| 1. |
- Dahlgren Lindström, Adam, 1993-
(författare)
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Learning, reasoning, and compositional generalisation in multimodal language models
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We humans learn language and how to interact with the world through our different senses, grounding our language in what we can see, touch, hear, and smell. We call these streams of information different modalities, and our efficient processing and synthesis of the interactions between different modalities is a cornerstone of our intelligence. Therefore, it is important to study how we can build multimodal language models, where machine learning models learn from more than just text. This is particularly important in the era of large language models (LLMs), where their general capabilities are unclear and unreliable. This thesis investigates learning and reasoning in multimodal language models, and their capabilities to compositionally generalise in visual question answering tasks. Compositional generalisation is the process in which we produce and understand novel sentences, by systematically combining words and sentences to uncover the meaning in language, and has proven a challenge for neural networks. Previously, the literature has focused on compositional generalisation in text-only language models. One of the main contributions of this work is the extensive investigation of text-image language models. The experiments in this thesis compare three neural network-based models, and one neuro-symbolic method, and operationalise language grounding as the ability to reason with relevant functions over object affordances.In order to better understand the capabilities of multimodal models, this thesis introduces CLEVR-Math as a synthetic benchmark of visual mathematical reasoning. The CLEVR-Math dataset involve tasks such as adding and removing objects from 3D scenes based on textual instructions, such as \emph{Remove all blue cubes. How many objects are left?}, and is given as a curriculum of tasks of increasing complexity. The evaluation set of CLEVR-Math includes extensive testing of different functional and object attribute generalisations. We open up the internal representations of these models using a technique called probing, where linear classifiers are trained to recover concepts such as colours or named entities from the internal embeddings of input data. The results show that while models are fairly good at generalisation with attributes (i.e.~solving tasks involving never before seen objects), it is a big challenge to generalise over functions and to learn abstractions such as categories. The results also show that complexity in the training data is a driver of generalisation, where an extended curriculum improves the general performance across tasks and generalisation tests. Furthermore, it is shown that training from scratch versus transfer learning has significant effects on compositional generalisation in models.The results identify several aspects of how current methods can be improved in the future, and highlight general challenges in multimodal language models. A thorough investigation of compositional generalisation suggests that the pre-training of models allow models access to inductive biases that can be useful to solve new tasks. Contrastingly, models trained from scratch show much lower overall performance on the synthetic tasks at hand, but show lower relative generalisation gaps. In the conclusions and outlook, we discuss the implications of these results as well as future research directions.
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| 2. |
- Hall, Caroline, 1979-
(författare)
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Empirical Essays on Education and Social Insurance Policies
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four self-contained essays. Essay 1: This paper evaluates the effects of the introduction of a more comprehensive upper secondary school system in Sweden in the 1990s. The reform reduced the differences between the academic and vocational educational tracks through prolonging and substantially increasing the academic content of all vocational tracks. The effects of this policy change are identified by exploiting a six year pilot scheme, which preceded the actual reform in some municipalities. The results show that the prolongation of the vocational tracks brought about an increased probability of dropping out among low performing students. Though one important motive behind the policy change was to enable all upper secondary school graduates to pursue a university degree, I find no effects on university enrolment or graduation. There are some indications, however, that attending the longer and more academic vocational tracks may have led to increased earnings in the long run. Essay 2: (co-authored with Peter Fredriksson, Elly-Ann Johansson and Per Johansson) We examine whether the impact of pre-school interventions on cognitive skills differs by immigrant background. The analysis is based on Swedish data containing information on childcare attendance, rich family background information, the performance on cognitive tests at age 13, and long-run educational attainment for cohorts born between 1967 and 1982. We find that childcare attendance reduces the gap in language skills between children from immigrant backgrounds relative to native-born children. We find no differential effects on inductive skills, however. Nor does childcare appear to affect the distribution of long-run educational attainment. Essay 3: (co-authored with Laura Hartman) This paper studies a specific type of moral hazard that arises in the interplay between two large public insurance systems in Sweden, namely the sickness insurance (SI) and the unemployment insurance (UI). Moral hazard can arise from the structure of the benefit levels as for some unemployed persons benefits from the SI are higher than benefits from the UI. We use a reform of the SI system that came into force on 1 July 2003 to identify the effect of economic incentives arising from the different benefit levels. The purpose of the reform was to eliminate the difference in benefits between the two insurance systems. Our results from a duration analysis show clearly that the higher the sickness benefits, the higher the probability of reporting sick. Essay 4: Previous research suggests that there are substantial interactions between the unemployment insurance (UI) and the sickness insurance (SI) in Sweden. Moral hazard arises in the interplay between these two social insurance systems, since by reporting sick an unemployed person can postpone the UI expiration date and sometimes also receive considerably higher benefits. This paper examines whether these interactions affect the transition rate from unemployment to employment. To study this question I utilize a reform which greatly reduced the incentives for unemployed persons to transfer to the SI. While there is evidence that this reform substantially lowered the incidence of sick reports among the unemployed, I find no evidence suggesting that the reduced sick report rate in turn affected the transition rate to employment.
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| 3. |
- Lannsjö, Marianne, 1956-
(författare)
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Mild Traumatic Brain Injury : Studies on outcome and prognostic factors
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To explore the prevalence and structure of self-reported disability after mild traumatic brain injury and the impact of traumatic brain pathology on such outcome.Material and methods: In study 1-3, symptoms data were collected by use of Rivermead Post-concussion Symptoms Questionnaire (RPQ) and data on global function by use of Glasgow Outcome Scale Extended (GOSE) from 2602 patients at 3 months after MTBI. RPQ data were subject to factor and Rasch-analyses Head CT data from 1262 patients were used in a prediction analysis that also included age and gender. In study 4, MRI and symptoms data were collected at 2-3 days and at 3-7 months follow-up after MTBI in 19 patients. Global function was assessed at follow-up by use of the Rivermead Head Injury Follow-Up Questionnaire (RHIFUQ) and GOSE.Results: I. Most respondents reported no remaining symptoms but 24% reported ≥3 and 10% ≥7 remaining symptoms. The factor analysis demonstrated that all symptoms are correlated but also identified subgroups of symptoms. II. Rasch-analysis of RPQ showed disordered category function, local dependency of items, poor targeting of persons to items and indications of 3 or more dimensions. There was no differential item functioning. III. Head CT pathology with no need for acute intervention was observed in 52 patients (4%) but was not associated with either frequency of remaining symptoms or global outcome at 3 months post injury. Female gender and age over 30 years were associated with less favourable outcome with respect to symptoms and GOSE. IV. Post-acute MRI indicated trauma-related pathology in one patient and follow-up MRI indicated loss of brain volume in 4 patients.Conclusions: A substantial proportion of patients with MTBI report remaining problems at three months after MTBI. RPQ is useful but not optimal to assess symptoms outcome after MTBI and calculation of a total sum score is not recommended. Female gender and older age are negative prognostic factors while brain pathology according to CT has no effect on self-reported outcome. Loss of brain volume after MTBI according to MRI may be a sensitive marker of traumatic brain pathology and deserves further studies.
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| 4. |
- Sjölander, Andreas, 1983-
(författare)
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Analyses of shotcrete stress states due to varying lining thickness and irregular rock surfaces
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Shotcrete is sprayed concrete applied pneumatically under high pressure and was invented in the beginning of the 1900's. This new technique decreased the construction time and since steel fibres were introduced in the shotcrete during the 1970's, shotcrete has been the primary support method for tunnels.Tunnels excavated with the drill and blast method creates a highly irregular rock surface which results in a shotcrete lining with varying thickness. The structural behaviour as well as the loads acting on the shotcrete lining depends on the interaction between the shotcrete, rock and rock bolts. There are several parameters influencing this interaction, e.g. bond strength, the stiffness of the rock and thickness of the shotcrete. All of these parameters are difficult to predict accurately which makes the structural design of the lining to a complex problem.This thesis present the first part of a research project with the long-term goal to improve the understanding of the structural behaviour of the shotcrete lining. To achieve this, numerical modelling have been used to study the build up of stresses and cracking of shotcrete when subjected to restrained loading caused by e.g. temperature differences and drying shrinkage. The response in the lining when subjected to a gravity load from a block has also been studied. The model is capable of describing the non-linear deformation behaviour of both plain and fibre reinforced shotcrete and uses presented in situ variations in thickness to more accurately account for the effects of expected variations in thickness. The thesis discuss and demonstrate the effect of important loads that acts on the shotcrete lining and how the irregular geometry of the rock surface in combination with the varying thickness of the shotcrete affect the development of stresses in the lining. It is also discussed how a full or partial bond failure affect the structural capacity of a shotcrete lining.
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| 5. |
- Hansson, Anna M., 1984-
(författare)
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Get it off the ground – Facilitating water-related environmental measures to support agricultural managers in business model innovation processes for sustainability
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Agricultural businesses, which currently maintain, manage, create, and capture economic value from natural resources on farmland, play an important role in creating sustainable economic, environmental, and social value through maintaining and utilising a variety of ecosystem services in addition to traditional food production. This thesis focuses on ecosystem services that derive from water-related environmental measures (WREMs). This focus is motivated by a growing awareness of WREMs in the agricultural landscape, and of their connection to climate effects and water quantity and quality issues, which have substantial societal impact. Even though many agricultural business managers have a genuine interest in sustainability concerns, they tend to favour food production at the cost of providing other ecosystem services. Part of the explanation is that ecosystem services’ ability to provide social and environmental value for the public good often lacks full-cost accounting and clear market demand. This results in uncertainties among agricultural business managers about how to capture economic value from WREMs and associated ecosystem services, leading to their benefits and value being only partly known or only indirectly connected to the main agricultural production, and therefore not included in current business models to any great extent.Business models can be developed to enable value capture from WREMs through the business model innovation process for sustainability (BMIpfS). The BMIpfS identifies changes of current activities and adapts existing business models to support sustainable development and produce positive (or reduce negative) environmental effects on society, while producing long-term prosperity for businesses and their stakeholders. Due to the wide range of activities and stakeholders, the BMIpfS is complex and needs to be incentivised and facilitated. To provide sufficient facilitation for the BMIpfS initiation, underlying barriers and drivers for business managers’ value intention (their business motives) for the BMIpfS need to be explored. Facilitation based on the value intention of business managers can ease the process and be used to support identification of value not yet captured in business models, as well as provide expertise to identify marketable sustainable products and services beyond existing markets. Facilitation can be managed through government-affiliated intermediaries who are in a favourable position to assess local conditions, identify needs and resources, and develop partnerships with stakeholders that align with current agri-environmental programmes. To facilitate sustainable business commitments in agriculture, a better understanding is needed of how government-affiliated intermediaries can support implementation of WREMs and promote the BMIpfS initiation by aligning agricultural business managers’ value intention with societal sustainability goals. Consequently, the overarching aim of this thesis is to explore how the facilitation of WREMs can support the BMIpfS through an improved understanding of (i) the value intention of agricultural business managers and (ii) how government-affiliated intermediaries can facilitate the process initiation.This thesis builds on four sequential studies, all conducted within external research projects. The first two are qualitative interview studies that build on each other to inductively explore agricultural business mangers’ incentives for taking on more long-term and high-effort WREMs and committing to value capture of sustainability-related measures. They identify barriers and drivers as part of the agricultural business managers’ value intention and analyse its connection to the BMIpfS initiation. The third study is quantitative and was conducted through a survey that more deductively explores how opportunities for sustainable value creation and business model innovation through WREMs can be facilitated to align with the managers’ value intention that emerged in the first two studies. Finally, the fourth study is a qualitative interview study that takes an evaluative approach to further clarify how the facilitation of WREMs can be structured and organised to promote BMIpfS initiation in agriculture. The results of this research show that business change incentives for sustainability activities are part of pre-initiation conditions of the BMIpfS through the value intention of business managers. The value intention is clarified as business managers’ (i) identification as producers of value, (ii) difficulties identifying uncaptured sustainability value, and (iii) prioritisation of profitability and practical benefits. Adding value intention to a pre-initiation process phase contributes to the BMIpfS literature by providing a better understanding of how to support the BMIpfS initiation and promote more long-term and high-effort sustainability commitments, and value creating and capturing activities, among business managers. The results also show how WREM commitments and initiation of the BMIpfS can be facilitated through government-affiliated intermediaries. The government-affiliated intermediation is explained as comprising structures and activities to promote: (i) WREMs that include synergy between environmental and business aspects from a long-term perspective on value creating and capturing activities; (ii) flexible approaches adapted to business managers’ needs, that promote autonomy, trust, and sense of control; and (iii) structured collaboration and networks for knowledge exchange between stakeholders on different societal levels. With the value intention of business managers as a foundation, these results complement previous research on government-affiliated intermediaries and show how they can be structured to facilitate sustainable agricultural business activities and promote the BMIpfS initiation in line with societal sustainability targets. To integrate its results, this thesis develops a framework that advances the understanding of how to facilitate business model innovation towards sustainability and capture a wider range of value from ecosystem services. Through facilitation, innovation of business models towards sustainability can be promoted to realise currently uncaptured value that could benefit business revenues and societal goals. In this way, agriculture could continue to provide the world’s population with food, in line with the goals of sustainable development, but with an expanded approach so that food production becomes a basis on which to build business activities that also improve the conditions for several other goals, such as protection of ecosystems and water resources.
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| 6. |
- Lindberg, Diana, 1970-
(författare)
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Exploring Selectivity and Hysteresis : Kinetic Studies on a Potato Epoxide Hydrolase
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The kinetic mechanism of an α/β hydrolase fold epoxide hydrolase from potato, StEH1, has been studied with the aims of explaining the underlying causes for enantio- and regioselectivity, both being important for product purity. Further effort has been laid upon understanding the causes of a hysteretic behavior discovered in the measurements leading to Paper I. The enantioselectivity was investigated with substrates differing only in substituent size at one carbon of the oxirane ring structure. In catalysis with trans-stilbene oxide and styrene oxide, enantioselectivity is the result of differences in alkylation rates. In pre-steady state measurement with trans-2-methylstyrene oxide (2-MeSO), a rate-limiting step involving slow transitions, referred to as hysteresis, was discovered. With this substrate enantioselectivity is proposed to be a consequence of the catalytic rate of (1R,2R)-enantiomer being more influenced by the hysteretic behavior than was the rate of the other enantiomer. In steady-state measurements with (1R,2R)-2-MeSO, at different temperatures and pH, hysteretic cooperativity was displayed. It can be concluded that this behavior is dependent on the relationship between kcat and the rate of transition between two Michaelis complexes. From the differences in pH dependence of kcat/KM in formation of the two diols resulting from low regioselectivity in catalysis of (1R,2R)-2-MeSO, it is suggested that hysteresis is a result of the substrates placed in different conformational modes within the active site cavity. Regioselectivity is proposed to be the result of specific interactions between the catalytically important Tyr and the substrate, with a link between KM-values and degree of regioselectivity. Furthermore, the hysteretic kinetic model proposed can explain hysteresis, cooperativity and regioselectivity resulting from StEH1 catalyzed hydrolysis of (1R,2R)-2-MeSO.
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| 7. |
- Lindberg, Richard, 1977-
(författare)
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Determination of Antibiotics in the Swedish Environment with Emphasis on Sewage Treatment Plants
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metoder har utvecklats för att kunna bestämma tolv antibiotikasubstanser, vanliga inom human medicin, i miljöprover. Fokus lades på trimetoprim samt substanser från följande grupper: fluorokinoloner, sulfonamider, penicilliner, cefalosporiner, nitroimidazoler, tetracykliner samt makrolider. Vid extraktion användes fast-fas extraktion för vattenprover och ultraljuds-assisterad fast-fas/vätske extraktion för fasta prover. För separering och bestämning användes vätskekromatografi tandemmasspektrometri. Interna standarder nyttjades för att öka noggrannhet och precision. Extraktionsutbyte låg mellan 50% och 100% för vattenfaser och 14% och 100% för fasta faser. Koncentrationer och massflöden bestämdes för antibiotikasubstanser i inkommande och utgående vatten och slam, från fem avloppreningsverk i Sverige, samt i avloppsvatten från ett sjukhus. I sjukhusavloppsvattnet så påträffades ciprofloxacin (en fluorokinolon) och metronidazol (en nitroimidazol) i höga halter (µg/L nivå). Screening-studien vid de fem avloppsreningsverken visade att norfloxacin, ofloxacin, ciprofloxacin och doxycyklin ofta förekom i inkommande och utgående vatten och slam. Trimetoprim och sulfametoxazol påvisades inte i slam men förekom i snarlika koncentrationer i det utgående vattnet relativt det inkommande. I vattenfasen så förekom de sex antibiotikasubstanserna i ng/L nivån och i slam förekom norfloxacin, ofloxacin, ciprofloxacin, och doxycyklin i låga mg/kg nivån. En studie genomfördes där beteendet hos antibiotikasubstanser under avloppsrening studerades. De två fluorokinolonerna, norfloxacin och ciprofloxacin, adsorberade till slam och mindre än 5% av den totala mängd som kommer till avloppsreningsverket påvisades i det utgående vattnet. I slam var motsvarande andel 70%. Resultat från en process som värmebehandlar rötat avvattnat slam antyder att cirka 50% av de två fluorokinolonerna bryts ner. Trimetoprim adsorberade inte till slam och 100% av total mängd återfanns i det utgående vattnet. Teoretiska beräkningar av koncentrationer och massflöden visade god korrelation till kvantitativa resultat. Ökad noggrannhet i beräkningarna fås genom att beakta stabilitet och fasfördelning. Effekten av antibiotikasubstanser i miljön är idag okänd. Resultat från testprotokoll där deras toxicitet bedöms är i många fall irrelevanta. Tester där organismer är kroniskt exponerade av biologiskt aktiva substanser vid låga koncentrationer är få. Dessutom så fokuserar de ej på de stora potentiella effekterna såsom utveckling eller bevaring av resistenta stammar av bakterier i miljön. Ytterligare studier av förekomst, öde och effekt av antibiotikasubstanser i miljön är nödvändiga.
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| 8. |
- Sjölander, Andreas, 1983-
(författare)
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Structural behaviour of shotcrete in hard rock tunnels
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tunnels in hard and jointed rock are normally excavated in an arch shape to enable the rock mass to support its weight. Since the beginning of the 1980's, fibre reinforced shotcrete (FRS) in combination with rock bolts have been the dominating support method for hard rock tunnels. This type of rock support is a complex composite structure in which the structural behaviour depends on interaction between shotcrete, rock and bolts. The design is commonly based on a rock mass classification system in combination with analytical solutions or finite element (FE) modelling. However, the in-situ variations of important properties of the shotcrete are normally neglected.The aim of this thesis is to describe and explain how the variations in shotcrete thickness and bond strength affect the structural behaviour and capacity for a shotcrete lining. Especially, the influence of local variations in shotcrete thickness and bond strength has been studied in detail. For this purpose, a numerical framework capable of simulating bond failure, cracking of FRS and pull-out failure of grouted rock bolts have been developed. Moreover, in-situ data for shotcrete thickness and bond strength have been collected and analysed to characterize the variations in important shotcrete parameters.The results in this thesis show that when shotcrete is subjected to shrinkage, local variations in shotcrete thickness affects the crack pattern. However, the number and width of the cracks are similar to the case with uniform thickness. Most importantly, a pattern of fine and narrow cracks develops in unreinforced shotcrete subjected to shrinkage when a continuous bond to the rock exists. When shotcrete is subjected to the load from a loose block, the force is transferred to the surrounding rock through bond stresses distributed over a narrow band. Simulations have shown that the structural capacity, with respect to bond failure, depends on the shotcrete thickness. Moreover, a strong linear correlation was found between the mean value of the bond strength and shotcrete thickness around the perimeter of the block and the structural capacity. Local weak areas, i.e. with low bond strength or thickness, may exist around the perimeter without having a significant effect on the structural capacity. Design of bolt-anchored shotcrete linings is based on failure modes previously derived from experimental testing. This thesis has contributed to an increased understanding of the failure mechanisms of the lining and has confirmed that the design can be based on individual failure mechanisms.
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| 9. |
- Al-Amin, Rasel A., Researcher, 1983-, et al.
(författare)
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Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ
- 2022
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 50:22, s. e129-e129
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Tidskriftsartikel (refereegranskat)abstract
- Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.
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| 10. |
- Al-Amin, Rasel A., 1983-, et al.
(författare)
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Target Engagement-Mediated Amplification for Monitoring Drug-Target Interactions in Situ
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- It is important to determine the localization of drugs or drug candidates at cellular and subcellular resolution in relevant clinical specimens. This is necessary to evaluate drug candidates from early stages of drug development to clinical evaluation of mutations potentially causing resistance to targeted therapy. We describe a technology where oligonucleotide-conjugated drug molecules are used to visualize and measure target engagement in situ via rolling-circle amplification (RCA) of circularized oligonucleotide probes (padlock probes). We established this target engagement-mediated amplification (TEMA) technique using kinase inhibitor precursor compounds, and we applied the assay to investigate target interactions by microscopy in pathology tissue sections and using flow cytometry for blood samples from patients, as well as in commercial arrays including almost half of all human proteins. In the variant proxTEMAtechnique, in situ proximity ligation assays were performed by combining drug-DNA conjugates with antibody-DNA conjugates to specifically reveal drug binding to particular on- or off-targets in pathological tissues sections. In conclusion, the TEMA methods successfully visualize drug-target interaction by experimental and clinically approved kinase inhibitors in situ and with kinases among a large collection of arrayed proteins.
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