Recently HER3, member of the epidermal growth factor receptor family (EGFR), has been found to play a crucial role in the development of resistance towards inhibitors that are given to patients with HER1- and HER2-driven cancers. As HER3 is up-regulated or over-activated in several types of human cancers, it is of outmost importance that new innovative drugs target its oncologic activity. The Affibody® Molecule Z08698 inhibits the heregulin induced signalling of HER3 with high affinity (KD~50 pM). As the Affibody® Molecule is small, has high solubility and outstanding folding kinetics, an effective penetration of tumour tissue is suggested together with a rationalized manufacturing process. Further coupling to an albumin binding domain (ABD) expands the plasma half-life of the molecule, hence increasing the molecule's potential of serving as a therapeutic. A process development for production of Z08698-VDGS-ABD094 has been established, where the molecule is efficiently produced in the E. coli host strain BL21(DE3), through a T7 based expression system. Cultivations were performed with a fed-batch fermentation process and the conditions were further optimized in order to obtain highest expression, while avoiding undesirable modifications like gluconoylations. By employing Design of experiments in combination with multivariate data analysis, a production process resulting in ~3.5 g product/ l culture could be verified. Moreover, thermolysis was evaluated as a suitable method for cell disruption, enabling an easy and cost-effective manufacturing process of the ABD fused Affibody® Molecule.

Integrally moulded hinges and tension bands are important features in packaging components for plastic closures and their function is critically dependent on the flow induced micromorphology in the hinge section. Polymer characteristics and processing of the hinge also have an influence on the hinge properties obtained. This study is aimed at obtaining interrelationships between polymer characteristics, in-cavity flow, microstructure development and hinge properties, to produce hinges with enhanced functional properties. Three different virgin polypropylene (PP) grades were investigated (homopolymer PP-H, random copolymer PP-RC and impact copolymer PP-IC) and injection moulding simulation was carried out using Moldflow software. In-cavity data acquisition has been carried out for different sets of injection moulding conditions, using high performance transducers and a data acquisition system. A comparison between Moldflow simulation and practical injection moulding data suggests that, for thin wall injection moulded components the real time pressure data are in close agreement during the injection stage. During the packing stage there is some disagreement between these data, since the thickness of hinge and tension band sections are 0.4 mm and 0.5 mm respectively, suggesting that these dimensions are extending the capability of the software. An extensive study using a design of experiments (DoE) approach was carried out on both practical and predictive data. Injection velocity and melt temperature were the most influential factors on the component mechanical properties. From the optical micrographs it is observed that PP-RC has a finer micro-structure compared to PP-H and PP-IC and some micrographs confirm Moldflow simulation results in which hesitation effects are evident, as the flow converges into the thin hinge and tension band sections. PP-clay nanocomposites (PP-CN) were prepared using a twin screw compounder. Transmission electron microscopy (TEM) has shown some evidence of dispersion and exfoliation of the clay particles in the PP matrix. However, X-ray diffraction (XRD) results show a reduction in inter-layer spacing of PPCN s possibly due to clay compaction. The addition of nano-clay however has not resulted in any significant improvements in the mechanical properties of hinges and tension bands. The high degree of molecular orientation induced in the hinge and tension-band sections appears to mask any improvements attributed to the addition of nano-clay. From the reprocessed and post consumer recyclate (PCR) study conducted on hinges and tension bands, it is seen that with an increase in both the re-processing and PCR content there is a decrease in the component strength of around 14%, giving scope to potentially use PCR in future packaging applications. Investigations conducted on colour pigments (violet and green) reveal that the onset of crystallisation for green pigmented mouldings is considerably higher (16°C) than for natural and violet mouldings. Optical micrographs also reveal a finer microstructural texture for green components, indicating a high nucleating capability of the green pigment. Irrespective of the colour, both for hinges and tension bands, the yield stress values were around twice as high as the values quoted in the manufacturer s data sheet for isotropic PP, due to the high levels of molecular orientation in the hinge and tension band sections. In order to industrially validate the findings from the DoE study, commercial closures were produced in industry on a production tool then characterised. In the case of tension bands, there was a good agreement between the results obtained from lab scale and industrial study due to the relatively simple geometry. For hinges this agreement is not so clear. Finally a comparison of mechanical properties of the 3 PP grades shows that PP-H has a higher yield stress compared to PP-IC and PP-RC and yield stress is significantly higher (yield strain values are lower) than values quoted by the manufacturer. The PhD study has confirmed the process conditions that are able to optimise all the interactive effects to improve functional properties in high volume parts in the packaging industry.

Hydrauliska högtryckskopplingar av typen FEM ½” studeras med avsikten att fastställa en effektiv beräkningsmetodik som kan användas till att prediktera kopplingarnas hållfasthet. Metodiken utgörs av finita element analyser (FEA), och valideras av experimentella trycktester utförda på kopplingstypen FEM ½”. Genom FEA kan kopplingarnas hållfasthetsbeteende och maximala belastningskapacitet studeras virtuellt, vilket minskar behovet av experimentella tester och medför potential för optimering av produkterna. Arbetet utförs på Parker Hannifin AB i Skövde. Experimentella tester utförs på 20 stycken kopplingspar av typen FEM ½” för att utöka förståelsen av kopplingarnas beteende under brottsförloppet och för att prediktera trycket som medför haveri. Testernas genomförande och struktur baseras på metodiken Design of Experiments (DOE). Kritiska komponenter identifieras utifrån experimentets resultat, vilka sedan studeras närmare via FEA. Analyserna valideras utifrån standarder som kopplingarna ska efterfölja, och mätdata insamlad under de experimentella testerna. Från de experimentella testerna är det komponenterna: kulhållaren, styrningen och nippelhuset som upptar belastning i störst utsträckning. Vid haveri framgår två brottmoder som vanliga, att kulhållaren slits isär samt att styrningen brister, båda fallen uppkommer vid approximativt samma tryck. FE-analyserna för styrningen och kulhållaren visar god överensstämmelse med experimentella resultat. Deformationerna skiljer sig dock mellan analyserna och de experimentella testerna, var nippelhusets analyser uppvisar störst avvikelser. FE-modellerna uppvisar god potential för att prediktera samt utvärdera kopplingarnas mekaniska beteende under tryckbelastning. Analyserna är dock helt beroende av ingående data, var saknaden av en verklig materialmodell medför avvikelser från experimentella resultat. Förhållandet framgår tydligt av nippelhuset, vars relaterade härdningsegenskaper saknas. / Hydraulic FEM ½" high pressure couplings are studied with the purpose of establishing an effective methodology that can be used to predict the strength of the couplings. The methodology consists of finite element analyzes (FEA) and is validated by experimental pressure tests, performed on the FEM ½” couplings pairs.  Using FEA, the couplings solid mechanical behavior and maximum load ability can be viewed virtual, reducing the need for experimental tests and gives the potential for optimized products. The work is performed at Parker Hannifin AB in Skovde. Experimental tests are performed on 20 FEM ½” couplings pairs, to understand the solid mechanical behavior of the couplings until failure occurs, and to predict the maximum pressure that can be applied. The experimental structure and performance is based on the method Design of Experiments (DOE). Critical components are identified based on the results from the experimental tests, which are then studied more closely through FEA. The analysis are validated based on the applied material model, and data collected during the experimental tests. From the experimental tests it is shown that the components: ball cage, guide and plug housing are the components in which failure occur. In case of failure, two failure modes appear as common, that the ball cage is worn apart and that the guide burst, both types of failure modes occur at a similar pressure. The analysis for the guide and ball cage corresponds with the experimental outcomes. Differences occurs however when looked at the deformations, in which the plug housing shows the largest deviation when compared to the experimental results. The usage of FE-models appears to be appropriate for predicting and evaluating the mechanical strengths of the couplings during pressure loads. The analysis are however entirely dependent on the input data, where an incorrect material model generates incorrect results. The relationship is shown for the plug housing, which lack the mechanical properties related to curing processes.

Submitted by Livia Mello (liviacmello@yahoo.com.br) on 2016-09-15T13:03:07Z No. of bitstreams: 1 DissPAFB.pdf: 2674729 bytes, checksum: fbbf96392e4ce675814ed1c32c1bacfb (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-21T18:30:18Z (GMT) No. of bitstreams: 1 DissPAFB.pdf: 2674729 bytes, checksum: fbbf96392e4ce675814ed1c32c1bacfb (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-21T18:30:25Z (GMT) No. of bitstreams: 1 DissPAFB.pdf: 2674729 bytes, checksum: fbbf96392e4ce675814ed1c32c1bacfb (MD5) / Made available in DSpace on 2016-09-21T18:30:32Z (GMT). No. of bitstreams: 1 DissPAFB.pdf: 2674729 bytes, checksum: fbbf96392e4ce675814ed1c32c1bacfb (MD5) Previous issue date: 2015-02-01 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / One of the main considerations in selecting materials to manufacture aircraft structures is related to weight saving [1]. In this context, the promising aluminum-lithium alloys have been receiving special attention in aerospace applications due to its attractive combination of low density, high specific strength and corrosion resistance [2-5]. Due to difficulties joining these alloys by conventional welding processes associated to their high thermal conductivity and low melting temperature, solid-state joining technologies emerge as great possibilities to simultaneously solve problems of solidification defects and increasing weight. The feasibility of Friction Spot Welding (FSpW) in joining sheets of lightweight material (e.g. aluminum alloys) places this technology as a potential replacement to the spot-like joint processes, as resistance spot welding (RSW) and laser spot welding (LSW), for application in automotive and aerospace industries [6-8]. In this work, the influence of hook defect on the lap shear strength (LSS) of AA2198-T8 friction spot welds was studied. The effects of process parameters was evaluated in terms of LSS and related to the microstructural configurations. The values of hook length measurements and the LSS were used as response in optimization process developed using the statistical tool of DoE technique with Taguchi Method. Finally it was possible to compare the hook behavior with lap shear strength results. The higher influence on the weld performance was exerted by plunge depth whereas rotational speed was found to be a less significant parameter. Through the minimization of the hook defect, a beneficial response on the weld performance was observed, which was associated to the absence of a potential site for crack nucleation. In spite of inherent discontinuities, promising results were found for aluminum joints for aerospace applications. / Uma das principais considerações na seleção de materiais para a fabricação de estruturas de aeronaves está relacionada à redução de peso [1]. Neste contexto, ligas de alumínio-lítio têm se destacado em aplicações aeroespaciais devido à sua atraente combinação de propriedades como baixa densidade, alta resistência específica e resistência à corrosão [2-5]. Devido às dificuldades para união destas ligas por processos convencionais de soldagem associadas às altas condutividades térmicas e baixas temperaturas de fusão, tecnologias de soldagem no estado sólido emergem com grande potencial para simultaneamente reduzir os defeitos de solidificação e aumento de peso. A viabilidade da Soldagem por Fricção por Ponto (do inglês – Friction Spot Welding – FSpW) para unir chapas de materiais leves posiciona esta tecnologia como potencial substituta para os processos de união por ponto, como soldagem por resistência (RSW) e soldagem a laser (LSW), para aplicação nas indústrias automotiva e aeroespacial [6-8]. O presente trabalho visou estudar a influência do defeito de cunha na resistência ao cisalhamento (RC) das juntas da liga de alumínio 2198-T8 fabricadas por FSpW. O efeito dos parâmetros de processo foi avaliado em relação à RC e relacionado com as configurações microestruturais. Os valores de comprimento de cunha e RC foram utilizados como resposta no processo de otimização desenvolvido utilizando-se a ferramenta estatística de planejamento de experimentos com o Método de Taguchi. Por fim, foi possível comparar o comportamento da cunha com os resultados de RC. A maior influência sobre o desempenho de solda foi exercida pela profundidade de penetração enquanto a velocidade de rotação foi um parâmetro menos significativo. Com a minimização da cunha obteve-se uma resposta benéfica no desempenho de solda, o que foi associado à ausência de uma região potencial para a nucleação de trincas. Apesar de descontinuidades inerentes, resultados promissores foram encontrados para juntas de alumínio para aplicações aeroespaciais.

Made available in DSpace on 2016-12-08T17:19:16Z (GMT). No. of bitstreams: 1 CAPA-INTRO.pdf: 65338 bytes, checksum: 29ebb2d21aacfe78d6df0edf9d832a57 (MD5) Previous issue date: 2012-02-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this work is evaluate the effect of incorporation of waste printed circuit boards (WPCB) in physical and mechanical properties of triaxial ceramics for coating. Through the technique of experiment with mixtures seven formulations were developed with clay (40, 53, 60 e 80%); phyllite (20, 33, 40 e 60%) and waste (0, 14, 20 e 40%). The WPCB was characterized by their particle size, chemical composition and thermal behavior. The mixtures were processed by wet milling, drying, granulation, uniaxial compaction and sintering at 1180 ° C. Properties measured were dried modulus of rupture (DMoR), linear firing shrinkage (LFS), fired modulus of rupture (FMoR) and water absorption (WA). Microstructures were analyzed by SEM and XRD. The thermal behavior was also studied. The WPCB showed melting behavior in the sintering process, but its addition to the material prejudice the DMoR. After firing, the FMoR is improved if are added moderate amounts of waste, but it decreases when there is an excess of waste. Was observed that the interaction between the phyllite and the waste increases the LFS, what is linked to the closing of the pores in the samples, and hence the flux characteristics of these materials. The WA also refers to this conclusion, since the addition of the waste decreases the absorption of 8.0 to 0.5%. Due the found behavior, it is possible to say that there are mixtures of clay-phyllite-WPCB, in certain proportions, that can be classified according to NBR 13818:1997 as stoneware. Microstructural characterization showed that the addition of the waste improves the sinterability of the material, however, in excess are formed glassy phase, not desired, weakening the material. The main phases present, verified by XRD are quartz and mullite, showing that the addition of the waste does not affect the formation of the main phases of interest ceramic. Thermal analysis showed that there is mass loss to 600 ° C, which can be related to the fraction of the polymer in the waste and the loss of water of constitution of the ceramics. In all cases there was an exothermic peak above 950 ° C which is related to the phase transformation of the ceramic material during sintering. / Este trabalho tem como objetivo avaliar o efeito da incorporação de resíduos de placas de circuito impresso (RPCI) nas propriedades físicas e mecânicas de misturas cerâmicas triaxiais para revestimento. Por meio da técnica de experimento com misturas foram desenvolvidas sete formulações com teor de argila de 40, 53, 60 e 80%, teor de filito de 20, 33, 40 e 60% e teor de resíduo de 0, 14, 20 e 40%. O resíduo foi caracterizado quanto à sua granulometria, constituição química e comportamento térmico. As misturas foram processadas por moagem à úmido, secagem, granulação, compactação uniaxial e sinterização a 1180°C. Foram medidas as propriedades de resistência mecânica a seco (RMS), retração linear no sinterizado (RLSi), resistência mecânica do sinterizado (RMSi) e absorção de água (AA). A verificação das microestruturas obtidas foi realizada por MEV, DRX e o comportamento térmico também foi analisado. O RPCI apresentou comportamento fundente no processo de sinterização, mas sua adição ao material prejudica a RMS. Após a sinterização, a RMSi é melhorada desde que sejam adicionadas quantidades moderadas de resíduo, pois este em excesso fragiliza o material. Observou-se que a interação entre o filito e o resíduo aumenta a RLSi, fato ligado ao fechamento dos poros nas amostras, e, portanto, às características fundentes desses materiais. A AA também remete a esta conclusão, pois a adição do resíduo diminui a absorção de 8,0 para 0,5%. Devido ao comportamento encontrado, verificou-se que a mistura de argila-filito- RPCI, em determinadas proporções, pode ser classificada, segundo a NBR 13818 : 1997 como semi-grês ou grês. A caracterização microestrutural mostrou que a adição do resíduo melhora a sinterabilidade do material, no entanto, em excesso, há formação de fase vítrea além do desejado, fragilizando o material. As principais fases presentes, verificadas por DRX, são quartzo e mulita, evidenciando que a adição do resíduo não prejudica a formação das principais fases de interesse cerâmico. A análise térmica mostrou que há perda de massa até 600°C, o que pode estar relacionado à fração polimérica do RPCI e à perda da água de constituição das cerâmicas. Para todos os casos ocorreu um pico exotérmico acima de 950°C, que está relacionado à transformação de fase do material cerâmico durante a sinterização.

Aronia (Aronia melanocarpa) is a berry fruit with distinctive sensory characteristics and health-promoting properties. Polyphenols are the main bioactive compounds found in aronia including natural pigments – anthocyanins. Bioactive compounds are usually obtained from natural materials by extraction, in this work, two methods of extraction were compared – maceration and PHWE. Based on the total phenolic content, maceration was chosen as a more suitable method and then was optimized with statistical model – Design of Experiment. Optimal conditions were set to temperature of 30 °C, extraction agent 50 % ethanol, solid-solvent ratio 10 g per 50 ml and time of extraction for 30 minutes. Extract obtained under these conditions was characterised by total phenolic content – 1441 ± 90 mg/100 g DW, total anthocyanin content 943 ± 8 mg/100 g DW and antioxidation activity by ABTS 24,78 ± 0,09 molTE/g. In total of 25 volatile compounds were indentified in the optimal extract with content > 0,5 %. Major part created aldehydes and esters, with the main compounds being benzaldehyde (32,25 %) and methyl hexanoate (21,37 %).

This master´s thesis deals with problems of wave soldering and application methods Design of Experiments for the new product production. Summarizes the basic knowledge of soldering technology, of solder alloys and Design of Experiments methods. Design of Experiments method has been applied to product to find the optimal for wave soldering setting.

The purpose of this thesis work was to develop a headspace solid phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) method to detect volatile organic compounds (VOCs) in board samples and to statistically investigate potential correlation between chromatographic data and flavor data obtained from a trained panel. The developed method would hopefully serve as a complement to the already established routine analyses at Stora Enso and gain an increased understanding of which VOCs in the board influence its flavor properties. The impact of incubation time and adsorption time on the area under curve (AUC) was studied with a Design of Experiment screening using the software MODDE. The screening data showed a correlation between large AUC and low repeatability measured as relative standard deviation (RSD). The data was hard to fit to a model due to the large RSD values for the replicates, AUC for identified compounds as response gave an acceptable fit. The regression coefficients for the model showed that a longer adsorption time gave larger AUC, while incubation time had no significant impact on the response.  Instead of following up the screening with an optimization, the focus was shifted to improving the repeatability of the method, i.e. lowering the RSD. The high RSD was believed to mainly be the result of leakage of analytes and unstable temperature during adsorption, preventing the system from reaching equilibrium. Different heating options and capping options for the vial was tested. Septum in crimp cap ensured a gas tight seal for the vial, giving lower RSD values and larger AUC compared to the other alternatives, showing that there was indeed a leakage. Using oil bath ensured stable temperature during the adsorption and detection of a larger number of VOCs but created a temperature gradient in the vial due to it not being fully submerged in the oil. Oil bath gave larger AUC, but still high RSD due to the temperature gradient making the method sensitive to variance in fiber depth in the vial. The final method was performed with 2 g of board sample in a 20 ml headspace vial sealed with a crimp cap with septa. The incubation and adsorption were performed with the vial immersed in a 90-degree oil bath. 20 min incubation time was chosen based on the time it took to get a stable temperature gradient in the vial, and 20 minutes adsorption time was chosen as a good compromise between large AUC and low RSD. Compared to Stora Ensos routine analysis, the developed SPME method gave chromatograms with an improved signal-to-noise ratio for the base line and several more peaks with larger AUC. For the board sample used during method development, the SPME-method identified 34 VOCs, while the routine analysis only identified 12. The developed method was applied on 11 archived board samples of the same quality that were selected based on their original flavor properties, to get a large diversity of samples. Flavor analysis was performed by letting a trained flavor panel describe the flavor based on intensity and character of the water that had individually been in indirect contact with one of the 11 board sample for 24 h. Potential correlation between chromatographic data obtained with the developed method and the flavor experience described by the flavor panelists was statistically investigated with the multivariate analysis software SIMCA. The correlation study showed that a combination of 12 VOCs with short retention time are most likely the main source of off-flavor which of 5 could only be identified with the developed SPME method. VOCs with long retention time did not contribute to an off-flavor and might have a masking effect on flavor given by other VOCS, however not confirmed in this study. Furthermore, the age of the board samples proved to be a good indicator for prediction of the flavor intensity, whereas the total AUC of the samples was not. Possible correlation between detected VOCs in the samples and flavor character given by the flavor panel were seen, however the variation in the data and the sample set were too small, preventing from making conclusions on individual VOCs impact on the flavor experience. The developed HS-SPME-GC-MS method would serve as a complement to the already established routine analyses at Stora Enso and has slightly increased the understanding of which VOCs in the board influence the flavor properties

Opioid Use Disorder is defined by the NIH as “the chronic use of opioids that causes clinically significant distress or impairment.”1 Due to a number of factors, the overuse of opioids has become an epidemic in the United States. In recent years there have been a number of lawsuits against pharmaceutical companies and other parties who have benefitted from the proliferation of this issue. In most cases, it is up to the states or local governments who receive these funds to determine their best use. The purpose of this Thesis is to analyze the resources recommended by Ballad Health’s Community Health Needs Assessments, and five additional panels of experts in this field, and to compare these recommendations with available resources, along with making recommendations for the distribution and use of funds coming from a number of lawsuits and settlements.

Turbine engine efficiency modeling depends on many parameters related to fluid dynamics and heat transfer. Many of these parameters change dynamically once the engine enters service and begins to experience surface degradation. This thesis presents a validation of the design and operation of an accelerated testing facility for the study of foreign deposit layers typical to the operation of land-based gas turbines. It also reports on the use of this facility in an effort to characterize the change in thermal resistance on the surface of turbine blades as deposits accumulate. The facility was designed to produce turbine deposits in a 4-hour test that would simulate 10,000 hours of turbine operation. This is accomplished by matching the net foreign particulate throughput of an actual gas turbine. Flow Mach number, temperature and particulate impingement angle are also matched. Validation tests were conducted to model the ingestion of foreign particulate typically found in the urban environment. The majority of this particulate is ceramic in nature and smaller than 10µm in size, but varies in size up to 80µm. Deposits were formed for flow Mach number and temperature of 0.3 and 1150°C respectively, using air plasma sprayed (APS) thermal barrier coat (TBC) material coupons donated from industry. These conditions are typical of a modern, first stage nozzle. Investigations over a range of impingement angles yielded samples with deposit thicknesses from 50 to 200µm in 4-hour, accelerated-service simulations. Above a threshold temperature, deposit thickness was dependent primarily upon particle concentration. Test validation was achieved using direct comparison with deposits from service hardware. Deposit characteristics affecting blade heat transfer via convection and conduction were assessed. Surface topography analysis indicated that the surface structure of the generated deposits were similar to those found on actual turbine blades. Scanning electron microscope (SEM) and x-ray spectroscopy analyses indicated that the deposit microstructures and chemical compositions were comparable to turbine blade deposit samples obtained from industry. A roadmap for the development of a theoretical model of thermal resistance using the SEM scan is presented. Thermal resistance experiments conducted with deposit samples indicate that a general decrease in thermal resistance occurs as the samples are exposed to operating conditions in the accelerated testing facility. This is likely due to sintering effects within the TBC dominating any thermal resistance increase arising from deposition. Recommendations for future research into the interaction between TBC sintering and deposit evolution are presented.