Accumulating evidence indicates that oxygen free radicals are involved in many diseases and pathological conditions, such as aging, inflammation, reperfusion damage of ischemic tissue and various cardiovascular diseases. Extracellular superoxide dismutase (ECSOD) thus plays a major role in the maintenance of cells by providing protection against these toxic substances in the extracellular space. Various animal studies have shown that ECSOD has the ability to protect against many of these disorders, and interest has therefore evolved in the potential therapeutic use of the enzyme. However, despite strenuous efforts, large-scale production of the enzyme has not been achieved. To overcome this problem, a mimic of the enzyme, PseudoECSOD, has previously been constructed. This chimera is easy to produce in large amounts and has all the structural, enzymatic and heparin-binding characteristics of ECSOD, making it a potential substitute for ECSOD in therapeutic situations. However, the copper content of PseudoECSOD has been shown to be rather low, and since the copper ion is very important for the catalytic function of the enzyme, a production system that utilizes a copper chaperone for proper insertion of copper into the active site of the enzyme was constructed. The results show that the copper content of PseudoECSOD produced by this system is close to 100 %. In order to use PseudoECSOD therapeutically, further investigations of its binding capability and protective properties are needed. Therefore, the binding of ECSOD and PseudoECSOD to heparin was investigated using isothermal titration calorimetry. The results show that although some purely ionic interactions are important for the binding between ECSOD and heparin, there is also a substantial contribution from non-ionic interactions. The investigation also showed that the C-terminal domain is the only part of ECSOD that contributes to productive binding, and that the binding of PseudoECSOD and ECSOD to heparin is similar. In addition, analysis of mutant proteins strongly indicated that the amino acids R210, K211 and R214 are important for optimal binding of ECSOD to heparin, accounting for about 30 % of the total binding energy. The structural placement of these amino acids in an α-helix also confirms the hypothesis postulated by Margalit et al., that a common structural motif for heparin-binding proteins may be two positively charged amino acids at a distance of approximately 20 Å in the 3D-structure, facing opposite directions of a α-helix. The importance of these residues was also confirmed by analysis of a phage display library of the C-terminal domain of ECSOD. The binding of PseudoECSOD to heparan sulfate on cell surfaces of two different cell types, HepG2 and endothelial cells, was also investigated. The results clearly show that PseudoECSOD binds to these cells in a very similar manner to ECSOD. To investigate the protective properties of PseudoECSOD against ischemia-reperfusion injuries, an isolated rabbit heart model was used. The results indicate that the enzyme has a protective effect. However, more experiments using the rabbit heart and other animal models are needed to identify the optimal dose for protective purposes. The protective properties of PseudoECSOD in human tissue should also be thoroughly investigated. In summary, the findings in these studies, together with earlier results showing the close resemblance of PseudoECSOD to ECSOD in structural, enzymatic and heparin-binding properties, further support the proposition that PseudoECSOD may be a good substitute for ECSOD to use in therapeutic interventions.

No description available.

<p>Godkännandedatum: 2015-01-02</p>

<p>As the need for and usage of biomaterials in medicine constantly increase, so do the requirements for increased biocompatibility and hemocompatibility. Initially in blood-biomaterial interactions, the surface of an implanted biomaterial is enclosed with adsorbed host proteins and the composition of the adsorbed protein layer depends mainly on the physical-chemical properties of the biomaterial. It is known that the adsorption of proteins on the biomaterial surface may be followed by conformational changes of the adsorbed proteins and subsequent activation of the complement system. For example, binding of complement component C1q to IgG and IgM associated with biomaterial surfaces mediates complement classical pathway activation. The aim of this degree project work was to prepare and evaluate IgG and IgM free sera with functional complement activity for complement activation studies. Further complement studies necessitated IgG and IgM free sera, since two novel polymers with different compositions needed evaluation regarding their ability to induce antibody-independent complement classical pathway activation. Initially, immunoglobulin deficient fetal bovine serum was evaluated regarding complement activity, but no detectable complement activation was present. Different methods for depleting human serum of IgG and IgM were instead utilized and evaluated. From the results, it can be concluded that a close to complete IgG-depletion of human serum is achievable with serum maintaining low but functional complement activity. None of the applied methods for IgM-depletion were however successful and necessitate further optimization and evaluation.</p>

Syftet med denna studie är att redogöra hur pedagoger i förskolan tänker runt ämnena naturvetenskap och teknik. Frågorna som undersöks är Vad anser pedagoger i förskolan att naturvetenskap och teknik är och hur kommer naturvetenskap och teknik till uttryck i förskolan. Studien har genomförts med kvalitativa intervjuer bland nio pedagoger på fe olika förskolor i tre olika kommuner. Resultaten av studien visar att pedagogerna har olika syn på vad naturvetenskap och teknik är. Beroende på pedagogernas bakgrund och utbildning varierade svaren på vad ämnena innebär. Resultaten visar också på att arbetet med naturvetenskap och teknik i förskolorna är undermåliga. Miljöerna är inte utvecklade på det sätt pedagogerna skulle vilja och de har svårt att veta hur de ska arbeta med ämnena.

Today’s data rates in wired networks can reach 100 Gbit/s using optical fiber while data rates in wireless networks are much lower - tens of Mbit/s for 3G mobile communication and 480 Mbit/s for ultra-wideband (UWB) short range wireless communications. This difference in data rates can mainly be explained by the limited allowed frequency spectrum, the nature of the radio signal and the high requirements imposed on all hardware designed for high speed and wideband wireless communications. However, the demand on wireless commercial applications at competitive costs is growing. The first step in regulations allowing higher data rates for wireless communications was taken in 2002, when the Federal Communication Commission (FCC) in USA released unlicensed the 3.1-10.6 GHz frequency band restricting only the power level (maximum mean equivalent isotropic radiated power density of a UWB transmitter is -41.3 dBm/MHz) in the band 3.1-10.6 GHz. But Europe, Japan and recently China have put additional restrictions on the 3.1-4.8 GHz band. The restrictions address the problems that have raised from the coexistence and colocation of the UWB systems with other narrowband wireless systems. Thus, the 6-9 GHz band combined with an increased modulation order scheme is of large interest. Operating at higher frequency and wider bandwidth than today’s communication technologies, with the general task of maximizing the wireless data rate while keeping the power consumption low, requires new communication system solutions and new circuit design approaches. These new solutions also require understanding of many multi-disciplinary areas which until the recent past were not directly related: from classic analog circuit design to microwave design, from modulation techniques to radio system architecture. In this thesis, new design techniques for wide bandwidth circuits above 3 GHz are presented. After focusing on ultra-wideband low-noise amplifier (UWB LNA) design for low-power and low-cost applications, the practical implementation and measurement of a 3.1-4.8 GHz UWB LNA is addressed. Passive distributed components of microstrip transmission lines are intensively used and their contribution to the UWB LNA performance is studied. In order to verify the design methodology while extending it to the UWB radio front-end, the UWB LNA is integrated on the same substrate with a pre-selecting filter with the frequency multiplexing function. In this way, the concept of frequencytriplexed UWB front-end is demonstrated for the Mode 1 multi-band UWB bandwidth 3.1-4.8 GHz. Using the proposed receiver front-end topology, better receiver sensitivity and selective operation can be achieved. The later part of the thesis investigates ultra-wideband 6-9 GHz receiver and transmitter front-end topologies for Gbit/s data rates and low power consumption. To capture the advantages offered by distributed passive components, both the transmitter and receiver use the six-port correlator as the core of a passive mixer. Modelling and design of the 6-9 GHz UWB front-end transceiver include different receiver topologies and different modulation schemes. Finally, the 7.5 GHz UWB transceiver front-end is implemented and evaluated. Measurement results confirm the large potential of the six-port UWB front-end to achieve multiple Gbit/s data rates. This may open for future solutions to meet the continuous challenge of modern communication systems: higher data rates at low power consumption and low cost.

Alumina-zirconia thin films have been deposited using dual magnetron sputtering. Film growth was performed at relatively low-to-medium temperatures, ranging from ~300°C to 810 °C. Different substrates were applied, including silicon (100), and industrially relevant materials, such as WC-Co hardmetal. Both radio-frequency sputtering and direct-current magnetron sputtering were utilised to achieve a range of film compositions. The influence of sputtering target was investigated; both ceramics and metals were used as sputtering sources. Microstructural characterisation was performed with a range of electron microscopy and x-ray diffraction techniques which show that the pure zirconia was deposited in the monoclinic phase. Reduced mobility of depositing species, as in the case of direct-current sputtering, yielded preferred crystallographic orientation in the {100} directions. The initial nucleation layer consisted of the metastable tetragonal zirconia phase. This phase could be grown over film thicknesses ~1 μm through the addition of ~3 at.% Al under similar low mobility conditions. For cases of higher mobility, as obtained through radio-frequency sputtering, the metastable cubic zirconia phase formed in the film bulk for alumina-zirconia nanocomposites. A combination of two mechanisms is suggested for the stabilisation of metastable zirconia phases: oxygen-deficiency and aluminium segregations with resultant restraint on the zirconia lattice. The sputter deposition process was investigated through energy resolved mass spectrometry in the case of radio-frequency sputtering; the sputter deposition flux contained a mixture of metallic ions, metaloxygen clusters, and oxygen ions. The presence of metal-oxygen clusters was found to be important in oxygen-stoichiometry and thus the phase selection of the resultant film. The energy distributions were similar when comparing sputtering from ceramic and metallic targets. A mass-balance model has also been developed for the transport phenomena and reactions of particles in reactive sputtering of two targets in a two-gas scenario for the alumina-zirconia system. Addition of nitrogen to the working gas was found to eliminate the hysteresis in the target poisoning for oxygen reactive sputtering. The higher reactivity of oxygen contributed to a higher oxygen content in resultant films compared to the oxygen content in the oxy-nitride working gas. The model was thus shown to be successful for tuning depositions in the alumina-zirconia oxy-nitride system.

This thesis concerns synthesis and characterization of carbon-based materials and theinvestigation of the possible use, of a selection of these materials, in biomedicalapplications. Protein adsorption and blood plasma tests were used for this purposeutilizing a surface sensitive technique called spectroscopic ellipsometry. The materials were synthesized by physical vapor deposition and characterizedregarding microstructure, mechanical properties and optical properties. The ternaries BC-N and Si-C-N as well as carbon and carbon nitrides (CNx) of different microstructureshave been examined. In the B-C-N work, the intention was to investigate the possibilityto combine the two materials CNx and BN, interesting on their own regarding highhardness and extreme elasticity, to produce a material with even better properties.Theoretical calculations were performed to elucidate the different element substitutionsand defect arrangements in the basal planes promoting curvature in the fullerene-likemicrostructure. The Si-C-N ternary was investigated with the consideration of finding away to control the surface energy for certain applications. Amorphous carbon and threemicrostructures of CNx were analyzed by spectroscopic ellipsometry in the UV-VIS-NIRand IR spectral ranges in order to get further insight into the bonding structure of thematerial. In the second part of this work focus was held on studies of macromolecularinteractions on silicon, carbon and CNx film surfaces using ellipsometry. One purposewas to find relevance (or not) for these materials in biological environments. Materials for bone replacement used today, e.g. stainless steel, cobalt-chromium alloys andtitanium alloys suffer from corrosion in body fluids, generation of wear particles inarticulating systems, infections and blood coagulation and cellular damage leading toimpaired functionality and ultimately to implant failure. Artificial heart valves made ofpyrolytic carbon are used today, with friction and wear problems. Thus, there is still aneed to improve biomaterials. The aim of the fourth paper was to investigate theinteraction between carbon-based materials and proteins. Therefore, amorphous carbon(a-C), amorphous (a), graphitic (g) and fullerene-like (FL) CNx thin films were exposedto human serum albumin and blood plasma and the amount of protein was measured insitu using spectroscopic ellipsometry. Surface located and accessible proteins after blood plasma incubations were eventually identified through incubations in antibody solutions. Antibody exposures gave indications of surface response to blood coagulation,complement activation and clotting. The a-C and FL-CNx films might according to theresults have a future in soft tissue applications due to the low immuno-activity, whereasthe g-CNx film possibly might be a candidate for bone replacement applications. "Layered" structures of fibrinogen, a fibrous but soft protein involved in manyprocesses in our body, were grown in situ and dynamically monitored by ellipsometry inorder to understand the adsorption process and molecule arrangement onto a siliconsurface. In the last paper of this thesis, the effects of ion concentration and proteinconcentration on the refractive index of water-based solutions used in in situ ellipsometrymeasurements were demonstrated and spectral refractive index data for water solutionswith different ionic strengths and protein concentrations have been provided.

¨This Thesis treats the growth and characterization of ternary transition metal nitride thin films. The aim is to probe deep into the Ti-Al-N system and to explore novel Sc-Al-N compounds. Thin films were epitaxially grown by reactive dual magnetron sputtering from elemental targets onto single-crystal substrates. Ion beam analyses were used for compositional analysis and depth profiling. Different X-ray diffraction techniques were employed, ex situ using Cu radiation and in situ during deposition using synchrotron radiation, to achieve information about phases, texture, and thickness of films, and to follow roughness evolution of layers during and after growth. Transmission electron microscopy was used for overview and lattice imaging, and to obtain lattice structure information by electron diffraction. In the Sc-Al-N system, the perovskite Sc3AlN was for the first time synthesized as a thin film and in single phase, with a unit cell of 4.40 Å. The hardness was found to be 14.2 GPa, the elastic modulus 21 GPa, and the room temperature resistivity 41.2 μΩcm. Cubic solid solutions of Sc1-xAlxN can be synthesized with AlN molar fraction up to ~60%. Higher AlN contents yield three different epitaxial relations to ScN(111), namely, #1 Sc1-xAlxN(0001) || ScN(111) with Sc1-xAlxN[11210] || ScN[110], #2 Sc1-xAlxN(1011) || ScN(110) with Sc1-xAlxN[1210] || ScN[110], and #3 Sc1-xAlxN(1011) || ScN(113). An in situ deposition and annealing study of cubic Sc0.57Al0.43N films showed volume induced phase separation into ScN and wurtzite structure AlN, via nucleation and growth at the domain boundaries. The first indications for phase separation are visible at 1000 °C, and the topotaxial relationship between the binaries after phase separation is AlN(0001) || ScN(001) and AlN&lt;01ɸ10&gt; || ScN &lt;1ɸ10&gt;. This is compared with Ti1-xAlxN, for which an electronic structure driving force leads to spinodal decomposition into isostructural TiN and AlN already at 800 °C. First principles calculations explain the results on a fundamental physics level. Up to ~22% ScN can under the employed deposition conditions be dissolved into wurtzite Sc1-xAlxN films, while retaining a single-crystal structure and with lattice parameters matching calculated values. In the Ti-Al-N system, the Ti2AlN phase was synthesized epitaxially by solid state reaction during interdiffusion between sequentially deposited layers of AlN(0001) and Ti(0001). When annealing the sample, N and Al diffused into the Ti layer, forming Ti3AlN(111) at 400 ºC and Ti2AlN(0001) at 500 ºC. The Ti2AlN formation temperature is 175 ºC lower than earlier reported results. Another way of forming Ti2AlN phase is by depositing understoichiometric TiNx at 800 °C onto Al2O3(0001). An epitaxial Ti2Al(O,N) (0001) oxynitride forms close to the interface between film and substrate through a solid state reaction. Ti4AlN3 was, however, not possible to synthesize when depositing films with a Ti:Al:N ratio of 4:1:3 due to competing reactions. A substrate temperature of 600 ºC yielded an irregularly stacked Tin+1AlNn layered structure because of the low mobility of Al ad-atoms. An increased temperature led to Al deficiency due to outdiffusion of Al atoms, and formation of the Ti2AlN phase and a Ti1-xAlxN cubic solid solution.

This thesis treats surface engineering with the purpose of improved quality of optical and electricalconnectors with a focus on electroplated and magnetron sputtered materials. In electroforming of tools formanufacturing optical connectors, the influence of ultrasonic agitation on intrinsic stresses and fillingproperties of electroplated Ni has been studied. It is established that the ultrasonic agitation at the substratesurface during deposition impacts the intrinsic stresses making it possible to increase deposition rate viacurrent density, with stress-free or low-stress levels in the Ni layers. Reduced variations of the intrinsicstress over the surface with the current density is a further important result. Filling of grooves byelectroplating of Ni using ultrasonic agitation is demonstrated. This is due to increasing mass transport ofspecies into the grooves compared to conventional pumped agitation. The enhanced filling propertiesmakes it possible to electroplate Ni in the bottom of high-aspect-ratio grooves. In order to industriallyimplement new nanocomposite coatings on electronic connectors, studies have been performed regardingthe thermal diffusion barrier properties against Cu for Ti-Si-C and Ti-Si-C-Ag nanocomposites, depositeddirectly onto Cu substrates or with sputtered Ni, Ti or electroplated Ni as an intermediate coating. Theapplication of an electroplated Ni diffusion barrier coating, hinders Cu from reaching the surface of thenanocomposites. Also, Ti-Si-C-Ag nanocomposite deposited on magnetron sputtered Ni or Ti on Cusubstrates hinder Cu from diffusing to the surface after annealing. The contact resistance of Ag-Pdtopcoated Ti-Si-C-Ag-Pd and Ti-Si-C-Ag nanocomposite coatings in contact with hard gold is shown tocompete with hard gold in contact with itself, as electrical contact coatings at contact forces around 5 N.Ag-Pd topcoated Ti-Si-C-Ag-Pd in contact with hard gold is shown to have approximately the same contactresistance as hard gold in contact with hard gold at contact forces around 0.1 N, which here is in the 10 mΩrange, while Ti-Si-C-Ag nanocomposite coatings in contact with hard gold has a contact resistance that isup to 10 times higher. The overall contribution of this thesis can be summarised as a deeper knowledge andunderstanding of techniques and coatings, that help reduce cost and increase reliability of electronics.