| 1. |
- Abdalla, Hassan, 1987-
(författare)
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Charge and Energy Transport in Disordered Organic Semiconductors
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Improvement of the performance of organic disordered semiconductors (OSC) is driven by the understanding of the underlying charge transport mechanisms and systematic exploitation thereof. There exists a multitude of materials and material systems based on polymers and small molecules with promising performance for use in organic light emitting diodes, photovoltaics, organic field-effect transistors and thermoelectrics. However, universal understanding of many classes of these materials has eluded researchers, due to their broad spectrum of morphologies, molecular structures and electrical properties. Building on the large body of existing models, this thesis deals with charge transport phenomena from the perspective of transport energetics, by studying the interplay between a few but important concepts commonly accepted to play a crucial role in all OSC materials; energetic disorder, charge carrier hopping and Coulomb interactions. The influence of these concepts on the energetic landscape through which charge carriers move and how this translates to experimentally observed transport phenomena are studied by a combination of experimental work, kinetic Monte Carlo (MC) simulations and empirical and analytical models.The universal scaling and collapse of the temperature and electric field dependence of the conductivity of PEDOT:PSS to a single curve is shown to be functionally equivalent to the scaling of the effective temperature, which describes the effect of field heating as a broadening of the charge carrier distribution. From numerical investigation of the energy relaxation, an empirical model is developed that relates the physical meaning behind both concepts to the heat balance between Joule heating of the carrier distribution via the effective temperature and energy loss to the lattice. For this universal description to be applicable a strongly energy- dependent density of states (DOS) as well as Coulomb interactions and large carrier concentrations are needed.Chemical doping is a common way of improving charge transport in OSC and is also beneficial for energy transport, which combined leads to an increased thermoelectric power factor. The ensuing thermoelectric investigations not only showed the potential of these materials for use in thermoelectric generators, but are also helpful in unraveling charge transport mechanism as they give direct insight into the energetics of a material. Interestingly, doped OSC exhibit the same universal power-law relationship between thermopower and conductivity, independent of material system or doping method, pointing towards a common energy and charge transport mechanism. In this thesis an analytical model is presented, which reproduces said universal power-law behavior and is able to attribute it to Variable Range Hopping (VRH) or a transition between Nearest Neighbour Hopping (NNH) and VRH at higher concentrations. This model builds on an existing three- dimensional hopping formalism that includes the effect of the attractive Coulomb potential of ionized dopants that leads to a broadening of the DOS. Here, this model is extended by including the energy offset between host and dopant material and is positively tested against MC simulations and a set of thermoelectric measurements covering different material groups and doping mechanisms.Organic field effect transistors (OFETs) have become increasingly comparable in electrical mobility to their inorganic (silicon) counterparts. The spatial extent of charge transport in OFETs has been subject to debate since their inception with many experimental, numerical and analytical studies having been undertaken. Here it is shown that the common way of analyzing the dimensionality of charge transport in OFETs may be prone to misinterpretations. Instead, the results in this thesis suggest that charge transport in OFETs is, in fact, quasi- two-dimensional (2D) due to the confinement of the gate field in addition to a morphology-induced preferred in-plane direction of the transport. The inherently large charge carrier concentrations in OFETs in addition to the quasi-2D confinement leads to increased Coulomb interaction between charge carriers as compared to bulk material, leading to a thermoelectric behavior that deviates from doped organic systems. At very large concentrations interesting charge transport phenomena are observed, including an unexpected simultaneous increase of the concentration dependence and the magnitude of the mobility, the appearance of a negative transconductance, indicating a transition to an insulating Mott-Hubbard phase. The experimental and numerical results in this thesis relate these phenomena the intricacies of the interplay between Coulomb interactions, energetic disorder and charge carrier hopping.
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| 2. |
- Abrikossova, Natalia, 1965-
(författare)
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Investigation of nanoparticle-cell interactions for development of next generation of biocompatible MRI contrast agents
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Progress in synthesis technologies and advances in fundamental understanding of materials with low dimensionality has led to the birth of a new scientific field, nanoscience, and to strong expectations of multiple applications of nanomaterials. The physical properties of small particles are unique, bridging the gap between atoms and molecules, on one side, and bulk materials on the other side. The work presented in this thesis investigates the potential of using magnetic nanoparticles as the next generation of contrast agents for biomedical imaging. The focus is on gadolinium-based nanoparticles and cellular activity including the uptake, morphology and production of reactive oxygen species.Gd ion complexes, like Gd chelates, are used today in the clinic, world-wide. However, there is a need for novel agents, with improved contrast capabilities and increased biocompatibility. One avenue in their design is based on crystalline nanoparticles. It allows to reduce the total number of Gd ions needed for an examination. This can be done by nanotechnology, which allows one to improve and fine tune the physico- chemical properties on the nanomaterial in use, and to increase the number of Gd atoms at a specific site that interact with protons and thereby locally increase the signal. In the present work, synthesis, purification and surface modification of crystalline Gd2O3-based nanoparticles have been performed. The nanoparticles are selected on the basis of their physical properties, that is they show enhanced magnetic properties and therefore may be of high potential interest for applications as contrast agents.The main synthesis method of Gd2O3 nanoparticles in this work was the modified “polyol” route, followed by purification of as-synthesized DEG-Gd2O3 nanoparticles suspensions. In most cases the purification step involved dialysis of the nanoparticle samples. In this thesis, organosilane were chosen as an exchange agent for further functionalization. Moreover, several paths have been explored for modification of the nanoparticles, including Tb3+ doping and capping with sorbitol.Biocompatibility of the newly designed nanoparticles is a prerequisite for their use in medical applications. Its evaluation is a complex process involving a wide range of biological phenomena. A promising path adopted in this work is to study of nanoparticle interactions with isolated blood cells. In this way one could screen nanomaterial prior to animal studies.The primary cell type considered in the thesis are polymorphonuclear neutrophils (PMN) which represent a type of the cells of human blood belonging to the granulocyte family of leukocytes. PMNs act as the first defense of the immune system against invading pathogens, which makes them valuable for studies of biocompatibility of newly synthesized nanoparticles. In addition, an immortalized murine alveolar macrophage cell line (MH-S), THP-1 cell line, and Ba/F3 murine bone marrow-derived cell line were considered to investigate the optimization of the cell uptake and to examine the potential of new intracellular contrast agent for magnetic resonance imaging. In paper I, the nanoparticles were investigated in a cellular system, as potential probes for visualization and targeting intended for bioimaging applications. The production of reactive oxygen species (ROS) by means of luminol-dependent chemiluminescence from human neutrophils was studied in presence of Gd2O3 nanoparticles. In paper II, a new design of functionalized ultra-small rare earth-based nanoparticles was reported. The synthesis was done using polyol method followed by PEGylation, and dialysis. Supersmall gadolinium oxide (DEG-Gd2O3) nanoparticles, in the range of 3-5 nm were obtained and carefully characterized. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. In paper III, cell labeling with Gd2O3 nanoparticles in hematopoietic cells was monitored by magnetic resonance imaging (MRI). In paper IV, ultra-small gadolinium oxide nanoparticles doped with terbium ions were synthesized as a potentially bifunctional material with both fluorescent and magnetic contrast agent properties. Paramagnetic behavior was studied. MRI contrast enhancement was received, and the luminescent/ fluorescent property of the particles was attributable to the Tb3+ ion located on the crystal lattice of the Gd2O3 host. Fluorescent labeling of living cells was obtained. In manuscript V, neutrophil granulocytes were investigated with rapid cell signaling communicative processes in time frame of minutes, and their response to cerium-oxide based nanoparticles were monitored using capacitive sensors based on Lab-on-a-chip technology. This showed the potential of label free method used to measure oxidative stress of neutrophil granulocytes. In manuscript VI, investigations of cell-(DEGGd2O3) nanoparticle interactions were carried out. Plain (DEG-Gd2O3) nanoparticles, (DEG-Gd2O3) nanoparticles in presence of sorbitol and (DEG-Gd2O3) nanoparticles capped with sorbitol were studied. Relaxation studies and measurements of the reactive oxygen species production by neutrophils were based on chemiluminescence. Cell morphology was evaluated as a parameter of the nanoparticle induced inflammatory response by means of the fluorescence microscopy.The thesis demonstrates high potential of novel Gd2O3-based nanoparticles for development of the next generation contrast agents, that is to find biocompatible compounds with high relaxivity that can be detected at lower doses, and in the future enable targeting to provide great local contrast.
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| 3. |
- Agnvall, Beatrix
(författare)
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Early domestication? : Phenotypic alterations of Red Junglefowl selected for divergent fear of humans
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Domestication is the process through which animals adapt to conditions provided by humans. The domesticated phenotype differs from wild ancestors in a number of traits relating to physiology, morphology and behaviour. One of the most striking differences is the animals’ fear response towards humans, and reduced fear of humans is assumed to have been an early prerequisite for the success of domestication. The early alterations seen in the domesticated phenotype may be traits developed as a correlated selection response due to tameness rather than selected upon one by one.This thesis summarizes a project where Red Junglefowl were selected for divergent fear of humans during six generations. In every generation, fear response to human was assessed in a standardized test and, according to fear score, the animals were bred for either high fear of humans (H) or low fear of humans (L). The animals were, above that of the standardized selection test, behaviourally phenotyped in different tests in each generation mainly focusing on fear, exploration and social behaviour. In addition to behaviour, the animals were phenotyped for body weight, egg weight, metabolism, feed intake, plumage condition, blood plasma corticosterone and peripheral serotonin. After culling, vital organs and brains were harvested and weighed.In paper I, we demonstrated that the selection trait has a significant genetic heritability and is genetically correlated with other behavioural responses associated with fearfulness and exploration. In paper II, we concluded that animals from the L strain had better plumage condition, higher weight, laid larger eggs and also generated larger offspring. Furthermore, when tested in a social dominance test with a limited resource, they received less and performed more aggression regardless of whether the restricted source was edible or not. In paper III, we revealed that animals from the L strain had higher basal metabolic rate as chicks, gained more weight in relation to feed intake and were bolder in a Novel Object test. Furthermore, the L males had higher plasma levels of peripheral serotonin, but the corticosterone after a restraint stress test did not differ. In paper IV and V, we concluded the project by comparing brain and organ weights as well as behaviour of the parental generation (P0) with the fifth selected generation (S5). The absolute brain weight as well as the weight specific brain weight were larger in the animals selected on H than in the L-animals. The relative weight of telencephalon was significantly higher in H whereas relative weight of cerebellum was significantly lower. Heart, liver, spleen and testes were all relatively heavier in H animals than in L. Interestingly, the behaviours assessed in P0 and S5 seemed to be rather resilient to the selection with only small differences in S5.To summarize, the selection on divergent tameness in Red Junglefowl has affected several phenotypic traits associated with the domesticated phenotype. The results of this project indicate that tameness in Red Junglefowl could be an underlying factor driving trait modifications towards the domesticated phenotype.
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| 4. |
- Ahlner, Alexandra, 1984-
(författare)
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Improved Methods for Characterization of Protein Dynamics by NMR spectroscopy and Studies of the EphB2 Kinase Domain
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins are essential for all known forms of life and in many lethal diseases protein failure is the cause of the disease. To understand proteins and the processes they are involved in, it is valuable to know their structures as well as their dynamics and interactions. The structures may not be directly inspected because proteins are too small to be visible in a light microscope, which is why indirect methods such as nuclear magnetic resonance (NMR) spectroscopy have to be utilized. This method provides atomic information about the protein and, in contrast to other methods with similar resolution, the measurements are performed in solution resulting in more physiological conditions, enabling analysis of dynamics. Important dynamical processes are the ones on the millisecond timeframe, which may contribute to interactions of proteins and their catalysis of chemical reactions, both of significant value for the function of the proteins.To better understand proteins, not only do we need to study them, but also develop the methods we are using. This thesis presents four papers about improved NMR techniques as well as a fifth where the kinase domain of ephrinB receptor 2 (EphB2) has been studied regarding the importance of millisecond dynamics and interactions for the activation process. The first paper presents the software COMPASS, which combines statistics and the calculation power of a computer with the flexibility and experience of the user to facilitate and speed up the process of assigning NMR signals to the atoms in the protein. The computer program PINT has been developed for easier and faster evaluation of NMR experiments, such as those that evaluate protein dynamics. It is especially helpful for NMR signals that are difficult to distinguish, so called overlapped peaks, and the soft- ware also converts the detected signals to the indirectly measured physical quantities, such as relaxation rate constants, principal for dynamics. Next are two new versions of the Carr-Purcell-Maiboom-Gill (CPMG) dispersion pulse sequences, designed to measure millisecond dynamics in a way so that the signals are more separated than in standard experiments, to reduce problems with overlaps. To speed up the collection time of the data set, a subset is collected and the entire data set is then reconstructed, by multi-dimensional decomposition co-processing. Described in the thesis is also a way to produce suitably labeled proteins, to detect millisecond dynamics at Cα positions in proteins, using the CPMG dispersion relaxation experiment at lower protein concentrations. Lastly, the kinase domain of EphB2 is shown to be more dynamic on the millisecond time scale as well as more prone to interact with itself in the active form than in the inactive one. This is important for the receptor function of the protein, when and how it mediates signals.To conclude, this work has extended the possibilities to study protein dynamics by NMR spectroscopy and contributed to increased understanding of the activation process of EphB2 and its signaling mechanism.
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| 5. |
- Aid, Graham, 1980-
(författare)
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Operationalizing Industrial Ecology in the Waste Sector : Roles and tactics for circular value innovation
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The take-make-waste approach to resource management in human production and consumption systems is contributing to a variety of environmental and social problems worldwide. Additionally, as the world’s population and affluence increase, so do the negative impacts of poor resource management. Lifting the waste management (WM) sector into a new phase of development, which takes its lead from the ideals of Industrial Ecology and circular economy, is seen by many scholars and practitioners as one potential to assist in alleviating these impacts. While there are many studies on how more efficient inter-organizational resource management is (or could be) constructed, there are relatively few business development studies which have explored novel approaches (from roles to tactics) that WM organizations might operationalize toward more efficient resource management.The aim of this thesis is to contribute to the development of knowledge and understanding of how the waste management sector can operationalize more effective and efficient resource management. In approaching this aim, two research questions guided the exploration of: 1) novel roles for WM and 2) support tactics for such roles. Grounded in the broader context of Industrial Ecology (IE) and Business Development, five studies were performed. Two studies, focused on the novel roles of inter-organizational resource management and high value secondary resource extraction, were performed through literature review and interviews, and market driver analysis respectively. In exploring support tactics, two design and proof of concept studies were carried out to investigate data analysis tools for inter-organizational resource management, and one long-term action research engagement project was coordinated to study hands-on inter-organizational collaboration tactics.The studies highlighted that the Swedish WM sector holds some key capacities for operationalizing (and in some cases, is already developing) the novel resource management roles identified: industrial symbiosis facilitator, eco-industrial park manager, holistic facility management, and high value resource extractor. However, depending on the portfolio of services to be performed in such roles, several capacities may need to be developed or strengthened. Main opportunities seen for these roles were – staying ahead of market developments, and aligning activities with organizational goals. The main general risk related to these roles was insufficient returns on investment. Looking forward, the main enablers identified were policy leadership for more balanced market mechanisms, increasing use of external knowledge, developing long term partnerships, lobbying, stockpiling resources, and carefully crafting new business models.The tools developed for strategically applying external information toward the identification of opportunities within new roles showed tactical potential. However, their implementation in broader development processes has yet to be fully validated. The hands-on exploration of change oriented collaboration, highlighted collective system framing and goal setting and face-to-face interaction as key activities for inter-organizational approaches within roles such as industrial symbiosis facilitator.Throughout the studies, several novel roles were investigated. Each of these roles will need to be individually evaluated by directing bodies of WM organizations, and evaluated from the organization’s vision and strategy. If certain roles are chosen to be explored in more detail, they will need to be developed within full business models - addressing issues such as income structure, internal processes and capacities to be developed, and key customers. Through applying IE and business development concepts and findings, WM organizations have possibilities to translate ambitious visions into novel offerings.
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| 6. |
- Ajjan Godoy, Fátima Nadia
(författare)
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Biohybrid Polymer Electrodes for Renewable Energy Storage
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Daily and seasonally fluctuating energy supply and demand requires adequate energy storage solutions. In recent years electrochemical supercapacitors have attracted considerable attention due to their ability to both store and deliver electrical energy efficiently. Our efforts are focused on developing and optimizing sustainable organic electrode materials for supercapacitors based on renewable bioorganic materials, offering a cheap, environmentally friendly and scalable alternative to store energy. In particular, we are using the second most abundant biopolymer in nature, lignin (Lig), which is an insulating material. However, when used in combination with electroactive and conducting polymers such as polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT), the biohybrid electrodes PPy/Lig and PEDOT/Lig display significantly enhanced energy storage performance as compared to the pristine conducting polymers without the lignin. Redox cyclic voltammetry and galvanostatic charge/discharge measurements indicate that the enhanced performance is due to the additional pseudocapacitance generated by the quinone moieties in lignin. Moreover, a conjugated redoxpolymer poly(aminoanthraquinone) PAAQ, with intrinsic quinone functions and excellentstability, has been combined with lignin and PEDOT resulting in a trihybrid bioelectrode. PEDOT compensates the low conductivity of PAAQ and provides electrical pathways to the quinone groups. The electrochemically generated quinones undergo a two electron, two protonredox process within the biohybrid electrodes as revealed by FTIR spectroelectrochemistry.These remarkable features reveal the exciting potential of a full organic energy storage device with long cycle life. Therefore, supercapacitor devices were designed in symmetric or asymmetric two electrode configuration. The best electrochemical performance was achieved by the asymmetric supercapacitor based on PEDOT+Lignin/PAAQ as the positive electrode and PEDOT/PAAQ as the negative electrode. This device exhibits superior electrochemical performance and outstanding stability after 10000 charge/discharge cycles due to the synergistic effect of the two electrodes. Finally, we have characterized the response of this supercapacitor device when charged with the intermittent power supply from an organic photovoltaic module. We have designed charging/discharging conditions such that reserve power was available in the storage device at all times. This work has resulted in an inexpensive fully organic system witht he dual function of energy conversion and storage.
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| 7. |
- Alam, Syed Asad, 1984-
(författare)
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Techniques for Efficient Implementation of FIR and Particle Filtering
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- FIR filters occupy a central place many signal processing applications which either alter the shape, frequency or the sampling frequency of the signal. FIR filters are used because of their stability and possibility to have linear-phase but require a high filter order to achieve the same magnitude specifications as compared to IIR filters. Depending on the size of the required transition bandwidth the filter order can range from tens to hundreds to even thousands. Since the implementation of the filters in digital domain requires multipliers and adders, high filter orders translate to a large number of these arithmetic units for its implementation. Research towards reducing the complexity of FIR filters has been going on for decades and the techniques used can be roughly divided into two categories; reduction in the number of multipliers and simplification of the multiplier implementation. One technique to reduce the number of multipliers is to use cascaded sub-filters with lower complexity to achieve the desired specification, known as FRM. One of the sub-filters is a upsampled model filter whose band edges are an integer multiple, termed as the period L, of the target filter's band edges. Other sub-filters may include complement and masking filters which filter different parts of the spectrum to achieve the desired response. From an implementation point-of-view, time-multiplexing is beneficial because generally the allowable maximum clock frequency supported by the current state-of-the-art semiconductor technology does not correspond to the application bound sample rate. A combination of these two techniques plays a significant role towards efficient implementation of FIR filters. Part of the work presented in this dissertation is architectures for time-multiplexed FRM filters that benefit from the inherent sparsity of the periodic model filters.These time-multiplexed FRM filters not only reduce the number of multipliers but lowers the memory usage. Although the FRM technique requires a higher number delay elements, it results in fewer memories and more energy efficient memory schemes when time-multiplexed. Different memory arrangements and memory access schemes have also been discussed and compared in terms of their efficiency when using both single and dual-port memories. An efficient pipelining scheme has been proposed which reduces the number of pipelining registers while achieving similar clock frequencies. The single optimal point where the number of multiplications is minimum for non-time-multiplexed FRM filters is shown to become a function of both the period, L and time-multiplexing factor, M. This means that the minimum number of multipliers does not always correspond to the minimum number of multiplications which also increases the flexibility of implementation. These filters are shown to achieve power reduction between 23% and 68% for the considered examples.To simplify the multiplier, alternate number systems like the LNS have been used to implement FIR filters, which reduces the multiplications to additions. FIR filters are realized by directly designing them using ILP in the LNS domain in the minimax sense using finite word length constraints. The branch and bound algorithm, a typical algorithm to implement ILP problems, is implemented based on LNS integers and several branching strategies are proposed and evaluated. The filter coefficients thus obtained are compared with the traditional finite word length coefficients obtained in the linear domain. It is shown that LNS FIR filters provide a better approximation error compared to a standard FIR filter for a given coefficient word length.FIR filters also offer an opportunity in complexity reduction by implementing the multipliers using Booth or standard high-radix multiplication. Both of these multiplication schemes generate pre-computed multiples of the multiplicand which are then selected based on the encoded bits of the multiplier. In TDF FIR filters, one input data is multiplied with a number of coefficients and complexity can be reduced by sharing the pre-computation of the multiplies of the input data for all multiplications. Part of this work includes a systematic and unified approach to the design of such computation sharing multipliers and a comparison of the two forms of multiplication. It also gives closed form expressions for the cost of different parts of multiplication and gives an overview of various ways to implement the select unit with respect to the design of multiplexers.Particle filters are used to solve problems that require estimation of a system. Improved resampling schemes for reducing the latency of the resampling stage is proposed which uses a pre-fetch technique to reduce the latency between 50% to 95% dependent on the number of pre-fetches. Generalized division-free architectures and compact memory structures are also proposed that map to different resampling algorithms and also help in reducing the complexity of the multinomial resampling algorithm and reduce the number of memories required by up to 50%.
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| 8. |
- Alnoor, Hatim, 1979-
(författare)
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Toward the Optimization of Low-temperature Solution-based Synthesis of ZnO Nanostructures for Device Applications
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One-dimensional (1D) nanostructures (NSs) of Zinc Oxide (ZnO) such as nanorods (NRs) have recently attracted considerable research attention due to their potential for the development of optoelectronic devices such as ultraviolet (UV) photodetectors and light-emitting diodes (LEDs). The potential of ZnO NRs in all these applications, however, would require synthesis of high crystal quality ZnO NRs with precise control over the optical and electronic properties. It is known that the optical and electronic properties of ZnO NRs are mostly influenced by the presence of native (intrinsic) and impurities (extrinsic) defects. Therefore, understanding the nature of these intrinsic and extrinsic defects and their spatial distribution is critical for optimizing the optical and electronic properties of ZnO NRs. However, identifying the origin of such defects is a complicated matter, especially for NSs, where the information on anisotropy is usually lost due to the lack of coherent orientation.Thus, the aim of this thesis is towards the optimization of the lowtemperature solution-based synthesis of ZnO NRs for device applications. In this connection, we first started with investigating the effect of the precursor solution stirring durations on the deep level defects concentration and their spatial distribution along the ZnO NRs. Then, by choosing the optimal stirring time, we studied the influence of ZnO seeding layer precursor’s types, and its molar ratios on the density of interface defects. The findings of these investigations were used to demonstrate ZnO NRs-based heterojunction LEDs. The ability to tune the point defects along the NRs enabled us further to incorporate cobalt (Co) ions into the ZnO NRs crystal lattice, where these ions could occupy the vacancies or interstitial defects through substitutional or interstitial doping. Following this, high crystal quality vertically welloriented ZnO NRs have been demonstrated by incorporating a small amount of Co into the ZnO crystal lattice. Finally, the influence of Co ions incorporation on the reduction of core-defects (CDs) in ZnO NRs was systematically examined using electron paramagnetic resonance (EPR).
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| 9. |
- Alonso, Fabiola, 1980-
(författare)
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Models and Simulations of the Electric Field in Deep Brain Stimulation : Comparison of Lead Designs, Operating Modes and Tissue Conductivity
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Deep brain stimulation (DBS) is an established surgical therapy for movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). A thin electrode is implanted in a predefined area of the brain with the use of stereotactic neurosurgery. In the last few years new DBS electrodes and systems have been developed with possibilities for using more parameters for control of the stimulation volume.In this thesis, simulations using the finite element method (FEM) have been developed and used for investigation of the electric field (EF) extension around different types of DBS lead designs (symmetric, steering) and stimulation modes (voltage, current). The electrode surrounding was represented either with a homogeneous model or a patient-specific model based on individual preoperative magnetic resonance imaging (MRI). The EF was visualized and compared for different lead designs and operating modes.In Paper I, the EF was quantitatively investigated around two lead designs (3389 and 6148) simulated to operate in voltage and current mode under acute and chronic time points following implantation.Simulations showed a major impact on the EF extension between postoperative time points which may explain the clinical decisions to change the stimulation amplitude weeks after implantation. In Paper II, the simulations were expanded to include two leads having steering function (6180, Surestim1) and patient-specific FEM simulations in the zona incerta. It was found that both the heterogeneity of the tissue and the operating mode, influence the EF distribution and that equivalent contact configurations of the leads result in similar EF. The steering mode presented larger volumes in current mode when using equivalent amplitudes. Simulations comparing DBS and intraoperative stimulation test using a microelectrode recording (MER) system (Paper III), showed that several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution and that the DBS EF volume can cover, but also extend to, other anatomical areas.Paper IV introduces a method for an objective exploitation of intraoperative stimulation test data in order to identify the optimal implant position in the thalamus of the chronic DBS lead. Patient-specific EF simulations were related to the anatomy with the help of brain atlases and the clinical effects which were quantified by accelerometers. The first results indicate that the good clinical effect in ET is due to several structures around the ventral intermediate nucleus of the thalamus.
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| 10. |
- Anandapadamanaban, Madhanagopal
(författare)
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Structural insights into protein-protein interactions governing regulation in transcription initiation and ubiquitination
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Virtually every aspect of the cellular processes in eukaryotes requires that the interactions between protein molecules are well coordinated in different regulatory pathways. Any protein dysfunction involved in these regulatory pathways might lead to various pathological conditions. Understanding the structural and functional peculiarities of these proteins molecular machineries will help in formulating structure-based drug design.The first regulatory process studied here is the RNA polymerase-II mediated transcription of the eukaryotic protein-coding genes to produce mRNAs. This process requires the formation of the ‘transcription initiation’ by the assembly of Pre-Initiation Complex (PIC) formation at a core promoter region. Regulation at this initiation level is a key mechanism for the control of gene expression that governs cellular growth and differentiation. The transcription Factor IID (TFIID) is a conserved multiprotein general transcription factor with an essential role in nucleating the PIC formation, composed of TATA Binding Protein (TBP) and about 14 TBP Associated Factors (TAFs). The here presented crystal structure (1.97Å) of TBP bound to TAND1 and TAND2 domains from TAF1 reveals a detailed molecular pattern of interactions involving both transcriptionally activating and repressing regions in TBP, thereby uncovering central principles for anchoring of TBP-binding motifs. Together with NMR and cellular analysis, this work provides the structural basis of competitive binding with TFIIA to modulate TBP in promoter recognition.In eukaryotes, another fundamental mechanism in the regulation of cellular physiology is the posttranslational modification of substrate proteins by ubiquitin, termed ‘ubiquitination’. Important actors in this mechanism are the ubiquitin-ligases (E3s) that culminate the transfer of ubiquitin to the substrate and govern the specificity of this system. One E3 ligase in particular, TRIM21, defines a subgroup of the Tripartite Motif (TRIM) family, which belongs to the major RING-type of E3 ubiquitin ligases, and plays an important role in pathogenesis of autoimmunity by mediating ubiquitination of transcription factors. The crystal structure (2.86Å) of the RING domain from TRIM21 in complex with UBE2E1, an E2 conjugating enzyme, together with the NMR and SAXS analysis as well as biochemical functional analysis, reveals the molecular basis for the dynamic binding interfaces. The TRIM21 mode of ubiquitin recognition and activation for catalytic transfer of ubiquitin can be modeled onto the entire TRIM family.Finally, we explored the concepts of conformational selection in proteins as a possible key component for protein-mediated transcriptional regulation. In this framework, MexR, a bacterial repressor of the MexAB-OprM efflux pump, and its mutant Arg21Trp were studied as an example for proteins presenting different conformations. The residue Arg21Trp mutation is clinically identified to cause of Multi-Drug Resistant (MDR) by attenuated DNA binding, and leads to the overexpression of the MexAB-OprM efflux pump. With the crystal structure (2.19Å) of MexR mutant Arg21Trp, in combination with MD-simulations and SAXS for both wild-type and mutant, we could unravel the atomic details of the wild-type conformations consisting in subsets of populations of DNA bound and unbound forms. Remarkably, the mutant Arg21Trp stabilize the DNA unbound state and shifts MexR in a pre-existing equilibrium, from a repressed to a derepressed state.Taken together, these studies substantially broaden our knowledge at a molecular level in protein interactions that are involved in transcriptional regulation and ubiquitination, studied by a carefully selected combination of complementary structural methods spanning different resolutions and time scales.
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| 11. |
- Andersson, Anders, 1983-
(författare)
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Distributed Moving Base Driving Simulators : Technology, Performance, and Requirements
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Development of new functionality and smart systems for different types of vehicles is accelerating with the advent of new emerging technologies such as connected and autonomous vehicles. To ensure that these new systems and functions work as intended, flexible and credible evaluation tools are necessary. One example of this type of tool is a driving simulator, which can be used for testing new and existing vehicle concepts and driver support systems. When a driver in a driving simulator operates it in the same way as they would in actual traffic, you get a realistic evaluation of what you want to investigate. Two advantages of a driving simulator are (1.) that you can repeat the same situation several times over a short period of time, and (2.) you can study driver reactions during dangerous situations that could result in serious injuries if they occurred in the real world. An important component of a driving simulator is the vehicle model, i.e., the model that describes how the vehicle reacts to its surroundings and driver inputs. To increase the simulator realism or the computational performance, it is possible to divide the vehicle model into subsystems that run on different computers that are connected in a network. A subsystem can also be replaced with hardware using so-called hardware-in-the-loop simulation, and can then be connected to the rest of the vehicle model using a specified interface. The technique of dividing a model into smaller subsystems running on separate nodes that communicate through a network is called distributed simulation.This thesis investigates if and how a distributed simulator design might facilitate the maintenance and new development required for a driving simulator to be able to keep up with the increasing pace of vehicle development. For this purpose, three different distributed simulator solutions have been designed, built, and analyzed with the aim of constructing distributed simulators, including external hardware, where the simulation achieves the same degree of realism as with a traditional driving simulator. One of these simulator solutions has been used to create a parameterized powertrain model that can be configured to represent any of a number of different vehicles. Furthermore, the driver's driving task is combined with the powertrain model to monitor deviations. After the powertrain model was created, subsystems from a simulator solution and the powertrain model have been transferred to a Modelica environment. The goal is to create a framework for requirement testing that guarantees sufficient realism, also for a distributed driving simulation.The results show that the distributed simulators we have developed work well overall with satisfactory performance. It is important to manage the vehicle model and how it is connected to a distributed system. In the distributed driveline simulator setup, the network delays were so small that they could be ignored, i.e., they did not affect the driving experience. However, if one gradually increases the delays, a driver in the distributed simulator will change his/her behavior. The impact of communication latency on a distributed simulator also depends on the simulator application, where different usages of the simulator, i.e., different simulator studies, will have different demands. We believe that many simulator studies could be performed using a distributed setup. One issue is how modifications to the system affect the vehicle model and the desired behavior. This leads to the need for methodology for managing model requirements. In order to detect model deviations in the simulator environment, a monitoring aid has been implemented to help notify test managers when a model behaves strangely or is driven outside of its validated region. Since the availability of distributed laboratory equipment can be limited, the possibility of using Modelica (which is an equation-based and object-oriented programming language) for simulating subsystems is also examined. Implementation of the model in Modelica has also been extended with requirements management, and in this work a framework is proposed for automatically evaluating the model in a tool.
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| 12. |
- Andersson, Niklas, 1975-
(författare)
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Design of Integrated Building Blocks for the Digital/Analog Interface
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The integrated circuit has, since it was invented in the late 1950's, undergone a tremendous development and is today found in virtually all electric equipment. The small feature size and low production cost have made it possible to implement electronics in everyday objects ranging from computers and mobile phones to smart prize tags. Integrated circuits are typically used for data communication, signal processing and data storage. Data is usually stored in digital format but signal processing can be performed both in the digital and in the analog domain. For best performance, the right partition of signal processing between the analog and digital domain must be used. This is made possible by data converters converting data between the domains. A device converting an analog signal into a digital representation is called an analog-to-digital converter (ADC) and a device converting digital data into an analog representation is called a digital-to-analog converter (DAC). In this work we present research results on these data converters and the results are compiled in three different categories. The first contribution is an error correction technique for DACs called dynamic element matching, the second contribution is a power efficient time-to-digital converter architecture and the third is a design methodology for frequency synthesis using digital oscillators.The accuracy of a data converter, i.e., how accurate data is converted, is often limited by manufacturing errors. One type of error is the so-called matching error and in this work we investigate an error correction technique for DACs called dynamic element matching (DEM). If distortion is limiting the performance of a DAC, the DEM technique increases the accuracy of the DAC by transforming the matching error from being signal dependent, which results in distortion, to become signal independent noise. This noise can then be spectrally shaped or filtered out and hereby increasing the overall resolution of the system. The DEM technique is investigated theoretically and the theory is supported by measurement results from an implemented 14-bit DAC using DEM. From the investigation it is concluded that DEM increases the performance of the DAC when matching errors are dominating but has less effect at conversion speeds when dynamic errors dominate.The next contribution is a new time-to-digital converter (TDC) architecture. A TDC is effectively an ADC converting a time difference into a digital representation. The proposed architecture allows for smaller and more power efficient data conversion than previously reported and the implemented TDC prototype is smaller and more power efficient as compared to previously published TDCs in the same performance segment.The third contribution is a design methodology for frequency synthesis using digital oscillators. Digital oscillators generate a sinusoidal output using recursive algorithms. We show that the performance of digital oscillators, in terms of amplitude and frequency stability, to a large extent depends on the start conditions of the oscillators. Further we show that by selecting the proper start condition an oscillator can be forced to repeat the same output sequence over and over again, hence we have a locked oscillator. If the oscillator is locked there is no drift in amplitude or frequency which are common problems for recursive oscillators not using this approach. To find the optimal start conditions a search algorithm has been developed which has been thoroughly tested in simulations. The digital oscillator output is used for test signal generation for a DAC or used to generate tones with high spectral purity using DACs.
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| 13. |
- Andersson Naesseth, Christian, 1986-
(författare)
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Machine learning using approximate inference : Variational and sequential Monte Carlo methods
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Automatic decision making and pattern recognition under uncertainty are difficult tasks that are ubiquitous in our everyday life. The systems we design, and technology we develop, requires us to coherently represent and work with uncertainty in data. Probabilistic models and probabilistic inference gives us a powerful framework for solving this problem. Using this framework, while enticing, results in difficult-to-compute integrals and probabilities when conditioning on the observed data. This means we have a need for approximate inference, methods that solves the problem approximately using a systematic approach. In this thesis we develop new methods for efficient approximate inference in probabilistic models.There are generally two approaches to approximate inference, variational methods and Monte Carlo methods. In Monte Carlo methods we use a large number of random samples to approximate the integral of interest. With variational methods, on the other hand, we turn the integration problem into that of an optimization problem. We develop algorithms of both types and bridge the gap between them.First, we present a self-contained tutorial to the popular sequential Monte Carlo (SMC) class of methods. Next, we propose new algorithms and applications based on SMC for approximate inference in probabilistic graphical models. We derive nested sequential Monte Carlo, a new algorithm particularly well suited for inference in a large class of high-dimensional probabilistic models. Then, inspired by similar ideas we derive interacting particle Markov chain Monte Carlo to make use of parallelization to speed up approximate inference for universal probabilistic programming languages. After that, we show how we can make use of the rejection sampling process when generating gamma distributed random variables to speed up variational inference. Finally, we bridge the gap between SMC and variational methods by developing variational sequential Monte Carlo, a new flexible family of variational approximations.
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| 14. |
- Ardeshiri, Tohid
(författare)
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Analytical Approximations for Bayesian Inference
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bayesian inference is a statistical inference technique in which Bayes’ theorem is used to update the probability distribution of a random variable using observations. Except for few simple cases, expression of such probability distributions using compact analytical expressions is infeasible. Approximation methods are required to express the a priori knowledge about a random variable in form of prior distributions. Further approximations are needed to compute posterior distributions of the random variables using the observations. When the computational complexity of representation of such posteriors increases over time as in mixture models, approximations are required to reduce the complexity of such representations.This thesis further extends existing approximation methods for Bayesian inference, and generalizes the existing approximation methods in three aspects namely; prior selection, posterior evaluation given the observations and maintenance of computation complexity.Particularly, the maximum entropy properties of the first-order stable spline kernel for identification of linear time-invariant stable and causal systems are shown. Analytical approximations are used to express the prior knowledge about the properties of the impulse response of a linear time-invariant stable and causal system.Variational Bayes (VB) method is used to compute an approximate posterior in two inference problems. In the first problem, an approximate posterior for the state smoothing problem for linear statespace models with unknown and time-varying noise covariances is proposed. In the second problem, the VB method is used for approximate inference in state-space models with skewed measurement noise.Moreover, a novel approximation method for Bayesian inference is proposed. The proposed Bayesian inference technique is based on Taylor series approximation of the logarithm of the likelihood function. The proposed approximation is devised for the case where the prior distribution belongs to the exponential family of distributions.Finally, two contributions are dedicated to the mixture reduction (MR) problem. The first contribution, generalize the existing MR algorithms for Gaussian mixtures to the exponential family of distributions and compares them in an extended target tracking scenario. The second contribution, proposes a new Gaussian mixture reduction algorithm which minimizes the reverse Kullback-Leibler divergence and has specific peak preserving properties.
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| 15. |
- Arja, Katriann, 1985-
(författare)
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Multimodal Porphyrin-Based Conjugates : Synthesis and characterization for applications as amyloid ligands, photodynamic therapy agents and chiroptical materials
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic compounds that interact both with certain biological targets and display specific photophysical properties can be utilized as molecular tools to visualize and possibly effect disease related processes taking place in living organisms. In this regard, porphyrins are a class of naturally occurring molecules that possess intriguingly interesting photophysical properties where they can act as luminescent probes by emitting detectable light, as well as photosensitizers in the light mediated therapy called photodynamic therapy. In this thesis, the porphyrin structure has been synthetically combined with other molecule classes to achieve compounds with desirable multimodal characteristics.Firstly, luminescent conjugated oligothiophenes (LCOs) that have extensively, and with great success, been utilized as fluorescent ligands for amyloid formations, have been conjugated to porphyrins to render oligothiophene porphyrin hybrids (OTPHs) comprising two optically active modalities. When applied as fluorescent amyloidophilic dyes for visualization of amyloid-β (Aβ), one of the pathological hallmarks in Alzheimer’s disease, an enhanced optical assignment of distinct aggregated forms of Aβ was afforded. Thus, properly functionalized OTPHs could give us more information about pathological processes underlying devastating disorders, such as Alzheimer’s disease. In addition, the OTPHs can be associated with synthetic peptides inducing peptide folding into certain three-dimensional helical structures giving rise to novel optically active materials.Secondly, this thesis also embraces porphyrins’ potential as photosensitizers in photodynamic therapy to kill cancer cells. Grounded on the prerequisites for an optimal photosensitizer, we designed porphyrin-based conjugates equipped with common carbohydrates for improved cancer cell selectivity and with a fluorinated glucose derivative, 2-fluoro 2-deoxy glucose, for advantageous metabolism in cancer cells. Furthermore, incorporation of a radioisotopic fluorine-18 atom into the glycoporphyrins could give the means for diagnostic use of the conjugates in positron emission tomography (PET).In order to tether together the above-mentioned molecular moieties in a controlled fashion, we developed a robust synthetic strategy for asymmetrical functionalization of porphyrin core. The method involves chlorosulfonation of this otherwise inert tetrapyrrolic structure, followed by alkynylation. Parallelly to amide coupling reactions, copper(I)-catalyzed alkyne azide cycloaddition is used for fast and high-yielding late-stage conjugations. Overall, this thesis demonstrates how combining different molecular moieties in synthetic organic chemistry yields novel molecules with combined and improved multimodal properties for biological and medicinal applications, guided by the design-by-function methodology.
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| 16. |
- Armakavicius, Nerijus, 1989-
(författare)
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Free charge carrier properties in group III nitrides and graphene studied by THz-to-MIR ellipsometry and optical Hall effect
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Development of silicon based electronics have revolutionized our every day life during the last five decades. Nowadays silicon based devices operate close to their theoretical limits that is becoming a bottleneck for further progress. In particular, for the growing field of high frequency and high power electronics, silicon cannot offer the required properties. Development of materials capable of providing high current densities, carrier mobilities and high breakdown fields is crucial for further progress in state of the art electronics.Epitaxial graphene grown on semi-insulating silicon carbide substrates has a high potential to be integrated in current planar device technologies. High electron mobilities and sheet carrier densities make graphene extremely attractive for high frequency analog applications. One of the remaining challenges is the interaction of epitaxial graphene with the substrate. Typically, much lower free charge carrier mobilities, compared to free standing graphene, and doping, due to charge transfer from the substrate, is reported. Thus, a good understanding of the intrinsic free charge carriers properties and the factors affecting them is very important for further development of epitaxial graphene.Group III-nitrides have been extensively studied and already have proven their high efficiency as light emitting diodes for short wavelengths. High carrier mobilities and breakdown electric fields were demonstrated for group III-nitrides, making them attractive for high frequency and high power applications. Currently, In-rich InGaN alloys and AlGaN/GaN high electron mobility structures are of high interest for the research community due to open fundamental questions such as free charge carrier properties at high temperatures and wavefunction hybridization in AlGaN/GaN heterostructures.Electrical characterization techniques, commonly used for the determination of free charge carrier properties, require good ohmic and Schottky contacts, which in certain cases can be difficult to achieve. Access to electrical properties of buried conductive channels in multilayered structures requires modification of samples and good knowledge of the electrical properties of all electrical junctions within the structure. Moreover, the use of contacts to electrically characterize two-dimensional electronic materials, such as graphene, can alter their intrinsic properties. Furthermore, the determination of effective mass parameters commonly employs cyclotron resonance and Shubnikov-de Haas oscillations measurements, which require long scattering times of free charge carriers, high magnetic fields and low temperatures.The optical Hall effect is an external magnetic-field induced birefringence of conductive layers due to the free charge carriers interaction with long-wavelength electromagnetic waves under the influence of the Lorentz force. The optical Hall effect can be measured by generalized ellipsometry and provides a powerful method for the determination of free charge carrier properties in a non-destructive and contactless manner. The optical Hall effect measurements can provide quantitative information about free charge carrier type, concentration, mobility and effective mass parameters at temperatures ranging from few kelvins to room temperature and above. It further allows to differentiate the free charge carrier properties of individual layers in multilayer samples. The employment of a backside cavity for transparent samples can enhance the optical Hall effect and allows to access free charge carrier properties at relatively low magnetic fields using permanent magnet.The optical Hall effect measurements at mid-infrared spectral range can be used to probe quantum mechanical phenomena such as Landau levels in graphene. The magnetic field dependence of the inter-Landau level transition energies and optical polarization selection rules provide information about coupling properties between graphene layers and the electronic band structure.Measurement of the optical Hall effect by generalized ellipsometry is an indirect technique requiring subsequent data analysis. Parameterized optical models are fitted to match experimentally measured ellipsometric spectra by varying physically significant model parameters. Analysis of the generalized ellipsometry data at long wavelengths for samples containing free charge carriers by optical models based on the classical Drude formulation, augmented with an external magnetic field contribution, allows to extract carrier concentration, mobility and effective mass parameters.The development of the integrated FIR and THz frequency-domain ellipsometer at the Terahertz Materials Analysis Center in Linköping University was part of the graduate studies presented in this dissertation. The THz ellipsometer capabilities are demonstrated by determination of Si and sapphire optical constants, and free charge carrier properties of two-dimensional electron gas in GaN-based high electron mobility transistor structures. The THz ellipsometry is further shown to be capable of determining free charge carrier properties and following their changes upon variation of ambient conditions in atomically thin layers with an example of epitaxial graphene.A potential of the THz OHE with the cavity enhancement (THz-CE-OHE) for determination of the free charge carrier properties in atomically thin layers were demonstrated by the measurements of the carrier properties in monolayer and multilayer epitaxial graphene on Si-face 4H-SiC. The data analysis revealed p-type doping for monolayer graphene with a carrier density in the low 1012 cm-2 range and a carrier mobility of 1550 cm2V-1s-1. For the multilayer graphene, n-type doping with a carrier density in the low 1013 cm-2 range, a mobility of 470 cm2V-1s-1 and an effective mass of (0.14 ± 0.03)m0 were extracted. Different type of doping among monolayer and multilayer graphene is explained as a result of different hydrophobicity among samples.Further, we have employed THz-CE-OHE to determine for the first time anisotropic mobility parameter in quasi-free-standing bilayer epitaxial graphene induced by step-like surface morphology of 4H-SiC. Correlation of atomic force microscopy, Raman scattering spectroscopy, scanning probe Kelvin probe microscopy, low energy electron microscopy and diffraction analysis allows us to investigate the possible scattering mechanisms and suggests that anisotropic mobility is induced by varying local mobility parameter due to interaction between graphene and underlaying substrate.The origin of the layers decoupling in multilayer graphene on C-face 4H-SiC was studied by MIR-OHE, transmission electron microscopy and electron energy loss spectroscopy. The results revealed the decoupling of the layers induced by the increased interlayer spacing which is attributed to the Si atoms trapped between graphene layers.MIR ellipsometry and MIR-OHE measurements were employed to determine the electron effective mass in a wurtzite In0.33Ga0.67N epitaxial layer. The data analysis revealed the effective mass parameters parallel and perpendicular to the c-axis which can be considered as equal within sensitivity of our measurements. The determined effective mass is consistent with linear dependence on the In content.Analysis of the free charge carrier properties in AlGaN/GaN high electron mobility structures with modified interfaces showed that AlGaN/GaN interface structure has a significant effect on the mobility parameter. A sample with a sharp interface layers exhibits a record mobility of 2332 ± 73 cm2V-1s-1. The determined effective mass parameters showed an increase compared to the bulk GaN value, which is attributed to the penetration of the electron wavefunction into the AlGaN barrier layer.Temperature dependence of free charge carrier properties in GaN-based high electron mobility transistor structures with AlGaN and InAlN barrier layers were measured by terahertz optical Hall effect technique in a temperature range from 7.2 K to 398 K. The results revealed strong changes in the effective mass and mobility parameters. At temperatures below 57 K very high carrier mobility parameters above 20000 cm2V-1s-1 for AlGaN-barrier sample and much lower mobilities of ~ 5000 cm2V-1s-1 for InAlN-barrier sample were obtained. At low temperatures the effective mass parameters for both samples are very similar to bulk GaN value, while at temperatures above 131 K effective mass shows a strong increase with temperature. The effective masses of 0.344 m0 (@370 K) and 0.439 m0 (@398 K) were obtained for AlGaN- and InAlN-barrier samples, respectively. We discussed the possible origins of effective mass enhancement in high electron mobility transistor structures.
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| 17. |
- Aronsson, Christopher
(författare)
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Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery.
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| 18. |
- Asgharian Bourkheili, Ehsan
(författare)
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Performance in Franchise Systems : The Franchisee Perspective
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last decades, franchising as an organizational form has received a lot of attention from researchers and practitioners alike. While many studies have examined various aspects of franchising from the franchisor's perspective, little research has taken the franchisee’s perspective. Therefore, given the importance of franchisees in a franchise system, the lack of research about consequences from the franchisee's perspective, and that many of the previous studies have taken a top-bottom view, this research concentrated on the franchisee's performance. This study focused on business format franchising in the restaurant industry in two countries, Iran and Sweden.In this study, the three perspectives of entrepreneurship, strategic management, and marketing were used to study the franchisee’s performance. Moreover, the resourcebased view, relational view, and relational exchange theory have been used to find the influential factors in a franchisee’s performance. Therefore, by considering franchising as a mutual relationship and examining the influential factors in a franchisee's performance, the related factors of both the franchisor and franchisee, as well as the relationship between them, were examined.According to the franchisee’s related factors, the franchisor's related factors, and the relationship and environmental factors, 12 main hypotheses and 9 sub-hypotheses were developed. In total, 191 usable questionnaires from Sweden and Iran, comprising a response rate of 22 percent, were returned from the franchisees. In this study, confirmatory factor analysis was used to test the construct measurement; to test the hypothesis, hierarchical multiple regression analysis was performed. Moreover, the Chow test was conducted to integrate the data from these two countries.A primary contribution of this study is taking a bottom-top view in franchising research. This study also provided a detailed and holistic view about the consequences of franchising for franchisees. Moreover, this study, offers important contributions toward understanding entrepreneurial activities, as a controversial issue, in franchising outlets.The results provide interesting insights into the franchisee’s performance. While the franchisees’ related factors of absorptive capacity, Kirznerian entrepreneurial orientation, and social capital positively affected their performance, Schumpeterian entrepreneurial orientation and human capital did not affect their performance. Moreover, the franchisor’s related factors of system profitability, brand reputation, advertisement and providing raw material had a positive influence on the performance. However, training did not cause a difference in the franchisee’s performance. All relationship factors also positively affected the performance, and conflict and satisfaction mediated the relationship between trust and performance. Finally, the implications of this study and suggestions for further contributions in this stream of research are discussed.
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| 19. |
- Atakan, Aylin, 1984-
(författare)
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Mesoporous material systems for catalysis and drug delivery
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hybrid material systems possess multi-functional properties which make them intriguing for the materials science community since very early dates. However, it is not straightforward to produce such material systems. A smart and efficient approach is necessary to extract the desired properties of each component under the desired conditions. This study evolved to its last form primarily around this notion, where the development of a hybrid material is the core of the work. This hybrid material is then further explored for two different applications in the catalysis and drug delivery fields.A nanoassembly was established around a mesoporous silica support. SBA-15 was picked as this support among the other mesoporous silica due to its well-defined pore structure and accessible pore volume. The silica framework was doped with Zr atoms and the pores were partly infiltrated with Cu nanoparticles resulting in a hybrid material with tunable properties. SBA-15 was synthesized by a sol-gel method where a micellar solution was employed as a template for the silica framework. To achieve the doped version, a Zr precursor was added to the synthesis solution. The effects of different synthesis conditions, such as the synthesis catalyst (F-or a Cl-salt) and the Si source (tetraethyl orthosilicate (TEOS) or sodium metasilicate (SMS)) on the characteristics of the final material were investigated. It was observed that these changes in the synthesis conditions yielded different particle morphology, pore size (11-15 nm), and specific surface area (400-700 m2/g). Cu nanoparticles (NPs) were grown in the (Zr-)SBA-15 support using infiltration (Inf) or evaporation induced wetness impregnation (EIWI) methods. The infiltration method is based on functionalizing the (Zr-)SBA-15 support surfaces before the Cu ion attachment whereas EIWI is based on slow evaporation of the liquid from the (Zr-)SBA-15 - Cu aqueous suspension. Both methods are designed to yield preferential growth of Cu NPs in the pores with a diameter smaller than 10 nm and in oxidized form. However, depending on the loading method used, different chemical states of the final material were achieved, i.e. Zr content and porous network properties are different. Cu-Zr-SBA-15 nanoassemblies produced under various synthesis conditions were used for the catalytic conversion of CO2into valuable fuels such as methanol and dimethyl ether (DME). The effect of different chemical states of the catalyst arising from variations in the synthesis parameters was investigated. It was found that the Si precursor (TEOS or SMS) had a considerable impact on the overall performance of the catalyst whereas the Cu loading method (Inf or EIWI) changed the catalytic selectivity between DME and methanol. The activity of the catalyst was further investigated in a time-evolution study where the accumulation of each product in the gas phase and the molecular groups attached to the catalyst surface were recorded over time. Accordingly, thermodynamic equilibrium was achieved on the 14th day of the reaction under 250°C and 33 bar. The resulting total CO2conversion was 24%, which is the thermodynamically highest possible conversion, according to theoretical calculations. It was also concluded from the experimental results that, DME is formed by a combination of two methoxy surface groups. Additionally, the formation of DME boosts the total CO2conversion to fuels, which otherwise is limited to 9.5%.The design of Cu-Zr-SBA-15 was also investigated for drug delivery applications, due to its potential as a biomaterial, e.g., a filler in dental composites, and the antibacterial properties of Cu. Also, the bioactivity of SiO2and ZrO2was considered to be an advantage. With this aim, Cu infiltrated Zr doped SBA-15 material was prepared by using TEOS as the silica precursor and the Inf-method to grow Cu NPs. The performance of the final material as a drug delivery vehicle was tested by an in-vitro delivery study with chlorhexidine digluconate.The nanoassemblies show a drug loading capacity of 25-40% [mg drug / mg (drug+carrier)]. The drug release was determined to be composed of two steps. First, a burst release of the drug molecules that are loosely held in the voids of the mesoporous carrier followed by the diffusion of the drug molecules that are attached to the carrier surface. The presence of Zr and Cu limits the burst release and beneficially slows down the drug release process. The effect of pore properties of SBA-15 was explored in a study where the antibiotic doxycycline hyclate was loaded in SBA-15 materials with different pore sizes. It was observed that the pore size is directly proportional to the drug loading capacity [mg drug / mg (drug+carrier)] and the released drug percentage (the released drug amount/total amount of loaded drug). The drug release was fast due to its weak interactions with the SBA-15 materials. In summary, this work demonstrates the multifunctional character of a smart-tailored nanoassembly which gives valuable insights for two distinct applications in catalysis and drug delivery.
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| 20. |
- Avgouleas, Ioannis M., 1983-
(författare)
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Cooperation and Resource Allocation in Wireless Networking towards the IoT
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Internet of Things (IoT) should be able to react with minimal human intervention and contribute to the Artificial Intelligence (AI) era requiring real-time and scalable operation under heterogeneous network infrastructures. This thesis investigates how cooperation and allocation of resources can contribute to the evolution of future wireless networks supporting the IoT.First, we examine how to allocate resources to IoT services which run on devices equipped with multiple network interfaces. The resources are heterogeneous and not interchangeable, and their allocation to a service can be split among different interfaces. We formulate an optimization model for this allocation problem, prove its complexity, and derive two heuristic algorithms to approximate the solution in large instances of the problem.The concept of virtualization is promising towards addressing the heterogeneity of IoT resources by providing an abstraction layer between software and hardware. Network function virtualization (NFV) decouples traditional network operations such a routing from proprietary hardware platforms and implements them as software entities known as virtualized network functions (VNFs). In the second paper, we study how VNF demands can be allocated to Virtual Machines (VMs) by considering the completion-time tolerance of the VNFs. We prove that the problem is NP-complete and devise a subgradient optimization algorithm to provide near-optimal solutions. Our numerical results demonstrate the effectiveness of our algorithm compared to two benchmark algorithms.Furthermore, we explore the potential of using intermediate nodes, the so-called relays, in IoT networks. In the third paper, we study a multi-user random-access network with a relay node assisting users in transmitting their packets to a destination node. We provide analytical expressions for the performance of the relay's queue and the system throughput. We optimize the relay’s operation parameters to maximize the network-wide throughput while maintaining the relay's queue stability. A stable queue at relay guarantees finite delay for the packets. Furthermore, we study the effect of the wireless links' signal-to-interference-plusnoise ratio (SINR) threshold and the self-interference (SI) cancellation on the per-user and network-wide throughput.Additionally, caching at the network edge has recently emerged as an encouraging solution to offload cellular traffic and improve several performance metrics of the network such as throughput, delay and energy efficiency. In the fourth paper, we study a wireless network that serves two types of traffic: cacheable and non-cacheable traffic. In the considered system, a wireless user with cache storage requests cacheable content from a data center connected with a wireless base station. The user can be assisted by a pair of wireless helpers that exchange non-cacheable content as well. We devise the system throughput and the delay experienced by the user and provide numerical results that demonstrate how they are affected by the non-cacheable packet arrivals, the availability of caching helpers, the parameters of the caches, and the request rate of the user.Finally, in the last paper, we consider a time-slotted wireless system that serves both cacheable and non-cacheable traffic with the assistance of a relay node. The latter has storage capabilities to serve both types of traffic. We investigate how allocating the storage capacity to cacheable and non-cacheable traffic affects the system throughput. Our numerical results provide useful insights into the system throughput e.g., that it is not necessarily beneficial to increase the storage capacity for the non-cacheable traffic to realize better throughput at the non-cacheable destination node.
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| 21. |
- Axin, Mikael
(författare)
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Mobile Working Hydraulic System Dynamics
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with innovative working hydraulic systems for mobile machines. Flow control systems are studied as an alternative to load sensing. The fundamental difference is that the pump is controlled based on the operator’s command signals rather than feedback signals from the loads. This control approach enables higher energy efficiency and there is no load pressure feedback causing stability issues. Experimental results show a reduced pump pressure margin and energy saving potential for a wheel loader application.The damping contribution from the inlet and outlet orifice in directional valves is studied. Design rules are developed and verified by experiments.A novel system architecture is proposed where flow control, load sensing and open-centre are merged into a generalized system description. The proposed system is configurable and the operator can realize the characteristics of any of the standard systems without compromising energy efficiency. This can be done non-discretely on-the-fly. Experiments show that it is possible to avoid unnecessary energy losses while improving system response and increasing stability margins compared to load sensing. Static and dynamic differences between different control modes are also demonstrated experimentally.
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| 22. |
- Baer, Katharina, 1984-
(författare)
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Simulation-Based Optimization of a Series Hydraulic Hybrid Vehicle
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hybrid transmissions are characterized by their utilization of more than one form of energy storage. They have the potential to help reduce overall fuel consumption and vehicle emissions by providing the possibility of brake energy recuperation and prime mover operation management. Electric hybrids and electric vehicle drives are nowadays ubiquitous, and mechanical energy storage in flywheel has been investigated in the past. The use of fluid power technology with a combustion engine has also been investigated since the late 1970s, and is frequently revisited.Hydraulic hybridization is especially attractive for heavy vehicles with frequent braking and acceleration which benefit most from fluid power components’ high power density, typically busses, delivery or refuse vehicles, and vehicles with existing hydraulic circuits and transmissions, such as forest and construction machinery, but have been considered for smaller vehicles as well.Due to the characteristic discharge profile of hydraulic energy storage, special attention needs to be paid to control aspects in the design process to guarantee drivability of the vehicle. In this respect, simulation models can be of use in early design process stages for cheaper and faster evaluation of concepts and designs than physical experiments and prototyping, and to generate better understanding of the system studied. Engineering optimization aids in the systematic exploration of a given design space, to determine limits and potentials, evaluate trade-offs and potentially find unexpected solutions. In the optimization of a hydraulic hybrid transmission, the integration of component and controller design is of importance, and different strategies (sequential, iterative, bi-level and simultaneous approaches) are conceivable, with varying consequences for the implementation.This thesis establishes a simulation-based optimization framework for a hydraulic hybrid transmission with series architecture. Component and control parameter optimization are addressed simultaneously, using a rule-based supervisory control strategy. The forward-facing dynamic simulation model at the centre of the framework is built in Hopsan, a multi-disciplinary open-source tool developed at Linköping University. The optimization is set up and conducted for an example application of an on-road light-duty truck over standard drive cycles. Both results from these experiments as well as the framework itself are studied and evaluated. Relevant design aspects, such as explicit design relations to be considered and performance requirements for more robust design, are identified and addressed, and the optimization problem is analysed with regard to algorithm performance and problem formulation. The final result is an optimization framework that can be adjusted for further in-depth studies, for example through the inclusion of additional components or optimization objectives, and extendable for comparative analysis of different topologies, applications and problem formulations.
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| 23. |
- Bakoglidis, Konstantinos
(författare)
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Low-friction and wear-resistant carbon nitride coatings for bearing components grown by magnetron sputtering
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The scope of this thesis is the investigation of magnetron sputtered carbon nitride coatings suitable for roller bearing components. The research field of tribology of bearings focuses on minimizing friction between components by improving the lubricants. The development of lubricants is, however, expensive and involves environmentally deleterious chemical byproducts. A solution to avoid such harmful conditions, reduce the processing cost, and more importantly, minimize the friction, is to apply a low-friction and wear-resistant coating on the surface of the bearing. The deposition of such coatings on components can substantially increase their lifetime, reduce the maintenance costs, and eventually increase the reliability of the machinery.Carbon nitride (CNx) coatings have high resiliency and can withstand the demanding conditions of bearing operation. The morphology of CNx coatings is highly affected by applying a negative substrate bias voltage. At high bias (100-120 V ), the coatings become denser and more homogeneous with decreased porosity, resulting in more wear-resistant materials. I also found that the duty cycle of the applied bias affects the layer morphology. Less homogeneous films are produced using lower duty cycles (i.e., in high power impulse magnetron sputtering, HiPIMS) for a specific value of bias voltage. Thus, changing bias voltage, we can manipulate the structure of CNx and design layers, depending on the requirements of the bearing application.My results show that denser films yield higher hardness and wear-resistance, but also higher compressive stress, which is a disadvantage for the coating-substrate adhesion. In order to obtain improved adhesion on bearing steel, we developed an in-situ surface treatment, prior to the CNx deposition, which also surpasses the limitations set by the properties of each material. The steel substrates are successfully pretreated using W or Cr ions originating from a HiPIMS source. Plasma ions are accelerated to the substrates with energies of 900 eV , due to the application of a synchronized high bias voltage, which clean effectively the substrate surface from residual contaminants and strengthen the interfacial bonding.CNx-coated rollers are tested in rolling operation and show the absence of run-in period in all lubrication regimes. This is a big advantage for applications which rotate under boundary lubrication (BL). The coated rollers yield friction coefficients in the range of 0:020 and 0:025 in elastohydrodynamic (EHDL) and hydrodynamic (HDL) lubrication regimes, being lower than the friction coefficients of 0:026-0:052, exhibited by the uncoated rollers. Here, friction decreases steadily with increasing number of cycles, due to the presence of CNx in the contact. In BL, CNx-coated rollers present an increased friction coefficient of 0:052, but the wear is much lower than in the case of uncoated rollers. All rollers are covered with CNx in the wear tracks after the tests, avoiding failures and presenting low abrasive wear. The obtained tribological performance of the CNx-coated rollers in rolling is overall improved compared to the established operation of uncoated rollers. Thus, CNx layers can function as low-friction and wear-resistant coatings protecting the steel components in several roller bearing applications, such as in gearboxes and wheels in automotive, aerospace, marine, and turbine industry.
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| 24. |
- Banda, Adson, 1576-
(författare)
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Coherent functors and asymptotic properties
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis we study properties of the so called coherent functors. Coherent functors were first introduced by Auslander in 1966 in a general setting. Coherent functors have been used since then as powerful tools for different purposes: to describe infinitesimal deformation theory, to describe algebraicity of a stack or to study properties of Rees algebras.In 1998, Hartshorne proved that half exact coherent functors over a discrete valuation ring ? are direct sums of the identity functor, Hom-functors of quotient modules of ? and tensor products of quotient modules of ?. In our first article (Paper A), we obtain a similar characterization for half exact coherent functors over a much wider class of rings: Dedekind domains. This fact allows us to classify half exact coherent functors over Dedekind domains.In our second article (Paper B), coherent functors over noetherian rings are considered. We study asymptotic properties of sets of prime ideals connected with coherent functors applied to artinian modules or finitely generated modules. Also considering quotient modules M /anM, where an is the nthpower of an ideal ?, one obtains that the Betti and Bass numbers of the images under a coherent functor of the quotient modules above are polynomials in n for large n. Furthermore, the lengths of these image modules are polynomial in ?, for large ?, under the condition that the image modules have finite length.
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| 25. |
- Bao, Qinye, 1985-
(författare)
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Interface Phenomena in Organic Electronics
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic electronics based on organic semiconductors offer tremendous advantages compared to traditional inorganic counterparts such as low temperature processing, light weight, low manufacturing cost, high throughput and mechanical flexibility. Many key electronic processes in organic electronic devices, e.g. charge injection/extraction, charge recombination and exciton dissociation, occur at interfaces, significantly controlling performance and function. Understanding/modeling the interface energetics at organic-electrode/organic-organic heterojunctions is one of the crucial issues for organic electronic technologies to provide a route for improving device efficiency, which is the aim of the research presented in this thesis.Integer charge transfer (ICT) states pre-existed in the dark and created as a consequence of Fermi level equilibrium at donor-acceptor interface have a profound effect on open circuit voltage in organic bulk heterojunction photovoltaics. ICT state formation causes vacuum level misalignment that yields a roughly constant effective donor ionization potential to acceptor electron affinity energy difference at the donor-acceptor interface, even though there is a large variation in electron affinity for the fullerene series. The large variation in open circuit voltage for the corresponding device series instead is found to be a consequence of trap-assisted recombination via integer charge transfer states. Based on the results, novel design rules for optimizing open circuit voltage and performance of organic bulk heterojunction solar cells are proposed.Doping and insertion of interlayer are two established methods for enhancing charge injection/extraction properties at organic-electrode interface. By studying the energy level alignment behavior at low to intermediate doping levels for molecule-doped conjugated polymer/electrode interfaces, we deduce that two combined processes govern the interface energetics: (i) equilibration of the Fermi level due to oxidation (or reduction) of polymer sites at the interface as per the ICT model and (ii) a double dipole step induced by image charge from the dopant-polymer charge transfer complex that causes a shift of the work function. Such behavior is expected to hold in general for low to intermediate level doped organic semiconductor systems. The unified model is further extended to be suitable for conjugated electrolyte/electrode interfaces, revealing the design rules for achieving the smallest charge injection/extraction barrier for both thin tunneling and thick charge transporting conjugated electrolyte interlayers.To probe into the energy level spatial extension at interfaces, we employ the original approach of building and characterizing multilayers composed of a well-defined number of polymer monolayers with the Langmuir-Shäfer method to control polymer film uniformity and thicknesses, avoiding the problems associated with spin-coating ultrathin films. The disordered/amorphous films feature smaller, and in fact negligible, energy level bending compared to the more well-ordered films, in contradiction with existing models. It is found that that energy level bending depends on the ICT state distribution rather than the density of states of the neutral polymer chains in relation to the Fermi energy, thus taking into account the Coulomb energy associated with charging the polymer chain and transferring a charge across the interface. Based on this work, a general model for energy level bending in absence of significant doping of conjugated polymer films is proposed.Organic semiconductors are sensitive to ambient atmosphere that can influence the energetics. The degradation effects of common PCBM film induced by oxygen and water are found to be completely different. Upon exposure to oxygen, the work function is down-shifted by ~ 0.15 eV compared to the ICT curve of the pristine PCBM film, originating from the weak interaction between the fullerene part of PCBM and oxygen, and this can be reversed by thermal treatment in vacuum. The down-shift in energetics will cause a loss in open circuit voltage at electrode interface, but aids free charge generation at donor-acceptor interface. Upon exposure to water, there is irreversible extensive broadening and bleaching of the valence electronic structure features as well as a substantial decrease of work function and ionization potential, severely degrading the transport properties.Overall, the research results in this thesis thus give a deeper understanding of interface phenomena in organic electronics, especially regard to organic solar cells, aimed to further improve the device operation efficiency and lifetime.
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