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  • 1.
    Abrahamsson, Louise
    Linköping University, Department of Thematic Studies, Tema Environmental Change.
    Improving methane production using hydrodynamic cavitation as pre-treatment2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    To develop anaerobic digestion (AD), innovative solutions to increase methane yields in existing AD processes are needed. In particular, the adoption of low energy pre-treatments to enhance biomass biodegradability is needed to provide efficient digestion processes increasing profitability. To obtain these features, hydrodynamic cavitation has been evaluated as an innovative solutions for AD of waste activated sludge (WAS), food waste (FW), macro algae and grass, in comparison with steam explosion (high energy pre-treatment). The effect of these two pre-treatments on the substrates, e.g. particle size distribution, soluble chemical oxygen demand (sCOD), biochemical methane potential (BMP) and biodegradability rate, have been evaluated. After two minutes of hydrodynamic cavitation (8 bar), the mean fine particle size decreased from 489- 1344 nm to 277- 381 nm (≤77% reduction) depending of the biomasses. Similar impacts were observed after ten minutes of steam explosion (210 °C, 30 bar) with a reduction in particle size between 40% and 70% for all the substrates treated.  In terms of BMP value, hydrodynamic cavitation caused significant increment only within the A. nodosum showing a post treatment increment of 44% compared to the untreated value, while similar values were obtained before and after treatment within the other tested substrates. In contrast, steam explosion allowed an increment for all treated samples, A. nodosum (+86%), grass (14%) and S. latissima (4%). However, greater impacts where observed with hydrodynamic cavitation than steam explosion when comparing the kinetic constant K. Overall, hydrodynamic cavitation appeared an efficient pre-treatment for AD capable to compete with the traditional steam explosion in terms om kinetics and providing a more efficient energy balance (+14%) as well as methane yield for A. nodosum.

  • 2.
    Aldén, Anna
    Linköping University, The Department of Physics, Chemistry and Biology.
    Optimization of the Liquefaction Process in Bioethanol Production & Development of Method for Quantification of Nonsolubilized Starch in Mash2008Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    Ethanol production at Lantmännen Agroetanol AB in Norrköping began in December 2000. The objective of this master's thesis is to find and optimize factors affecting the yield of the liquefaction, a part of the upstream process. To measure successfulness of liquefaction it is desired that amount of non-solubilized starch is quantified, and hence a method for determination of non-solubilized starch in mash has to be developed.

    Starch is a carbon reserve in plants. Starch granules are polymers of amylose and amylopectin which are polysaccharides of glucose. When a starch/water solution is heated the starch granules start to absorb water and swell, a process termed gelatinization. The swelling makes the granules susceptible to hydrolysis by enzymes such as alpha-amylase, this is called liquefaction. Eventually the granular structure is broken and the slurry contains solubilized starch which can be saccharified to glucose by glucoamylase. In the bioethanol production process, the milled grain is mixed with water and enzymes. The slurry is heated, gelatinization and liquefaction occurs. Saccharification occurs simultaneously to fermentation. Ethanol is purified from the fermented mash during downstream processing.

    Starch in the form of starch granules cannot be quantified. The adopted principle for determination of non-solubilized starch in liquefied mash is to wash away the solubilized starch, then quantitatively hydrolyze non-solubilized starch to glucose and quantify glucose.

    To find and optimize factors significant for yield of liquefaction multiple factor experiments were conducted where eight factors were studied. pH, temperature in mixtank and temperature in liquefaction tank 1 were the most significant factors. The temperature in liquefaction tank 1 should be kept as is is at 74°C. A small rise in pH should shorten the mean length of dextrins which is preferable. An increase of pH from 5.2 to 5.4 is therefore proposed. The temperature in mixtank should also be increased by a few degrees. The yield of the process should be carefully evaluated during the modifications.

  • 3.
    Almquist, Robert
    Linköping University, Department of Physics, Chemistry and Biology.
    Electrochemical synthesis of electroactive polymers for drugrelease for bio scaffolds.2010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Stem cell based therapy has the potential to treat several severe diseases; Parkinson’s

    disease is one well- known example. Transplantation of stem cell derived cells into

    animal models is unfortunately often associated with tumour formation or- uncontrolled

    growth of the transplanted cells. One strategy to suppress this tumour formation might be

    to induce differentiation of these cells, which in turn would prevent them from dividing.

     

    Neuroblastoma tumors are known to demonstrate the complete transition from an

    undifferentiated state to a completely harmful, differentiated appearance and derived cells

    can be used as a model for cell differentiation and tumor suppression.

     

    In this Master Thesis’s the conducting polymers PEDOT and PPy, that upon formation

    can be doped with biologically active compounds which in- turn can be released in a

    controlled manner through electrical stimulation, were formed together with various

    drugs (e.g. Methotrexate and Mycophenolic Acid), here shown to have effect on

    Neuroblastoma cells. Neuroblastoma- derived cell line SH- SY5Y was used as a model

    system for neuronal differentiation and tumour inhibition. Release profiles of

    neuroblastoma active drugs following electrical stimulation were evaluated and the

    effects from electrochemical processes on simultaneously growing SH- SY5Y cells were

    investigated.

     

    The methods to deposit and release the drugs were based on electropolymerization and

    electrochemically controlled release, respectively. Controlled release of various drugs

    and compounds was monitored using Vis- and UV- spectroscopy and on some occasions

    using HPLC.

     

    The electrochemically controlled release of a biologically inactive compound that can be

    used as a negative control for electrochemical release in future experiments was shown

    and that resulting electrochemical processes have negative effects on neuroblastoma cell

    growth.

  • 4.
    Altgärde, Noomi
    Linköping University, Department of Physics, Chemistry and Biology.
    Local release of lithium from sol-gel coated orthopaedic screws: an in vitro and in vivo study2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

     

    In orthopaedic practice, fractures are usually stabilised with metal screws or rods. This is done in order to keep the fracture parts in place during the rather slow healing process. The healing time can potentially be reduced by local- or systemic treatment with different bone promoting drugs. In later years, lithium, otherwise used to treat bipolar disease, has shown promise to be such a drug.

     

    The aim of this master thesis was to find a way to coat metal bone screws with lithium and to characterise the coating. The coating was to be designed in such a way that it could release lithium to the surrounding bone tissue.

     

    Lithium chloride was incorporated into a titanate sol-gel and attached to silicon wafers and stainless steel screws by dip coating. Wafers were used for initial in vitro studies of how lithium changed coating characteristics. This was studied using ellipsometry, AFM and SEM. Lithium is most probably physisorbed and not incorporated into the network building up the sol-gel. Coating structure is changed as more lithium is incorporated. For large amounts of lithium, the nanoparticles normally formed when curing the sol-gel are inhibited. One effect of this is reduced bioactivity, seen as a reduced ability for calcium phosphate crystals to nucleate on the coating when immersed in simulated body fluid.

    Lithium release was investigated using AAS. Lithium is released from the coating, showing a burst effect. By changing the number of coating layers used, the release profile can be partly altered. The coating was also applied to screws, showing good attachment, and the lithium release profile was similar to the one seen from wafers.

    Finally, a screw model was used in rats to assess the effect of local lithium treatment from screws and systemic lithium treatment on fracture healing. In the model, a screw was inserted in tibia, mimicking a fracture. When the bone around the screw was healed, a pullout test was performed, giving information about the strength of the bone surrounding the screw. No significant difference could be found for either local- or systemic lithium treatment compared to control. However, when evaluating the strength of intact bone in a similar way, a positive effect of systemic lithium treatment could be seen. Therefore, it is still likely that lithium has a positive effect on bone and further studies are needed to fully evaluate its role in fracture healing.

     

  • 5.
    Andersson, Jim
    et al.
    Luleå University of Technology, Sweden.
    Lundgren, Joakim
    Luleå University of Technology, Sweden.
    Malek, Laura
    Lund University, Sweden.
    Hultegren, Christian
    Lund University, Sweden.
    Pettersson, Karin
    Chalmers University of Technology, Gothenburg, Sweden.
    Wetterlund, Elisabeth
    Linköping University, Department of Management and Engineering, Energy Systems. Linköping University, The Institute of Technology.
    System studies on biofuel production via integrated biomass gasification2013Report (Other academic)
    Abstract [en]

    A large number of national and international techno-economic studies on industrially integrated gasifiers for production of biofuels have been published during the recent years. These studies comprise different types of gasifiers (fluidized bed, indirect and entrained flow) integrated in different industries for the production of various types of chemicals and transportation fuels (SNG, FT-products, methanol, DME etc.) The results are often used for techno-economic comparisons between different biorefinery concepts. One relatively common observation is that even if the applied technology and the produced biofuel are the same, the results of the techno-economic studies may differ significantly.

    The main objective of this project has been to perform a comprehensive review of publications regarding industrially integrated biomass gasifiers for motor fuel production. The purposes have been to identify and highlight the main reasons why similar studies differ considerably and to prepare a basis for “fair” techno-economic comparisons. Another objective has been to identify possible lack of industrial integration studies that may be of interest to carry out in a second phase of the project.

    Around 40 national and international reports and articles have been analysed and reviewed. The majority of the studies concern gasifiers installed in chemical pulp and paper mills where black liquor gasification is the dominating technology. District heating systems are also well represented. Only a few studies have been found with mechanical pulp and paper mills, steel industries and the oil refineries as case basis. Other industries have rarely, or not at all, been considered for industrial integration studies. Surprisingly, no studies regarding integration of biomass gasification neither in saw mills nor in wood pellet production industry have been found.

    There are several reasons why the results of the reviewed techno-economic studies vary. Some examples are that different system boundaries have been set and that different technical and economic assumptions have been made, product yields and energy efficiencies may be calculated using different methods etc. For obvious reasons, the studies are not made in the same year, which means that different monetary exchange rates and indices have been applied. It is therefore very difficult, and sometimes even impossible, to compare the technical as well as the economic results from the different studies. When technical evaluations are to be carried out, there is no general method for how to set the system boundaries and no right or wrong way to calculate the system efficiencies as long as the boundaries and methods are transparent and clearly described. This also means that it becomes fruitless to compare efficiencies between different concepts unless the comparison is done on an exactly equal basis.

    However, even on an equal basis, a comparison is not a straight forward process. For example, calculated efficiencies may be based on the marginal supply, which then become very dependent on how the industries exploit their resources before the integration. The resulting efficiencies are therefore very site-dependent. Increasing the system boundaries to include all in- and outgoing energy carriers from the main industry, as well as the integrated gasification plant (i.e. total plant mass and energy balance), would inflict the same site-dependency problem. The resulting system efficiency is therefore a measure of the potential improvement that a specific industry could achieve by integrating a biomass gasification concept.

    When estimating the overall system efficiency of industrial biorefinery concepts that include multiple types of product flows and energy sources, the authors of this report encourage the use of electrical equivalents as a measure of the overall system efficiency. This should be done in order to take the energy quality of different energy carriers into concern.

    In the published economic evaluations, it has been found that there is a large number of studies containing both integration and production cost estimates. However, the number of references for the cost data is rather limited. The majority of these have also been published by the same group of people and use the same or similar background information. The information in these references is based on quotes and estimates, which is good, however none of these are publically available and therefore difficult to value with respect to content and accuracy.

    It has further been found that the variance in the operational costs is quite significant. Something that is particularly true for biomass costs, which have a high variance. This may be explained by natural variations in the quality of biomass used, but also to the different markets studied and the dates when the studies were performed. It may be seen from the specific investment costs that there is a significant spread in the data. It may also be seen that the differences in capital employed and process yields will result in quite large variations in the production cost of the synthetic fuels. On a general note, the studies performed are considering future plants and in some cases assumes technology development. It is therefore relevant to question the use of today’s prices of utilities and feedstock’s. It is believed that it would be more representative to perform some kind of scenario analysis using different parameters resulting in different cost assumptions to better exemplify possible futures.

    Due to the surprising lack of reports and articles regarding integration of biomass gasifiers in sawmills, it would be of great interest to carry out such a study. Also larger scale wood pellet production plants could be of interest as a potential gasification based biorefinery.

  • 6.
    Arkstål, Emil
    Linköping University, Department of Computer and Information Science, Human-Centered systems.
    Interactive Analytics and Visualization for Data Driven Calculation of Individualized COPD Risk2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Chronic obstructive pulmonary disease (COPD) is a high mortality disease, second to stroke and ischemic heart disease. This non-curable disease progressively exacerbates, leading to high personal and societal economic impact, reduced quality of life and often death. General treatment plans for COPD risk mistreating the individuals’ condition. To be effective, the treatment should be individualized following the practices of precision medicine. The aim of this thesis was to develop a data driven algorithm and system with visualization to assess individual COPD risk. With MRI body composition profile measurements, it is possible to accurately assess propensity of a multitude of metabolic conditions, such as coronary heart disease and type 2 diabetes.  The algorithm and system has been developed using Wolfram Language and R within the Wolfram Mathematica framework. The algorithm calculates individualized virtual control groups metabolically similar to the patient’s body composition and spirometric profile. Using UK Biobank data, our tool was used to assess patient COPD propensity using an individual-specific virtual control group with AUROC 0.778 (female) and 0.758 (men). Additionally, the tool was used to identify new body composition profiles related to COPD and associated comorbid conditions.

  • 7.
    Ask, Per
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    EDWALL, G
    Tibbling, Lita
    ESOPHAGEAL PH MEASUREMENTS USING AN ANTIMONY ELECTRODE1980In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 18, no 1Article in journal (Refereed)
  • 8.
    Ask, Per
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Öberg, Åke
    Linköping University, Department of Biomedical Engineering.
    Tibbling, Lita
    ESOPHAGEAL MANOMETRY - DETERMINATION OF BANDWIDTH REQUIREMENTS BY SIGNAL ANALYSIS1980In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 25, no 5Article in journal (Refereed)
  • 9.
    Axelsson, Josefin
    Linköping University, Department of Physics, Chemistry and Biology.
    Separate Hydrolysis and Fermentation of Pretreated Spruce2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Bioethanol from lignocellulose is expected to be the most likely fuel alternative in the near future. SEKAB E-Technology in Örnsköldsvik, Sweden develops the technology of the 2nd generation ethanol production; to produce ethanol from lignocellulosic raw material. The objective of this master’s thesis was to achieve a better knowledge of the potential and limitations of separate hydrolysis and fermentation (SHF) as a process concept for the 2nd generation ethanol production. The effects of enzyme concentration, temperature and pH on the glucose concentration in the enzymatic hydrolysis were investigated for pretreated spruce at 10% DM using a multiple factor design. Enzyme concentration and temperature showed significant effects on the glucose concentration, while pH had no significant effect on the concentration in the tested interval of pH 4.5-5.5. To obtain the maximum glucose concentration (46.4 g/l) for a residence time of 48 h, the optimal settings within the studied parameter window are a temperature of 45.7⁰C and enzyme concentration of 15 FPU/g substrate. However, a higher enzyme concentration would probably further increase the glucose concentration. If enzymatic hydrolysis should be performed for very short residence times, e.g. 6 h, the temperature should be 48.1⁰C to obtain maximum glucose concentration. The efficiency of the enzymes was inhibited when additional glucose was supplied to the slurry prior to enzymatic hydrolysis. It could be concluded that end product inhibition by glucose occurs and results in a distinct decrease in glucose conversion. No clear conclusions could be drawn according to different techniques for slurry and enzymes, i.e. batch and fed-batch, in the enzymatic hydrolysis process. Investigations of the fermentability of the hydrolysate revealed that the fermentation step in SHF is problematic. Inhibition of the yeast decrease the fermentation efficiency and it is therefore difficult to achieve the 4% ethanol limit. Residence time for enzymatic hydrolysis (48 h) and fermentation (24 h) need to be prolonged to achieve a sufficient SHF process. However, short processing times are a key parameter to an economically viable industrial process and to prolong the residence times should therefore not be seen as a desirable alternative. SHF as a process alternative in an industrial bioethanol plant has both potential and limitations. The main advantage is the possibility to separately optimize the process steps, especially to be able to run the enzymatic hydrolysis at an optimal temperature. Although, it is important to include all the process steps in the optimization work. The fermentation difficulties together with the end product inhibition are two limitations of the SHF process that have to be improved before SHF is a preferable alternative in a large scale bioethanol plant. 

  • 10.
    Beijer, Ronja
    Linköping University, Department of Physics, Chemistry and Biology.
    Enzymatic treatement of wastewater sludge in presence of a cation binding agent: improved solubilisation and increased methane production2008Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Stockholm Water is a water and sewage company with Henriksdal as one of two wastewater treatment plants (WWTPs). At Henriksdal wastewater sludge generated in the wastewater treatment process is digested which generate biogas; a mixture of mainly methane and carbon dioxide. If purified to methane content of 96 - 98 % this gas is called biomethane.

    Biogasmax is a project aiming to reduce the use of fossile fuels in Europe by providing that biogas is a good technical, economical and environmental alternative as vehicle fuel. The specific aim for Stockholm Water is to increase the biogas production at the existing plant in Henriksdal. Enzymatic treatment of wastewater sludge is an innovative technique earlier proofed to increase the biogas production from wastewater sludge with up to 60 %. The enzyme activity is in turn proven to significantly increase in the presence of a cation binding agent.

    One aim with this thesis was to investigate if the sludge from Henriksdal wastewater treatment process at all is affected of enzymatic treatment in presence of a cation binding agent since this has shown to have some significance. The chemical oxygen demand (COD) was measured in the liquid phase of sludge after treatment and used as a measurement of treatment effect. Another aim of this thesis was to look into the possibility to increase the methane production from sludge at Henriksdal WWTP. This was investigated through batch laboratory digestion tests.

    The sludge from Henriksdal WWTP was shown to be a good substrate for the enzymes added. COD in the liquid phase was increased with 17 – 32 % depending on the dose of enzymes and sodium citrate added. Digestion of sludge with a total addition of 18.6 mg enzymes per 1 g total solids (TS) and a concentration of 5 mM sodium citrate increased the methane production with almost 18 % compared to untreated sludge. This equals an increase of 18.3 % when converted to represent a totally blended and continuous digestion chamber at Henriksdal WWTP. The increased methane production also results in a sludge reduction out from the digestion chambers. The increased methane production and sludge reduction though does not fulfil the increased costs for the enzymes and sodium citrate applied. These doses must be decreased and the costs for both enzymes and sodium citrate must be reduced for this technique to be economically feasible in a full scale operation.

  • 11.
    Bengtsson, Katarina
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Design of a galvanotaxic track for cells, using polymer electrodes.2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Galvanotaxis is the movement of cells in an applied electric field. The first steps to design a chip for observations of galvanotaxic behavior of cells were done in this work. The chip is a miniaturised system of previous larger galvanotaxis systems and uses materials which are thought to be biocompatible. The system was constructed on microscope slides with a channel in PDMS with adjacent polymer electrodes. The polymer electrodes were made from poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS), glycerol and Silquest A-187. The PEDOT:PSS electrodes were connected with either an evaporated metal electrode of titanium and gold or a gold net. Systems with PEDOT:PSS are neutralised when put in excessive amount of PBS (pH=7.4) for 24 hours. The final system had a channel with dimension length=14 mm, width=0.5 mm and height=0.25 mm. PEDOT:PSS worked as an electrode material and the achieved electric field through the channel was between 55 V/m and 160 V/m with an applied voltage of 1 V. The decrease of the electric field within the first hour was between 10 % and 30%.  Further development of this system could give an easy way to observe galvanotaxic behaviour of cells or an instrument that can distinguish between different cell types.

  • 12.
    Björk, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics . Linköping University, The Institute of Technology.
    Biological Sensing and DNA Templated Electronics Using Conjugated Polymers2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Conjugated polymers have been found useful in a wide range of applications such as solar cells, sensor elements and printed electronics, due to their optical and electronic properties. Functionalization with charged side chains has enabled water solubility, resulting in an enhanced interaction with biomolecules. This thesis focus on the emerging research fields, where these conjugated polyelectrolytes (CPEs) are combined with biomolecules for biological sensing and DNA nanowire assembling.

    CPEs have shown large potential in biomolecular detection where the optical read out is due to the geometrical alternation in the backbone and aggregation state. This thesis focused on transferring the biomolecular detection to a surface of CPEs. The characterization of the CPE layer show that a hydrogel can be formed, and how the layer can undergo geometrical changes upon external stimulus such as pH change. A selective sensor surface can be created by imprinting ssDNA or an antibody in the CPE layer. The discrimination for complementary DNA hybridization and specific antibody interaction can be monitored by surface plasmon resonance or quartz crystal microbalance. We have also taken the step out from the controlled test tube experiments to the complex environment of the cell showing the potential for staining of compartments and structures in live and fixed cell. Depending on the conditions and CPE used, cell nuclei, acidic vesicles and cytoskeleton structure can be visualized. Furthermore, the live staining shows no sign of toxic effect on cultured fibroblasts.

    CPEs can also be a valuable element when assembling electronics in the true nano regime. I have used DNA as building template due to its attractive size features, with a width of around 2 nm and a length scale in the µm regime, and the inbuilt base-paring recognition elements. This thesis shows how DNA can be decorated with CPEs and stretched on surfaces into a model for aligned semiconducting nanowire geometries. Not only making the template structures is of importance, but also how to place them on the correct surface position, i.e. on electrodes. Strategies for positioning DNA nanowires using transfer printing and surface energy patterning methods have therefore been developed in the thesis. The stretched DNA decorated with CPE also offers a way to further study the molecular binding interaction between the two molecules. Single molecular spectroscopy in combination with polarization has given information of the variation of the CPE binding along a DNA chain.

    List of papers
    1. Dynamics of complex formation between biological and luminescent conjugated polyelectrolytes - a surface plasmon resonance study
    Open this publication in new window or tab >>Dynamics of complex formation between biological and luminescent conjugated polyelectrolytes - a surface plasmon resonance study
    Show others...
    2005 (English)In: Biosensors and Bioelectronics, ISSN 0956-5663, Vol. 20, no 9, p. 1764-1771Article in journal (Refereed) Published
    Abstract [en]

    A water-soluble polythiophene, POWT, with zwitterionic peptide like side chains possess good characteristics for biosensor applications. The zwitterionic side chains of the polymer can couple to biomolecules via electrostatic and hydrogen bonding. This creates possibilities to imprint biomolecules to spin-coated polymer films with maintained functionality, and use the resulting matrix as a biosensor. Polymer-biomolecular interaction studies done with surface plasmon resonance (SPR) reveal a well performing sensor matrix with high affinity for DNA hybridizations as well as for protein detection. The responses are distinct and very specific. A directional dependence of antibodies binding to POWT layer has also been observed. The polymer films have also been characterized by optical methods. Emission and absorption measurements in different buffer systems confirm that the polymer matrix can undergo structural and conformational changes on surfaces. The dielectric function in the interval 300–800 nm of POWT is reported, based on variable angle spectroscopic ellipsometry. This modeling reveals that a considerable amount of water is included in the material. The polymer layer possesses the characteristics needed for biochip applications and micro array techniques.

    Keywords
    DNA; Protein; SPR; Sensor; Conjugated polymer; Ellipsometry
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-12725 (URN)10.1016/j.bios.2004.07.001 (DOI)
    Available from: 2007-12-07 Created: 2007-12-07 Last updated: 2014-04-08
    2. Hydrogels from a water-soluble Zwitterionic polythiophene: dynamics under pH change and biomolecular interactions observed using quartz crystal microbalance with dissipation monitoring
    Open this publication in new window or tab >>Hydrogels from a water-soluble Zwitterionic polythiophene: dynamics under pH change and biomolecular interactions observed using quartz crystal microbalance with dissipation monitoring
    2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 16, p. 7292-7298Article in journal (Refereed) Published
    Abstract [en]

    The water-soluble zwitterionic polythiophene, poly(3-((S)-5-amino-5- carboxyl-3-oxapentyl)-2,5-thiophene) hydrochloride (POWT), is a conjugated polyelectrolyte (CPE) with properties well suited for biochip applications. CPEs readily form hydrogels when exposed to water-based buffer solutions or biomolecule solutions. In this work, we used in situ quartz crystal microbalance with dissipation (QCM-D) monitoring to collect information on the interaction between POWT films exposed to buffers with different pH and POWT/DNA chains. Our data show that POWT swells significantly when exposed to low-pH buffers, such as pH 4 acetate, this is seen as an increase in thickness and decrease in viscosity obtained via a Voight-based modeling of combined f and D QCM-D measurements. The magnitude of thickness and viscosity change upon changing from a pH 10 carbonate buffer to pH 4 acetate is 100% increase in thickness and 50% decrease in viscosity. The response of the hydrogel under pH change is well correlated with fluorescence data from POWT films on glass. The state of the hydrogel is important during interaction with biomolecules; illustrated by the observation that a swollen CPE hydrogel adsorbs a higher amount of DNA than a compacted one. In agreement with previous results, the QCM-D data confirmed that the POWT/DNA hydrogel sense complementary DNA specifically and with negligible binding of noncomplementary DNA. These results are important for efficient constructions of biochips in water environments using this class of materials.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-12726 (URN)10.1021/la050479e (DOI)
    Available from: 2007-12-07 Created: 2007-12-07 Last updated: 2017-12-14
    3. Conjugated polythiophene probes target lysosome-related acidic vacuoles in cultured primary cells
    Open this publication in new window or tab >>Conjugated polythiophene probes target lysosome-related acidic vacuoles in cultured primary cells
    Show others...
    2007 (English)In: Molecular and Cellular Probes, ISSN 0890-8508, Vol. 21, no 5-6, p. 329-337Article in journal (Refereed) Published
    Abstract [en]

    Conformation-sensitive optical probes for studying biological processes and structures are of great interest. The present work shows for the first time that conjugated polyelectrolyte (CPE) probes can be used for specific targeting of chromatin, nuclear and cytoplasmatic vesicles, and cytoskeletal components in a complex system of cultured cells. One of the probes could also be used for vital staining of live cells. When bound to different entities, the polythiophene derivative probes emitted light with different colors due to the unique spectral properties of these conformation sensitive probes. The physical pre-requisites for binding could also be exploited for characterization of the target. Unexpectedly, lysosome-related acidic vacuoles were targeted in cultured primary cells by both anionic, cationic, and zwitter-ionic polythiophene derivatives. Pre-treatment with Bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, caused redistribution of the staining. The targeting of lysosome-related acidic vesicles could not be demonstrated in transformed cells (melanoma, neuroblastoma, and prostate cancer cell lines), indicating a difference in the localization, structure, accessibility, or quantity of the target in cultured normal cells as compared with the malignant cell lines. The chemical nature of the conjugated polyelectrolyte complex in the cytoplasmatic vacuoles remains elusive.

    Keywords
    Conjugated polyelectrolyte; Polythiophene; Fibroblast; Lysosome; Cancer
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12727 (URN)10.1016/j.mcp.2007.04.005 (DOI)
    Available from: 2007-12-07 Created: 2007-12-07 Last updated: 2014-04-08
    4. Soft lithographic printing of patterns of stretched DNA and DNA/electronic polymer wires by surface-energy modification and transfer
    Open this publication in new window or tab >>Soft lithographic printing of patterns of stretched DNA and DNA/electronic polymer wires by surface-energy modification and transfer
    2006 (English)In: Small, ISSN 1613-6810, Vol. 2, no 8-9, p. 1068-1074Article in journal (Refereed) Published
    Abstract [en]

    Aligned and stretched λ DNA is directed to specific locations on solid substrates. Surface-energy modification of glass substrates by using patterned polydimethylsiloxane (PDMS) stamps is used to direct DNA onto the surface-energy-modified micrometer-scale pattern through molecular combing. As an alternative, patterned and nonpatterned PDMS stamps modified with polymethylmethacrylate (PMMA) are utilized to direct the stretched DNA to the desired location and the results are compared. The DNA is elongated through molecular combing on the stamp and transfer printed onto the surfaces. PMMA-modified stamps show a more defined length of the stretched DNA, as compared to bare PDMS stamps. A combination of these two methods is also demonstrated. As an application example, transfer printing of DNA decorated with a semiconducting conjugated polyelectrolyte is shown. The resulting patterned localization of stretched DNA can be utilized for functional nanodevice structures, as well as for biological applications.

    Keywords
    conjugation, DNA, lithography, patterning, polymers
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-12728 (URN)10.1002/smll.200600126 (DOI)
    Available from: 2007-12-07 Created: 2007-12-07
    5. Single molecular imaging and spectroscopy of conjugated polyelectrolytes decorated on stretched aligned DNA
    Open this publication in new window or tab >>Single molecular imaging and spectroscopy of conjugated polyelectrolytes decorated on stretched aligned DNA
    2005 (English)In: Nano Letters, ISSN 1530-6984, Vol. 5, no 10, p. 1948-1953Article in journal (Refereed) Published
    Abstract [en]

    DNA is the prototype template for building nanoelectronic devices by self-assembly. The electronic functions are made possible by coordinating electronic polymer chains to DNA. This paper demonstrates two methods for fabrication of aligned and ordered DNA nanowires complexed with conjugated polyelectrolytes (CPEs). The complex can be formed either in solution prior to stretching or after stretching of the bare DNA on a surface. Molecular combing was used to stretch the complexes on surface energy patterned surfaces, and PMMA for the bare DNA. Single molecular spectroscopy, in fluorescence, and microscopy, in atomic force microscopy, give evidence for coordination of the short CPE chains to the aligned DNA.

    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-12729 (URN)10.1021/nl051328z (DOI)
    Available from: 2007-12-07 Created: 2007-12-07 Last updated: 2009-02-13
    6. Structural studies of a well defined conjugated polyelectrolyte and its interaction with DNA
    Open this publication in new window or tab >>Structural studies of a well defined conjugated polyelectrolyte and its interaction with DNA
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-12730 (URN)
    Available from: 2007-12-07 Created: 2007-12-07 Last updated: 2010-01-13
  • 13.
    Björn (Fredriksson), Annika
    et al.
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Shakeri Yekta, Sepehr
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Ziels, Ryan
    Linköping University, Biogas Research Center. Department of Civil Engineering, University of British Columbia, Columbia, Canada.
    Karl, Gustafsson
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Svensson, Bo H
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Anna, Karlsson
    Linköping University, Biogas Research Center. Scandinavian Biogas Fuels AB, Stockholm, Sweden.
    Feasibility of OFMSW co-digestion with sewage sludge for increasing biogas production at wastewater treatment plants2017In: Euro-Mediterranean Journal for Environmental Integration, ISSN 2365-6433, Vol. 2, no 21Article in journal (Refereed)
    Abstract [en]

    Sweden has the ambition to increase its annual biogas production from the current level of 1.9 to 15 TWh by 2030. The unused capacity of existing anaerobic digesters at wastewater treatment plants is among the options to accomplish this goal. This study investigated the feasibility of utilizing the organic fraction of municipal solid waste (OFMSW) as a co-substrate, with primary and waste-activated sewage sludge (PWASS) for production of biogas, corresponding to 3:1 ratio on volatile solid (VS) basis. The results demonstrated that co-digestion of OFMSW with PWASS at an organic loading rate of 5 gVS l−1 day−1 has the potential to increase the biogas production approximately four times. The daily biogas production increased from 1.0 ± 0.1 to 3.8 ± 0.3 l biogasl−1 day−1, corresponding to a specific methane production of 420 ± 30 Nml methane gVS−1 during the laboratory experiment. Co-digestion of OFMSW with PWASS showed a 50:50 distribution of hydrogenotrophic and aceticlastic methanogens in the digester and enhanced the turnover kinetics of intermediate products (acetate, propionate, and oleate). Practical limitations potentially include the need for sludge dewatering to maintain a sufficient hydraulic retention time (17 days in this study), as well as additional energy consumption for mixing due to an increased sludge apparent viscosity (from 1.8 ± 0.1 to 45 ± 4.8 mPa*s in this study) at elevated OFMSW-loading rates.

  • 14.
    Blissing, Annica
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Thiopurine S-methyltransferase - characterization of variants and ligand binding2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Thiopurine S-methyltransferase (TPMT) belongs to the Class I S-adenosylmethionine-dependent methyltransferase (SAM-MT) super family of structurally related proteins. Common to the members of this large protein family is the catalysis of methylation reactions using S-adenosylmethionine (SAM) as a methyl group donor, although SAM-MTs act on a wide range of different substrates and carry out numerous biologically important functions. While the natural function of TPMT is unknown, this enzyme is involved in the metabolism of thiopurines, a class of pharmaceutical substances administered in treatment of immune-related disorders. Specifically, methylation by TPMT inactivates thiopurines and their metabolic intermediates, which reduces the efficacy of clinical treatment and increases the risk of adverse side effects. To further complicate matters, TPMT is a polymorphic enzyme with over 40 naturally occurring variants known to date, most of which exhibit lowered methylation activity towards thiopurines. Consequently, there are individual variations in TPMTmediated thiopurine inactivation, and the administered dose has to be adjusted prior to clinical treatment to avoid harmful side effects.

    Although the clinical relevance of TPMT is well established, few studies have investigated the molecular causes of the reduced methylation activity of variant proteins. In this thesis, the results of biophysical characterization of two variant proteins, TPMT*6 (Y180F) and TPMT*8 (R215H), are presented. While the properties of TPMT*8 were indistinguishable from those of the wild-type protein, TPMT*6 was found to be somewhat destabilized. Interestingly, the TPMT*6 amino acid substitution did not affect the functionality or folding pattern of the variant protein. Therefore, the decreased in vivo functionality reported for TPMT*6 is probably caused by increased proteolytic degradation in response to the reduced stability of this protein variant, rather than loss of function.

    Also presented herein are novel methodological approaches for studies of TPMT and its variants. Firstly, the advantages of using 8-anilinonaphthalene-1-sulfonic acid (ANS) to probe TPMT tertiary structure and active site integrity are presented. ANS binds exclusively to the native state of TPMT with high affinity (KD ~ 0.2 μm) and a 1:1 ratio. The stability of TPMT was dramatically increased by binding of ANS, which was shown to co-localize with the structurally similar adenine moiety of the cofactor SAM. Secondly, an enzyme activity assay based on isothermal titration calorimetry (ITC) is presented. Using this approach, the kinetics of 6-MP and 6-TG methylation by TPMT has been characterized.

  • 15.
    Boons, Frank
    et al.
    University of Manchester, UK.
    Spekkink, Wouter
    Delft University of Technology, The Netherlands.
    Isenmann, Ralf
    Munich University of Applied Sciences, Germany.
    Baas, Leenard
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    Eklund, Mats
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    Brullot, Sabrina
    Institut Charles Delaunay, France.
    Deutz, Pauline
    University of Hull, UK.
    Gibbs, David
    University of Hull, UK.
    Massard, Guillaume
    Université de Lausanne, Switzerland.
    Romero Arozamena, Elena
    University of Cantabria, Spain.
    Ruiz Puente, Carmen
    University of Cantabria, Spain.
    Verguts, Veerle
    Flemish Land Agency, Belgium.
    Davis, Chris
    Delft University of Technology, The Netherlands.
    Korevaar, Gijsbert
    Delft University of Technology, The Netherlands.
    Costa, Inês
    3Drivers.
    Baumann, Henrikke
    Chalmers tekniska högskola, Sweden.
    Comparing industrial symbiosis in Europe: towards a conceptual framework and research methodology2015In: International perspectives on industrial ecology / [ed] Pauline Deutz, Donald I Lyons, Jun Bi, Cheltenham: Edward Elgar Publishing, 2015, p. 69-88Chapter in book (Other academic)
    Abstract [en]

    Industrial symbiosis (IS) continues to raise the interest of researchers and practitioners alike. Individual and haphazard attempts to increase linkages among co-located firms have been complemented by concerted efforts to stimulate the development of industrial regions with intensified resource exchanges that reduce environmental impact. Additionally, there are examples of both spontaneous and facilitated linkages between two or more firms involving flows of materials/energy waste. A striking feature of IS activities is that they are found across diverse social contexts and vary considerably in form (Lombardi et al., 2012); there are substantial differences in the ways in which IS manifests itself. Equally diverse are the activities of policy makers to stimulate such linkages. Such diversity can already be found within Europe, as became apparent in a first meeting among some of the present authors in 2009 (Isenmann and Chernykh, 2009). Researchers present there decided to create a network of European researchers on IS, with the explicit aim to develop a comparative analysis. We can thus provide insight to the relationship between the style of IS and its context and thereby the potential for policy makers in different contexts to learn from each other. Policy learning can be a tempting route to IS, but is fraught with difficulties if the influence of context is not appreciated (e.g., Wang et al., Chapter 6, this volume).

  • 16.
    Borg, Ann-Louise
    Linköping University, Department of Physics, Chemistry and Biology.
    Investigation of a Method for Determination of Anticomplementary Activity (ACA) in Octagam2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This Master Thesis was conducted at Octapharma AB in Stockholm.

    Anticomplementary activity (ACA) is a measure of the product’s abilities to activate the complement system. IgG aggregates are mainly responsible for this activation. Two different performances of a method for determination of ACA in Octagam® are available. The two performances are based on the reference method for test of ACA in immunoglobulins in the European Pharmacopoeia Commission Guideline 6.0 (chapter 2.6.17). The method is carried out either in test tubes or on microtiter plates. The test tube method can be performed either in a manual manner or modified, being more automated. The latter performance has been applied in this study. The plate method is more automated than both of the tube methods. The plate method and the manual tube method have earlier seemed to result in different outcomes, which was the basis for this thesis.

    The plate method and the modified test tube method have been compared and robustness parameters have been studied in order to see which factors influence on the end result. The adequacy of using Human Biological Reference Preparation (human BRP) as a control for the ACA method in general has also been investigated. Samples of the product are outside the scope of this thesis and have not been investigated.

    According to this study, the plate method and the modified tube method are not comparable with regard to complement titration results and to ACA of the BRP control. A higher precision is gained with the plate method. This in combination with the higher degree of automation makes the plate method advantageous in several aspects. When it comes to the robustness of the ACA method in general, the sheep red blood cells (SRBC) used are critical. Haemolysin dilution and complement activity seem to be critical as well.

    Human BRP is, according to this study more adequate as a reference for the plate method than for the tube method. An In house control is believed to be more representative to the ACA method in general as it is of the same nature as the samples analysed, in contrast to the human BRP.

  • 17.
    Cardell, Lina
    Linköping University, The Tema Institute, Department of Water and Environmental Studies.
    Anaerobic digestion of pre-treated biological sludge from pulp and paper industry using heat, alkali and electroporation2010Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The biological sludge formed in the pulp and paper wastewater treatment constitutes a costlyproblem to dispose off due to poor dewaterability. It is often incinerated or used as soilconditioner improvement. By using anaerobic digestion of the biological sludge, thedewaterability can be increased. Thanks to the formation of biogas, the sludge volume isdecreased and energy can be recovered as methane. By pre-treating the sludge, the biogasproduction can be increased, making the anaerobic digestion more economically feasible.

    Eleven samples of biological sludges from six Swedish pulp and paper mills, chosen torepresent different types and sizes of mills available in Sweden, were pre-treated with alkali(NaOH, pH12), heat (80˚C, 1 hr) and electroporation (2000 pulses, 10 kV/cm). Initialmethane production rate and methane potential of all sludges and pre-treatments weredetermined using batch experiment. A combination of two sludges (from the same mill) pretreatedwith alkali and heat was further investigated in a semi-continuous digester experiment.

    The batch experiments showed that alkali pre-treatment had the greatest positive effect onmethane production. Heat treatment performed second best, whereas electroporation had no orlittle effect. Overall, pre-treatments increased the initial methane production rate, but withinsignificant effects on the methane potential. Heat pre-treatment showed no difference inbiogas production compared to the control in the semi-continuous digester experiment. Alkalitreatment was shown to inhibit biogas production and cause high accumulation of acetate. Itcould not be concluded whether it was an effect from hydroxide or sodium ion addition.Further analysis of the NaOH impact on floc structure, toxicity and bioavailability issuggested to determine the suitability of alkali-treated sludge for anaerobic digestion.

  • 18.
    Cardemil, Carina
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
    Effects of antiresorptive agents on inflammation and bone regeneration in different osseous sites - experimental and clinical studies2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The biological mechanisms involved in bone regeneration in osteoporotic bone and the effect of antiresorptive drugs in relation to surgically inserted biomaterials are not fully understood. Improved osseointegration of titanium implants but also adverse effects of antiresorptive therapies, such as osteonecrotic jaw have been described in the literature. The aims of this research project were, firstly, to investigate and to understand the biological events determining bone regeneration and implant integration, after administration of antiresorptive agents; secondly, to determine the cellular and molecular patterns of bone regeneration at implants and synthetic bone substitutes under osteoporotic conditions and, thirdly, to determine how different skeletal sites are affected. The present research included a study of jawbone morphology and gene expression in patients treated with systemic bisphosphonates. When compared to controls, higher gene expression levels of IL-1β was observed in bisphosphonate treated patients with osteonecrosis while bisphosphonate treated patients without necrosis showed lower expression levels of caspase 8, an apoptosis marker involved in the immune response. In ovariectomised rats, zoledronic acid resulted in site-specific differences in the rate of osseointegration and also of gene expression involved in bone healing and regeneration. Strontium-doped calcium phosphate inserted in the rat femur induced lower expression of osteoclastic markers compared to hydroxyapatite and higher bone formation in the periphery of the defects. Whereas major structural changes were demonstrated in the long bones of the ovariectomised rat, less structural alterations were shown in the mandible. However, ovariectomy resulted in lower expression of genes coding for bone formation and angiogenesis in the mandible. In conclusion, the present study shows that the mandible is differently affected by experimentally induced estrogen deficiency than the long bones. Bisphosphonates, administered systemically to estrogen deficient animals, impair osseointegration in the mandible, at least partly related to a downregulation of genes important for the osteogenic process. These observations may have implications for understanding the mechanisms involved in the deranged bone healing observed in the jawbone of bisphosphonate treated patients.

    List of papers
    1. The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.
    Open this publication in new window or tab >>The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.
    Show others...
    2013 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 34, no 5, p. 1546-1561Article in journal (Refereed) Published
    Abstract [en]

    Bisphosphonates reverse the negative effects of ovariectomy on bone, but they have also been associated with adverse processes in human jawbone. The molecular events determining bone regeneration and implant integration in osteoporotic conditions, with and without bisphosphonate treatment, are unclear. In this study, ovariectomised rats, to which a single dose of saline (NaCl) or zoledronic acid (Zol) was administered, received titanium alloy implants in their tibiae and mandibles. An enzyme-linked immunosorbent assay, gene expression analysis and histomorphometry were performed. The results show that ovariectomy, per se, upregulated the expression of genes denoting bone formation in the tibia, bone remodelling in the mandible and apoptosis in the tibia and mandible. Zoledronic acid administration resulted in lower levels of a remodelling marker in serum and downregulated gene expression for inflammation, bone formation, angiogenesis and apoptosis, mainly in the mandible, after 28 d of healing. Histomorphometry revealed improved bone-to-implant contact in the tibia, while the opposite was observed in the mandible. The present data show that a systemic single dose of zoledronic acid, in ovariectomised animals, results in site-specific differences in the regulation of genes involved in bone healing and regeneration in association with implant installation. These events occur in parallel with site-specific differences in the rate of osseointegration, indicating diverse tissue responses in the tibia and mandible after zoledronic acid treatment. The zoledronic acid effect on gene expression, during the late phase of healing in the mandible, suggests negative effects by the anti-resorptive agent on osseointegration at that particular site.

    National Category
    Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-135755 (URN)10.1016/j.biomaterials.2012.11.003 (DOI)23182921 (PubMedID)
    Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2018-01-13
    2. Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats
    Open this publication in new window or tab >>Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats
    Show others...
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84932Article in journal (Refereed) Published
    Abstract [en]

    The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.

    National Category
    Biomaterials Science Medical Materials Medical Biotechnology Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-136113 (URN)10.1371/journal.pone.0084932 (DOI)24376855 (PubMedID)
    Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2018-01-13Bibliographically approved
  • 19.
    Cardemil, Carina
    et al.
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden .
    Elgali, Ibrahim
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Xia, Wei
    Applied Materials Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Emanuelsson, Lena
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Norlindh, Birgitta
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Omar, Omar
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Thomsen, Peter
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden .
    Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84932Article in journal (Refereed)
    Abstract [en]

    The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.

  • 20.
    Cecilia, Bill
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Improving anti-drug antibody assay performance in Gyrolab for therapeutic recombinant antibody Infliximab2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Monoclonal antibodies can be used as targeting therapies for several diseases. One major concern when using these therapies is anti-drug antibodies which may hamper the drugs efficiency. Gyrolab is an automated platform which can be used to develop bridging immunoassays where the anti-drug antibodies affinity towards the monoclonal antibody is utilized. Anti-drug antibody immunoassay development on Gyrolab is limited mainly by three factors which may inappropriately affect signal intensity levels. In this project different variants of bridging immunoassays based on drug Fab fragments have been developed for monoclonal antibody Infliximab, with the purpose to illustrate the effects of these three factors.

    Findings indicate that an assay based completely on drug Fab fragments is more sensitive compared to an assay based on intact drug since less affected by unspecific interactions between drug reagents and complex formations. Surprisingly findings also indicate that an assay based completely on drug Fab fragments is affected by human anti-hinge antibodies which decrease assay sensitivity. The most optimal assay variant is based on the combination between intact capture drug and Fab fragment as detection. This variant is insensitive to false positive reactions caused by Rheumatoid factor and human anti-hinge antibodies, less prone to form unspecific interactions between drug reagents and complex formations in the presence of anti-drug antibodies. The optimal assay variant also demonstrates best drug tolerance in combination with acid dissociation.

  • 21.
    Choong, Ferdinand X.
    et al.
    Karolinska Institute, Sweden.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Steiner, Svava E.
    Karolinska Institute, Sweden.
    Melican, Keira
    Karolinska Institute, Sweden.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Edlund, Ulrica
    KTH Royal Institute Technology, Sweden.
    Richter-Dahlfors, Agneta
    Karolinska Institute, Sweden.
    Nondestructive, real-time determination and visualization of cellulose, hemicellulose and lignin by luminescent oligothiophenes2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35578Article in journal (Refereed)
    Abstract [en]

    Enabling technologies for efficient use of the bio-based feedstock are crucial to the replacement of oil-based products. We investigated the feasibility of luminescent conjugated oligothiophenes (LCOs) for non-destructive, rapid detection and quality assessment of lignocellulosic components in complex biomass matrices. A cationic pentameric oligothiophene denoted p-HTEA (pentamer hydrogen thiophene ethyl amine) showed unique binding affinities to cellulose, lignin, hemicelluloses, and cellulose nanofibrils in crystal, liquid and paper form. We exploited this finding using spectrofluorometric methods and fluorescence confocal laser scanning microscopy, for sensitive, simultaneous determination of the structural and compositional complexities of native lignocellulosic biomass. With exceptional photostability, p-HTEA is also demonstrated as a dynamic sensor for real-time monitoring of enzymatic cellulose degradation in cellulolysis. These results demonstrate the use of p-HTEA as a non-destructive tool for the determination of cellulose, hemicellulose and lignin in complex biomass matrices, thereby aiding in the optimization of biomass-converting technologies.

  • 22.
    Christoffersson, Jonas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Distribution of Sca-1+ cardiac progenitor cells in the healthy and the post-MI heart2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The myocardial infarction (MI) is one of the leading causes of death in the world today. Accumulated atherosclerotic plaque occluding cardiac blood vessels results in a lack of oxygen supply to parts of the heart, and consequentially the death cardiomyocytes. The damaged area is replaced by scar tissue because of the heart’s insufficient regenerative capability, and the contraction property of the post-MI heart is therefore compromised. The recent findings of an endogenous cardiac progenitor cell (CPC) population gives hope for the establishment of new methods for medical treatments of the post-MI heart. Compared to other stem/progenitor cell sources, the CPCs are committed to a cardiac fate which places them in the forefront of interesting cell sources for regenerative treatments. In this thesis, the distribution of stem cell antigen 1 (Sca-1) positive CPCs in the healthy mouse myocardium, as well as the healthy and post-MI rat left ventricle was determined and compared to the total amount of nuclei. An immunohistochemistry protocol for the detection of Sca-1+ cells was established, and the number of Sca-1+ cells and the total number of nuclei in the different mouse and rat tissue samples were counted using laser scanning cytometry (LSC). The results could conclude a significantly higher distribution of Sca-1+ cells in the mouse atrium compared to the mouse ventricle, and a significantly higher distribution of Sca-1+ cells in the 8 days post-MI rat left ventricle compared to the healthy rat left ventricle. Furthermore, a heterogeneous distribution within the 8 days post-MI rat left ventricle was observed.

  • 23.
    Danielsson, Per-Erik
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Implementations of the Convolution Operation1982Report (Other academic)
    Abstract [en]

    The first part of this article surveys a large number of implementations of the convolution operation (which is also known as the sum-of-products, the inner product) based on a systematic exploration of index permutations. First we assume a limited amount of parallelism in the form of an adder. Next, multipliers and RAM:s are utilized. The so called distributed arithmetic follows naturally from this approach.

    The second part brings in the concept of pipelining on the bitlevel to obtain high throughput convolvers adapted for VLSI-design (systolic arrays). The serial/parallel multiplier is analyzed in a way that unravels a vast amount new variations. Even more interesting, all these new variations can be carried over to serial/parallel convolvers. These novel devices can be implemented as linear structures of identical cells where the multipliers are embedded at equidistant intervals.

  • 24.
    Djahedi, Cyrus
    Linköping University, Department of Physics, Chemistry and Biology.
    Design and application of software sensors for monitoring of fed-batch cultivations containing recombinant Escherichia coli2010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Bioprocesses are industrial processes that use living cells to produce desired products. These processes are complex and require advanced monitoring and control in order to reach their highest potential. Software sensors are a potent tool for real time monitoring and control of bioprocesses. In this project, three novel software sensors were designed and tested in three fed-batch cultivations containing recombinant Escherichia coli producing green fluorescence protein (GFP). Special attention was given to the sensors for reacting to any stress triggered when production of the recombinant protein was initiated by an inducer molecule.

     

    The sensors calculated the oxygen consumption per substrate, carbon emission per substrate and the sum of the specific growth rates of various acids. Their mathematical algorithms were derived from already existing software sensors and programmed on to computer software designed for monitoring and control.

     

    The results showed that all three sensors gave stable signals as expected. Unfortunately they did not provide any useful information regarding the recombinant protein expression in this particular study. Complications such as measurement errors and incorrect system configurations also created difficulties. It is clear however, that the sensors work well and should be highly considered for further studies.

  • 25.
    Eiderbrant, Kristina
    Linköping University, Department of Clinical and Experimental Medicine.
    Development of quantitative PCR methods for diagnosis of bacterial vaginosis and vaginal yeast infection2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Vaginitis is a vaginal infection which affects many women all over the world. The disorder is characterized by an infection of the vaginal area which can cause problems like abnormal vaginal discharge, itching and redness.

    The two most common causes of vaginitis are bacterial vaginosis and Candida vaginitis. The prevalence of bacterial vaginosis in Sweden is around 10-20 % and approximately 75 % of all women will once in their lifetime suffer from vaginal yeast infection.

    The clinical symptoms of vaginal infections are not specific and the diagnosis methods of bacterial vaginosis and Candida vaginitis are subjective and depended on the acuity of the clinician. Due to the lack of standardized and objective diagnostic tools, misdiagnosis and consequently incorrect treatment may occur.

    As vaginal infections and symptoms impact greatly of women´s quality of life and vaginitis have been associated with serious public health consequences, it is essential to diagnose and treat the conditions correctly. Hence, there is a great need of better methods of diagnosing these conditions.

    The aim of this master thesis was to develop quantitative species-specific real-time PCR assays to use in diagnosing the two most common causes of vaginitis i.e. bacterial vaginosis and Candida vaginitis.

    Potential markers for bacterial vaginosis (Atopobium vaginae, BVAB2, Gardnerella vaginalis, Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus iners, Megasphaera type 1, Megasphaera type 2, Mobiluncus curtisii, Mobiluncus mulieris and Leptotrichia/Sneathia species) and Candida vaginitis (Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis) were chosen. Primers and probes were designed and tested on reference strains and vaginal samples. Single- and multiplex PCR reactions were successfully optimized with the designed oligonucleotides. Furthermore, standard curves with excellent linearity were created and covered more than five orders of magnitude. These developed quantitative species-specific real-time PCR assays will, in a prospective medical validation, quantify 300 vaginal samples from women visiting the RFSU Clinic in Stockholm.

  • 26.
    Einarsson, Ellen
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology.
    Evaluation of 5´- and 3´-UTR Translation Enhancing Sequences to Improve Translation of Proteins in CHO Cells2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The purpose of this project was to identify and evaluate nucleotide sequences enhancing translation of proteins in Chinese hamster ovary (CHO) cells. Candidate sequences were placed in the 5´-untranslated region (UTR) or 3´ UTR respectively and evaluated in a CHO-based expression system with a fluorescent Fc-fusion protein as a model protein.Five plasmid vectors were constructed, two of which designed to have a randomized nucleotide library in their 5´ and 3´ UTR respectively, and three of which designed to hold varying repeats of a known enhancing translation (ET) sequence in their 5´ or 3´ UTR. The plasmid constructs were transfected into CHO cells and the protein expression was analyzed both by fluorescence intensity in single cells using flow cytometry and in bulk by monoclonal antibody titer analysis based on Protein A affinity.The main result is that both flow cytometry and titer analysis indicate that insertion of five repeats of the ET in the 5´UTR has a negative effect on protein expression as compared to the control which had no ET repeats. Results related to the insertion of three ETs in the 5´ UTR were ambiguous. The titer analysis indicated that it had a negative effect on the protein expression compared to the control which had no ET repeats, whereas the flow cytometry results suggest that the effect is negligible. Transfection of library plasmids was unsuccessful; hence no library expression analysis results were achieved. Due to the time constraints of the project, the reason for the unsuccessful transfection of library plasmids was not investigated, but the LTX transfection method is stated as a highly plausible cause.Based on the outcome of this study, two recommendations for future work are suggested. The first one is to continue the focus on UTR sequences in terms of library screening, and to improve the method of transfecting library plasmid constructs into CHO cells using lipofection. The second suggestion for further studies is to test different UTR sequence lengths without involving potential ETs, to rule out the effect and positions of the ETs and investigate the expressional effect of UTR length solely.

  • 27.
    Ekstrand, Eva-Maria
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Anaerobic digestion in the kraft pulp and paper industry: Challenges and possibilities for implementation2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pulp and paper industry is a large producer of wastewater and sludge, putting high pressure on waste treatment. In addition, more rigorous environmental legislation for pollution control and demands to increase the use of renewable energy have put further pressure on the pulp and paper industry’s waste treatment, where anaerobic digestion (AD) and the production of methane could pose a solution. Kraft pulping makes up 80% of the world production of virgin wood pulp, thus, the wastewaters from this sector represent a large unused potential for methane production.

    There are three main types of substrates available for AD at pulp and paper mills, the wastewaters, the primary sludge/fibre sludge, and the waste activated sludge. AD treatment of these streams has been associated with several challenges, such as the presence of inhibiting compounds or low degradability during AD. The aim of this thesis was to experimentally address these challenges and potentials, focusing on wastes from kraft mills.

    Methane potential batch tests showed that many wastewater streams still posed challenges to AD, but the alkaline elemental chlorine-free bleaching stream and the condensate effluents had good methane potentials. Further, the methane potential of kraft mill fibre sludge was high, and co-digestion of kraft mill fibre sludge and waste activated sludge was feasible in stirred tank reactors with sludge recirculation. By increasing the organic loading in a pilot-scale activated sludge facility and thereby lowering the sludge age, the degradability of the waste activated sludge was improved. The higher wastewater treatment capacity achieved by this method provides an opportunity for the mills to increase their pulp and paper production. Further, by dewatering the digestate after AD and returning the liquid to the activated sludge treatment, costs for nutrient supplementation can be reduced.

    In conclusion, the thesis shows that AD of wastes from the kraft pulp and paper industry was feasible and carried many benefits regarding the generation of methane as a renewable energy carrier, improved wastewater treatment and reduced costs. Different strategies on how AD may be implemented in the kraft pulp and paper industry were formulated and discussed.

    List of papers
    1. Methane potentials of the Swedish pulp and paper industry - A screening of wastewater effluents
    Open this publication in new window or tab >>Methane potentials of the Swedish pulp and paper industry - A screening of wastewater effluents
    Show others...
    2013 (English)In: Applied Energy, ISSN 0306-2619, E-ISSN 1872-9118, Vol. 112, p. 507-517Article in journal (Refereed) Published
    Abstract [en]

    With the final aim of reducing the energy consumption and increase the methane production at Swedish pulp and paper mills, the methane potential of 62 wastewater effluents from 10 processes at seven pulp and/or paper mills (A-G) was determined in anaerobic batch digestion assays. This mapping is a first step towards an energy efficient and more sustainable utilization of the effluents by anaerobic digestion, and will be followed up by tests in lab-scale and pilot-scale reactors. Five of the mills produce kraft pulp (KP), one thermo-mechanical pulp (TMP), two chemical thermo-mechanical pulp (CTMP) and two neutral sulfite semi-chemical (NSSC) pulp. Both elementary and total chlorine free (ECF and TCF, respectively) bleaching processes were included. The effluents included material from wood rooms, cooking and oxygen delignification, bleaching (often both acid- and alkali effluents), drying and paper/board machinery as well as total effluents before and after sedimentation. The results from the screening showed a large variation in methane yields (percent of theoretical methane potential assuming 940 NmL CH4 per g TOC) among the effluents. For the KP-mills, methane yields above 50% were obtained for the cooking effluents from mills D and F, paper machine wastewater from mill D, condensate streams from mills B, E and F and the composite pre-sedimentation effluent from mill D. The acidic ECF-effluents were shown to be the most toxic to the AD-flora and also seemed to have a negative effect on the yields of composite effluents downstream while three of the alkaline ECF-bleaching effluents gave positive methane yields. ECF bleaching streams gave higher methane yields when hardwood was processed. All TCF-bleaching effluents at the KP mills gave similar degradation patterns with final yields of 10-15% of the theoretical methane potential for four of the five effluents. The composite effluents from the two NSSC-processes gave methane yields of 60% of the theoretical potential. The TMP mill (A) gave the best average yield with all six effluents ranging 40-65% of the theoretical potential. The three samples from the CTMP process at mill B showed potentials around 40% while three of the six effluents at mill G (CTMP) yielded 45-50%.

    Place, publisher, year, edition, pages
    Elsevier, 2013
    Keywords
    Biogas; Anaerobic digestion; Kraft pulp; Chemical thermo-mechanical pulp; Neutral sulfite semi-chemical pulp; Bleaching
    National Category
    Social Sciences
    Identifiers
    urn:nbn:se:liu:diva-104129 (URN)10.1016/j.apenergy.2012.12.072 (DOI)000329377800053 ()
    Available from: 2014-02-07 Created: 2014-02-07 Last updated: 2019-05-07
    2. High-rate anaerobic co-digestion of kraft mill fibre sludge and activated sludge by CSTRs with sludge recirculation
    Open this publication in new window or tab >>High-rate anaerobic co-digestion of kraft mill fibre sludge and activated sludge by CSTRs with sludge recirculation
    Show others...
    2016 (English)In: Waste Management, ISSN 0956-053X, E-ISSN 1879-2456, Vol. 56, p. 166-172Article in journal (Refereed) Published
    Abstract [en]

    Kraft fibre sludge from the pulp and paper industry constitutes a new, widely available substrate for thebiogas production industry, with high methane potential. In this study, anaerobic digestion of kraft fibresludge was examined by applying continuously stirred tank reactors (CSTR) with sludge recirculation.Two lab-scale reactors (4L) were run for 800 days, one on fibre sludge (R1), and the other on fibre sludgeand activated sludge (R2). Additions of Mg, K and S stabilized reactor performance. Furthermore, theCa:Mg ratio was important, and a stable process was achieved at a ratio below 16:1. Foaming was abatedby short but frequent mixing. Co-digestion of fibre sludge and activated sludge resulted in more robustconditions, and high-rate operation at stable conditions was achieved at an organic loading rate of 4 gvolatile solids (VS) L1 day1, a hydraulic retention time of 4 days and a methane production of230 ± 10 Nm L per g VS.

    Place, publisher, year, edition, pages
    Elsevier, 2016
    Keywords
    Pulp and paper Anaerobic digestion Sludge recirculation High-rate CSTR Fibre sludge Activated sludge
    National Category
    Renewable Bioenergy Research Production Engineering, Human Work Science and Ergonomics Production Engineering, Human Work Science and Ergonomics Water Engineering
    Identifiers
    urn:nbn:se:liu:diva-131780 (URN)10.1016/j.wasman.2016.06.034 (DOI)000383827700020 ()27453288 (PubMedID)
    Funder
    Swedish Energy Agency
    Note

    Funding agencies: Swedish Energy Agency [32802-1]; Scandinavian Biogas Fuels AB; Poyry AB; BillerudKorsnas AB; SCA; Fiskeby Board AB; Purac AB

    Available from: 2016-10-05 Created: 2016-10-05 Last updated: 2019-05-07Bibliographically approved
    3. Combining high-rate aerobic wastewater treatment with anaerobic digestion of waste activated sludge at a pulp and paper mill
    Open this publication in new window or tab >>Combining high-rate aerobic wastewater treatment with anaerobic digestion of waste activated sludge at a pulp and paper mill
    2018 (English)In: Water Science and Technology, ISSN 0273-1223, E-ISSN 1996-9732, Vol. 77, no 8, p. 2068-2076Article in journal (Refereed) Published
    Abstract [en]

    The activated sludge process within the pulp and paper industry is generally run to minimize the production of waste activated sludge (WAS), leading to high electricity costs from aeration and relatively large basin volumes. In this study, a pilot-scale activated sludge process was run to evaluate the concept of treating the wastewater at high rate with a low sludge age. Two 150 L containers were used, one for aeration and one for sedimentation and sludge return. The hydraulic retention time was decreased from 24 hours to 7 hours, and the sludge age was lowered from 12 days to 2–4 days. The methane potential of the WAS was evaluated using batch tests, as well as continuous anaerobic digestion (AD) in 4 L reactors in mesophilic and thermophilic conditions. Wastewater treatment capacity was increased almost four-fold at maintained degradation efficiency. The lower sludge age greatly improved the methane potential of the WAS in batch tests, reaching 170 NmL CH4/g VS at a sludge age of 2 days. In addition, the continuous AD showed a higher methane production at thermophilic conditions. Thus, the combination of high-rate wastewater treatment and AD of WAS is a promising option for the pulp and paper industry.

    Keywords
    Activated sludge, sludge age, anaerobic digestion, biochemical methane potential, CSTR, pulp and paper
    National Category
    Bioprocess Technology
    Identifiers
    urn:nbn:se:liu:diva-146089 (URN)10.2166/wst.2018.120 (DOI)000435663800011 ()29722692 (PubMedID)
    Note

    Funding agencies: Swedish Energy Agency [32802-2]; Scan-dinavian Biogas Fuels AB; Poyry AB; BillerudKorsnas AB; SCA; Fiskeby Board AB; Purac AB

    Available from: 2018-05-07 Created: 2018-05-07 Last updated: 2019-05-07Bibliographically approved
  • 28.
    Fornander, Erik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology.
    Ozone Treatment Targeting Pharmaceutical Residues: Validation and Process Control in a Wastewater Treatment Plant2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    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.

  • 29.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering.
    Visualisering och beräkning av hudkapillärer2004Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this thesis was to develop an objective and automatic method for identifying capillaries in microscope images of the skin. Furthermore, statistical data about the identified capillaries and the capillary distribution should be computed and stored in a database. The method was implemented using the platform independent programming language Java. An analysis of microscope improvement using various polarization filter setups and wavelength filtershas also been performed, as well as a pilot study of the effect of applying a local anaesthetic cream on the skin. The method is developed and aimed at research on various pathological skin conditions affecting the capillary distribution. Hypertension, diabetes, inflammation, ischemia, connective tissue disease, and erythromelalgia are all examples of diseases or pathological conditions which are supposed to affect the distribution of the skin capillaries.

  • 30.
    Gerlach, Inga
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Operator Training Simulators towards Industrial Biotechnology2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biotechnological processes are carried out by applying advanced and demanding process strategies. Thus, fundamental understanding and knowledge about the applied microorganism is required to achieve high productivity and profitability. Therefore, computer-based simulation has been integrated into training methodologies for supplementing and expanding academic education and industrial operator training, in order to provide more effective as well as cost- and time-efficient training.

    Operator training simulators (OTS) are computer-based training tools that represent the real laboratory or plant within an interactive, virtual environment. Trainees can learn about cause-and-effect relationships during the virtual process to improve process understanding. Also, trainees and operators get the opportunity to develop, maintain and improve their operational skills. The virtual environment allows delayed operational actions and operational faults, as they are not interfering with the real process. Acceleration of the simulation speed makes training more effective. For instance, different procedures such as start-up and shut-down can be trained in a limited period of training time. Incident and trouble-shooting training can be realized in a safe, virtual environment without exposing the operator to potential risks. So far, OTS are mainly used in military, aviation, medicine and chemical industries. However, there are only a few examples where OTS are applied in biotechnological process applications.

    The aim of this thesis is to expose the benefits of using OTS for biotechnological process applications in academic education and industrial operator training. For this purpose, the feasibility of developing and applying OTS was investigated and discussed. Three OTS for the production of bio-ethanol and recombinant protein production were developed in order to investigate the benefits and their requirements as well as to assess the training effectiveness of these. To visualize the technical system including equipment and distributed control system (DCS), graphical user interfaces (GUIs) were designed, allowing the user to interact with the simulator. Mathematical models were developed and implemented in the OTS to ensure dynamic simulation of the process, where cause-and-effect relationships are realistically described. The essential part of an OTS for biotechnological process applications is the embedded sub-model which describes the biological production system. It is important that the cell growth behaviour within a bioreactor can be  simulated with sufficient accuracy in order to ensure high training effectiveness.

    In the assessment of the training effectiveness in academic education, it was observed that the students’ capability of understanding and controlling complex biotechnological processes improved after OTS training. Students showed better performance in laboratory experiments after participating in OTS pre-training. Moreover, the development of an OTS for an industrial, large-scale bio-ethanol plant illuminates the needs of OTS in biotechnological process industries. It was shown how the conceptual design methodology can be applied in designing an OTS, based on training needs from the industrial user perspective. Also, construction of the OTS including the formulation of mathematical models, the model structure which is embedded in the OTS and the design of the GUIs is covered in this thesis. Whether the use of the OTS will become cost-effective and assure maximum transfer of training depends on long term evaluation. However, application and evaluation of the developed OTS reveal the benefits and training effectiveness of these systems. The findings of the thesis might considerably facilitate the introduction of OTS into academic education and industrial operator training for biotechnological process applications.

    List of papers
    1. Virtual bioreactor cultivation for operator training and simulation: application to ethanol and protein production
    Open this publication in new window or tab >>Virtual bioreactor cultivation for operator training and simulation: application to ethanol and protein production
    2013 (English)In: Journal of chemical technology and biotechnology (1986), ISSN 0268-2575, E-ISSN 1097-4660, Vol. 88, no 12, p. 2159-2168Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUNDDuring recent years several computer-based operator training simulators (OTS) have been developed that are suitable for the virtual training of operators and other professionals. In the field of bioprocess engineering OTS are rarely used. Furthermore, the effects of using training simulators in bioprocess applications have not been evaluated. less thanbrgreater than less thanbrgreater thanRESULTSThe OTS BioProcessTrainer was applied to bioreactor operations for two biological processes, Saccharomyces cerevisiae, for ethanol production, and recombinant Escherichia coli, for production of green fluorescence protein (GFP). The simulator used a multi-shell model platform that described the biological and physical conditions of the bioreactor for the two bioprocess systems. The simulator enabled the user to plan, operate and control the processes in real or accelerated time. The training resulted in improved ability to manage the whole bioreactor procedure for the two processes. less thanbrgreater than less thanbrgreater thanCONCLUSIONThe study showed that the simulator can be an efficient tool for training of operation, optimization and control of bioprocesses. The mathematical model framework of the simulator can be adapted to a variety of industrial bioprocesses. Thus, it appears likely that this type of OTS may serve as a useful resource in industry for training and continuing education of plant operators and engineers.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2013
    Keywords
    operator training simulators, bioprocess models, bioengineering training, educational benefit
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-102072 (URN)10.1002/jctb.4079 (DOI)000326462900005 ()
    Note

    Funding Agencies|Linkoping University||

    Available from: 2013-12-03 Created: 2013-11-29 Last updated: 2019-01-22
    2. Operator training in recombinant protein production using a structured simulator model
    Open this publication in new window or tab >>Operator training in recombinant protein production using a structured simulator model
    Show others...
    2014 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 177, p. 53-59Article in journal (Refereed) Published
    Abstract [en]

    Model-based operator training simulators ( OTS) could be powerful tools for virtual training of operational procedures and skills of production personnel in recombinant protein processes. The applied model should describe critical events in the bioprocess so accurately that the operators ability to observe and alertly act upon these events is trained with a high degree of efficiency. In this work is shown how this is accomplished in a structured multi-compartment model for the production of a recombinant protein in an Escherichia coli fed-batch process where in particular the induction procedure, the stress effects and overflow metabolism were highlighted. The structured model was applied on the OTS platform that virtually simulated the operational bioreactor procedures in real or accelerated time. Evaluation of training using the model-based OTS showed that trained groups of operators exhibited improved capability compared with the untrained groups when subsequently performing real laboratory scale cultivations. The results suggest that this model-based OTS may provide a valuable resource for enhancing operator skills in large scale recombinant protein manufacturing.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Training simulator; Recombinant protein production; Cultivation; Modelling
    National Category
    Bioprocess Technology
    Identifiers
    urn:nbn:se:liu:diva-106511 (URN)10.1016/j.jbiotec.2014.02.022 (DOI)000333811200007 ()2-s2.0-84896536648 (Scopus ID)
    Available from: 2014-05-12 Created: 2014-05-09 Last updated: 2019-01-22Bibliographically approved
    3. Operator training simulation for integrating cultivation and homogenisation in protein production
    Open this publication in new window or tab >>Operator training simulation for integrating cultivation and homogenisation in protein production
    2015 (English)In: Biotechnology Reports, ISSN 2215-017X, Vol. 6, p. 91-99Article in journal (Refereed) Published
    Abstract [en]

    Operating training simulators (OTS) are virtual simulation tools used for training of process operators in industry in performing procedures and running processes. Based on structured mathematical models of the unit operations of a bioprocess an OTS can train a process operator by visualising changing conditions during the process, allow testing operator actions, testing controller settings, experience unexpected technical problems and getting practice in using prescribed standard procedures for a plant. This work shows the design of an OTS where two sequential steps of a recombinant protein production process, a fed-batch cultivation and a high-pressure homogenisation, are integrated. The OTS was evaluated on a user test group and showed that the OTS promoted and developed their understanding of the process, their capability to identify parameters influencing process efficiency and the skills of operating it.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Training simulator, Recombinant protein production, Cultivation, Homogenisation, Integrated process
    National Category
    Bioprocess Technology
    Identifiers
    urn:nbn:se:liu:diva-121472 (URN)10.1016/j.btre.2015.03.002 (DOI)
    Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2019-01-22Bibliographically approved
    4. Conceptual Design of an Operator Training Simulator for a Bio-Ethanol Plant
    Open this publication in new window or tab >>Conceptual Design of an Operator Training Simulator for a Bio-Ethanol Plant
    2015 (English)In: Processes, ISSN 2227-9717, Vol. 3, no 3, p. 664-683Article in journal (Refereed) Published
    Abstract [en]

    Conceptual design methodology for the configuration and procedural training with an operating training simulator (OTS) in a large-scale plant for commercial bio-ethanol production is described. The aim of the study is to show how the methodology provides a powerful way for finding the best configuration and training structure of the OTS before constructing and implementing the software of the OTS. The OTS principle, i.e., to use a computer-based virtual representation of the real process plant intended for efficient training of process operators, has long since been applied in aviation and process industries for more efficient and flawless operations. By using the conceptual design methodology (sometimes referred to as bio-mechatronics) a variety of OTS configurations with this capacity was generated. The systematic approach of for targeting the users’ (i.e., the plant management and process operators) needs resulted in better understanding and efficiency in training of hands-on skills in operating the plant. The training included general standard operating procedures for running the plant under normal operation conditions with different starch materials, handling of typical frequent disturbances as well as acting in situations not described in the standard operation procedures and applying trouble-shooting

    Place, publisher, year, edition, pages
    MPDI Open Access Publishing, 2015
    Keywords
    Conceptual design; systematic design; bio-refinery; bioprocess engineering; bio-mechatronics
    National Category
    Bioprocess Technology
    Identifiers
    urn:nbn:se:liu:diva-121473 (URN)10.3390/pr3030664 (DOI)000363981100009 ()
    Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2019-01-22Bibliographically approved
    5. Operator training simulator for an industrial bio-ethanol plant
    Open this publication in new window or tab >>Operator training simulator for an industrial bio-ethanol plant
    2015 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The development of a software-based operator training simulators (OTS) for an industrial bioethanol plant is described. OTS are used in the process industry for training of process operators since several years but few examples are reported for their use in biochemical and biotechnological industry. This study describes the implementation of an OTS at a large-scale bio-plant producing ethanol. The study includes the implementation of models and graphical user interfaces of the OTS as well as the experience of the operator training with it. The OTS encompasses the whole process, i.e. the sections for hydrolysis, fermentation, separation and distillation. The implementation was carried out on the commercial process control software WinErs. The graphical user interfaces, including all essential distributed control systems of the plant, show high fidelity with the real system. Dynamic process models were able to efficiently train operators in running and controlling the process under standard, start-up, shut-down and critical conditions. The models show a sufficient accuracy and robustness at different simulation speeds. Experiences of applying the OTS in the industrial operator environment of the large-scale plant implies that the OTS can be a useful tool for making operator training more time- and cost-efficient in the biochemical and biotechnological industry.

    Keywords
    Training simulator; Recombinant protein production; Cultivation; Modellin
    National Category
    Bioprocess Technology
    Identifiers
    urn:nbn:se:liu:diva-121474 (URN)
    Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2019-01-22Bibliographically approved
  • 31.
    Gerlach, Inga
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology. University of Applied Sciences, Bremen, Germany.
    Bruening, Simone
    University of Applied Sciences, Bremen, Germany .
    Gustavsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Hass, Volker C.
    University of Applied Sciences Furtwangen, Villingen-Schwenningen, Germany .
    Operator training in recombinant protein production using a structured simulator model2014In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 177, p. 53-59Article in journal (Refereed)
    Abstract [en]

    Model-based operator training simulators ( OTS) could be powerful tools for virtual training of operational procedures and skills of production personnel in recombinant protein processes. The applied model should describe critical events in the bioprocess so accurately that the operators ability to observe and alertly act upon these events is trained with a high degree of efficiency. In this work is shown how this is accomplished in a structured multi-compartment model for the production of a recombinant protein in an Escherichia coli fed-batch process where in particular the induction procedure, the stress effects and overflow metabolism were highlighted. The structured model was applied on the OTS platform that virtually simulated the operational bioreactor procedures in real or accelerated time. Evaluation of training using the model-based OTS showed that trained groups of operators exhibited improved capability compared with the untrained groups when subsequently performing real laboratory scale cultivations. The results suggest that this model-based OTS may provide a valuable resource for enhancing operator skills in large scale recombinant protein manufacturing.

  • 32.
    Gerlach, Inga
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Hass, Volker C.
    Hochschule Furtwangen, University of Applied Sciences Furtwangen, Germany.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Conceptual Design of an Operator Training Simulator for a Bio-Ethanol Plant2015In: Processes, ISSN 2227-9717, Vol. 3, no 3, p. 664-683Article in journal (Refereed)
    Abstract [en]

    Conceptual design methodology for the configuration and procedural training with an operating training simulator (OTS) in a large-scale plant for commercial bio-ethanol production is described. The aim of the study is to show how the methodology provides a powerful way for finding the best configuration and training structure of the OTS before constructing and implementing the software of the OTS. The OTS principle, i.e., to use a computer-based virtual representation of the real process plant intended for efficient training of process operators, has long since been applied in aviation and process industries for more efficient and flawless operations. By using the conceptual design methodology (sometimes referred to as bio-mechatronics) a variety of OTS configurations with this capacity was generated. The systematic approach of for targeting the users’ (i.e., the plant management and process operators) needs resulted in better understanding and efficiency in training of hands-on skills in operating the plant. The training included general standard operating procedures for running the plant under normal operation conditions with different starch materials, handling of typical frequent disturbances as well as acting in situations not described in the standard operation procedures and applying trouble-shooting

  • 33.
    Gerlach, Inga
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering. Department of Environmental- and Bio-Technology, Hochschule Bremen University of Applied Sciences Bremen, Bremen, Germany.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Hass, Volker C.
    Faculty of Medical and Life Sciences, Hochschule Furtwangen University of Applied Sciences Furtwangen, Germany.
    Operator training simulation for integrating cultivation and homogenisation in protein production2015In: Biotechnology Reports, ISSN 2215-017X, Vol. 6, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Operating training simulators (OTS) are virtual simulation tools used for training of process operators in industry in performing procedures and running processes. Based on structured mathematical models of the unit operations of a bioprocess an OTS can train a process operator by visualising changing conditions during the process, allow testing operator actions, testing controller settings, experience unexpected technical problems and getting practice in using prescribed standard procedures for a plant. This work shows the design of an OTS where two sequential steps of a recombinant protein production process, a fed-batch cultivation and a high-pressure homogenisation, are integrated. The OTS was evaluated on a user test group and showed that the OTS promoted and developed their understanding of the process, their capability to identify parameters influencing process efficiency and the skills of operating it.

  • 34.
    Gerlach, Inga
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology. University of Applied Sciences, Bremen, Germany.
    Tholin, Sören
    Lantmännen Reppe AB, Lidköping, Sweden.
    Hass, Volker C.
    Hochschule Furtwangen University of Applied Sciences Furtwangen, Villingen- Schwenningen, Germany.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Operator training simulator for an industrial bio-ethanol plant2015Manuscript (preprint) (Other academic)
    Abstract [en]

    The development of a software-based operator training simulators (OTS) for an industrial bioethanol plant is described. OTS are used in the process industry for training of process operators since several years but few examples are reported for their use in biochemical and biotechnological industry. This study describes the implementation of an OTS at a large-scale bio-plant producing ethanol. The study includes the implementation of models and graphical user interfaces of the OTS as well as the experience of the operator training with it. The OTS encompasses the whole process, i.e. the sections for hydrolysis, fermentation, separation and distillation. The implementation was carried out on the commercial process control software WinErs. The graphical user interfaces, including all essential distributed control systems of the plant, show high fidelity with the real system. Dynamic process models were able to efficiently train operators in running and controlling the process under standard, start-up, shut-down and critical conditions. The models show a sufficient accuracy and robustness at different simulation speeds. Experiences of applying the OTS in the industrial operator environment of the large-scale plant implies that the OTS can be a useful tool for making operator training more time- and cost-efficient in the biochemical and biotechnological industry.

  • 35.
    Ghareh Baghi, Ghareh Baghi
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Assessment of Valvular Aortic Stenosis by Signal Analysis of the Phonocardiogram2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aortic stenosis (AS) is one of the most prevalent valvular heart diseases in elderly people. According to the recommendations of both the American Heart Association and the European Society of Cardiology, severity assessment of AS is primarily based on echocardiographic findings. The experience of the investigator here play important roles in the accuracy of the assessment, and therefore in the disease management. However, access to the expert physicians could be limited, especially in rural health care centers of developing countries.

    This thesis aims to develop processing algorithms tailored for phonocardiographic signal with the intension to obtain a noninvasive diagnostic tool for AS assessment and severity grading. The algorithms employ a phonocardiogram as input signal and perform analysis for screening and diagnostics. Such a decision support system, which we call “the intelligent phonocardiography”, can be widely used in primary healthcare centers.

    The main contribution of the thesis is to present innovative models for the phonocardiographic analysis by taking the segmental characteristics of the signal into consideration. Three novel methodologies are described, based on the presented models, to perform robust classification. In the first attempt, a novel pattern recognition framework is presented for screening of AS-related murmurs. The framework offers a hybrid model for classifying cyclic time series in general, but is tailored to detect the murmurs as a special case study. The time growing neural network is another method that we use to classify short time signals with abrupt frequency transition. The idea of the growing frames is extended to the cyclic signals with stochastic properties for the screening purposes. Finally, a combined statistical and artificial intelligent classifier is proposed for grading the severity of AS.

    The study suggests comprehensive statistical validations not only for the evaluation and representation of systolic murmurs but also for setting the methodology design parameters, which can be considered as one of the significant features of the study. The resulting methodologies can be implemented by using web and mobile technologies to be utilized in distributed healthcare system.

    List of papers
    1. A pattern recognition framework for detecting dynamic changes on cyclic time series
    Open this publication in new window or tab >>A pattern recognition framework for detecting dynamic changes on cyclic time series
    2015 (English)In: Pattern Recognition, ISSN 0031-3203, E-ISSN 1873-5142, Vol. 48, no 3, p. 696-708Article in journal (Refereed) Published
    Abstract [en]

    This paper proposes a framework for binary classification of the time series with cyclic characteristics. The framework presents an iterative algorithm for learning the cyclic characteristics by introducing the discriminative frequency bands (DFBs) using the discriminant analysis along with k-means clustering method. The DFBs are employed by a hybrid model for learning dynamic characteristics of the time series within the cycles, using statistical and structural machine learning techniques. The framework offers a systematic procedure for finding the optimal design parameters associated with the hybrid model. The proposed  model is optimized to detect the changes of the heart sound recordings (HSRs) related to aortic stenosis. Experimental results show that the proposed framework provides efficient tools for classification of the HSRs based on the heart murmurs. It is also evidenced that the hybrid model, proposed by the framework, substantially improves the classification performance when it comes to detection of the heart disease.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Hybrid model, cyclic time series, time series, phonocardiogram, systolic murmurs
    National Category
    Biomedical Laboratory Science/Technology Medical Biotechnology
    Identifiers
    urn:nbn:se:liu:diva-110177 (URN)10.1016/j.patcog.2014.08.017 (DOI)000347747000008 ()
    Available from: 2014-09-04 Created: 2014-09-04 Last updated: 2017-12-05Bibliographically approved
    2. Detection of systolic ejection click using time growing neural network
    Open this publication in new window or tab >>Detection of systolic ejection click using time growing neural network
    2014 (English)In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 36, no 4, p. 477-483Article in journal (Refereed) Published
    Abstract [en]

    In this paper, we present a novel neural network for classification of short-duration heart sounds: the time growing neural network (TGNN). The input to the network is the spectral power in adjacent frequency bands as computed in time windows of growing length. Children with heart systolic ejection click (SEC) and normal children are the two groups subjected to analysis. The performance of the TGNN is compared to that of a time delay neural network (TDNN) and a multi-layer perceptron (MLP), using training and test datasets of similar sizes with a total of 614 normal and abnormal cardiac cycles. From the test dataset, the classification rate/sensitivity is found to be 97.0%/98.1% for the TGNN, 85.1%/76.4% for the TDNN, and 92.7%/85.7% for the MLP. The results show that the TGNN performs better than do TDNN and MLP when frequency band power is used as classifier input. The performance of TGNN is also found to exhibit better immunity to noise.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Systolic ejection click; Time growing neural network; Time delay neural network; Heart sound
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-106865 (URN)10.1016/j.medengphy.2014.02.011 (DOI)000334976800008 ()
    Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2017-12-05
    3. A novel method for discrimination between innocent and pathological heart murmurs
    Open this publication in new window or tab >>A novel method for discrimination between innocent and pathological heart murmurs
    2015 (English)In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, no 7, p. 674-682Article in journal (Refereed) Published
    Abstract [en]

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Growing-time support vector machine, support vector machine, phonocardiogram signal, heart murmurs, innocent murmurs.
    National Category
    Medical Engineering
    Identifiers
    urn:nbn:se:liu:diva-117825 (URN)10.1016/j.medengphy.2015.04.013 (DOI)000357354400007 ()26003286 (PubMedID)
    Note

    At the time for thesis presentation publication was in status: Manuscript

    Available from: 2015-05-08 Created: 2015-05-08 Last updated: 2017-12-04Bibliographically approved
    4. An Automatic Tool for Pediatric Heart Sounds Segmentation
    Open this publication in new window or tab >>An Automatic Tool for Pediatric Heart Sounds Segmentation
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    In this paper, we present a novel algorithm for pediatric heart sound segmentation, incorporated into a graphical user interface. The algorithm employs both the Electrocardiogram (ECG) and Phonocardiogram (PCG) signals for an efficient segmentation under pathological circumstances.First, the ECG signal is invoked in order to determine the beginning and end points of each cardiac cycle by using wavelet transform technique. Then, first and second heart sounds within the cycles are identified over the PCG signal by paying attention to the spectral properties of the sounds. The algorithm is applied on 120 recordings of normal and pathological children, totally containing 1976 cardiac cycles. The accuracy of the segmentation algorithm is 97% for S1 and 94% for S2 identification while all the cardiac cycles are correctly determined.

    National Category
    Biomedical Laboratory Science/Technology Medical Biotechnology
    Identifiers
    urn:nbn:se:liu:diva-110179 (URN)
    Available from: 2014-09-04 Created: 2014-09-04 Last updated: 2014-09-04Bibliographically approved
    5. Severity assessments of aortic stenosis using intelligent phonocardiography
    Open this publication in new window or tab >>Severity assessments of aortic stenosis using intelligent phonocardiography
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To study capabilities of the intelligent phonocardiography (IPCG) in automatic grading severity of the aortic stenosis (AS).

    Methods: Phonocardiogram signals were recorded from the patients with AS, as diagnosed by echocardiography. The patient group is comprised of signals, recorded from 5 patients (2 recordings from each), mostly elderly referrals (>60 years) with mild to severe AS. An advanced processing algorithm, consisted of the wavelet transform and the stepwise regression analysis, characterizes the systolic murmur caused by the AS in order to predict the 5 indicators; mean pressure gradient over the aortic valve (MPG), maximum jet velocity (MJV), aortic valve area (AVA), velocity time integral and the ejection period. The automatic assessment is performed by an artificial neural network using the predicted values of the indicators as the input data. Reliability of the IPCG is validated by applying repeated random sub-sampling (RRSS) with 70%/30% of the training/testing data, and calculating the accuracy. The RRSS is also employed to validate reproducibility of the IPCG by using 70% of the signals for training and the second recording of the same individuals for  testing.

    Results: Accuracy of the IPCG is estimated to be and (95% confidence interval) for the reliability and the reproducibility, respectively. Linear correlation between the characterized systolic murmur and the MPG (r>0.81), the MJV (r>0.82) and the AVA (r>0.85) is observed.

    Conclusions: The IPCG has the potential to objectively serve as a clinical tool for grading severity of the aortic stenosis.

    National Category
    Biomedical Laboratory Science/Technology Medical Biotechnology
    Identifiers
    urn:nbn:se:liu:diva-110181 (URN)
    Available from: 2014-09-04 Created: 2014-09-04 Last updated: 2014-09-04Bibliographically approved
  • 36.
    Golabi, Mohsen
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology.
    Functionalised surfaces for bacterial discrimination2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Bacterial detection and identification is a critical step in many arenas, including food and water safety, clinical diagnostics, bioprocess control and biosecurity. Social hygiene has a direct correlation with the strict control of microorganisms in these fields. The worldwide cases of bacterial infectious disease is assessed to be 1-2 billion annually, and these have a massive negative effect on the global economy. Although many precise techniques are currently available, a huge mortality and morbidity related to bacterial infection disease continues to be reported annually due to misdiagnosis or delay in diagnosis. Increasing efficiency and reliability of pathogen detection methods will potentially improve social health and protect society against pathogenic diseases.

    The development of culture media for selective isolation and differentiation of bacteria started in the late 19th century. Immunological assays and then genotyping techniques were developed in 20th century, in addition to many less commonly used techniques for bacterial detection. Each of the currently used methods has its advantages and weaknesses in terms of speed, cost and accuracy. Much effort has recently been devoted to developing biosensors for bacterial detection for simpler and more rapid use.

    This thesis is focused on functionalised surfaces for the development of biosensors for bacterial discrimination and detection, and is divided in three subsections. First, we explored a new approach for bacterial discrimination based on pattern recognition. Traditional culturing methods discriminate bacteria based on their metabolic activity pattern. Taking inspiration from the extensive body of work that reports the use of electronic-noses to differentiate bacteria based on the volatiles patterns they produce, we explored the possibility of bacteria differentiation based on adhesion patterns. By altering the electropolymerisation conditions, the physicalchemical surface properties of polypyrrole (PPy) can be tuned to fabricate a range of dissimilar surfaces. The adhesion of different bacteria on a series of polymers was measured. Data analysis of the adhesion patterns proved that bacteria can be discriminated by examining their adhesion to dissimilar surfaces. Next, we developed a new functionalisation of PPy by doping PPy with 4-N-Pentylphenylboronic Acid and investigated the modulation of bacteria binding to those surfaces. In this second section, a new electropolymerisation technique for whole-cell imprinting was developed based on different functional monomers. 3-Aminophenyl boronic acid was shown to be a good monomer to produce whole-cell imprinted polymers (CIP) with high affinity for bacterial cells with improved releasing ability. Finally, in the third section aptamers, which are promising synthetic recognition elements, were explored for bacterial detection testing. A specific aptamer was used to fabricate of a prototype of label-free aptasensor for bacterial detection. Also, the SELEX process was used to produce a pool of aptamers, or “polyclonal” aptamers, which targeted a group of bacteria species. Using polyclonal aptamers as a recognition element enables biosensors to enhance their resolution to detect broader types of bacterial species using a single serological-like test.

    List of papers
    1. Tuning the surface properties of polypyrrole films for modulating bacterial adhesion.
    Open this publication in new window or tab >>Tuning the surface properties of polypyrrole films for modulating bacterial adhesion.
    2016 (English)In: Macromolecular Chemistry and Physics, ISSN 1022-1352, E-ISSN 1521-3935, Vol. 217, no 10, p. 1128-1135Article in journal (Refereed) Published
    Abstract [en]

    Tuning the physical–chemical properties of polypyrrole (PPy) opens up potentially exciting new applications, especially in the area of bacterial adhesion. Polypyrrole is electrochemically synthesized under various conditions and the physical properties of the films and their effects on bacterial adhesion are characterized. Five types of dopants—chloride (Cl), perchlorate (ClO4), p-toluene-sulfonate (ToS), dodecylbenzene sulfonate (DBS), and poly sodium styrene sulfonate (PSS)—are used to fabricate PPy films at two different constant potentials (0.500 and 0.850 V) with and without Fe3+. Their thickness, roughness, and wettability are measured. The adhesion tendency of Escherichia coli, as a model bacterium, to the four polymers is studied. E. coli shows greater adhesion tendency to the hydrophobic, rough surface of PPy-DBS, and less adhesion tendency to the smooth and hydrophilic surface of PPy-PSS. The results facilitate the choice of appropriate electropolymerization conditions to modulate bacterial adhesion.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2016
    Keywords
    Biopolymer surface, modulating bacterial adhesion, polymer thickness, polypyrrole roughness, wettability
    National Category
    Polymer Technologies
    Identifiers
    urn:nbn:se:liu:diva-128197 (URN)10.1002/macp.201500445 (DOI)000380018100004 ()
    Note

    Funding agencies:  Iranian Ministry of Science, Research and Technology; Linkoping University; Swedish Research Council [VR-2014-3079]

    Available from: 2016-05-20 Created: 2016-05-20 Last updated: 2019-10-09
    2. Tunable conjugated polymers for bacterial differentiation
    Open this publication in new window or tab >>Tunable conjugated polymers for bacterial differentiation
    2016 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 222, p. 839-848Article in journal (Refereed) Published
    Abstract [en]

    A novel rapid method for bacterial differentiation is explored based on the specific adhesion pattern of bacterial strains to tunable polymer surfaces. Different types of counter ions were used to electrochemically fabricate dissimilar polypyrrole (PPy) films with diverse physicochemical properties such as hydrophobicity, thickness and roughness. These were then modulated into three different oxidation states in each case. The dissimilar sets of conducting polymers were exposed to five different bacterial strains, Deinococcus proteolyticus, Serratia marcescens, Pseudomonas fluorescens, Alcaligenes faecalis and Staphylococcus epidermidis. By analysis of the fluorescent microscope images, the number of bacterial cells adhered to each surface were evaluated. Generally, the number of cells of a particular bacterial strain that adhered varied when exposed to dissimilar polymer surfaces, due to the effects of the surface properties of the polymer on bacterial attachment. Similarly, the number of cells that adhered varied with different bacterial strains exposed to the same surface, reflecting the different surface properties of the bacteria. Principal component analysis showed that each strain of bacteria had its own specific adhesion pattern. Hence, they could be discriminated by this simple, label-free method based on tunable polymer arrays combined with pattern recognition. (C) 2015 Elsevier B.V. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE SA, 2016
    Keywords
    Conducting polymer; Polypyrrole; Rapid microbial detection; Bacterial adhesion; Pattern recognition; Principal component analysis (PCA)
    National Category
    Polymer Chemistry Textile, Rubber and Polymeric Materials
    Identifiers
    urn:nbn:se:liu:diva-122780 (URN)10.1016/j.snb.2015.09.033 (DOI)000363815800109 ()
    Note

    Funding Agencies|Iranian Ministry of Science, Research and Technology; Linkoping University; Swedish Research Council [VR-2014-3079]

    Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2019-10-09
    3. Doping Polypyrrole Films with 4-N-Pentylphenylboronic Acid to Enhance Affinity towards Bacteria and Dopamine
    Open this publication in new window or tab >>Doping Polypyrrole Films with 4-N-Pentylphenylboronic Acid to Enhance Affinity towards Bacteria and Dopamine
    Show others...
    2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166548Article in journal (Refereed) Published
    Abstract [en]

    Here we demonstrate the use of a functional dopant as a fast and simple way to tune the chemical affinity and selectivity of polypyrrole films. More specifically, a boronic-functionalised dopant, 4-N-Pentylphenylboronic Acid (PBA), was used to provide to polypyrrole films with enhanced affinity towards diols. In order to prove the proposed concept, two model systems were explored: (i) the capture and the electrochemical detection of dopamine and (ii) the adhesion of bacteria onto surfaces. The chemisensor, based on overoxidised polypyrrole boronic doped film, was shown to have the ability to capture and retain dopamine, thus improving its detection; furthermore the chemisensor showed better sensitivity in comparison with overoxidised perchlorate doped films. The adhesion of bacteria, Deinococcus proteolyticus, Escherichia coli, Streptococcus pneumoniae and Klebsiella pneumoniae, onto the boric doped polypyrrole film was also tested. The presence of the boronic group in the polypyrrole film was shown to favour the adhesion of sugar-rich bacterial cells when compared with a control film (Dodecyl benzenesulfonate (DBS) doped film) with similar morphological and physical properties. The presented single step synthesis approach is simple and fast, does not require the development and synthesis of functional monomers, and can be easily expanded to the electrochemical, and possibly chemical, fabrication of novel functional surfaces and interfaces with inherent pre-defined sensing and chemical properties.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2016
    National Category
    Other Chemistry Topics
    Identifiers
    urn:nbn:se:liu:diva-133388 (URN)10.1371/journal.pone.0166548 (DOI)000388886000017 ()27875555 (PubMedID)
    Note

    Funding Agencies|Ministry of Science Research and Technology of Iran; Linkoping University; Swedish Research Council [VR-2014-3079]; Erasmus exchange program of the European Commission

    Available from: 2016-12-27 Created: 2016-12-22 Last updated: 2019-10-09
    4. Electrochemical bacterial detection using poly(3-aminophenylboronic acid)-based imprinted polymer.
    Open this publication in new window or tab >>Electrochemical bacterial detection using poly(3-aminophenylboronic acid)-based imprinted polymer.
    Show others...
    2017 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 93, p. 87-93Article in journal (Refereed) Published
    Abstract [en]

    Biosensors can deliver the rapid bacterial detection that is needed in many fields including food safety, clinical diagnostics, biosafety and biosecurity. Whole-cell imprinted polymers have the potential to be applied as recognition elements in biosensors for selective bacterial detection. In this paper, we report on the use of 3-aminophenylboronic acid (3-APBA) for the electrochemical fabrication of a cell-imprinted polymer (CIP). The use of a monomer bearing a boronic acid group, with its ability to specifically interact with cis-diol, allowed the formation of a polymeric network presenting both morphological and chemical recognition abilities. A particularly beneficial feature of the proposed approach is the reversibility of the cis-diol-boronic group complex, which facilitates easy release of the captured bacterial cells and subsequent regeneration of the CIP. Staphylococcus epidermidis was used as the model target bacteria for the CIP and electrochemical impedance spectroscopy (EIS) was explored for the label-free detection of the target bacteria. The modified electrodes showed a linear response over the range of 103–107 cfu/mL. A selectivity study also showed that the CIP could discriminate its target from non-target bacteria having similar shape. The CIPs had high affinity and specificity for bacterial detection and provided a switchable interface for easy removal of bacterial cell.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    National Category
    Physical Sciences
    Identifiers
    urn:nbn:se:liu:diva-133647 (URN)10.1016/j.bios.2016.09.088 (DOI)000399259000013 ()27751788 (PubMedID)
    Note

    Funding agencies: Ministry of Science Research and Technology of Iran [MSRT 89100094]; Linkoping University [1259 00 0200]; Swedish Research Council [VR-2014-3079]

    Available from: 2017-01-05 Created: 2017-01-05 Last updated: 2019-10-09
    5. Diazonium-based impedimetric aptasensor for the rapid label-free detection of Salmonella typhimurium in food sample
    Open this publication in new window or tab >>Diazonium-based impedimetric aptasensor for the rapid label-free detection of Salmonella typhimurium in food sample
    Show others...
    2016 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 80, p. 566-573Article in journal (Refereed) Published
    Abstract [en]

    Fast and accurate detection of microorganisms is of key importance in clinical analysis and in food and water quality monitoring. Salmonella typhimurium is responsible for about a third of all cases of food borne diseases and consequently, its fast detection is of great importance for ensuring the safety of foodstuffs. We report the development of a label-free impedimetric aptamer-based biosensor for S. typhimurium detection. The aptamer biosensor was fabricated by grafting a diazonium-supporting layer onto screen printed carbon electrodes (SPEs), via electrochemical or chemical approaches, followed by chemical immobilisation of aminated-aptamer. FTIR-ATR, contact angle and electrochemical measurements were used to monitor the fabrication process. Results showed that electrochemical immobilisation of the diazonium-grafting layer allowed the formation of a denser aptamer layer, which resulted in higher sensitivity. The developed aptamer-biosensor responded linearly, on a logarithm scale, over the concentration range 1 x 10(1) to 1 x 10(8) CFU mL(-1), with a limit of quantification (LOQ) of 1 x 10(1) CFU mL(-1) and a limit of detection (LOD) of 6 CFU mL(-1). Selectivity studies showed that the aptamer biosensor could discriminate S. typhimurium from 6 other model bacteria strains. Finally, recovery studies demonstrated its suitability for the detection of S. typhimurium in spiked (1 x 10(2), 1 x 10(4) and 1 x 10(6) CFU mL(-1)) apple juice samples. (C) 2016 Elsevier B.V. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER ADVANCED TECHNOLOGY, 2016
    Keywords
    Diazonium grafting; Aptamer; S. typhimurium; Label-free detection; Electrochemical impedance spectroscopy; Food analysis
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-127249 (URN)10.1016/j.bios.2016.02.024 (DOI)000372558500079 ()26894987 (PubMedID)
    Note

    Funding Agencies|Vetenskapsradet (Pathoscreen project; Swedish Research Link) [D0675001]; Ministry of Science Research and Technology of Iran

    Available from: 2016-04-20 Created: 2016-04-19 Last updated: 2019-10-09Bibliographically approved
  • 37.
    Griffith, May
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lee, Chyan-Jang
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Buznyk, Oleksiy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Filatov Inst Eye Dis and Tissue Therapy, Ukraine.
    Artificial Corneas, and Reinforced Composite Implants for High Risk Donor Cornea Transplantation2017In: The Stem Cell Microenvironment and its Role in Regenerative Medicine and Cancer Pathogenesis, RIVER PUBLISHERS , 2017, Vol. 7, p. 93-102Conference paper (Refereed)
    Abstract [en]

    Here, we review examples of artificial corneas that have been developed as alternatives to donor cornea transplantation. These consist of artificial corneas developed as prostheses and regenerative scaffolds. Examples of reinforced and composite implants developed within our group are profiled.

  • 38.
    Gustafsson, Mattias
    Linköping University, The Department of Physics, Chemistry and Biology.
    Utvärdering av selenmetionins och nitroglycerins påväxthindrande effekter på havstulpaner för eventuell användning i båtbottenfärger: Evaluation of selenomethionine and nitro glycerine for possible use in boat paint to prevent barnacle fouling2005Independent thesis Basic level (professional degree), 10 points / 15 hpStudent thesis
    Abstract [en]

    Biological growth on boats and other objects that are placed in water is a big and expensive problem over the entire world. In Sweden, the barnacle, Balanus improvisius, grows the most easily. This barnacle has many larvae stages before it becomes mature. During the larvae stage when it searching for a surface to settle on it is called cyprid. It takes between three days and a couple of weeks before a cyprid chooses a spot to settle on. It chooses the spot to settle on very carefully because it will spend the rest of its life on that exact place.

    A lot of research goes into to finding a good alternative to today’s toxic boat paints. Tin organic compounds, as used to counteract settling of cyprids on boats, will be totally forbidden in January, 2008. As a replacement, copper compounds are being added more often to paints. These are not much better for the environment. Today there are many environmentally friendly paints, as for example silicon-based paint, but they do not work as well as the paints with metals. Research is also looking at mechanically changing a boat’s surface so that barnacles cannot attach as easily.

    The substances that are tested in this report are selenomethionine and nitro glycerine. They were tested in different concentration intervals and in different mixes with each other with the hope of that selenomethionine will bound into compounds and then the reaction velocity with thioles will be reduced and give toxic effects. The nitro glycerine will make the barnacle passive through the idea that the NO is binding into a heme group instead of oxygen. It was hoped that the substances show a synergistic effect when they are mixed, allowing lower concentrations to be used. With too high concentrations in the paint, the paint becomes too expensive and likely has a bigger negative influence on the environment.

    Selenomethionine showed an indication to reduce the likelihood that barnacles would settle on a pained surface, but nitro glycerine, on the other hand, caused an increased rate of cyprid settling. It was also shown that the substances had a synergistic effect and thus the concentrations for the substances can be lowered.

  • 39.
    Gustavsson, Malin
    et al.
    Linköping University, Department of Management and Engineering, Environmental Technology and Management.
    Wasell, Ellen
    Linköping University, Department of Management and Engineering, Environmental Technology and Management.
    Torrötning och våtrötning av avvattnad gödsel: Biogasproduktion i labskala och systemanalys av en torrötningsanläggning2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Den dominerande tekniken vid framställning av biogas från organiskt avfall är idag att använda kontinuerlig våtrötning. Utöver våtrötning finns också ett fåtal torrötningsanläggningar i Sverige. Torrötning skapar möjlighet att införa fler substrat på marknaden, substrat som annars kan vara problematiskt att röta i en våt process. Jordbrukssektorn har stor potential att bidra med organiskt avfall som kan nyttjas som substrat vid biogasproduktion. Förutom att öka den totala användningen av torra substrat från jordbrukssektorn är en möjlig åtgärd att öka biogasproduktion från gödsel, varför en lösning är avvattning. Efter separation erhålls en fast fraktion som kan spädas in i en våt process, eller användas som substrat vid en ny central torrötningsanläggning. Som slutprodukt erhålls biogas och biogödsel. Att avvattna gödseln innan rötning ger en annan gödselhantering än den konventionella. Detta eftersom att lägre volymer kan transporteras vid varje tillfälle jämfört med transport av flytgödsel som innehåller mycket vatten. 

    Syftet med examensarbetet var att analysera avvattnad gödsel som substrat till produktion av biogas, samt att studera effekten av att lägga till avvattning som ett alternativ till hanteringen av gödsel. För att klargöra hur mycket metangas som kunde bildas från avvattnad gödsel utfördes experiment i labskala med kontinuerlig våtrötning och satsvis torrötning. Parallellt med laborationsförsöken genomfördes en teoribaserad systemstudie med syfte att utreda central storskalig produktion med avvattnad gödsel som substrat. Utöver biogasproduktion analyserades gödselhantering med ett livscykelperspektiv där de olika systemalternativens direkta utsläpp av växthusgaser studerades. Systemmodellen innehöll tre scenarier vilka involverade olika system för att hantera gödseln (konventionell gödselhantering, våtrötning av flytgödsel samt våtrötning och torrötning med avvattnad gödsel som substrat).

    Laborationsförsöket visade att avvattnad gödsel är lämpligt som substrat vid biogasproduktion. Kontinuerlig våtrötning kunde genomföras med stabil process och liknade storskalig produktion. De kemiska analyser som utfördes under försöksperioden (pH, alkalinitet, VFA och kväve) uppvisade alla stabila värden utan processtörningar. Efter tre uppehållstider hade i medeltal 246 Nml CH4 per/g VS producerats från avvattnad gödsel vilket var i nivå med uppgifter från litteratur (200-300 Nml CH4/g VS). Vidare visade det satsvisa torrötningsförsöket varierande resultat beroende på val av ymp, samt hur stor mängd ymp som blandades in i testflaskorna. Vid inblandning av ymp från Tekniska verkens samrötningsanläggning i Linköping bildades i genomsnitt 222±8,6 Nml CH4/g VS (5 % VS ymp) respektive 236±10,8 Nml CH4/g VS (10 % VS ymp). Bildad metan 3 var inom rimligt intervall för välfungerande process, om än med lång uppehållstid (83 dagar). Försöksuppställningen för satsvis torrötning utformades så att laborationsförsöket skulle simulera så kallad garagerötning. Dock saknades utrustning för recirkulering av vätska, istället vändes testflaskorna dagligen. Då recirkulering av vätska ofta förekommer i storskaliga torrötningsanläggningar som drivs enligt garage-koncept är det önskvärt att utveckla laborationsförsöket vidare, med målet att bättre efterlikna en verklig process.

    I förhållande till konventionell hantering av gödsel visade systemstudien miljöfördelar för central torrötningsanläggning som använder avvattnad gödsel som substrat vid biogasproduktion. Miljönyttan var dels i händelse av att den bildade biogasen uppgraderas till fordonsbränsle och används som substitut till fossila drivmedel, men också om hantering av vätskefasen kan förbättras. Avvattnad gödsel ger en vätskefas som vid spridning och lagring ger upphov till emissioner av växthusgaser (lustgas, metan och koldioxid) som har negativ påverkan på miljön. Att skapa lösning för hantering av vätskefasen som reducerar emissioner innebär att biogassystem med avvattnad gödsel som substrat kan vara fördelaktigt ur ett miljöperspektiv jämfört med våtrötning av flytgödsel. Systemstudien inkluderade även en osäkerhetsanalys som visade att resultatet varierade beroende på vilket antagande som valdes för systemets parametrar. Den parameter som påverkade resultatet i störst utsträckning var antaganden kring metankonverteringsfaktorn (MCF). Sammanfattningsvis visade systemmodellen att det saknas tillräckligt underlag för att avgöra vilken rötningsteknik som är mest gynnsam vid produktion av biogas från avvattnad gödsel, varför fler studier är att rekommendera. 

  • 40.
    Gustavsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Development of soft sensors for monitoring and control of bioprocesses2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the manufacture of bio-therapeutics the importance of a well-known process is key for a high product titer and low batch to batch variations. Soft sensors are based on the concept that online sensor signals can be used as inputs to mathematical models to derive new valuable process information. This information could then be used for better monitoring and control of the bioprocess.

    The aim of the present thesis has been to develop soft sensor solutions for upstream bioprocessing and demonstrate their usefulness in improving robustness and increase the batch-to-batch reproducibility in bioprocesses. The thesis reviews the potential and possibilities with soft sensors for use in production of bio-therapeutics to realize FDA´s process analytical technology (PAT) initiative. Modelling and hardware sensor alternatives which could be used in a soft sensor setup are described and critically analyzed. Different soft sensor approaches to control glucose feeding in fed-batch cultures of Escherichia coli are described. Measurements of metabolic fluxes and specific carbon dioxide production was used as control parameters to increase product yield and decrease the variability of produced recombinant proteins. Metabolic heat signals were used in uninduced cultures to estimate and control the specific growth rate at a desired level and thereby also estimate the biomass concentration online. The introduction of sequential filtering of the signal enabled this method to be used in a down-scaled system. The risk and high impact of contaminations in cell cultures are also described. An in situ microscope (ISM) was used as an online tool to estimate cell concentration and also to determine cell diameter size which enabled the detection of contaminant cells at an early stage.

    The work presented in this thesis supports the idea that soft sensors can be a useful tool in the strive towards robust and reliable bioprocesses, to ensure high product quality and increased economic profit.

    List of papers
    1. Mini-review: soft sensors as means for PAT in the manufacture of bio-therapeutics
    Open this publication in new window or tab >>Mini-review: soft sensors as means for PAT in the manufacture of bio-therapeutics
    2015 (English)In: Journal of chemical technology and biotechnology (1986), ISSN 0268-2575, E-ISSN 1097-4660, Vol. 90, no 2, p. 215-227Article, review/survey (Refereed) Published
    Abstract [en]

    This mini-review discusses how soft sensors can contribute to accomplish FDAs process analytical technology (PAT) ambitions in the manufacture of bio-therapeutics. Focus is on applications with protein-based drugs (proteins, antibodies), but also gene therapy vectors as well as cell cultures are considered where chemical and bio-analytical as well as mathematical and statistical methods are used as tools. An overview of existing soft sensor alternatives and how these can be configured to meet typical industrial needs is provided. It is noted how several of these needs coincide with the PAT regulatory incentives but do also address process economic aspects of bio-therapeutic manufacture. Evaluation of soft sensor alternatives is highlighted in relation to the production targets, quality attributes and the specification of these as well as shortcomings and needs for further improvements.

    Place, publisher, year, edition, pages
    Wiley, 2015
    Keywords
    Bioprocesses; Bioreactors; Monitoring; Process Control
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-114232 (URN)10.1002/jctb.4477 (DOI)000347778100002 ()
    Available from: 2015-02-16 Created: 2015-02-16 Last updated: 2019-01-22
    2. Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein
    Open this publication in new window or tab >>Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein
    2013 (English)In: Bioprocess and biosystems engineering (Print), ISSN 1615-7591, E-ISSN 1615-7605, Vol. 36, no 10, p. 1375-1384Article in journal (Refereed) Published
    Abstract [en]

    A soft sensor approach is described for controlling metabolic overflow from mixed-acid fermentation and glucose overflow metabolism in a fed-batch cultivation for production of recombinant green fluorescence protein (GFP) in Escherichia coli. The hardware part of the sensor consisted of a near-infrared in situ probe that monitored the E. coli biomass and an HPLC analyzer equipped with a filtration unit that measured the overflow metabolites. The computational part of the soft sensor used basic kinetic equations and summations for estimation of specific rates and total metabolite concentrations. Two control strategies for media feeding of the fed-batch cultivation were evaluated: (1) controlling the specific rates of overflow metabolism and mixed-acid fermentation metabolites at a fixed pre-set target values, and (2) controlling the concentration of the sum of these metabolites at a set level. The results indicate that the latter strategy was more efficient for maintaining a high titer and low variability of the produced recombinant GFP protein.

    Place, publisher, year, edition, pages
    Springer Verlag (Germany), 2013
    Keywords
    Soft sensors, Software sensors, Bioprocess monitoring and control, Fed-batch cultivation control, Overflow metabolism, Mixed-acid fermentation
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-98661 (URN)10.1007/s00449-012-0840-z (DOI)000324214400005 ()
    Note

    Funding Agencies|Linkoping University||

    Available from: 2013-10-10 Created: 2013-10-10 Last updated: 2019-01-22Bibliographically approved
    3. Control of specific carbon dioxide production in a fed-batch culture producing recombinant protein using a soft sensor
    Open this publication in new window or tab >>Control of specific carbon dioxide production in a fed-batch culture producing recombinant protein using a soft sensor
    2015 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 200, p. 44-51Article in journal (Refereed) Published
    Abstract [en]

    The feeding of a fed-batch cultivation producing recombinant protein was controlled by a soft sensor setup. It was assumed that the control approach could be based on the cells production of carbon dioxide and that this parameter indicates the metabolic state occurring at induced protein expression. The soft sensor used the on-line signals from a carbon dioxide analyser and a near-infrared (NIR) probe for biomass to estimate the specific production rate (q(CO2)). Control experiments were carried out with various q(CO2) set-points where we observe that the feeding of nutrients to the culture could easily be controlled and resulted in a decreased variability compared to uncontrolled cultivations. We therefore suggest that this control approach could serve as an alternative to other commonly applied methods such as controlling the cells overflow metabolism of acetate or the cells specific growth rate. However, further studies of the internal metabolic fluxes of CO2 during protein expression would be recommended for a more precise characterization of the relationship between q(CO2) and protein expression in order to fully interpret the control behaviour.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Reproducibility; Variance; Carbon dioxide production rate; Bioprocess regulation; Monitoring; Software sensor
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-117361 (URN)10.1016/j.jbiotec.2015.02.030 (DOI)000352017700009 ()25746902 (PubMedID)
    Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2019-01-22Bibliographically approved
    4. A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals
    Open this publication in new window or tab >>A Soft Sensor for Bioprocess Control Based on Sequential Filtering of Metabolic Heat Signals
    2014 (English)In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 14, no 10, p. 17864-17882Article in journal (Refereed) Published
    Abstract [en]

    Soft sensors are the combination of robust on-line sensor signals with mathematical models for deriving additional process information. Here, we apply this principle to a microbial recombinant protein production process in a bioreactor by exploiting bio-calorimetric methodology. Temperature sensor signals from the cooling system of the bioreactor were used for estimating the metabolic heat of the microbial culture and from that the specific growth rate and active biomass concentration were derived. By applying sequential digital signal filtering, the soft sensor was made more robust for industrial practice with cultures generating low metabolic heat in environments with high noise level. The estimated specific growth rate signal obtained from the three stage sequential filter allowed controlled feeding of substrate during the fed-batch phase of the production process. The biomass and growth rate estimates from the soft sensor were also compared with an alternative sensor probe and a capacitance on-line sensor, for the same variables. The comparison showed similar or better sensitivity and lower variability for the metabolic heat soft sensor suggesting that using permanent temperature sensors of a bioreactor is a realistic and inexpensive alternative for monitoring and control. However, both alternatives are easy to implement in a soft sensor, alone or in parallel.

    Place, publisher, year, edition, pages
    MDPI, 2014
    Keywords
    bioprocess control; bio-calorimetry; software sensors; soft sensor implementation; bioprocess user interface
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-112839 (URN)10.3390/s141017864 (DOI)000344455700001 ()25264951 (PubMedID)
    Available from: 2015-01-08 Created: 2014-12-17 Last updated: 2019-01-22
  • 41.
    Gustavsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology .
    On-line control of glucose feeding in an Escherichia coli fed-batch cultivation expressing a recombinant protein.2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Soft sensors have been suggested as potent tools for on-line estimations of critical bioprocess variables to be able to control the biological process in an as high extent as possible. The formation of inhibitory by-products in the form of organic acids, caused by an overflow of glucose, is a problem in most bioprocesses expressing recombinant proteins. 

     

    In this project a new method of controlling the glucose feeding in an Escherichia coli fed-batch cultivation expressing the green fluorescent protein (GFP) was investigated. The new controller system implemented in the software controlled the feed rate based on on-line HPLC measurements of the concentration of organic acids.   

     

    The results showed that the controller managed to down-regulate the inhibitory organic acids to a low level as it tried to keep the glucose uptake rate at an optimum for maximum cell growth. The results suggested that the controller could be a powerful tool to create a more secure reproducibility and to generate high product yields in recombinant protein productions.   

  • 42.
    Gårdhagen, Roland
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Carlsson, Fredrik
    ANSYS Sweden, Gothenburg, Sweden.
    Karlsson, Matts
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Large Eddy Simulation of Steady and Pulsating Flow in Asymmetric Stenosed Pipe2010In: ASME 2010 Summer Bioengineering Conference: Parts A and B, The American Society of Mechanical Engineers (ASME) , 2010, p. 573-574Conference paper (Refereed)
    Abstract [en]

    Local hemodynamics and its impact on the development of cardiovascular disease and the blood itself have gained increasing attention during the last decades. Regions with low and/or oscillatory Wall Shear Stress (WSS) have been correlated with increased risk for development of atherosclerosis [1]; and turbulence in the cardio vascular system is suggested to increase the risk for hemolysis as well as platelet activation and thrombus formation [2, 3]. Furthermore, turbulent flows are inherently oscillatory with large spatial as well as temporal fluctuation, and hence possibly a risk for atherosclerosis development per se.

  • 43.
    Haglund, Emelie
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, The Institute of Technology.
    Systematisk bedömning av våtmarksväxter som substrat för biogasproduktion2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Two environmental problems today are the increased concentrations of greenhouse gases in the atmosphere and eutrophication.  Therefore, two challenges are reducing greenhouse gas emissions and fluxes of nutrients. Another challenge is to secure the energy supply in a world where energy demand is increasing. New renewable energy sources need to be developed both to secure the energy supply, but also to reduce the use of fossil energy. A renewable energy source is biogas that can be used for electricity, heating and as vehicle fuel. It is predicted that substrate for biogas production will be a limitation in the future, therefore, new substrate need to be evaluated. Wetland plants are an alternative substrate for biogas production and evaluated in this study.  Wetlands and it is plants are interesting to study because they can reduce the concentration of nutrients and therefore help to reduce the problem of eutrophication.  The study was performed within a project at Biogas Research Center and was a literature study with the study of a case. The method used has been developed in the project and is a Multi Criteria Assessment (MCA), which means that there are several different areas being studied. Areas taking into account the biological, economic, chemical, environmental and technological aspects. In order to structure the data, a matrix consisting of the different key areas was used. To clarify the opportunities and obstacles a semi-qualitative assessment was done for each key area. The case studied was a wetland in an agricultural landscape. The wetland is 5 ha and was constructed a few years ago to work as nitrogen and phosphorous trap. There is no vegetation in the wetland because it is relatively new. The plants that were studied during the study was therefore plants that are potential to grow in the wetland in the future. The studied plants were reed, reed canary grass and cattail. In the wetland it is possible to regulate the water and thereby drain the water to facilitate harvesting.   The results showed that the technology available today for the harvesting and chopping needs to be developed because it does not meet the required standards. There are various techniques for digestion, but since the dry matter is high for the plants dry fermentation is preferable, or a two-stage system in which the first step is dry digestion. A wetland provides a relatively small amount of biomass and therefore it is better to co-digest the plants on a farm biogas plant.  Wetland plants are not approved substrates for certification of bio fertilizer, which can be an obstacle. The bio fertilizer also has a low value because the plants contain low levels of nutrients.Wetlands reduce the amount of nutrients and harvest of wetland plants contributes to the retention of phosphorus increases. Wetlands emit methane and nitrous oxide that affect global warming.Today, there is no economic viability of harvesting wetlands. A system in which compensation is obtained for the environmental benefit that harvest provides is an option to increase profitability.

  • 44.
    Hagman, Linda
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    How do biogas solutions influence the sustainability of bio-based industrial systems?2018Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biomass is a valuable and limited resource that should be used efficiently. The potential of replacing fossil-based products with bio-based ones produced in biobased industrial systems is huge. One important aim of increasing the share of biobased products is to improve the sustainability of systems for production and consumption. Therefore, it is important to evaluate what solutions are available to improve the sustainability performance of bio-based industrial systems, and if they also bring negative impacts. The thesis focuses on assessing the role of biogas solutions in developing sustainable bio-based systems. Such assessments are often quite narrow in their scope and focus on quantitative environmental or economic aspects. This thesis aims at also including feasibility related aspects involving the contextual conditions that are assessed more qualitatively. Biogas solutions are identified as a versatile approach to treat organic materials which are generated in large volumes in bio-based industrial systems. The results show that biogas solutions in bio-based industrial systems (i) improve circular flows of energy and nutrients, (ii) are especially viable alternatives when the quality of the by-product streams become poorer, and (iii) may improve the profitability of the bio-based industrial system. To perform better assessments of these systems, it seems valuable to broaden the set of indicators assessed and include feasibility-related indicators, preferably through the involvement of relevant stakeholders as they contribute with different perspectives and can identify aspects that influence the sustainability in different areas. Future studies could benefit from applying those broader assessments on more cases to build on a more generalisable knowledge base.

    List of papers
    1. The role of biogas solutions in sustainable biorefineries
    Open this publication in new window or tab >>The role of biogas solutions in sustainable biorefineries
    2018 (English)In: Journal of Cleaner Production, ISSN 0959-6526, E-ISSN 1879-1786, Vol. 172, p. 3982-3989Article in journal (Refereed) Published
    Abstract [en]

    Biorefineries strive to maximise product mix and value while contributing to the bioeconomy. Circularityand waste valorisation are some important but often neglected concepts in this context. As such, biogassolutions in biorefineries could be a key technology to improve sustainability. This study has, through aliterature review and investigation into three Swedish case studies, analysed this relationship betweenbiogas solutions and biorefineries by assessing the added value and development potential to whichbiogas solutions may contribute. This analysis across agricultural, forest, and marine sectors indicatesthat biogas solutions contribute with several added values, including through making the biorefinerymore sustainable and competitive. The study also shows that biogas solutions can be an enabler ofbiorefinery development through making the system more resilient and versatile, as well as throughimproving the value of the product portfolio.

    Place, publisher, year, edition, pages
    Elsevier, 2018
    Keywords
    Biorefinery, biogas, bioeconomy, valorisation, anaerobic digestion, waste management, Bioraffinaderi, biogas, bioekonomi, avfallshantering
    National Category
    Other Environmental Engineering
    Identifiers
    urn:nbn:se:liu:diva-143022 (URN)10.1016/j.jclepro.2017.03.180 (DOI)000423002500084 ()2-s2.0-85016415075 (Scopus ID)
    Funder
    Swedish Energy Agency
    Note

    Funding agencies: Biogas Research Center (BRC); Swedish Energy Agency

    Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2019-06-13Bibliographically approved
  • 45.
    Hagman, Linda
    et al.
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    Eklund, Mats
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    Svensson, Niclas
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Science & Engineering.
    Assessment of By-product Valorisation in a Swedish Wheat-Based Biorefinery2019In: Waste and Biomass Valorization, ISSN 1877-2641, E-ISSN 1877-265XArticle in journal (Refereed)
    Abstract [en]

    Biorefineries are examples of industries striving towards a circular and bio-based economy through valorising natural raw materials to a spectrum of products. This is a resource-efficient process which also decreases overall environmental impact, as the products from a biorefinery can replace fossil-based products such as plastics or fuels. To become even more resource efficient, an optimisation of the by-product use can increase the performance. This study will evaluate different scenarios for the valorisation of stillage coming from a wheat-based biorefinery. The alternatives range from the direct use of the stillage for fodder, fertiliser or incineration to three different biogas production-based scenarios. The biogas scenarios are divided into the production of fuel at a local or distant plant and the alternative of creating heat and power at the local plant. The results show how locally produced biogas for vehicle fuel and fodder usage are the better alternatives regarding greenhouse gas emissions, the finances of the biorefinery, energy balance and nutrient recycling. The results also indicate that biorefineries with several high-value products may receive lower quality by-product flows, and to these, the biogas solutions become more relevant for valorising stillage while improving value and performance for the biorefinery.

  • 46.
    Hansson, Anna
    Linköping University, Department of Physics, Chemistry and Biology.
    Mechanism of zeolite activity in biogas co-digestion2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Biogas is a source of renewable energy and is produced at anaerobic conditions. The gas consists mainly of methane (55-70 %) and carbon dioxide (30-45 %). Biogas can be used as vehicle fuel after the gas has been upgraded to a methane content of approximately 97 %. There are several companies in Sweden producing biogas. Svensk biogas AB in Linköping is one of the largest. The company has two biogas production plants; one in Linköping and one in Norrköping.

    To meet the surge demand for biogas it is not only important to increase the volumetric capacity of the digesters, but also to optimize the process at the existing production plants in different ways. Zeolites, a clay mineral, have earlier been shown to have a positive effect on anaerobic digestion of certain substrates. The aim of this master’s thesis was to investigate if the organic loading rate could be increased and/or if the hydraulic retention time could be reduced by addition of zeolites to a reactor treating slaughterhouse waste as a substrate. The aim was further to investigate which substance/substances that zeolites possibly could affect.

    Addition of the zeolite clinoptilolite in a continuously stirred lab tank reactor showed a significantly lower accumulation of volatile fatty acids compared to that in a control reactor without zeolites added, when the hydraulic retention time was kept low (30 days) and the organic loading rate was high (4.8 kg VS/ (m3 × day)). The same results were observed upon zeolite addition in a batch experiment, which also showed a decreased lag phase. Neither the specific gas production nor the methane concentration was significantly affected by addition of zeolites. Furthermore, addition of a possible inhibitor, long-chain fatty acids (LCFA), increased the lag phase further when slaughterhouse waste was used as a substrate. The conclusion from the observed results is that a metabolite or metabolites produced during the anaerobic degradation is/are the reason to inhibition and an increased lag phase.

  • 47.
    Hedberg, Lilia
    Linköping University, Department of Clinical and Experimental Medicine.
    Identification of obesity-associated SNPs in the human genome: Method development and implementation for SOLiD sequencing data analysis2010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Over the last few years, genome-wide association studies (GWAS) have been used to identify numerous obesity associated SNPs in the human genome. By using linkage studies, candidate obesity genes have been identified. When SNPs in the first intron of FTO were found to be associated to BMI, it became the first gene to be linked to common obesity. In order to look for causative explanations behind the associated SNPs, a re-sequencing of FTO had been performed on the SOLiD sequencing platform. In-house candidate gene, SLCX, was also sequenced in order to evaluate a potential obesity association. The purpose of this project was to analyse the sequences and also to evaluate the quality of the SOLiD sequencing. A part of the project consisted in performing PCRs and selecting genomic regions for future sequencing projects. I developed and implemented a sequence analysis strategy to identify obesity associated SNPs. I found 39 obesity-linked SNPs in FTO, a majority of which were located in introns 1 and 8. I also identified 3 associated intronic SNPs in SLCX. I found that the SOLiD sequencing coverage varies between non-repetitive and repetitive genomic regions, and that it is highest near amplicon ends. Interestingly, coverage varies significantly between different amplicons even after repetitive sequences have been removed, which indicates that it is affected by features inherent to the sequence. Still, the observed allele frequencies for known SNPs were highly correlated with the SNP frequencies documented in HapMap. In conclusion, I verify that SNPs in FTO are associated with obesity and also identify a previously unassociated gene, SLCX, as a potential obesity gene. Re-sequencing of genomic regions on the SOLiD platform was proven to be successful for SNP identification, although the difference in sequencing coverage might be problematic.

  • 48.
    Hellman, Emil
    Linköping University, The Tema Institute, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Lagringstidens påverkan på metanpotentialen i matavfall2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Biogas is a renewable energy source that is produced when organic materials like food waste is degraded by microorganisms under anaerobic (oxygen-free) conditions. The Swedish Government has set goals for a higher sorting of food waste, leading to increased amounts of available substrate for biogas production.

    Collected food waste begin to break down during the time it is transported and stored. The purpose of this study was to investigate the length of the storage, produce a representative recipe for an average food waste in Sweden and evaluate how much methane potential is lost from food waste with respect to the storage time, collection method (paper or plastic bag) and storage temperature (22°C and 6°C) through laboratory tests.

    The average storage time of food waste from houses and apartment buildings in the survey was six days. A recipe for food waste has been developed with the help of literature search and modification of recipes in ‘’Avfall Sverige’’ report U2010:10. Laboratory tests showed that the difference in methane potential between the plastic and paper were clear at 22°C, with decreasing methane potential, but non-existent at 6°C.

    To achieve maximum methane production from food waste during the warmer part of the year, plastic bags are better because they have a preservative effect on the food waste. This can be related to the fact that plastic are denser than paper and therefore holds volatile compounds better.

  • 49.
    Hjersing, Charlotte
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Hydrogen production in Escherichia coli: Genetic engineering of the formate hydrogenlyase complex2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Biofuels that are renewable and environmentally benign constitute an important area of research, as the supply of fossil fuels decreases and the amount of green house gases in the atmosphere increases. Biohydrogen is not as well explored as other biofuels, but its properties render it a promising complement, as it is clean and can be used directly in fuel cells to generate electricity, the only waste products being water and heat. Hydrogenproducing microorganisms have the potential to be used to recycle industrial waste, such as carbohydrates from food manufacturing. Hence the cost of waste disposal could be reduced whilst biofuel is being produced through microbial processes.

    Escherichia coli is a well-known microorganism that produces hydrogen under fermentative conditions, through the conversion of formate to hydrogen gas and carbon dioxide, via an enzyme complex called formate hydrogenlyase (FHL). The complex is anchored to the inner cell membrane and consists of seven subunits: a formate dehydrogenase, a [Ni-Fe] hydrogenase, three electron carrier proteins, which together make up a large ‘hydrophilic domain’, and two integral membrane proteins (the ‘membrane domain’).

    Even though the entire bacterial genome is known, the FHL complex remains little understood and has proven difficult to isolate and characterise. During this project, a genetically modified strain producing only the hydrophilic domain of FHL was constructed, and the resultant sub-complex was purified. It was hoped that, if a stable and homogenous core complex could be isolated, it might be subjected to further analysis, such as elucidating the subunit stoichiometry and solving the structure.

    Furthermore, FHL is notoriously oxygen labile, which hampers its study and technological development. However, oxygen tolerance is a natural feature found in some other [Ni-Fe] hydrogenases, and recent research shows that this property is likely dependent on the presence of extra cysteine residues near an important metal cluster in the enzyme. These cysteines are not present in FHL and a complex that could be active in both aerobic and anaerobic conditions may be a useful tool in optimising microbial biohydrogen processes. Thus, three strains that each expressed a modified FHL variant carrying single Cysteine-for-Glycine substitutions were constructed. The modified FHL complexes proved to remain active in vivo, and can serve as the basis of genetically engineering oxygen tolerance into this important enzyme.

  • 50. HULTEN, J
    et al.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    A DEVICE FOR BLADDER PRESSURE MONITORING DURING TRANS-URETHRAL RESECTION1984In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, no 82, p. 75-80Article in journal (Refereed)
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