| 1. |
- Andersson, Ki, 1975-
(author)
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Aspects of locomotor evolution in the Carnivora (Mammalia)
- 2003
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Doctoral thesis (other academic/artistic)abstract
- In this thesis, the shape of the distal humerus trochlea is analysed using landmark-based morphometrics and multivariate methods, with the aim of exploring locomotor evolution in carnivorans. Elbow joint morphology is used together with body size and craniodental morphology to characterize past and present carnivorans. Evolutionary implications are studied at the ordinal, familial, and species levels, testing specific hypotheses about scaling, morphological constraints, evolutionary trajectories, and potential for social pack-hunting behaviour. The circumference of the distal humerus trochlea is found to be highly correlated with body mass, and appears to scale similarly throughout the order Carnivora. A general predictive model for carnivoran bodymass is presented (a=0.601; b= 2.552; r2=0.952, SEE=0.136, p<0001, n=92), which removes the need for the investigator to actively choose between the diverging estimates that different predictors and their equations often produce. At the elbow joint, manual manipulation and locomotion appear to be conflicting functions, thus suggesting mutually exclusive lifestyles involving either forelimb grappling or pursuit. At large body sizes, carnivorans are distributed over a strongly dichotomised pattern (grappling or locomotion), a pattern coinciding with the postulated threshold in predator-prey size ratio at 21.5-25 kg. This pattern is compared to that of two carnivoran faunas from the Tertiary. In the Oligocene (33.7-23.8 Myr BP), the overall pattern is remarkably similar to that observed for extant Carnivora. In the Miocene (23.8-11.2 Myr BP) carnivores show a similarly dichotomised pattern as the Oligocene and Recent, although the whole pattern is shifted towards larger body sizes. This difference is suggested to be a reflection of the extraordinary species richness of browsing ungulates in the early Miocene of North America. Such an increase in prey spectrum would create a unique situation, in which large carnivores need not commit to a cursorial habitus in order to fill their nutritional requirements. Finally, the elbow joints and craniodental morphology (14 measurements) of fossil canids were examined with the aim of assessing the potential for pack-hunting in fossil canids. It is clear that small and large members of the Recent Caninae share similar craniodental morphologies. However, this pattern is not present in Borophaginae and Hesperocyoninae. In the latter, large representatives are characterized by being short-faced, with reduced anterior premolars and enlarged posterior premolars, thus approaching a “pantherine-like” craniodental configuration. These traits are interpreted as an adaptation for killing prey with canine bites. It is similarly determined that, unlike recent Caninae, all analyzed species of borophagines and hesperocyonines have retained the ability to supinate their forearms. It is therefore likely that manual manipulation was part of their hunting behaviour, thus removing an essential part of the argument for social pack-hunting in these forms, as the benefits of such a strategy become less obvious.
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| 2. |
- Alizadeh Khameneh, Mohammad Amin, 1983-
(author)
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Optimal Design in Geodetic GNSS-based Networks
- 2017
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Doctoral thesis (other academic/artistic)abstract
- An optimal design of a geodetic network helps the surveying engineers maximise the efficiency of the network. A number of pre-defined quality requirements, i.e. precision, reliability, and cost, of the network are fulfilled by performing an optimisation procedure. Today, this is almost always accomplished by implementing analytical solutions, where the human intervention in the process cycle is limited to defining the requirements. Nevertheless, a trial and error method can be beneficial to some applications. In order to analytically solve an optimisation problem, it can be classified to different orders, where an optimal datum, configuration, and optimal observation weights can be sought such that the precision, reliability and cost criteria are satisfied.In this thesis, which is a compilation of six peer-reviewed papers, we optimised and redesigned a number of GNSS-based monitoring networks in Sweden by developing new methodologies. In addition, optimal design and efficiency of total station establishment with RTK-GNSS is investigated in this research.Sensitivity of a network in detecting displacements is of importance for monitoring purposes. In the first paper, a precision criterion was defined to enable a GNSS-based monitoring network to detect 5 mm displacements at each network point. Developing an optimisation model by considering this precision criterion, reliability and cost yielded a decrease of 17% in the number of observed single baselines implying a reliable and precise network at lower cost. The second paper concerned a case, where the precision of observations could be improved in forthcoming measurements. Thus a new precision criterion was developed to consider this assumption. A significant change was seen in the optimised design of the network for subsequent measurements. As yet, the weight of single baselines was subject to optimisation, while in the third paper, the effect of mathematical correlations between GNSS baselines was considered in the optimisation. Hence, the sessions of observations, including more than two receivers, were optimised. Four out of ten sessions with three simultaneous operating receivers were eliminated in a monitoring network with designed displacement detection of 5 mm. The sixth paper was the last one dealing with optimisation of GNSS networks. The area of interest was divided into a number of three-dimensional elements and the precision of deformation parameters was used in developing a precision criterion. This criterion enabled the network to detect displacements of 3 mm at each point.A total station can be set up in the field by different methods, e.g. free station or setup over a known point. A real-time updated free station method uses RTK-GNSS to determine the coordinates and orientation of a total station. The efficiency of this method in height determination was investigated in the fourth paper. The research produced promising results suggesting using the method as an alternative to traditional levelling under some conditions. Moreover, an optimal location for the total station in free station establishment was studied in the fifth paper. It was numerically shown that the height component has no significant effect on the optimal localisation.
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| 3. |
- Alvarsson, Jonathan, 1981-
(author)
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Ligand-based Methods for Data Management and Modelling
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Drug discovery is a complicated and expensive process in the billion dollar range. One way of making the drug development process more efficient is better information handling, modelling and visualisation. The majority of todays drugs are small molecules, which interact with drug targets to cause an effect. Since the 1980s large amounts of compounds have been systematically tested by robots in so called high-throughput screening. Ligand-based drug discovery is based on modelling drug molecules. In the field known as Quantitative Structure–Activity Relationship (QSAR) molecules are described by molecular descriptors which are used for building mathematical models. Based on these models molecular properties can be predicted and using the molecular descriptors molecules can be compared for, e.g., similarity. Bioclipse is a workbench for the life sciences which provides ligand-based tools through a point and click interface. The aims of this thesis were to research, and develop new or improved ligand-based methods and open source software, and to work towards making these tools available for users through the Bioclipse workbench. To this end, a series of molecular signature studies was done and various Bioclipse plugins were developed.An introduction to the field is provided in the thesis summary which is followed by five research papers. Paper I describes the Bioclipse 2 software and the Bioclipse scripting language. In Paper II the laboratory information system Brunn for supporting work with dose-response studies on microtiter plates is described. In Paper III the creation of a molecular fingerprint based on the molecular signature descriptor is presented and the new fingerprints are evaluated for target prediction and found to perform on par with industrial standard commercial molecular fingerprints. In Paper IV the effect of different parameter choices when using the signature fingerprint together with support vector machines (SVM) using the radial basis function (RBF) kernel is explored and reasonable default values are found. In Paper V the performance of SVM based QSAR using large datasets with the molecular signature descriptor is studied, and a QSAR model based on 1.2 million substances is created and made available from the Bioclipse workbench.
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| 4. |
- Andersson, David E.
(author)
-
Hedonic prices and center accessibility : conceptual foundations and an empirical hedonic study of the market for condominium housing in Singapore
- 1997
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Doctoral thesis (other academic/artistic)abstract
- One aim of this study is to compare and evaluateprespecified and data-specific functional forms for theestimation of hedonic price functions. One prespecifiedfunction and three types of data-specific Box-Cox functions areused to estimate hedonic price functions. A second aim of thestudy is to test alternative monocentric and polycentrichypotheses according to a system of successive variablerejections constructed for this study, whereby requiredsignificance levels are influenced by the results of aselection of earlier hedonic price functions.The possibility of constructing internally consistentcriteria for variable elimination is one of the merits ofemploying a prespecified functional form. Other advantagesinclude the simplicity and transparency of the derived results,and the robustness of key parameter estimates in the face ofmisspecified functions. Using a prespecified form will on theother hand as a rule not yield the likeliest functional form tohave generated the data and cannot be relied on to generatewell-behaved residuals.Being assured of well-behaved residuals - as is the casewith data-specific Box-Cox functions - is advantageous, eventhough it makes the detection of potential heteroskedasticitymore difficult. Box-Cox models with more than onetransformation parameter are however especially prone to yielddescriptions of unique data sets at the expense of potentialreplicability. Because of the sensitivity of the t-values ofthe estimated independent variables to the estimated Box-Coxt:ransformation parameters - where the log-likelihood partlydepends on the set of independent variables - it becomesdifficult to avoid an arbitrary selection of independentvariables. This is true of all Box-Cox functions, althoughespecially of functions that estimate more than onetransformation parameter.Although regression results provide detailed information onvariable effects, much of that information is not generalizableowing to interspatial and intertemporal instability. Because ofsupply and demand fluctuations and specification problems, itis argued that is preferable to draw qualitative rather thanquantitative conclusions.An analysis of the Singapore condominium market illustratesthe conceptual discussion of various approaches to hypothesistesting, with an emphasis on testing hypotheses concerning thenumber and nature of urban centers. The data strongly supportthe realism of the monocentric model with one dominantemployment center. Alternative polycentric and service-centerhypotheses are unambiguously rejected. The signs, averageimplicit prices and t-values of the independent variables arerelatively robust over the range of estimated functional forms- whether pre-specified or Box-Cox - given the set of variablesto be included in the hedonic price equation.Keywords:Hedonic prices, Box-Cox function, monocentric,polycentric, accessibility, hypothesis testing, rejection ofvariables, data-specific function, prespecified function.
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| 5. |
- Andersson, David E.
(author)
-
The Emergence of Markets for Technology : Patent Transfers and Patenting in Sweden, 1819–1914
- 2016
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Doctoral thesis (other academic/artistic)abstract
- This thesis is concerned with the emergence of markets for technology and studies the evolution of patent transfers and its determinants, patent agencies and independent versus firm patenting in Sweden during the 19th century and the turn of 20th century. It explores how and why markets for technology emerge and under what circumstances by investigating the evolution of Swedish patent legislation and the patterns of patent transfers between individuals and firms. It presents a three-pronged framework studying: structure and actors, technology and transactions.Using a new and unique database covering every Swedish privilege and patent over the 1819–1914 period the empirical analysis reveals that although the transferability of intellectual property goes all the way back to the 18th century patent transfers did not start to increase significantly until the first modern Swedish patent law was passed in 1884. Along with the new law a market for patenting services also emerged where actors such as patent agents and the firms they founded, patent agencies, functioned as intermediaries in the market for patents and international networks of patenting. A few older patent agencies managed to create an oligopolistic setting where they introduced price controls through special interest groups.The thesis also questions the current dichotomous classification of independent and firm patenting. The methodological contribution lies in showing that research that depend too much on patent statistics run the risk of underestimating the importance of the firm when patents granted to individuals actually cover inventive activities that has taken place inside the boundaries of firms.Finally, the study shows that special marketplaces for the sale of patented and unpatented technology were created to help inventors find buyers and financiers for their invention and to help firms find new technology. The patent law of 1884 made it possible to trade in several submarkets of technology where the right to patent a certain invention could be bought, ideas could be financed, pending patent applications or the priority right to foreign markets could be bought and sold.The results lend support to the research emphasizing the role of intellectual property as a disclosure and diffusion mechanism for new technology.
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| 6. |
- Andersson, E. Axel
(author)
-
Blood Vessels, Biomarkers, and Broken Barriers: lnvestigations of the Brain Vasculature in Models of Neonatal Brain lnjuries
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Brain injury during the perinatal period can lead to lifelong impairment in cognitive and motor function, or an early death. Term neonatal encephalopathy and preterm germinal matrix haemorrhage are two conditions that can irreversibly injure the brain, but clinical tools for diagnosing and treating these pathologies are lacking. It is known that the cerebrovasculature, i.e. the blood vessels of the brain and blood/brain barrier (BBB) plays a role during the course and recovery of injury. This thesis investigated the cerebrovascular involvement in two animal models of neonatal brain injury in an attempt to elucidate injury mechanisms, find potential new treatments, and identify biomarkers for brain vascular dysfunction. Using rodent models for hypoxic/ischemic encephalopathy (HIE) and germinal matrix‐intraventricular haemorrhage (GM‐IVH) we found raised levels of tight‐junction proteins claudin‐5 and occludin, two integral components of the BBB, in blood plasma and cerebrospinal fluid at different time points. In the HIE model, levels of tight‐junction proteins in the circulation were sex‐dependent and the amount of claudin‐5 in CSF correlated with the severity of brain injury. These proteins thus have potential as biomarkers for early detection of cerebrovascular insults. In addition, we did in‐depth assessments of the BBB function in both models and detailed the temporal and regional increases of barrier permeability after injury by measuring the extravasation of radiolabelled sucrose, visible dyes, and molecular tracers. Studies of the cerebral vasculature and angiogenesis after HI showed that the density of proliferating endothelial cells were largely unaffected after injury, but the number of growing endothelial tip cells were strongly reduced in the entire brain, accompanied by changes in the expression of angiogenesis genes. The thesis also includes the first trial of endogenous RNAse A as a neuroprotective treatment for neonatal brain injury, a treatment that has shown promise in adult models of other pathologies with cardiovascular aspects. We found significant reductions of grey and white matter tissue loss after RNAse A administration in HI animals, but no protection of BBB function or evidence for a reduced neuroinflammatory response. Taken together, this thesis contains new insights into several aspects of the vascular mechanisms involved in the pathogenesis of two major forms of injury that can occur in the neonatal brain.
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| 7. |
- Andersson, Ida E., 1982-
(author)
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Modified Glycopeptides Targeting Rheumatoid Arthritis : Exploring molecular interactions in class II MHC/glycopeptide/T-cell receptor complexes
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that leads to degradation of cartilage and bone mainly in peripheral joints. In collagen-induced arthritis (CIA), a mouse model for RA, activation of autoimmune CD4+ T cells depends on a molecular recognition system where T-cell receptors (TCRs) recognize a complex between the class II MHC Aq protein and CII259-273, a glycopeptide epitope from type II collagen (CII). Interestingly, vaccination with the Aq/CII259-273 complex can relieve symptoms and cause disease regression in mice. This thesis describes the use of modified glycopeptides to explore interactions important for binding to the Aq protein and recognition by autoimmune T-cell hybridomas obtained from mice with CIA. The CII259-273 glycopeptide was modified by replacement of backbone amides with different amide bond isosteres, as well as substitution of two residues that anchor the glycopeptide in prominent pockets in the Aq binding site. A three-dimensional structure of the Aq/glycopeptide complex was modeled to provide a structural basis for interpretation of the modified glycopeptide’s immunological activities. Overall, it was found that the amide bond isosteres affected Aq binding more than could be explained by the static model of the Aq/glycopeptide complex. Molecular dynamics (MD) simulations, however, revealed that the introduced amide bond isosteres substantially altered the hydrogen-bonding network formed between the N-terminal 259-265 backbone sequence of CII259-273 and Aq. These results indicated that the N-terminal hydrogen-bonding interactions follow a cooperative model, where the strength and presence of individual hydrogen bonds depended on the neighboring interactions. The two important anchor residues Ile260 and Phe263 were investigated using a designed library of CII259-273 based glycopeptides with substitutions by different (non-)natural amino acids at positions 260 and 263. Evaluation of binding to the Aq protein showed that there was scope for improvement in position 263 while Ile was preferred in position 260. The obtained SAR understanding provided a valuable basis for future development of modified glycopeptides with improved Aq binding. Furthermore, the modified glycopeptides elicited varying T-cell responses that generally could be correlated to their ability to bind to Aq. However, in several cases, there was a lack of correlation between Aq binding and T-cell recognition, which indicated that the interactions with the TCRs were determined by other factors, such as presentation of altered epitopes and changes in the kinetics of the TCR’s interaction with the Aq/glycopeptide complex. Several of the modified glycopeptides were also found to bind well to the human RA-associated DR4 protein and elicit strong responses with T-cell hybridomas obtained from transgenic mice expressing DR4 and the human CD4 co-receptor. This encourages future investigations of modified glycopeptides that can be used to further probe the MHC/glycopeptide/TCR recognition system and that also constitute potential therapeutic vaccines for treatment of RA. As a step towards this goal, three modified glycopeptides presented in this thesis have been identified as candidates for vaccination studies using the CIA mouse model.
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| 8. |
- Andersson, Jonas E, 1964-
(author)
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Architecture and Ageing : On the Interaction between Frail Older People and the Built Environment
- 2011
-
Doctoral thesis (other academic/artistic)abstract
- This doctoral thesis deals with the type of architecture that materializes when age-related problems become a long-term condition (LTC) and gradually restrain the individual’s ability to perform activities in daily life (ADL). Their life situation necessitates a support from relatives or municipal eldercare staff in order for them to continue to participate in everyday living. In addition, the architectural space requires a close adjustment to the personal panorama of cognitive or functional impairments. The habitat can be a flat appropriated many years previously or in a residential care home for dependent and frail seniors. Architecture for ageing with dependency demonstrates how space can be used either to affirm or oppress the older person’s attempts to maintain an independent life style. By use of design theory, case study methodology and a heterogeneous research strategy, this study uses a threefold approach—a retrospective, a contemporaneous, and a future-oriented approach—to explore frail older people’s interaction with the architectural space of residential care homes. This has resulted in seven papers that focus on aspects of these human interactions with the built environment. Based on twelve exemplary models, the research paper I concludes that national guidelines result in a homelike, a hotel-like or a hospital-like environment. Research paper II is a retrospective study that examines the use of architecture competitions as a socio-political instrument to define architectural guidelines. Research paper III focuses on dependent seniors’ spatial appropriation of the communally shared space of a ward in a residential care home. Research paper IV employs two environmental assessment methods from the architecture profession and gerontological research (TESS-NH) in order to evaluate the use of interior colouring when refurbishing two residential care homes while the residents remained in place. Research paper V displays a municipal organizer’s considerations to opt for an architecture competition as a means of renewing architecture for the ageing population. Research paper VI examines competition documentation of three municipal architecture competitions organized during the period of 2006 to 2009. Research paper VII, the final study, explores notions concerning the appropriate space for ageing found among a group of municipal representatives, and people from organizations defending older people’s right. It supplies a model for understanding the appropriate space for ageing. This study illustrates the absence of older people with frailties in the public discussion about appropriate architecture for ageing. During the 20th century, the multi-dimensional idea of an architectural space with a homelike appearance has been used to contrast the negatively charged opposite—the complete and austere institution. The overarching conclusion of this study is that architecture for dependent and frail seniors constitutes a particular type of built space that requires an extended dialogue involving dependent seniors, architects, building contractors and care planners in order to conceive appropriate architecture for the ageing society.
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| 9. |
- Andersson, John E., 1944
(author)
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Neonatal hip instability. The anterior-dynamic ultrasound method. Population screening and re-evaluation of some aetiological factors
- 2000
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Doctoral thesis (other academic/artistic)abstract
- To evaluate neonatal hip instability, the values for the physiologically normal movement of the femoral head by provocation were determined by an anterior-dynamic ultrasound method. The maximal movement of the femoral head with the acetabulum at provocation was 6.0, 6.6 and 6.8 mm for the birth weights 2,000, 3,000 and 4,000 g. The femoral head diameter was found to be 16.08 ± 1.49 mm and 15.56 ± 1.43 mm. Five infants had four consecutive examinations performed. No significant difference was found between degree of movement after the first and the fourth examination. By using the ultrasound method as the only diagnostic the frequency of treatment fell from 1.7% to 0.18% and no late cases were diagnosed before walking age.The sensitivity for the clinical examination was low: for paediatricians 24% and for trained technicians 53%. The breech malposition was confirmed to predispose to neonatal hip instability. The instability was manifest before delivery and was surely not a result of delivery forces. Vaginal delivery after an external version to vertex presentation and caesarean section without an attempted version represents the same risk for neonatal hip instability. Breech malposition and vertex presentation after an external or spontaneous version should both be considered risk factors for neonatal hip instability.Blood samples from the umbilical cord were saved from all neonates born during one year to evaluate whether intrauterine exposure to high levels of the maternal hormones could be an aetiological factor in neonatal hip instability. The hormone relaxin could not be detected except in three samples from three neonates in the control group. In infants without hip instability S-17 b-oestradiol concentrations were higher in male newborns compared to females, depending on the fact, that most girls with high oestradiol levels were cases. A trend to inverse relationship between oestradiol and parity was demonstrated. Using logistic regression analysis with adjustment for the associations to breech presentation, parity and gender, a significant association between S-oestradiol and neonatal hip instability was demonstrated in male newborns with low serum concentrations. S-oestradiol (<10 nmol/l) gave an increased risk of hip instability. In contrast, high S-oestradiol (>15) tended to be associated with an increased risk of hip instability in female newborns.From this study we conclude that:Population screening is necessary if both the dislocatable and the dislocated hip joints are to be identified.The anterior-dynamic ultrasound method is well suited to the screening situation and is shown to be reliable and reproducible.The anterior-dynamic ultrasound method can identify all neonatal hip dislocations within the first two days of life.The normal values for the physiological movement of the femoral head are a reliable standard dividing the population into two groups: those in need of medical attention and those with normal hip joints.Breech malposition is a risk factor for neonatal hip instability. The instability is present before delivery and is unaffected by delivery by caesarean section and/or attempted external version.An increased serum concentration in cord blood of the maternal hormone relaxin is not a cause of neonatal hip instability.S-17 ß-oestradiol in the umbilical cord blood is associated with gender as well as parity, but no firm conclusion on the association between 17 ß-oestradiol and neonatal hip instability can be made from this limited study.
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| 10. |
- Andersson, Kristina E
(author)
-
Cholesterol-lowering and anti-atherogenic effects of oats in mice
- 2009
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Doctoral thesis (other academic/artistic)abstract
- The cholesterol-lowering effect of oats is well established, but the crucial properties eliciting this effect need to be further investigated to optimize the use of oats as functional foods. Furthermore, there are almost no reports investigating the effect of oats on atherosclerosis development. This thesis describes our work with finding suitable mouse models to study cholesterol-lowering and anti-atherogenic effects of oats, the mechanism behind, and how processing of oat foods might interfere with these beneficial effects. We found that supplementation of oat bran to an atherogenic diet significantly reduced plasma cholesterol and LDL+VLDL concentrations in C57BL/6 mice. The responsiveness to oats did however differ between two substrain of mice. Oat intake resulted in reduced plasma cholesterol, increased faecal excretion of bile acids and cholesterol, and increased expression of the bile acid producing enzyme CYP7A1 in the C57BL/6NCrl substrain. None of these parameters were altered in the C57BL/6JBomTac mice. The different expression of CYP7A1 in the two substrains of C57BL/6 strongly supports the importance of increased bile acid excretion, together with increase of bile acid synthesis from cholesterol, for oats to reduce levels of cholesterol in plasma. To address how processing of oats might interfere with its cholesterol-lowering properties, oat beta-glucans were enzymatically digested to different molecular weights and then fed to C57BL/6NCrl mice. Reducing the molecular weight of the beta-glucans affected its viscous properties in vitro. It also affected the production of short chain fatty acids in caecal contents of the mice, but did not influence the cholesterol-lowering properties. Thus molecular weight and viscous properties of beta-glucans do not seem to be crucial parameters for the cholesterol-lowering properties of oats in the C57BL/6 mice. When studying effects of oats on atherogenesis and inflammation we used a mouse model developing more pronounced hypercholesterolaemia, the LDL-receptor deficient mice. Oats reduced plasma cholesterol and levels of LDL+VLDL in this model too, and also reduced plasma concentrations of the inflammation markers fibrinogen and soluble vascular adhesion molecule-1 (sVCAM-1). Most importantly oat bran in the diet reduced incidence of atherosclerotic lesions in both the aortic root and the descending aorta. These findings demonstrate that oats have anti-atherogenic properties, and support health claims that oats can reduce risk of cardiovascular disease.
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