade lagren visade sig vara tunnare och jämnare än förväntat vilket sannolikt ledde till en relativt liten minskning av kontaktyta och molekylär adhesion mellan fibrerna vilket kan förklara den relativt sett låga effekten av tillsatserna. De tunna lagren kan också vara en förklaring till varför ingen nämnvärd skillnad detekteras för olika antal av bildade bilager. Eftersom enbart maximalt 3 bilager studerades kan det vara rimligt att anta att en ytterligare adsorption av bilager kan leda till en ytterligare minskning av knuthalten och defibreringsenergin.  Eftersom MMT-partiklarna inte var direkt synliga i SEM-analyserna är det svårt att säga exakt hur de är fördelade på fiberytan. Antingen är de jämnt fördelade eller så har vissa områden på fiberytan inte blivit täckta av MMT.  Resultaten indikerar också att det finns många intressanta sätt att förbättra lagren för att nå lägre defibrerinsergier och knuthalter. Genom att tex. adsorbera större partiklar istället för tunna MMT-partiklar skulle det vara möjligt att skapa en högre ytråhet och därmed en minskad kontaktyta mellan fibrerna vilket i sin tur skulle kunna minska knuthalten och defibreringsenergin. / Fluff pulp is indeed a fluffy material, it is most commonly composed of pulp fibers from wood and it serves as a vital constituent in diapers, feminine hygiene products, napkins and a variety of other products. The purpose of fluff pulp in absorbent products is mainly to distribute fluids, increase absorption speed and hold superabsorbent polymers within the network. Two important quality parameters of fluff pulp are the defibration energy and the knot content, which are related to the ease at which the fibers can be separated from each other under dry to moist conditions. This separation of fibers is an essential step in generating the fluffy material from sheets.   This project aims to reduce the defibration energy and the knot content by treating fibers with inorganic particles according to the Layer-by-Layer (LBL) technique. The main assumption was that by applying coatings to the fibers, the inter-fiber interactions can be reduced leading to a lowered defibration energy and knot content. The study showed that some effect was accomplished using layers of pDADMAC (diallydimethylammoinium chloride) and MMT (montmorillonite clay), the knot content was reduced from 35% to around 20%, but the defibration energy was unchanged compared to the untreated reference sample. The formed LBL layers appeared to be thinner and smoother than anticipated which likely lead to only a slight decrease in contact area between the fibers, hence, the reduction of knot content was detectable but not very large. Since the formed LBL layers were so thin it was difficult to find any distinguishable difference for the different numbers of bilayers, however, the maximum number of bilayers produced was only three and additional layers could lead to an amplified effect.  Since the MMT particles could not be clearly visualized from the SEM instruments, it is difficult to conclude exactly how the clay platelets were distributed on the fibers. Either the MMT was distributed rather evenly across the surface of the fibers, or some areas of the fibers were left free from LbLs.   The results from the present investigation show that there are many interesting ways to further improve the layers to reach lower defibration energies and knot contents. As an example the adsorption of larger particles instead of thin MMT platelets could be used allowing for a minimization of the contact area between the fibers due to an increased surface roughness of to the fiber surfaces.

Arbetet handlar om en studie i alternativa fyllnadsmaterial för mindre fanerskador. Syftet är att tydliggöra och vidga konservatorns palett av alternativa fyllnadsmaterial och skapa riktlinjer för lagning av mindre fanerskador med hjälp av dessa material. Parallellt med min undersökande del diskuteras även andra frågor såsom vilka värden möbler bär på samt vikten av att skapa ett nätverk med informationsutbyte för vidareutveckling av metoder och material inom möbelkonservering. I arbetet redogör jag för generella skillnader mellan möbelkonservering och möbelrestaurering. Undersökningen baserar sig på en analys av svar från mitt frågeformulär där svarspersonernas erfarenheter och praktiska undersökningar delvis har legat till grund för urvalet av material jag valt att gå vidare med i mina undersökningar. I dessa undersökningar testade jag olika fyllnadsmaterial på provplattor fanerade med björk och valnöt. I arbetet redogör jag för traditionella fyllnadsmaterial och i slutsatsen redogör jag för de material som jag anser kan utvecklas till att bli lämpliga komplement till de traditionella fyllnadsmaterialen, till exempel Aquazol 500 och Arbocel. / This is a study of alternative filling materials for smaller damages in veneer. The aim is to document and expand the palette of filling materials for furniture conservators and to create guidelines for the conservation and restoration of smaller damages in veneer. Parallel to this study I discuss other issues, such as the different values that can be found in an object. The importance of networking and the giving and sharing of information which is essential for the development of new techniques and materials. The difference between furniture conservation and furniture restoration is presented briefly. My tests are based on an analysis of the answers from my questionnaire where the respondents experience and practical skills serve as a partial base for the choice of materials that I have chosen to examine. My tests were executed on both birch and walnut veneer. I describe the pros and cons of traditional filling materials and in the conclusion, I present the filling materials that I believe can be a good complement to the traditional filling materials, such as Aquazol 500 and Arbocel.

<p>This thesis deals with the engineering of novel nanomaterials, particularly nanocomposites and nanostructured surfaces with enhanced functionalities. The study includes two parts; in the first part, an in situ sol-gel polymerization approach is used for the synthesis of polymer-inorganic hybrid material and its exceptional transparent UV-shielding effect has been investigated. In the second part, electrodeposition process has been adapted to engineer surfaces and the boiling performance of the fabricated nanostructured surfaces is evaluated.</p><p>In the first part of the work, polymer-inorganic hybrid materials composed of poly(methylmethacrylate) (PMMA) and zinc compounds were prepared by in situ sol-gel transition polymerization of zinc complex in PMMA matrix. The immiscibility of heterophase of solid organic and inorganic constituents was significantly resolved by an in situ sol-gel transition polymerization of ZnO nanofillers within PMMA in the presence of dual functional agent, monoethanolamine, which provided strong secondary interfacial interactions for both complexing and crosslinking of constituents.</p><p>In the second part of the work, nanoengineering on the surface of copper plates has been performed in order to enhance the boiling heat transfer coefficient. Micro-porous surfaces with dendritic network of copper nanoparticles have been obtained by electrodeposition with dynamic templates. To further alter the grain size of the dendritic branches, the nanostructured surfaces underwent a high temperature annealing treatment.</p><p>Comprehensive characterization methods of the polymer-inorganic hybrid materials and nanoengineered surfaces have been undertaken. XRD, 1H NMR, FT-IR, TGA, DSC, UV-Vis, ED, SEM, TEM and HRTEM have been used for basic physical properties. Pool boiling tests were performed to evaluate the boiling performance of the electrodeposited nanostructured micro-porous structures.</p><p>The homogeneous PZHM exhibited enhanced UV-shielding effects in the entire UV range even at very low ZnO content of 0.02 wt%. Moreover, the relationship between band gap and particle size of incorporated ZnO by sol-gel process was in good agreement with the results calculated from the effective mass model between bandgap and particle size. The fabricated enhanced surface has shown an excellent performance in nucleate boiling. At heat flux of 1 W/cm2, the heat transfer coefficient is enhanced over 15 times compared to a plain reference surface. A model has been presented to explain the enhancement based on the structure characteristics.</p>

Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) pose significant health risks and enduring remediation challenges. Engineered nanoparticles (NPs) provide a novel platform for sensing/remediation of these toxicants, in addition to the growing use of NPs in many industrial and biomedical applications, but there remains concern for their potential long-term health effects. Research highlighted herein also represents a transdisciplinary approach to address human health challenges associated with exposure to PCBs and NPs. The objectives of this dissertation research are two-fold, 1) to develop effective methods for capture/sensing and remediation of environmental toxicants, and 2) to better understand associated risks and to elucidate relevant protective mechanisms, such as lifestyle-related modulators of environmental disease. Prevalent engineered nanoparticles, including aluminum oxide and titanium dioxide, have been studied to better understand effective nanoparticle dispersion methods for in vitro nanotoxicology studies. This work has served both to effectively stabilize these nanoparticles under physiological conditions and to better understand the associated mechanisms of toxicity, which links these metal nanoparticles to endothelial oxidative stress and inflammation through phosphorylation of key cellular signaling molecules and increased DNA binding of pro-inflammatory NFκB. Surface functionalization, though, is being found to limit potential toxicity and has been utilized in subsequent research. A novel polyphenol-functionalized, NP-based system has been developed which combines the biomimetic binding capabilities of nutrient polyphenols with the separation and heating capabilities of superparamagnetic iron oxide NPs for the capture/sensing of organic contaminants in polluted water sources. Magnetic nanocomposite microparticles (MNMs) incorporating the fluorescent polyphenols quercetin and curcumin exhibit high affinity for model organic pollutants followed by rapid magnetic separation, addressing the need for sustainable pollutant remediation. Further work has been performed to both better understand health concerns associated with environmental toxicants such as PCBs and to determine effective methods for modulating their toxicity. This research has shown that PCB remediation through dechlorination is a viable technique for decreasing endothelial inflammation, although complete dechlorination to biphenyl is necessary to effectively eliminate superoxide production, NFκB activation, and induction of inflammatory markers. Additionally, the nutrient polyphenol EGCG, found in green tea, has been shown to serve as a biomedical modulator of in vivo PCB toxicity by up-regulating a battery of antioxidant enzymes transcriptionally controlled by AhR and Nrf2 proteins.

This thesis entails the utilisation of ab initio density functional theory (DFT) in conjunction with neutron and synchrotron spectroscopy to study the mechanical, vibrational, and dielectric response of metal-organic framework (MOF) materials at the molecular level. MOFs are crystalline materials with nanoscale porosity, which have garnered immense scientific and technological interest for a wide variety of innovative engineering applications. One part of the thesis involves using low-frequency lattice vibrations to characterise the various physical motions that are possible for framework materials. These collective modes detected at terahertz (THz) frequencies have been used to reveal a broad range of exciting possibilities. New evidence has been established to demonstrate that THz modes are intrinsically linked to anomalous elasticity underpinning gate-opening and pore-breathing mechanisms, and to shear-induced phase transitions and the onset of structural instability. The phenomenon of molecular rotor mechanisms and trampoline-like motions are also observed, along with the first experimental confirmation of coordinated shear dynamics. Additionally, a new method to characterise the effects of temperature, and hence thermally-induced structural amorphisation is reported. Finally, for the first time, the frequency-dependent (dynamic) dielectric response of MOF materials, across the extended infrared (IR) spectral region was reported. The results were obtained from experimental synchrotron radiation IR reflectivity and DFT to reveal the low-&kcy; dielectric response of MOFs and established structure-property trends that highlight them as promising systems for microelectronic device applications.

<p>The development of new materials has been inspired by lessons learned from natural systems. In the area of underwater adhesion and adhesives, inspiration has come from the complex protein adhesives generated by marine organism such as barnacle and mussels. These protein systems have a high incorporation of a unique amino acid, dihydroxyphenylalanine, and provides the unique adhesive qualities synthetic systems strive to emulate.</p> <p>By understanding how marine mussels stick to a variety of surfaces, new strategies can be explored for preventing the adhesion of biological organisms to various substrates. A continuous concern for marine vessels is the detrimental impact caused by biofouling on the hull of the ship. Fuel consumption can increase as the vessel’s drag increasing fuel consumption and non-native species can be introduced into new environments. Taking inspiration from catechol curing, new oxidative surfaces were investigated as potential antifouling coatings.</p> <p>Further insight into the marine mussels ability to apply and cure its adhesive on a variety of substrate has also inspired various synthetic polymers. The catechol moiety can be incorporated into a polymer backbone to give a new solvent based adhesive. Further investigation of the poly(styrene-co-(3,4-dihydroxystyrene)) adhesive system was done to formulate an underwater adhesive for unique use cases. A terpolymer was also explored as an ideal adhesive taking inspiration from the mussels by incorporating flexible, stiff, and sticky components to give a tunable adhesive.</p> <p>Having a strong bonding synthetic adhesive that can be used on a laboratory scale is good for academic investigation, but not of use outside the lab if it cannot easily be produced on a commercial scale. With the goal of large scale synthesis, a new polymerization method was introduced addressing some of the issues currently preventing commercial scale production.</p><br>