| 1. |
- Andersson, Carl
(författare)
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Deep probabilistic models for sequential and hierarchical data
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Consider the problem where we want a computer program capable of recognizing a pedestrian on the road. This could be employed in a car to automatically apply the brakes to avoid an accident. Writing such a program is immensely difficult but what if we could instead use examples and let the program learn what characterizes a pedestrian from the examples. Machine learning can be described as the process of teaching a model (computer program) to predict something (the presence of a pedestrian) with help of data (examples) instead of through explicit programming.This thesis focuses on a specific method in machine learning, called deep learning. This method can arguably be seen as sole responsible for the recent upswing of machine learning in academia as well as in society at large. However, deep learning requires, in human standards, a huge amount of data to perform well which can be a limiting factor. In this thesis we describe different approaches to reduce the amount of data that is needed by encoding some of our prior knowledge about the problem into the model. To this end we focus on sequential and hierarchical data, such as speech and written language.Representing sequential output is in general difficult due to the complexity of the output space. Here, we make use of a probabilistic approach focusing on sequential models in combination with a deep learning structure called the variational autoencoder. This is applied to a range of different problem settings, from system identification to speech modeling.The results come in three parts. The first contribution focus on applications of deep learning to typical system identification problems, the intersection between the two areas and how they can benefit from each other. The second contribution is on hierarchical data where we promote a multiscale variational autoencoder inspired by image modeling. The final contribution is on verification of probabilistic models, in particular how to evaluate the validity of a probabilistic output, also known as calibration.
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| 2. |
- Asmuth, Henrik
(författare)
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Efficient Large-eddy Simulation for Wind Energy Applications
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Modelling the interaction of wind turbines with the ambient flow is essential for almost all technical aspects of wind energy exploitation. Large-eddy simulation (LES) is the most detailed approach feasible to model this complex interaction of wind turbines with the atmospheric boundary layer and the wakes of upstream turbines. Despite more than twenty years of fundamental research on wind turbine modelling with LES, applications of the method remain limited to academic use cases to date. The main bottleneck hindering a broader adoption of LES in the industrial practice is the large computational demand of the method. Nevertheless, it holds enormous potential for addressing various modelling challenges arising from current trends in wind energy.A promising alternative to classical numerical approaches for LES is the lattice Boltzmann method (LBM). In particular, GPU-based (graphics processing unit) implementations of the method provide significant performance gains and have enabled unprecedented computational efficiencies for LES in different fields of fluid dynamics. Still, the LBM´s potential for wind energy applications remains untapped due to open questions, some of which are specific to the field. This thesis addresses two specific problems in applications of LES to wind turbine and farm simulations. First, is the representation of wind turbines with the actuator line technique. And, second, is the modelling of the surface shear stress in simulations of atmospheric boundary layers. Both aspects are crucial to enable LES for wind energy applications with the LBM, as is usually done with conventional approaches.As for the former, an LBM implementation of the actuator line model is applied in multiple studies on wind turbine wakes. Code-to-code comparisons and experimental validations show that the model can accurately capture the aerodynamic forces acting on the turbine blades as well as the wake characteristics. For the simulation of boundary layer flows a novel LBM-specific wall model is developed. The model, referred to as inverse momentum exchange method, imposes the surface shear stress at the first offwall grid points by adjusting the slip velocity in bounce-back boundary schemes. Simulations are compared to theoretical, numerical, and experimental reference data of isothermal boundary layer flows. It is consistently found that both mean quantities and higherorder turbulence statistics can be well-captured by wall-modelled lattice Boltzmann LES using the presented wall model and the employed cumulant collision scheme.The results presented illustrate that the LBM is a suitable approach for state-of-the-art LES of wind turbine wakes and boundary layer flows. Moreover, the applied method is shown to be robust, and, above all, extremely computationally efficient. Based on the observed computational efficiencies, it is concluded that industry LES for wind energy applications is possible with GPU-based LBM solvers. Furthermore, additional studies presented in this thesis illustrate further potentials of the method. Such are applications of reinforcement learning to wind farm control or large-scale data generation for the training of deep learning models for wake predictions.
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| 3. |
- Augstein, Frauke
(författare)
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Mechanisms of plant root xylem developmental plasticity in response to water deficiency and salt
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Plants may be exposed to a variety of different environmental conditions including water deficiency and salt, both affecting the uptake of water into the plant. Water is taken up from the soil by the roots and distributed throughout the plant via the water conducting tissue, the xylem. Plants are remarkably plastic and have evolved different mechanisms to sense the environment and adjust their development accordingly. However, how xylem development may respond to water availability is not clear. In this thesis, I show how water deficiency and salt affect xylem development and how the observed phenotypic alterations are regulated on a molecular level. We found that upon water deficiency additional protoxylem strands were formed along with an early differentiation of the inner metaxylem. These phenotypes were regulated both by non-cell autonomous and cell autonomous signaling via the hormone abscisic acid (ABA). The expression of microRNA165 was induced by ABA signaling in the endodermis leading to downregulation of homeo domain leucine zipper class III (HD-ZIP III) transcription factors in the stele. This caused a shift in xylem identity from meta- to protoxylem and the formation of additional protoxylem strands. At the same time, cell autonomous ABA signaling upregulated several VASCULAR RELATED NAC DOMAIN (VND) transcription factors including VND7, which promoted the shift in xylem identity as well as VND2 and VND3, which promoted early differentiation of the inner metaxylem. In contrast, during an initial phase of salt stress, we observed the formation of protoxylem gaps specifically in response to ionic stress and distinct from ABA-signaling. We identified that protoxylem gaps were caused by lowered levels and signaling of the growth regulator gibberellin (GA). Downstream of GA-signaling, protoxylem gap formation upon salt was controlled by genes involved in secondary cell wall formation including the xylem master regulator VND6 and factors involved in cell wall modification. Salt tolerance assays suggested that protoxylem gaps may contribute to salt tolerance and the phenotypes that we observed upon water deficiency have been suggested to confer drought tolerance. We observed similar effects on xylem developmental plasticity in response to water deficiency and salt in various different dicot species indicating an evolutionary conservation. Thus, xylem development is of high relevance for breeding programs to generate plant varieties better adapted to a changing climate.
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| 4. |
- Bacic, Luka
(författare)
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Molecular mechanisms underlying the activation of ALC1 nucleosome remodeling
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Packaging DNA into chromatin represses essential DNA-based processes, such as transcription, DNA replication, and repair. To change the accessibility of DNA, cells have evolved a set of enzymes referred to as chromatin remodelers that act on the basic repeat unit of chromatin, the nucleosome. Chromatin remodelers are critical for normal cell physiology and development. Dysfunction or aberrant regulation of chromatin remodelers can lead to multisystem developmental disorders and cancers. DNA damage represents a major threat to eukaryotic cells. When DNA damage persists, the cell can enter programmed cell death. To avoid such a dramatic outcome, cells must rapidly recognize the DNA damage and trigger DNA repair pathways. An early event following DNA damage is the relaxation of chromatin. Chromatin relaxation depends on ATP consumption and ADP-ribosylation, where the site of DNA damage is marked with ADP-ribose units. ADP-ribose, in turn, can be recognized by the macro domain of the remodeler ALC1 (Amplified in Liver Cancer 1). ALC1 has therefore been implicated in the DNA damage response. In the absence of DNA damage, the macro domain of ALC1 is placed against its ATPase motor to inhibit its activity. However, it is unclear how ALC1, in its active state, engages the nucleosome. Moreover, the mechanism by which ALC1 is fully activated upon recruitment is poorly understood, and the impact of ALC1-catalyzed nucleosome sliding in the vicinity of a DNA damage site is unknown. This thesis investigates how ALC1 engages its substrate, the nucleosome, and how histone modifications can regulate ALC1 activity. Structural and biophysical approaches revealed an ALC1 regulatory segment that binds to the acidic patch, a prominent feature on the nucleosome surface. Further analysis showed that the interaction between ALC1 and the acidic patch is required to fully activate ALC1. Moreover, in vitro ADP-ribosylation of nucleosomes enabled us to form a stable complex of nucleosome-bound ALC1 amenable to structural determination by cryogenic electron microscopy. Our structural models visualize nucleosomal epitopes that play an important role in stimulating productive remodeling by ALC1, as confirmed by various biochemical approaches. Taken together, our data suggested a possible mechanism by which ALC1 could render DNA breaks more accessible to downstream repair factors. Since recent studies defined ALC1 as an attractive anti-cancer target, this thesis provides insights into the molecular mechanisms that regulate ALC1 activity as a potential starting point for structure-based drug development.
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| 5. |
- Bagnall, Andrew J.
(författare)
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Novel electrode and photoelectrode materials for hydrogen production based on molecular catalysts
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The PhD project focussed on the application of a cobalt tetraazamacrocyclic complex, in the literature commonly referred to as [Co(CR)Cl2]+ as a molecular catalyst for the hydrogen evolution reaction (HER). This was within the broader scope of the EU MSCA H2020 ITN ‘eSCALED’ project, which primarily aimed to create artificial leaf devices for the storage of solar energy in chemical fuels and, as part of this, sought the development of novel bio-inspired and scalable materials. This included researching molecular catalysts without platinum group metals (PGMs) currently relied upon in commercial technology.Three main projects were pursued: firstly, studies of the mechanism of the catalyst itself under organic electrocatalytic conditions. Catalytic intermediates were generated and identified using spectroscopy (UV-vis, NMR, EPR) and the catalytic behaviour was followed with electrochemical techniques. An ECEC mechanism with a rate-determining second protonation step associated with the release of H2 was identified, noting in particular an initial protonation step on the macrocycle at the Co(II) state that was hypothesised to involve the macrocycle amine group acting as a proton relay under the investigated conditions.Secondly, a new synthetic strategy towards novel derivatives of [Co(CR)Cl2]+ was developed to prepare a derivative for anchoring onto sp2-carbon surfaces by pi-stacking interactions. The immobilised catalyst was studied by electrochemical methods and compared with another derivative from collaborators at ICIQ, showing that both derivatives work as heterogenised electrocatalysts for the HER with high faradaic efficiencies and good stability over one hour at pH 2 and especially pH 7, but one derivative displays higher current densities and stability, invoking some consideration of rational design principles for modifying molecular catalysts.Thirdly, studies of a photocatalytic system made up of copper indium sulfide quantum dots (CuInS2 QDs) as a photosensitiser with either [Co(CR)Cl2]+ or its benzoic acid-functionalised derivative were carried out in ascorbate buffer, focussing on the photocatalytic performance and electron transfer (ET) processes between the CuInS2 QDs and the catalyst to explain the remarkable activity and robustness reported for closely related systems. CuInS2 QDs modified to have a ‘hybrid-passivation’ ligand system for compatibility with NiO films were used. Rapid QD-catalyst ET processes were noted for both catalysts. A static binding model with a strong binding equilibrium was adapted for the system, applying a Poisson distribution. This prompts a reconsideration of the importance of anchoring groups for QD-catalyst ET efficiency in solution.
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| 6. |
- Baur, Julian
(författare)
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Condition dependent germline maintenance in seed beetles
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the work presented in this thesis is to investigate how costly adaptations promoted by sexual selection affect fertility and offspring quality through changes in germline maintenance. Germline maintenance, comprising mechanisms maintaining DNA-integrity and homeostasis within germ cells, is known to be costly and, therefore, may trade-off with other costly reproductive traits that are under sexual selection. However, sexual selection may also act on condition dependent traits that reflect the overall genetic quality of its bearer, in which case sexual selection for high quality mates may lead to improved germline maintenance. Using experimental evolution lines of the seed beetle Callosobruchus maculatus, evolving under three different mating regimes that manipulated the opportunity for sexual and natural selection, I show evidence indicating that sexual selection can lead to improved germline maintenance through selection on condition dependent traits. However, I also found evidence for the alternative hypothesis, suggesting that when sexual selection is much stronger than natural selection it may lead to excessive investment into mating traits that trade-off with and reduce germline maintenance. We present an RNA expression analysis suggesting 18 candidate genes responding to DNA-damage and sociosexual interactions that may be involved in trade-offs between sexual selection and germline maintenance. I also found that the fertility of males and females that evolved under intense sexual selection was more sensitive to heat stress, and male sensitivity of fertility to heat stress was genetically correlated to sperm competitive ability. This suggests a trade-off between male postcopulatory reproductive success and the thermal sensitivity of fertility. The increased sensitivity to heat was also reflected in the fertility of females, suggesting that female heat tolerance may have evolved via genetic correlations with sexually selected male reproductive traits. The work presented in this thesis shows that sexual selection indeed affects germline maintenance. Sexual selection can increase germline maintenance through selection on condition dependent traits. But at the same time, traits under sexual selection can trade off with aspects of germline maintenance. If traits evolved under sexual selection and only weak constraints by natural selection, evolved allocation shifts in response to sexual selection can lead to deleterious repercussions when stressful environmental conditions increase demands on germline maintenance. The results presented in this thesis highlight important aspects of how sexual selection affects condition dependent germline maintenance with significant implications for the maintenance of genetic variation, adaptive processes, and mate choice processes in species under sexual selection.
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| 7. |
- Bazargan, Mohsen
(författare)
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Numerical and laboratory studies of seismic properties and elements of rock fabric from the microscale to the macroscale
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Physical properties of rocks studied in the laboratory are useful to provide constraints on the dynamics of Earth’s interior. This may include direct constraints on in-situ seismic properties, such as elastic wave velocity measurements that can be compared to seismological data, or petrofabric indicators such as anisotropy of magnetic susceptibility (AMS). Another approach that provides predictive insight into the physical properties of Earth’s interior are computer models. Numerical modelling, in particular, can be used to investigate the dynamic propagation of elastic waves or the flow of a material to generate a fabric or texture (i.e., petrofabric in rocks). This thesis focuses on an integrative approach, utilizing both laboratory measurements and numerical modelling, to understand physical properties and petrofabric development in rocks originating in Earth’s crust. The physical properties of rocks are affected by both intrinsic sources (e.g., inherent to crystals) and extrinsic sources (e.g., layering, microcracks, shape preferred orientation of crystals, grain size, presence of geological fluids). A versatile numerical elastic wave propagation model is constructed with COMSOL Multiphysicsâ and benchmarked against a stainless-steel standard used for laboratory elastic wave measurements. The numerical model is flexible and enables setup of composite materials with different sample geometries, which is of importance when modeling the physical properties of rocks in realistic geological scenarios. Using the elastic wave propagation model, this thesis explores different scenarios and their influence on seismic properties, including the effect of grain size on bulk elastic wave speed and compositional layering on seismic anisotropy. The first application focuses on a joint laboratory and numerical study of similar composition gabbro samples, with distinctly different grain size. The numerical model is used to evaluate the relationship between wavelength and grain size. The second application utilizes laboratory measurements as input data for the models, to determine seismic properties of compositionally layered materials. It is shown that the seismic properties, and in particular anisotropy, of a layered material depends on 1) the combination of the inherent rock properties and layering and 2) the wavelength (l) to layer thickness ratio (d). Importantly, independent of scale, the physical properties are wavelength dependent, showing a decrease (apparent dispersion) in velocity, when transitioning from a ray medium (l/d < 1) to an effective medium (l/d > 10). In the second part of this thesis, another COMSOL Multiphysics modelling approach is used to investigate how crystals rotate in a magmatic flow, and how a petrofabric in different magmatic rocks may develop. A set of different magmatic flow scenarios are explored, with direct application to natural examples of dykes and magma chambers. These numerical models may serve as useful predictors of petrofabric in igneous rocks where determination of flow direction of magma is of interest.
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| 8. |
- Beckel, Ruth A.
(författare)
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Active and passive seismic methods for investigating the glacially-triggered Burträsk fault
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glacially-triggered faults are of high scientific interest since their formation was likely accompanied by major earthquakes and they are still a centre of seismicity in northern Fennoscandia, today. Imaging their deeper structure mainly relies on reflection seismics since the method generally has the best resolving power at depth of all geophysical methods. This thesis uses data acquired at the glacially-triggered Burträsk fault to advance active and passive seismic imaging methods and improve the understanding of the area. Reprocessing of a vintage, crooked-line reflection dataset using a newly developed module for a local cross-dip correction improved the quality of the reflection image significantly and provided important 3D information for the interpretation of the fault and its surroundings. A fault segment to the southwest of the profile was imaged with a dip of approximately 50° but the segment intersecting the profile was not imaged, likely due to insufficient shot coverage close to the fault. Since the Burträsk area is seismically the most active area in Sweden, passive imaging using a dataset of local microearthquakes was attempted. As a first step, the earthquakes were re-located using a stacking-based location method. In spite of the poor azimuthal coverage of the array, the method yielded surprisingly good location results within 30–40 km from the array. The most important factors for success proved to be combined P- and S-wave location with down-weighted S-wave signals, and the use of a polarity-sensitive characteristic function. The distribution of the hypocentres confirmed that the trace of the Burträsk fault is the currently active fault plane. Disappointingly, passive seismic processing using reflection seismic interferometry (RSI) did not image the known reflections. To improve the planning of future studies, different aspects of imaging dipping faults with RSI were investigated using synthetic data. The results showed that reconstructing steeply dipping reflections requires sources in the hanging-wall and that the interpretation of the RSI sections is complicated due to strong artefacts caused by P-S converted arrivals. Thus, passive imaging needs careful planning and a good knowledge of the source positions for distinguishing between artefacts and subsurface structures. This knowledge can be obtained using the stacking-based location method.
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| 9. |
- Behra, Phani Rama Krishna
(författare)
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Comparative genomics of the genus Mycobacterium : Genome evolution, phylogeny and diversity
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The genus Mycobacterium includes more than 190 species, and many cause severe diseases such as tuberculosis and leprosy. According to the "World Health Organization", in year 2019 alone, 10 million people developed TB, and 1.4 million died. TB had been in decline in developed countries, but made its reappearance as an opportunistic pathogen targeting immuno-compromised AIDS victims. Also, non-tuberculosis mycobacteria (NTM) infections have emerged as a major infectious agent in recent times. NTM occupy diverse ecological niches and can be isolated from soil, tap water, and groundwater. This thesis has investigated the Mycobacterium species from a genomic perspective, focusing on the biology of virulence factors, mobile genetic elements, tRNAs, and non-coding RNAs and their evolutionary distribution and possible relationship with phenotypic diversity. As part of this study, we have sequenced 153 mycobacterial genomes, including type strains, environmental samples, isolates from hospital patients, infected fish, and outbreak samples in an animal facility at Uppsala University. We have provided a phylogenetic tree based on 387 (and 56) core genes covering most species (244 genomes) constituting the Mycobacterium genus. The core gene phylogeny resulted in 33 clades. Subsequently, we have covered different clade groups, such as, M. marinum, M. mucogenicum, M. chelonae and M. chlorophenolicum and investigated the NTM clade-specific genome diversity and evolution. Our examination of non-coding genes showed that the total number of tRNA genes per species varies between 42 and 90. Among the species with more than 50 tRNAs, additional tRNA genes are likely acquired through horizontal gene transfer (HGT), as supported by the presence of closely linked HNH endonuclease gene and GOLLD RNA. We have explored the presence of selenocysteine utility and the gene for selenoprotein "formate dehydrogenase" among 244 mycobacterial genomes. For the M. chlorophenolicum clade, we have explored genes with a role in the bioremediation process. Comparative genomics of M. marinum and M. chelonae clade groups suggest new clusters or subspecies. Mutational hotspots are relatively higher in M. marinum compared to that in M. tuberculosis and M. salmoniphilum. Relatively higher number of hotspots in M. marinum is likely related to its ability to occupy different ecological niches. Finally, the thesis uncovered IS elements, phage sequences, plasmids, tRNA, and ncRNA contributing to mycobacterial evolution.
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| 10. |
- Bender, Anke
(författare)
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Environmental Effects from Wave Power : Artificial Reefs and Incidental No-take Zones
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Marine renewable technologies have rapidly been developing over the past decade. Wave power is one of the renewable sources and has the potential securing the renewable electricity production. However, all renewable energy extraction affects the environment in some way and for a true sustainable energy generation, environmental effects need to be investigated. Beside uncertain effects from the technologies to habitats or organisms e.g., collision risks, electromagnetic fields, noise, past studies have also shown benefits on diversity, size and abundance of species around marine renewable technologies as a result of habitat creation by the devices and fishery exclusion in designated offshore park areas.This thesis deals with environmental effects from heaving point-absorber wave energy converters developed at Uppsala University and deployed on the Swedish west coast at the Lysekil research site and the Sotenäs Project wave power park over a period of four years. The scope was the investigation of artificial reef effects from wave power foundations on local mobile, mega and macrofauna during visual inspections using scuba diving on the first hand. On the second hand, the effects from the incidental no-take zone on decapods and two sea pen species were investigated applying cage fishing and ROV seabed surveys. A third focus was on environmental monitoring around MRE sites and monitoring of MRE installations, both in an experimental and theoretical approach.In the Lysekil research site, the results highlight that abundance and diversity can be enhanced locally around wave power foundations compared to control areas. The abundance and size of decapods were not significantly different within the wave power park and up to a distance of 360 m outside of it. In the Sotenäs Project wave power park a positive effect on Nephrops norvegicus size and burrow density but not on abundance was found on a scale of up to 1230 m. Sea pen abundance was enhanced inside the wave power park. However, interannual variation was strong.In conclusion, wave power foundations can influence abundance and diversity of marine organisms around foundations on a very local scale (meters). With the methods in this study, the investigations did not reveal strong effects on the abundance and size of decapods on a larger scale up to 1230 m away from foundations as a result of the no-take zone. However, a focus should be put on a further development of environmental monitoring routines around MRE sites and their evaluation.
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