In this thesis work, Cellruptor pre-treatment was evaluated in order to increase biogas yield. Initially, the effects of residence time (30, 60, 90, 120 and 180 min) and substrate release (rapid/non-rapid) from the draining port of Cellruptor on biosludges were investigated to find the optimum operating conditions of Cellruptor. Under these optimum operating conditions, the effect of Cellruptor pre-treatment on batch reactors of various substrates and semi-continuous digester of biosludge were investigated at mesophil biosludge, dewatered sludge, digested sludge, fibre sludge, hay, maize silage, minced meat, orange peel, seaweed and yeast. From the initial study, 90 min residence time and rapid release of pre-treated substrate from draining port were found to be optimum operating conditions of Cellruptor. From the batch experiments, Cellruptor pretreatment showed maximum and minimum increase of methane yield in hay (32%) and dewatered sludge (2%) respectively. The semi-continuous digester experimental results showed increase in biogas production by 22.4% from Cellruptor pre-treatment of biosludge at HRT of 15 days and OLR of 2.0 g VS/L/day. With further studies, Cellruptor pre-treatment may be deployed in large-scale biogas plants to improve biogas yield.

Paper A: In this paper, the development and implementation of a contact algorithm based on C2-continuous surface representations is discussed. In 3D contact simulations involving models with arbitrarily curved surfaces (as in the case of vessel walls), the discretization of the contact surfaces by means of facet-based techniques could lead to numerical instabilities and finally loss of quadratic convergence. These instabilities arise mainly due to the sliding of contractor (slave) nodes over the boundaries of target (master) contact facets, where jumps of the normal vector are experienced. The paper addresses successfully this problem, by discretization of the target surfaces by means of C2-continuous parameterization schemes. Initially, the uniform cubic B-spline surfaces are introduced. Next, in an attempt for more accurate representations of the geometric models of the contact surfaces, a new parameterization based on the expression of cubic B-splines is developed. The two approaches are implemented into a finite element framework and more specifically, into the multipurpose finite element analysis program FEAP. The special merits of the developed algorithms and the advantages of the smooth surfaces over facet-based approaches are exhibited through a classical contact mechanics problem, considering incompressibility, finite deformations and large slidings. Next, a simulation of balloon angioplasty with stenting is presented, where the contact between both medical devices (balloon and stent) with the arterial wall is modeled. The arterial wall is modeled in this first approach, as hyperelastic, homogeneous, isotropic, while a cylindrically orthotropic model is developed to capture the nonlinear, anisotropic behavior of the balloon catheter under pressure. Two stents with the same geometry but different strut thickness, are studied. Both are considered elasto-plastic. The performed simulations point out the outcome of the balloon angioplasty and stenting in terms of luminal gain and mechanical strains. Finally, a comparison between the two stent configurations is presented. Paper B: The second paper makes use of the contact tool developed in Paper A and focuses on the changes of the mechanical environment of the arterial wall due to stenting, as a function of a set of stent design parameters. In particular, Paper B presents a detailed geometric and material model of a postmortem human iliac artery, composed by distinct tissue components, each associated with specific mechanical properties. The constitutive formulation for the artery considers anisotropic, highly nonlinear mechanical characteristics under supraphysiological loadings. The material and structural parameters of the arterial model are obtained through uniaxial tensile tests on stripes extracted from the several arterial tissues that form the stenosis, axially and circumferentially oriented. Through cooperation with a well-established stent manufacturing company, an iliac stent was acquired. The dimensions of the stent are measured under a reflected-light microscope, while it is parameterized in such a way as to enable new designs to be simply generated through variations of its geometric parameters. The 3D balloon-stent-artery interaction is simulated by making use of the smooth contact surfaces with C2-continuity, as previously mentioned. Next, scalar quantities attempt to characterize the arterial wall changes after stenting, in form of contact forces induced by the stent struts, stresses within the individual components and luminal change. These numerically derived quantities allow the determination of the most appropriate stent configuration for an individual stenosis. Therefore, the proposed methodology has the potential to provide a scientific basis for optimizing treatment procedures, stent material and geometries on a patient-specific level. / <p>QC 20101118</p>

Banana peels account for about 61 million tons of waste each year globally. The aim of this project was to investigate the possibility of using banana peels as a substrate to cultivate edible filamentous fungi. The peels were subjected to physical and thermal pretreatments while variables such as changes in the medium pH, biomass concentration, fungal strain dependence, and protein content of the fungal biomass were analyzed. The experiments were carried out in three phases. The purpose of phase I was to identify which of the four fungal strains among Neurospora intermedia, Aspergillus oryzae, Rhizopus oryzae, and Rhizopus oligosporus could grow in a medium containing ball-milled banana peel powder (BPP) only. In phase II, the best performing strains from phase I in terms of biomass concentration, i.e., A. oryzae and R. oryzae, were cultivated using banana peel broth (BPB) obtained from thermal pretreatment of BPP. During this phase, the impact of medium supplementation with yeast extract was also assessed. The biomass yield for A. oryzae and R. oryzae 2.9 g/L and 1.6 g/L, respectively, yeast supplementation compared to 2.7 g/L and 0.7 g/L, respectively, without supplementation. In phase III, the experiments performed in phase II without yeast extract supplementation were scaled up, after which protein analysis was performed. A crude protein content of 8.82% was determined for A. oryzae, while in R. oryzae, a higher value of 21.1% was obtained. The protein content from both fungal strains was much higher than that present in the BPP, which was 4.8 g/L. The results showed the potential of using banana peel as a substrate to produce edible fungal biomass with higher protein content and thus has potential applications as animal feed or human food. Further studies are needed to optimize the process in order to raise the fungal biomass yield as well as increase the protein content of the biomass. In addition, comprehensive characterization of the fungal biomass would reveal other important components, such as the amino acid profile.

Anaerob jäsning antas vara en bra och effektiv metod för behandling av organiskt avfall. Avloppsvatten från denna process är mer utmanande beroende främst på dess höga innehåll av bland annat flyktiga fettsyror (VFA). Mikroalger har en stor potential för hållbart avlägsnande av näringsämnen från vatten samtidigt som algbiomassa kan användas för produktion av bio-gödsel, biobränsle och bioplaster. Därför var syftet med denna studie att undersöka möjligheten att odla två svenska stammar av mikroalger, anpassade till det nordiska klimatet, på olika syntetiska kulturer. Kulturerna innehöll två bestämda totalkoncentrationer av ättiksyra, propionsyra och smörsyra med tre olika förhållande till varandra. Stammarna som studeras i detta experiment var Chlorella vulgaris (13–1) och Chlorococcum sp. (MC-1). Stammarna visade olika förmågor att tolerera VFA som kolkälla. Chlorococcum sp. kunde ge betydligt högre biomassakoncentrationer i närvaro av VFA än C. vulgaris. Vid totalkoncentrationen 2 g/L VFA och den största halten av ättiksyra erhölls den högsta biomassakoncentrationen. C. vulgaris i kulturerna med VFA visade samma beteende som i referensodlingen utan VFA. De slutliga biomassakoncentrationerna i närvaro av VFA liknade den biomassakoncentrationen från referensodlingen. Att Chlorococcum sp. kan växa på VFA kan minska miljöpåverkan av industriella utflöden från anaerob jäsning i Sverige och andra nordiska länder. / Anaerobic fermentation is believed to be a good and effective method for treating organic waste. Wastewater from this process is more challenging mainly due to its high content of for instance volatile fatty acids (VFA). Microalgae have shown great potential for the sustainable removal of nutrients from water sources. At the same time, algal biomass can be used to produce bio-fertilizer, biofuel, and bioplastics. Therefore, the purpose of this study was to investigate the possibility of growing two Swedish microalgae strains, adapted to the Nordic climate, on different synthetic cultures. The cultures contain two determined total concentrations of acetic acid, propionic acid, and butyric acid with three different ratios to each other. The strains studied in this experiment were Chlorella vulgaris (13–1) and Chlorococcum sp. (MC-1). The strains showed different abilities to tolerate VFA as a carbon source under the same biotic and abiotic conditions. Chlorococcum sp. was able to produce significantly higher biomass concentrations in the presence of VFA than in the reference culture without VFA. The culture with the total concentration of 2 g/L of VFA and the ratio that had the greatest content of acetic acid gave the highest biomass concentration. C. vulgaris was not affected by VFA and the algal cells in the cultures with VFA show the same behaviour as in the reference culture. Moreover, the final biomass concentrations in the presence of VFA were similar to the biomass concentration from the optimal culture. Since Chlorococcum sp. could grow on VFA it can reduce the environmental impact of industrial effluents from anaerobic fermentation in Sweden and other Nordic countries.

The circular economy is about rethinking the definition of waste into resource. Tempeh boiling water is cheap and would otherwise be washed into the river and pollute the water which would affect the environment badly. Tempeh boiling water is going to be used as substrate to produce mycoprotein with the fungi Rhizopus oligosporus. This study is about making a mycoprotein nugget and evaluate it with a sensory evaluation and to evaluate the protein content in the nugget and chemical oxygen demand of the boiling water. The sensory evaluation will have 65 panellists to assess the liking of the nugget with two control samples. The purpose of this project was to evaluate the potential of tempeh boiling water for the circular economy as substrate. To produce high mycoprotein nugget that will be accepted by the community. Assess the protein content in the mycoprotein nugget and assess the carbon used by the fungi with chemical oxygen demand analyse. The target group for evaluating the fungal nugget was students studying at Gadjah Mada University, Yogyakarta, Indonesia. The project was done in multiple following stages: Finding best formula of mycoprotein, mycoprotein production, sensory evaluation, and protein analyse with Kjeldahl method and COD analyse of the boiling water.The result of this study is that the mycoprotein nugget were not liked nor disliked with the average score of 3,9 out of 7. The overall characteristics (appearance, colour, texture, and taste) were 4,0 out of 7. The COD before and after fermentation were 6,6 g/L. The most COD were removed by pre-treatment of the boiling water from 172 to 121 g/L.The protein content of the mycoprotein nugget were 23,8%. The social aspect to produce healthy foods to a low cost at the same time improve water quality by removing foods for toxic microorganisms.

Xyloglucans are polysaccharides found as storage polymers in seeds and tubers, and as cross-linking glycans in the cell wall of plants. Their structure is complex with intricate branching patterns, which contribute to the physical properties of the polysaccharide including its binding to and interaction with other glycans such as cellulose. Xyloglucan is widely used in bulk quantities in the food, textile and paper making industries. With an increasing interest in technically more advanced applications of xyloglucan, such as novel biocomposites, there is a need to understand and control the properties and interactions of xyloglucan with other compounds, to decipher the relationship between xyloglucan structure and function, and in particular the effect of different branching patterns. However, due to the structural heterogeneity of the polysaccharide as obtained from natural sources, relevant studies have not been possible to perform in practise. This fact has stimulated an interest in synthetic methods to obtain xyloglucan mimics and analogs with well-defined structure and decoration patterns. Glycosynthases are hydrolytically inactive mutant glycosidases that catalyse the formation of glycosidic linkages between glycosyl fluoride donors and glycoside acceptors. Since its first conception in 1998, the technology is emerging as a useful tool in the synthesis of large, complex polysaccharides. This thesis presents the generation and characterisation of glycosynthases based on xyloglucanase scaffolds for the synthesis of well-defined homogenous xyloglucan oligo- and polysaccharides with regular substitution patterns.

<p>Opioid addiction has become a global epidemic and a national health crisis in recent years. In 2016, approximately 64,000 Americans under 50 years old were killed because of opioid overdoses. The aim of developing an abuse deterrent opioid is to render any form of manipulation that encourages abuse challenging and therefore, non-profitable. With this goal, the Food and Drug Administration (FDA) is extensively supporting research into the development of abuse deterrent technologies and prioritizing their production as a public health necessity. Abuse deterrent approaches include but are not limited to the following: (1) using a physical barrier (e.g., Polyethylene oxide PEO) that basically limit the release of the drugs in the blood or the digestive tract and prevent mechanical alteration of the drugs by crushing, grating, grinding, chewing etc, (2) using chemical barriers that employ gelling agents that prevent the aqueous or organic extraction of the drugs, and (3) combining the drug with an antagonist that blocks the post-abuse euphoria.</p> <p>PEO is a popular polymer used as a matrix in these complex opioid products. The polymer is responsible for the abuse deterrent properties as well as extended release behavior of opioid drugs. PEO hinders the extraction of Opioid drugs from Abuse Deterrent Formulations (ADF), makes it challenging to be injected, and resists mechanical stress and pulverization when crushed. PEO can be subjected to thermal processing such as thermal curing, compression molding, melt extrusion, and injection molding owing to its thermoplasticity.</p> <p>Assessment of the impact of using various manufacturing processes to develop ADFs and the effect of using various grades of this polymer is essential to improve upon the next generation of ADFs. There are three main categories of premarket studies: Category 1 – laboratory based (in-vitro manipulations and drug extractions), category 2 – pharmacokinetic and category 3 –clinical. These studies are required by the FDA to demonstrate that a given formulation exhibit abuse deterrent properties before a drug product is released to the market. In vitro laboratory based manipulation and extraction studies which are used to assess AD properties of these products are challenging, but essential for product development and generic abuse deterrent product approvals. It is important to realize that there is a great correlation between the laboratory based in vitro manipulation and extraction studies and the expectations of potential abuse and misuse of opioid drugs. The ability of these studies to mimic the manipulation techniques applied by abusers to defeat the abuse deterrent properties of a given formulation optimizes predictions on post-market abuse and misuse potential of ADFs. These studies should also correlate well with <i>in-vivo</i> studies since there is a direct correlation with the concentration (mg/mL in water) and the “high” obtained by an abuser. </p> <p>This research aimed to conduct laboratory based in vitro manipulation and extraction studies to investigate failure modes of PEO-based prescription opioids and Promethazine Hydrochloride PMZ HCl tablets. It highlighted the formulation components and the manufacturing parameters that might affect the dose dumping of Active Pharmaceutical Ingredients (APIs). Furthermore, this research identified model compounds that can be used as surrogates for Oxycodone and the best experimental setup that can be used to conduct smoking simulation experiments. Moreover, it provided an overview of the societal impacts of the opioid crisis in the state of Indiana.</p> <p>Investigations of the failure modes of the PEO-based prescription opioids and PMZ HCL tablets showed that physical manipulation techniques via chopping or grinding are much more effective in the destruction of the PEO matrix than thermal manipulation via the application of heat thus promoting the fast release. The factor with the most significant effect on the failure modes of PMZ HCL tablets was the application of physical manipulation, while the one with the lowest impact was the polymer grade. Moreover, producing PEO-based matrix tablets via Direct Compression DC significantly affected dose dumping behavior of the API from the drug products. The production of the PEO-based matrix tablets via DC was found to be favored over the usage of the melt extrusion method and molding techniques. It was clear that DC kept the integrity of the polymer, allowed for slow and controlled release fashion of the API, and rendered the extraction process relatively hard compared to the Hot Melt Extrusion HME and Molding techniques.</p> <p>Furthermore, the release profile of the investigated PMZ HCL products consisted of various phases of polymer swelling and API release. Thermal manipulations via the application of heat were found to accelerate the dose dumping behavior (90% release) of the APIs from the compressed, extruded, and molded PEO-based matrix formulations similarly. On the other hand, heating was much more effective in the extraction of APIs than chopping or grinding thus promoting the ability to<b> </b>draw a solution containing the API into a syringe for injection relatively easy and facilitate higher % API recovery.</p> <p>Among the formulation components that might have an impact on the AD properties of the PEO-based drug products are; the choice of the antioxidant, the use of complexing agents, chelating agents, and plasticizers. On the other hand, manufacturing process variables that might have a critical impact on AD properties of the PEO-based drug products include but are not limited to; processing temperature compared to the melting point of the polymer and time of exposure</p> <p>PMZ HCl was used as a model drug for Oxycodone in dissolution and extractability studies, while Caffeine and L-Nicotine were used as model drugs in smoking simulation experiments. The combination of the propane torch and Kugelrohr apparatus mimic the real-world scenario for smoking Opioids; however, this experimental setup caused thermal degradation rather than vaporization of some model drugs.</p> <p>According to the National Center for Health Statistics; a statistically significant increase in drug overdose death rates was reported in 2016 in the state of Indiana among other states. The number of deaths related to opioid pain relievers increased by 3732 folds in 2017 compared to the number of deaths in 2014. Moreover, Males were more affected by the opioid crisis than females. On the other hand, the age group 25-44 years, and white people were the most affected by the opioid crisis in Indiana. </p>

Major studies conducted in Europe and North America has concluded that the current processes in wastewater treatment plants insufficiently degrade micropollutants e.g. pharmaceutical residues. Several sorption and oxidation methods has therefore been investigated with the purpose of removing or degrading micropollutants in wastewater. The main purpose of this project was, firstly, to validate the results from a pilot study conducted by Tekniska verken i Linköping AB (2014) which investigated the use of ozone to degrade pharmaceutical residues. Secondly, to investigate and design a suitable process control strategy for the ozonation process. Four different tests were conducted during the project, a dose-response test, step-response tests, a trace test, and a performance test. A poorer average reduction of pharmaceutical residues was observed in this project compared to the pilot study. An average reduction of approximately 80% was observed at the highest tested dose, 0.67 mg O3/mg DOC, N corr. Whilst an average reduction of 90% was observed at approximately 0.46 mg O3/mg DOC, N corr, in the pilot study. However, the quality of the wastewater was worse during this project compared to the pilot study. ΔUVA254 and offgas concentration of ozone were found to be suitable control parameters for process control. A control strategy based on a combination of these parameters was designed, where ΔUVA254 was used as the main control parameter and the off-gas concentration of ozone was used as a limiting controller to ensure a sufficient mass transfer in the system. In conclusion, a suitable flow proportional base ozone dose valid for current water conditions has been identified, 10 mg/L. Differences in wastewater quality which heavily influence the ozonation process have been identified. Lastly, a control strategy for process control of the ozonation have been identified, designed and is ready for implementation.

Hyaluronic acid (HA) is an unbranched polysaccharide consisting of the repeating disaccharide unit β(1→4)-GlcA-β(1→3)-GlcNAc and is a naturally occurring biopolymer in bacteria and vertebras. HA is predominantly found in the extracellular matrix (ECM) and the in vivo function of HA can vary depending on molecular weight (Mw) for instance high Mw HA is reported to be anti-angiogenic while low Mw HA induces angiogenesis. HA is a popular component for hydrogels such as dermal fillers. HA is commonly used in dermal fillers. However, other materials, such as other polymers, can be used as well. The project goal was to investigate different degradation processes for production of target Mw HA. Alkaline and acidic degradation processes in combination with increased temperatures seemed as the most promising methods. Degradation tests performed both in aqueous solution as well as heterogeneously in ethanol were evaluated. The acidic degradation in aqueous solution was proven to have the largest degradation constant. Both a robustness test as well as a Design of Experiments (DoE) was performed to investigate the influence different factors had on the degradation speed. The investigated factors were HA concentration, HCl concentration and temperature. Temperature and HCl concentrations proved to be the most influencing factors and a model was developed in the DoE software MODDE to describe how the factors influenced the degradation constant. The model was established as a good significant model with a Q2 value of 0.998 and relative standard deviation (RSD) value of 0.022 after a logarithmic transformation was performed as well as a simplification of the model by excluding some of the factor interactions. The acidic degradation method also proved to be a highly robust method which easily could be used to produce target Mw HA.

Poultry meat consumption in New Zealand has been increasing since 1975 with the highest peak reported in 2006. The total poultry meat consumption was 36.5 kg per capita in the year ending September 2006. Consumption of contaminated food with raw poultry can lead to campylobacteriosis, which is a food-borne disease that causes gastroenteritis in humans and it is a major problem in New Zealand. There were 12,776 reported cases of campylobacteriosis in 2007, which accounts for 65.9% of the overall notified diseases. Campylobacteriosis can lead to Guillain-Barré syndrome in some patients, an autoimmune disorder of the peripheral nervous system. Campylobacteriosis is caused by consumption of either Campylobacter jejuni or Campylobacter coli. Campylobacter spp. have been found in commercially raised poultry being infected predominantly by C. jejuni. C. jejuni has been found associated with biofilms of other bacterial species in the watering supplies and plumbing systems of animal husbandry facilities and animalprocessing plants. A biofilm is an assemblage of microbial cells that is associated with a surface and the cells are enclosed in a matrix of polysaccharides, which provides a survival advantage to the bacteria in the film. In this study, the ability to form biofilm was measured in a laboratory assay using microtitre plates. C. jejuni strains in monoculture were shown to attach to the abiotic surface and form biofilms to various degrees, thus potentially enhancing their survivability in the poultry environment. C. jejuni was also shown to have the ability to attach and survive in mixed-microbial populations. Biofilm formation may play a role in the epidemiology of C. jejuni infections. Enterococcus faecalis and Staphylococcus simulans may play a role in the biofilm formation in the poultry environment as both of these microorganisms were able to form, and harbour C. jejuni in their biofilms. Pseudomonas aeruginosa seemed to inhibit biofilm formation and C. jejuni in the mixed-microbial population. Further studies are required to establish control measures against the formation of biofilms containing C. jejuni in poultry processing plants and farms in New Zealand to reduce the reservoir of contamination and thus reduce the incidence of campylobacteriosis.