Faculty of Science and Technology / Fakulteten för naturvetenskap och teknik
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Item 1:1 i klassrummet – analyser av en pedagogisk praktik i förändring(2015-02-06) Tallvid, MartinI denna avhandling analyseras resultaten från två utvärderingsprojekt av 1:1-införande som genomförts på två högstadieskolor (2007-2011) och fyra gymnasieskolor (2012-2014) i Sverige. Data från enkäter, intervjuer och observationer har analyserats för att svara på frågeställningar om hur olika aspekter av den pågående digitaliseringen påverkar verksamheten i skolan. Den teoretiska utgångspunkten tas i ett sociokulturellt perspektiv på skola som verksamhet, på teknologi som medierande redskap och på utveckling och lärande som socialt grundade. För att beskriva komplexiteten i läraruppdraget används det teoretiska ramverket TPACK. Ramverket beskriver integrationen mellan de teknologiska, pedagogiska och innehållsliga kunskapsdomäner som tillsammans bildar kärnan i en lärares kompetens i en digitaliserad skola. Resultaten visar att det krävs kunskap om och förståelse för praktikens förutsättningar för att kunna avgöra huruvida digitalisering och 1:1-satsningar påverkar. Ur ett makroperspektiv förefaller klassrumsaktiviteterna vara i stort sett opåverkade av 1:1-införandet. Undervisningen tycks pågå som tidigare och förefaller i huvudsak traditionell och kontrollerad av en reglerande diskurs. Å andra sidan, när skolan studeras ur ett mesoperspektiv är det möjligt att urskilja ett antal väsentliga förändringar av verksamheten. Teknologin påverkar verksamheten, men det innebär inte automatiskt en förändring av den övergripande strukturen för hur utbildningen praktiseras. Ett 1:1-införande leder först till förändringar på praktiknivå med utmaningar av lärares och elevers verksamhet. Delstudierna i avhandlingen visar att digitaliseringen påverkar lärares lektionsplanering, och att elevers användning av de digitala redskapen förändras över tid. Dessutom diskuteras lärares argument för att inte integrera digitala verktyg i den pedagogiska praktiken.Avhandlingen har konsekvenser för praktikfältet genom att den identifierar och diskuterar några av följderna av digitaliseringen av skolan. De klassrumsnära studierna visar att IT-användningen är varierande och ojämn, och att införandet av 1:1 är en komplicerad process som utmanar verksamheten i skolan på flera nivåer.Item 20 years of bibliometric data illustrates a lack of concordance between journal impact factor and fungal species discovery in systematic mycology(2024) Nilsson, Henrik; Jansson, Arnold Tobias; Wurzbacher, Christian; Anslan, Sten; Belford, Pauline; Corcoll, Natàlia; Dombrowski, Alexandra; Ghobad-Nejhad, Masoomeh; Gustavsson, Mikael; Gómez Martinez, Daniela; Kalsoom Khan, Faheema; Khomich, Mariya; Lennartsdotter, Charlotte; Lund, David; Van Der Merwe, Breyten; Mikryukov, Vladimir; Peterson, Marko; Porter, Teresita M.; Põlme, Sergei; Retter, Alice; Sanchez-Garcia, Marisol; Svantesson, Sten; Svedberg, Patrik; Vu, Duong; Ryberg, Martin; Abarenkov, Kessy; Kristiansson, Erik; University of Gothenburg, Gothenburg Global Biodiversity Centre, Department of Biological and Environmental Sciences, Box 463, 405 30 Göteborg, SwedenJournal impact factors were devised to qualify and compare university library holdings but are frequently repurposed for use in ranking applications, research papers, and even individual applicants in mycology and beyond. The widely held assumption that mycological studies published in journals with high impact factors add more to systematic mycology than studies published in journals without high impact factors nevertheless lacks evidential underpinning. The present study uses the species hypothesis system of the UNITE database for molecular identification of fungi and other eukaryotes to trace the publication history and impact factor of sequences uncovering new fungal species hypotheses. The data show that journal impact factors are poor predictors of discovery potential in systematic mycology. There is no clear relationship between journal impact factor and the discovery of new species hypotheses for the years 2000-2021. On the contrary, we found journals with low, and even no, impact factor to account for substantial parts of the species hypothesis landscape, often discovering new fungal taxa that are only later picked up by journals with high impact factors. Funding agencies and hiring committees that insist on upholding journal impact factors as a central funding and recruitment criterion in systematic mycology should consider using indicators such as research quality, productivity, outreach activities, and teaching ability directly rather than using publication in high impact factor journals as a proxy for these indicatorsItem A circular economy approach for sustainable feed in Swedish aquaculture: A nutrition and physiology perspective(2019-10-25) Hinchcliffe, JamesOne major challenge in aquaculture is the issue of fishmeal replacement as a protein source in aquafeeds. It is agreed that the rate of demand has now outpaced the rate of supply due to the rapid expansion of aquaculture. In Sweden, work is being done to establish a knowledge base for the development of sustainable marine aquaculture, focusing on two species: Atlantic wolffish, Anarhichas lupus and European lobster, Hommarus gammarus, as well as on two novel protein ingredients. The goal of this thesis was to contribute to a knowledge base for the farming biology and culture operations of the two species, with a circular economy model and minimal environmental impact in mind in line with UNs agenda 2030. In paper I, work was done to optimize the pH-shift process, a novel protein extraction technology with potential to produce a highly concentrated protein ingredient from industrial seafood by-products. Three combinations of herring by-products were chosen along with two different process settings and differences in final proximate composition were characterized. Results showed the alkaline version of the process gave significantly higher protein yields and all forms of by-products were deemed as promising. Paper II initiated four feeding experiments (novel feed types, feeding regime and feed size and cannibalism effects) on growth and survival, to inform and update husbandry protocols in H. gammarus. Overall, we found that feed offered six times daily, small‐grade dry feed (250–360 μm) and larvae fed different proportions of dry feed and/or conspecifics in both communal and individual rearing systems all improved growth and survival rates. This underlines the impact of cannibalism on survival in H. gammarus larviculture. In paper III we examined the suitability of locally produced, novel protein sources from by-products on the growth of recently metamorphosed post-larva. We found that, that a diet containing a proportion of shrimp, created from local industry by-products, was the best source of a sustainable lobster feed for the emerging lobster aquaculture sector. The nutritional requirements of Atlantic wolffish are not known. In paper IV six experimental diets were formulated to test differing protein increments, 35-60%. We found that there was a high protein requirement in the diet (50-60%) but observations suggested that individual wolffish were able to compensate for this by increasing individual feed intake. The aim of paper V was to establish the stress response of Atlantic wolffish exposed to an acute and chronic temperature challenge. Overall we found evidence confirming a stress response in selected parameters, suggesting that at 15°C, the high allostatic load of this temperature leaves no scope for growth. However, no evidence of a primary stress response (cortisol) could be found, suggesting that cortisol may not be a good parameter to measure welfare in this species in future studies and aquaculture operationsItem A contribution to the design and analysis of phase III clinical trials(2013-11-08) Lisovskaja, VeraClinical trials are an established methodology for evaluation of the effects of a new medical treatment. These trials are usually divided into several phases, namely phase I through IV. The earlier phases (I and II) are relatively small and have a more exploratory nature. The later phase III is confirmatory and aims to demonstrate the efficacy and safety of the new treatment. This phase is the final one before the treatment is marketed, with phase IV consisting of post-marketing studies. Phase III is initiated only if the conductors of the clinical study judge that the evidence from earlier stages indicates clearly that the new treatment is effective. However, several studies performed in recent years show that this assessment is not always correct. Two papers written on the subject point out average attrition rates of around 45\% and 30\%. In other words, it is estimated that only around two thirds of the compounds that enter phase III finish it successfully. This thesis examines some of the possible ways of improving efficiency in phase III clinical trials. The thesis consists of four papers on various topics that touch this subject, these topics being adaptive designs (paper I), number of doses (paper II) and multiplicity correction procedures (papers III and IV). The first paper examines the properties of the so called dual test, which can be applied in adaptive designs with sample size re-estimation. This test serves as a safeguard against unreasonable conclusions that may otherwise arise if an adaptive design is used. However, there is a price of possible power loss as compared to the standard test that is applied in such situations. The dual test is evaluated by considering several scenarios where its use would be natural. In many cases the power loss is minimal or non-existing. The second paper considers the optimal number and placement of doses used in phase III, with the probability of success of the trial used as optimality criterion. One common way of designing phase III trials is to divide the patients into two groups, one group receiving the new drug and another a control. However, as is demonstrated in paper II, this approach will be inferior to a design with two different doses and a control if there is enough uncertainty in the dose-response model prior to the initiation of the trial. The last two papers study possible gain that results from optimization of the multiplicity correction procedure that is applied if more than one hypothesis is tested in the same trial. Two families of such procedures are considered. The first one, examined in paper III, consists of a combination of a weighted Bonferroni test statistic with the principle of closed testing. The second one, examined in paper IV, is based on combining the same principle with a "pooled" test statistic. Paper III demonstrates that optimizing a multiplicity testing procedure can lead to a significant power increase as compared to simpler, non-optimized, procedures. The optimization is performed with respect to expected utility, an approach that originates from decision theory. Paper IV examines the difference between the Bonferroni-based and the pooled-based multiplicity corrections, finding the latter to be superior to the former if the test statistics follow a known multivariate Normal distribution.Item A Fragile Hold on the Electron: Probing the Limits of Negative Ion Studies(2025-04-25) Nichols, MirandaNegativa joner är unika kvantsystem vars struktur och dynamik i hög grad påverkas av elektronkorrelationseffekter. På grund av deras svagt bundna natur och avsaknaden av långräckviddiga Coulomb-potentialer saknar dessa system ofta optiskt tillåtna övergångar, vilket försvårar högupplösta spektroskopiska studier i jämförelse med neutrala atomer. Forskningen har därför traditionellt fokuserat på mätningar mellan bundna tillstånd och kontinuerliga tillstånd, i synnerhet bestämning av elektronaffinitet (EA) med metoder såsom laserfotodetachement-tröskelspektroskopi (LPTS). För joner där elektroner lossnar till ett p-vågskontinuum har EA-bestämningen dock varit begränsad, till följd av den långsamma fotodetachementprocessen precis ovanför tröskeln och de generellt små tvärsnitten. I denna avhandling bemöts dessa utmaningar genom en vidareutveckling av en kombinerad metod baserad på LPTS och resonansjonisationsspektroskopi (RIS), vilket möjliggör tillståndsselektiva mätningar av partiella fotodetachementtvärsnitt. En ny detektionsstrategi har införts för att särskilja signal från bakgrund, vilket avsevärt förbättrar selektiviteten och den experimentella upplösningen. Den förbättrade LPTS-RIS-metoden demonstrerades genom förbättrade EA-mätningar av cesium (Cs) och rubidium (Rb), där noggrannheten överträffade tidigare resultat för p-vågströsklar och bekräftade metodens användbarhet för framtida studier av mer komplexa atomära system. För att möjliggöra experiment med radioaktiva negativa joner krävs effektiva produktionstekniker. I detta arbete visas att laddningsutbytesreaktioner med uran kan användas för att framställa sådana joner. En kompletterande teoretisk studie undersökte elektroninfångning och energiförlustprocesser vid atom-jon-kollisioner och identifierade avgörande faktorer som påverkar banstrukturer. Genom att inkludera elektron-nukleär koppling i modellen uppnåddes en fördjupad förståelse, vilket är centralt för vidare modellutveckling av produktionsprocesser. Ett av avhandlingens viktigaste resultat är introduktionen av en helt ny spektroskopisk metod för att studera tidigare otillgängliga förbjudna bundna-bundna övergångar i negativa joner. Genom att utnyttja möjligheterna hos en kryogen jonlagringsring har den första mätningen av isotopförskjutning (IS) för en elektriskt dipolförbjuden övergång genomförts, med tennanjonen Sn⁻ som testfall. Metodens känslighet för elektronkorrelationseffekter, särskilt via komponenten för specifik massförskjutning, understryker dess potential. Arbetet visar att en kombinerad experimentell och teoretisk metodik kan övervinna centrala begränsningar inom spektroskopi av negativa joner och möjliggöra studier av system och övergångar som tidigare varit otillgängliga. Genom att tillämpa högprecisionstekniker på tunga och radioaktiva joner, utveckla robusta men enkla teoretiska modeller och utforska förbjudna övergångar, utvidgar denna avhandling forskningsfältets räckvidd och öppnar nya vägar inom atomär, nukleär och kvantmekanisk mångkroppsfysik.Item A Holistic View on Aquaporins: Production, Structure, Function and Interactions(2020-10-21) Schmitz, FlorianAquaporins are specialised membrane proteins, which regulate the water homeostasis of cells. In eukaryotic organisms, this process is tightly regulated, and aberrations in aquaporin functionality lead to severe pathologies in humans. The aim of this thesis is to shed light on the aquaporin function and regulation, both as individual protein targets and in the cellular context, as well as exploring various applications for human aquaporin 4, specifically. A wide range of biochemical methods have been applied, ranging from the importance of robust protein production methods, for targets as well as for their complexes, to functional and structural characterization. For biochemical characterization and structural analysis, large amounts of pure, homogeneous and stable recombinant protein are needed. The methylotrophic yeast Pichia pastoris was utilized for the overproduction of the soluble protein Sirtuin2, an indirect up-regulator of Aquaporin4 in humans. The highest yet-reported yield of the protein (40 mg/l) was achieved, facilitating modulation trials of the potential drug target. The P. pastoris overproduction system was also employed for the expression of human AQP4, facilitating new research applications, such as improved Neuromyelitis Optica diagnosis, and a better understanding of the intermolecular binding between the monomeric subunits. In addition, the novel structural characteristics of AQP1 from the fish Anabas testudineus was studied in this thesis and key residues responsible for the molecular mechanisms for osmoregulation were identified by mutational analysis combined with functional studies. By combining stopped-flow assays and molecular dynamics simulations, a novel extracellular gating mechanism could be elucidated for this particular aquaporin isoform, being less efficient in water transport than AQP4 and phosphorylation of Tyrosine 107 leads to a closed conformation involving loop C. Functional studies were also performed for the development of a new method for testing the transport specificity of aquaporins regarding hydrogen peroxide. The transport rate can be standardized in relation to protein quantity, resulting in a more accurate determination of transport rates as compared to cell growth assays. Interactions between proteins are difficult to evaluate, but using bimolecular fluorescence complementation, membrane protein complexes could be quantified and screened in vivo in a high-throughput manner. During the course of this work, we standardized sample preparation and defined criteria which allow the discrimination between constructive and random interactions. Taken together, the results presented in this thesis lay the fundament for future screening for novel interaction partner using a cDNA library, a method that is not limited to aquaporins.Item A hydrogeological approach for sustainable technical solutions in tunnel construction.(2024) Surendran, PramodEconomic, environmental sustainability and management of climate changes are closely related to how we plan, build, and develop our society. The thesis aims to define and implement methodologies for providing technical solution (Hydrogeological Reference Conditions (HRCs)) prior to the construction and predict the requirement of cement grouting in underground tunnel construction (Grouting Domains). Performing grouting in rock tunnel is important to reduce the impact, effect and consequences that occur due to the water ingress through rock fractures. The suggested HRCs in a location south of Sweden are Crystalline bedrock (HRC1), Glacial till over bedrock (HRC2), Glaciofluvial deposits (HRC3), Wave-washed deposits, (HRC4), and Clay-covered areas (HRC5) each of which has specific stratigraphy from regional geological characteristics. The topographic map, quaternary deposit map, bedrock map, paleoshoreline map, soil depth map and geological history (sedimentology) were used for desktop study and the obtained result compared with the available borehole. Another focus on this thesis is to implement “grouting domains”, a hydrogeological description in Södertörn tunnel in Stockholm. The grouting domain follows demand assessed grouting to predict the requirement of grouting or no grouting. Grouting domains are classified into A, B and C, where each of which have specific standardized parameter limits and grouting classes. Water loss measurements and pressure built-up tests in core drilled boreholes are used for extraction of relevant hydrogeological data which in turn to the identification of domain classes. The prediction could provide information about the requirement of sounding boreholes and grouting boreholes. Moreover, the selection of effective hydraulic conductivity (Keff) in inleakage estimation is performed using K2D and K3D. Where K2D and K3D are upscaled hydraulic conductivities. The dimensionality of hydraulic conductivity (K2D or K3D) is identified based on the ratio of total section transmissivity (∑Ti) and full borehole transmissivity (Tfull). The weighing of the hydrogeological parameters helps to identify the dominant domain. Moreover, Class A presence sounding boreholes with no pre-grouting required while Class C requires pre-grouting. The prediction of specific domain classes could optimize the amount of grouting and deliberately helps to make better judgement for grouting prior to the execution.Item A Light-Weight Defect Classification Scheme for Embedded Automotive Software Development(2013-01-25) Mellegård, Niklas; Staron, Miroslaw; Törner, Fredrik; Chalmers University of Technology; University of Gothenburg; Volvo Car CorporationObjective: Systematic software defect documentation is an essential part of software development process models as a means of early identification of patterns in defect inflow. Such documentation, however, may often be a tedious task requiring analysis work in addition to what is necessary to resolve the issue. Furthermore, generic defect documentation approaches often have a strong focus on source-code aspects making them unsuitable for development contexts with supplier-side implementation. To increase documentation efficiency in a development context with limited access to source-code, adapted schemes are needed. In this paper a light-weight defect classification scheme adapted to automotive software development is presented. Method: A case study was conducted at Volvo Car Corporation to adapt the IEEE Std. 1044 for the development of embedded automotive safety features. Results: The results consist of a detailed description of a defect classification scheme that complies with the IEEE Std. 1044. The main adaptations to the scheme consisted of raising the level of abstraction of the captured data items, shifting the focus from source-code to other artefacts and activities, and by conforming to the terminology of the company. Conclusions: We conclude that the IEEE Std. 1044 can be successfully adapted to a development context where source-code is not the main development artefact. Furthermore, initial evaluation showed that the adapted classification scheme captures what is currently tacit knowledge and has the potential of revealing patterns in the defects detected in different project phases. As a result we are currently in the process of incorporating the classification scheme into the company’s defect reporting system.Item A Play of Light and Spins: Excitation and Detection of Non-linear Magnetization Dynamics using Light(2020-09-02) Muralidhar, ShreyasThe excitation and detection of magnetization dynamics play key roles in the field of spintronics and magnonics. In this thesis, we investigate a contactless method of exciting nonlinear magnetization dynamics using a femtosecond pulsed laser, and study the same with a Brillouin Light Scattering (BLS) microscope. Further, we explore the synchronization characteristics of spin-Hall nano-oscillator (SHNO) arrays and their applicability to neuromorphics and Ising machines, using electrical measurement as well as optical measurements utilizing a phase-resolved BLS microscope. After a brief introduction to the basic phenomena and techniques, the optical setup unique to this work is described in detail in Chapter 1. By using a frequency comb to pump the system, a strong enhancement of the weak scattering amplitude of the selected spin wave (SW) modes is observed. Additionally, the pump laser can be focused down to the diffraction limit and scanned along the focal plane to study the propagation characteristics of elementary excitations. Frequency-comb-enhanced BLS microscopy was used to excite SWs in NiFe thin films (20 nm) and to study their characteristics. As the duration between consecutive pump pulses is shorter than the decay time of the magnons, sustained coherent emission of selected SW modes was observed. The BLS counts versus laser power follows a stronger than square dependence. This is in accordance with the Bloch T3/2 law. The spatial map of the SW amplitude depicts strong unidirectional propagation of the main SW mode, whose direction of propagation can be controlled by changing the angle of the in-plane component of the applied field. An in-depth analysis of SW propagation at different fields showed a caustic X-pattern for high k-vector SWs, which has potential applications in the field of magnonics. Chapter 3 lays the emphasis on two-dimensional SHNO arrays that show robust mutual synchronization up to arrays of 64 oscillators. Well-resolved BLS maps of the magnetization dynamics in the 2D arrays show that the oscillators in line with the direction of current synchronize first, which is followed by the four chains synchronizing together at higher currents. The applicability of 2D SHNO arrays in neuromorphics is demonstrated by injecting two external microwave signals, creating a synchronization map, like the one used for neuromorphic vowel recognition using vortex oscillators. Additionally, at higher powers of the injected signal, we demonstrate phase binarization of the microwave output using a phase-resolved BLS microscope. A direct application for solving combinatorial optimization (CO) problems using a SHNO array-based Ising machine is shown.Item A Scholarship Approach to Model-Driven Engineering(2014-09-26) Burden, HåkanModel-Driven Engineering is a paradigm for software engineering where software models are the primary artefacts throughout the software life-cycle. The aim is to define suitable representations and processes that enable precise and efficient specification, development and analysis of software. Our contributions to Model-Driven Engineering are structured according to Boyer's four functions of academic activity - the scholarships of teaching, discovery, application and integration. The scholarships share a systematic approach towards seeking new insights and promoting progressive change. Even if the scholarships have their differences they are compatible so that theory, practice and teaching can strengthen each other. Scholarship of Teaching: While teaching Model-Driven Engineering to under-graduate students we introduced two changes to our course. The first change was to introduce a new modelling tool that enabled the execution of software models while the second change was to adapt pair lecturing to encourage the students to actively participate in developing models during lectures. Scholarship of Discovery: By using an existing technology for transforming models into source code we translated class diagrams and high-level action languages into natural language texts. The benefit of our approach is that the translations are applicable to a family of models while the texts are reusable across different low-level representations of the same model. Scholarship of Application: Raising the level of abstraction through models might seem a technical issue but our collaboration with industry details how the success of adopting Model-Driven Engineering depends on organisational and social factors as well as technical. Scholarship of Integration: Building on our insights from the scholarships above and a study at three large companies we show how Model-Driven Engineering empowers new user groups to become software developers but also how engineers can feel isolated due to poor tool support. Our contributions also detail how modelling enables a more agile development process as well as how the validation of models can be facilitated through text generation. The four scholarships allow for different possibilities for insights and explore Model-Driven Engineering from diverse perspectives. As a consequence, we investigate the social, organisational and technological factors of Model-Driven Engineering but also examine the possibilities and challenges of Model-Driven Engineering across disciplines and scholarships.Item A Soot Transformation Study: Interactions Between Soot, Sulfuric Acid and Secondary Organic Aerosol (SOA)(2018-01-19) Pei, XiangyuAtmospheric black carbon (BC), generally called soot, is the most important aerosol component that warms the Earth’s climate significantly, and reducing atmospheric soot level has been proposed as a strategy for near-term climate change mitigation. However, policy development is hampered by large uncertainties in models’ predictions regarding the global warming induced by BC. These uncertainties primarily result from a limited scientific understanding of the transformations soot undergoes upon interacting with other aerosol components such as sulfuric acid and secondary organic aerosol (SOA). Unlike soot, sulfuric acid and SOA are thought to induce cooling effects. However, soot – sulfuric acid – SOA interactions are postulated to amplify soot’s warming effect. Condensed materials such as sulfuric acid and SOA can modify soot’s morphology, i.e. the distribution of soot aggregates and condensates in space, thereby altering its properties and atmospheric life time. The overall aim of this thesis is to characterize freshly emitted soot and the transformations in morphology and optical properties it undergoes upon condensation of sulfuric acid and SOA. Two frameworks were developed for quantifying the in-situ morphological properties of BC mixed with either primary organic aerosol (POA) during evaporation process or sulfuric acid and/or SOA during condensation process. The morphological transformation of soot particles was quantified with these frameworks in terms of void fractions, effective densities, and in-situ dynamic shape factors. Soot morphological transformation during condensation process was shown to occur via two complementary and sequential processes: the filling of voids within particles and mobility diameter growth. In addition, the light absorption of soot from two flame types (an industrial flame and three lab-scale flames) was studied. Significant quantities of light absorbing organics (referred to as brown carbon, BrC) were observed in lab-scale flames, but the mature soot in the industrial flame did not contain BrC. The mass absorption cross section (MAC) of BC and BrC from lab-scale flames was quantified, and the values for BrC proved to be comparable to those for BC at a short wavelength (405 nm). The most widely used model for quantifying the optical properties of coated soot at present is core-shell Mie theory, in which the key parameter is the refractive index. This study identified and evaluated alternatives to Mie theory. It was found that the nature of the condensed material can significantly influence the light absorption of coated soot particles, and that reaction between soot and sulfuric acid can have particularly important effects. The absorption cross section of soot was significantly reduced (by up to 26%) upon interaction of the soot surface with sulfuric acid, whereas the absorption cross section increased significantly when soot was coated with SOA or acidity-mediated SOA. Field studies of soot coated with other aerosol components, i.e. organics, sulfate and nitrate, were conducted in Beijing, and the results were compared to the lab studies. The findings suggested that ambient BC particles during summertime in Beijing was internally mixed and heavily coated since their effective density was similar to the material density of the coatings.Item A tale of two songs: oligomeric and monomeric functions of the molecular chaperone CCT(2024-11-07) Córdoba Beldad, Carmen Maria; Córdoba Beldad, Carmen MariaThe chaperonin-containing tailless complex polypeptide 1 (CCT) is a 1 MDa barrel shaped molecular chaperone present in the cytoplasm of all eukaryotes. Eight different subunits, located in a fixed position, form CCT, which is mostly studied as the folding machinery of the cytoskeletal proteins actin and tubulin. Roles beyond folding have been reported for the CCT oligomer and together with the increasing evidence of monomeric CCT subunit functions, have elevated the importance of studying the chaperone CCT. Here, we show that the transcription factor STAT3, a previously reported oligomeric binding partner of CCT, does not behave as an obligate folding substate but rather is sequestered by CCT. To expand our knowledge of the monomeric roles of the CCT subunits, we have studied the interaction between CCTδ and p150Glued, a component of the dynactin complex involved in crucial biological processes such as mitosis. We show that monomeric CCTδ is required for the correct localisation of p150Glued at spindle poles and for accurate chromosome segregation. Furthermore, we explore interactions between two other CCT subunits and two regulatory components of mitosis, the centromeric protein Mis18BP1 and the outer kinetochore component KNL1. Taken together the work in this thesis extends the understanding of both oligomeric and monomeric functions of CCT beyond folding.Item A two-stage numerical procedure for an inverse scattering problem(Chalmers University of Technology and University of Gothenburg, 2015) Bondestam Malmberg, John; Department of Mathematical Sciences, Chalmers University of Technology and University of GothenburgIn this thesis we study a numerical procedure for the solution of the inverse problem of reconstructing location, shape and material properties (in particular refractive indices) of scatterers located in a known background medium. The data consist of time-resolved backscattered radar signals from a single source position. This relatively small amount of data and the ill-posed nature of the inversion are the main challenges of the problem. Mathematically, the problem is formulated as a coefficient inverse problem for a system of partial differential equations derived from Maxwell’s equations. The numerical procedure is divided into two stages. In the first stage, a good initial approximation for the unknown coefficient is computed by an approximately globally convergent algorithm. This initial approximation is refined in the second stage, where an adaptive finite element method is employed to minimize a Tikhonov functional. An important tool for the second stage is a posteriori error estimates – estimates in terms of known (computed) quantities – for the difference between the computed coefficient and the true minimizing coefficient. This thesis includes four papers. In the first two, the a posteriori error analysis required for the adaptive finite element method in the second stage is extended from the previously existing indirect error estimators to direct ones. The last two papers concern verification of the two-stage numerical procedure on experimental data. We find that location and material properties of scatterers are obtained already in the first stage, while shapes are significantly improved in the second stage.Item A Waterborne Colloidal Model System Consisting of Fluorinated Spheres Bearing Grafted PEG: Synthesis, Characterization and Properties(2016-01-08) Ulama, JeanetteModel systems have expanded our knowledge of numerous phenomena in Colloid Science, such as the appearance of glasses, order-disorder transitions involving crystals and attraction induced formation of gels. So far, the existing colloidal model systems have been limited mainly to nonaqueous media. Given that water is such an important solvent, an aqueous colloidal model system is called for. Here we present such an aqueous colloidal model system with core-shell particle morphology, where the interior is composed of spherical fluorinated cores and the exterior of a poly(ethylene glycol) (PEG) polymer graft. To synthesize these colloids, we have adopted a semi-batch emulsion polymerization, in which the initiator is slowly fed into the reaction mixture. Using this approach not only can monodisperse, low refractive index and sterically stabilized colloids be produced, but also various lengths of the PEG polymer could be successfully grafted onto the particles. Throughout this thesis, several different instrumental techniques have been used to gain an insight into the collective phenomena of these particles and how particle interactions contribute to the observed phase behavior. Although steric stabilization is very robust way of stabilizing colloidal particles against aggrega- tion, attractions between particles can nevertheless appear, e.g. through the addition of certain salts or addition of a non-solvent. The origin of these attractions is not fully understood. Our results show that colloidal stability increases with decreasing length of the steric stabilizer and that the polymer graft contracts as the solvent quality is worsened. The contraction is accompanied by moderately strong attractions even though the van der Waals force due to core-core interactions is essentially absent. It follows that the attractions are caused by purely polymer-mediated interactions.Item Absolute Asymmetric Synthesis(2010-02-03T08:00:57Z) Lennartson, AndersAbsolute asymmetric synthesis is the synthesis of optically active products from achiral or racemic precursors only. This has generally been regarded as impossible and is relevant in the discussion of the origins of biomolecular homochirality. A possible route to absolute asymmetric synthesis involves total spontaneous resolution, which is possible for stereochemically labile substances which crystallise as conglomerates (i.e. the enantiomers crystallise in separate crystals). Using total spontaneous resolution it was, for the first time, possible to prepare bulk-quantities of configurationally labile five-, seven-, and nine-coordinate enantiomers, containing only achiral ligands. Previously, only four- and six-coordinate complexes have been prepared enantiomerically pure in bulk quantities. Spontaneous resolution of eight-coordinate complexes has also been reported. It was also possible to perform total spontaneous resolution of a diaryl sulphide, an octanuclear organo(oxo)zinc complex, and a diindenylzinc complex. In the case of a helical coordination polymer based on copper(I) chloride and triallylamine, it was found that repeated synthesis always yielded an excess of the same enantiomer, possibly due to the influence of cryptochirality. It has previously been practically impossible to measure enantiomeric excesses in stereochemically labile microcrystalline samples. A method utilising quantitative solid-state CD spectroscopy has been introduced to solve this problem. In the case of the chiral organometallic reagent di(3-picoline)di(1-indenyl)zinc, it was possible to perform reactions with N-chlorosuccinimide in the presence of methanol and p-benzoquinone yielding optically active stereochemically inert 1-chloroindene in high yield and high enantiomeric excess (up to 89% ee). During the cause of theses studies, three cases of concomitant crystallisation of racemic and chiral phases have been discovered. This is a rare phenomenon of considerable interest e.g. in structure prediction. The first synthetic route to well-defined hydridoalkylzincates is also reported.Item Absolute Asymmetric Synthesis(2011-04-18) Lennartson, AndersAbsolute asymmetric synthesis is the synthesis of optically active products from achiral or racemic precursors only. This has generally been regarded as impossible and is relevant in the discussion of the origins of biomolecular homochirality. A possible route to absolute asymmetric synthesis involves total spontaneous resolution, which is possible for stereochemically labile substances which crystallise as conglomerates (i.e. the enantiomers crystallise in separate crystals). Using total spontaneous resolution it was, for the first time, possible to prepare bulk-quantities of configurationally labile five-, seven-, and nine-coordinate enantiomers, containing only achiral ligands. Previously, only four- and six-coordinate complexes have been prepared enantiomerically pure in bulk quantities. Spontaneous resolution of eight-coordinate complexes has also been reported. It was also possible to perform total spontaneous resolution of a diaryl sulphide, an octanuclear organo(oxo)zinc complex, and a diindenylzinc complex. In the case of a helical coordination polymer based on copper(I) chloride and triallylamine, it was found that repeated synthesis always yielded an excess of the same enantiomer, possibly due to the influence of cryptochirality. It has previously been practically impossible to measure enantiomeric excesses in stereochemically labile microcrystalline samples. A method utilising quantitative solid-state CD spectroscopy has been introduced to solve this problem. In the case of the chiral organometallic reagent di(3-picoline)di(1-indenyl)zinc, it was possible to perform reactions with N-chlorosuccinimide in the presence of methanol and p-benzoquinone yielding optically active stereochemically inert 1-chloroindene in high yield and high enantiomeric excess (up to 89% ee). During the cause of theses studies, three cases of concomitant crystallisation of racemic and chiral phases have been discovered. This is a rare phenomenon of considerable interest e.g. in structure prediction. The first synthetic route to well-defined hydridoalkylzincates is also reported.Item Acclimation of boreal Norway spruce to climate change: Empirical and modelling approaches(2019-09-04) Lamba, ShubhangiThe findings of this thesis have important implications for the projections of future carbon and water fluxes for the boreal region. The observed boreal longterm acclimation responses of respiration and stomatal regulation differ from those of most temperate regions. Furthermore, the findings guide modellers by quantifying the relative importance of different types of acclimation responses. Physiological acclimation generally dampened instantaneous responses and it is critical to incorporate these responses into vegetation models to improve projections of atmosphere-biosphere interactions of boreal regions in a changing climate.Item Acquired brain injury in children and adolescents: Investigating assessments of communicative participation in daily life situations(2017-02-03) Fyrberg, ÅsaAims The overall aim of this thesis was to explore assessments of communicative participation in children and adolescents (hereafter: adolescents) with acquired brain injuries, mainly through evaluations in the Communicative Effectiveness Index (CETI) and in interviews with the participants. The aim was also to capture important changes in communication over time. Five sub-studies were carried out, presented in Papers I-V. Methods Paper I: Pragmatic evaluations were explored in eight participants with severe brain injuries. The data were obtained in clinical surroundings by a speech language pathologist and rehabilitation assistants, using clinically applied pragmatic taxonomy, the Pragmatic Protocol (PP). Paper II: Descriptive and comparative methods were used to assess the communication outcome in an adolescent with ABI. The investigations included linguistic and cognitive test data and adolescent/parent evaluations of communication skills in the CETI, post-injury and at follow-up. Video recordings to explore communication management were analysed through self-evaluation and interview procedures. Paper III: The contribution of CETI in the assessment of ABI was examined through parent evaluations of communication in 30 adolescents, which were compared with linguistic, cognitive and brain injury data. Paper IV: Assessments of daily communication skills delivered by the parents of eight adolescents were compared with self-evaluations by the adolescents themselves. Interview data were analysed in particular by applying activity-based communication analysis, ACA (Allwood, 2013), and the theory of distributed cognition (Hutchins, 1995a). Paper V: Change scores in 30 adolescents between post-injury measurements and follow-up results were estimated. Results Paper I: Seven of eight participants with severe brain injuries were assessed as having a highly reduced capacity to communicate within all the assessed pragmatic parameters that involved speech and language skills. Paper II: Self-evaluation of the video recordings and analyses of communication management in Paper II confirmed impaired communication, related to language comprehension difficulties, high speech rate and the number of speakers involved. Paper III: The CETI data showed that adolescents with more communication difficulties, according to their parents, also obtained significantly lower scores in tests of grammar comprehension and verbal IQ. The trend was similar for word comprehension, naming and perceptual IQ, although this was not supported by significant results. However, complex communicative interactions, such as fast conversations with several speakers involved, were affected in all participants, including those with higher results in linguistic and cognitive tests. As a result, complex communicative situations appeared to be particularly vulnerable to the effects of the brain injuries, regardless of injury severity. The aetiologies of the injuries did not affect the outcome in individual results. However, the majority of adolescents with more communication difficulties according to parent evaluations had left-hemisphere brain lesions. Paper IV: Overall high agreement between the adolescent and parental assessments was found. However, complex communicative situations more frequently received lower scores in the parental ratings. Analyses using the ACA and distributed cognition models and interview data pointed to the usability of a systematic comparison of the shared views on communication after ABI in adolescence, to increase knowledge of the participation perspective in real-life communication. Paper V: The nature and extent of communication abilities after communication strategies applied by the parents at home showed a significant increase in ability in 30 participants (p < .01), but some tasks did not improve as much, even showing a reduction in capacity after the one-year application of communication strategies, according to parental estimations. Conclusions One general conclusion in this thesis is that evaluations of communication abilities in adolescents with ABI benefit from analyses of interaction in everyday situations. The data obtained in the clinical surroundings, in particular, the results from cognitive, linguistic and cerebral lesion site data, appear to have a certain predictive value in terms of the communication outcomes rated in the CETI, thereby strengthening the content validity of the CETI in adolescent participants with ABI. The findings further point to the important role parents play in exploring the adolescents’ communicative participation in real life by sharing their opinions in interviews, based on the CETI results. The participation perspective can be addressed in the self-assessments by the adolescents themselves, as was shown in analyses of video recordings and in the interviews exploring the activitybased communication analysis and distributed cognition perspectives. The mixed-method design applied in this thesis could provide information which could contribute to shaping fruitful individualised rehabilitation programmes in adolescents with ABI.Item Actions over Core-closed Knowledge Bases(2022) Cauli, Claudia; Ortiz, Magdalena; Piterman, NirWe present new results on the application of semantic- and knowledge-based reasoning techniques to the analysis of cloud deployments. In particular, to the security of Infrastructure as Code configuration files, encoded as description logic knowledge bases. We introduce an action language to model mutating actions; that is, actions that change the structural configuration of a given deployment by adding, modifying, or deleting resources. We mainly focus on two problems: the problem of determining whether the execution of an action, no matter the parameters passed to it, will not cause the violation of some security requirement (static verification), and the problem of finding sequences of actions that would lead the deployment to a state where (un)desirable properties are (not) satisfied (plan existence and plan synthesis). For all these problems, we provide definitions, complexity results, and decision procedures.Item Active Matter in a Critical State: From passive building blocks to active molecules, engines and droplets(2020-12-19) Schmidt, FalkoThe motion of microscopic objects is strongly affected by their surrounding environment. In quiescent liquids, motion is reduced to random fluctuations known as Brownian motion. Nevertheless, microorganisms have been able to develop mechanisms to generate active motion. This has inspired researchers to understand and artificially replicate active motion. Now, the field of active matter has developed into a multi-disciplinary field, with researchers developing artificial microswimmers, producing miniaturized versions of heat engines and showing that individual colloids self-assemble into larger microstructures. This thesis taps into the development of artificial microscopic and nanoscopic systems and demonstrates that passive building blocks such as colloids are transformed into active molecules, engines and active droplets that display a rich set of motions. This is achieved by combining optical manipulation with a phase-separating environment consisting of a critical binary mixture. I first show how simple absorbing particles are transformed into fast rotating microengines using optical tweezers, and how this principle can be scaled down to nanoscopic particles. Transitioning then from single particles to self-assembled modular swimmers, such colloidal molecules exhibit diverse behaviour such as propulsion, orbital rotation and spinning, and whose formation process I can control with periodic illumination. To characterize the molecules dynamics better, I introduce a machine-learning algorithm to determine the anomalous exponent of trajectories and to identify changes in a trajectory’s behaviour. Towards understanding the behaviour of larger microstructures, I then investigate the interaction of colloidal molecules with their phase-separating environment and observe a two-fold coupling between the induced liquid droplets and their immersed colloids. With the help of simulations I gain a better physical picture and can further analyse the molecules’ and droplets’ emergence and growth dynamics. At last, I show that fluctuation-induced forces can solve current limitations in microfabrication due to stiction, enabling a further development of the field towards smaller and more stable nanostructures required for nowadays adaptive functional materials. The insights gained from this research mark the path towards a new generation of design principles, e.g., for the construction of flexible micromotors, tunable micromembranes and drug delivery in health care applications.