Kunnskapsbaserte metoder som håndterer komplekse avhengighetsstrukturer : anvendelser på genekspresjonsdata

Microarray gene expression data are usually associated with a large number of correlated variables measured on few samples. This type of data typically contain high levels of noise, and the biological signals may be difficult to extract. The classical approach for analysing gene expression data is to test individual genes for differential expression. This basically implies performing tests on possibly thousands of dependent variables while incorrectly assuming statistical independence. The probability of doing false positive discoveries is accordingly high, the results of the analysis may be difficult to reproduce, and the outcome may be a list of biologically unrelated genes that leaves very much to the imagination. An increasing number of publications have therefore started to focus on incorporating prior biological information about gene dependencies in the analysis of gene expression data. Vast amounts of knowledge about relationships between genes based on previous studies are available. The motivation behind analysing the data in light of this information, include increased sensitivity and robustness of the analysis, better reproducibility of the results and easier interpretation. The prior information can for example be groups of genes with a similar function, or gene networks that describe some relationship between genes. With this information in hand, the focus can be turned from identifying important individual genes, to identifying larger groups of important genes that are also related. The aim of this thesis has been to improve and adapt existing methods to accommodate gene expression data from various types of experimental designs, in addition to developing novel procedures that incorporate prior information. A central part of this work has been concerned with significance testing in data sets with few and dependent samples. Most existing methods in this field use permutation tests to assess significance when the distribution of the test statistics is unknown. This is however problematic in data sets with very small sample sizes and complex experimental designs. In paper I we adopt a popular method for analysing gene sets, and replace the permutation test with a rotation test to accommodate it to small sample sizes. Paper III and IV introduce improvements to the method in paper I by adapting it to data from complex experimental designs and time series data. In paper II we propose a novel method that uses gene networks to improve test statistics for individual genes.Genekspresjonsdata fra mikromatriser assosieres ofte med et stort antall korrelerte variabler målt på få observasjoner. Denne typen data inneholder vanligvis mye irrelevant variasjon, og de biologiske signalene kan være vanskelig å skille fra bakgrunnsstøyet. Den vanligste måten å analysere geneekspresjonsdata på, har vært å teste hvert enkelt gen for differensiell ekspresjon. Dette innebærer å utføre tester på potensielt tusenvis av avhengige variabler, samtidig som man antar statistisk uavhengighet. Sannsynligheten for å finne falske positive er tilsvarende høy, resultatene kan være vanskelig å reprodusere, og utfallet av analysen kan være en liste med gener uten biologisk relasjon som overlater veldig mye til fantasien. Et økende antall publikasjoner har derfor begynt å fokusere på inkludering av a priori informasjon om genavhengigheter i analyse av genekspresjonsdata. Fra tidligere studier finnes store mengder biologisk kunnskap om relasjoner mellom gener. Ved å analysere dataene i lys av denne informasjonen, ønsker man å oppnå en mer sensitiv og robust analyse med resultater som er enklere å reprodusere og tolke. Forhåndsinformasjonen kan for eksempel bestå av grupper av gener med lignende funksjon eller gennettverk som beskriver relasjoner mellom gener. Med denne informasjonen for hånden, kan fokuset flyttes fra viktige enkeltgener, til grupper av viktige gener som også har noe felles. Målet med denne avhandlingen har vært å forbedre og tilpasse eksisterende metoder til genekspresjonsdata med forkjellige typer forsøksdesign, samt utvikling av nye metoder som benytter seg av a priori informasjon. En sentral del av dette arbeidet har vært knyttet til testing av signifikans i datasett med få og avhengige observasjoner. De fleste eksisterende metoder innenfor dette feltet bruker permutasjonstester for å evaluere signifikans når testobservatoren har en ukjent fordeling. Dette er imidlertid problematisk for datasett med veldig få observasjoner som ikke kan antas uavhengige grunnet forsøksdesignet. I artikkel I tar vi for oss en populær metode for å analysere gengrupper og bytter ut permutasjonstesten med en rotasjonstest for å tilpasse metoden til små utvalgsstørrelser. I artikkel III og IV introduseres forbedringer av metoden i artikkel I ved å tilpasse den til data med komplekse forsøksdesign og tidsseriedata. I artikkel II foreslår vi en ny metode som bruker gennettverk til å forbedre testobservatoren til enkeltgener

Encounter rates and distribution of Inia geoffrensis and Sotalia fluviatilis in the middle Juruá region, western Amazonia, Brazil

The Amazon Basin and its floodplains are a highly productive ecosystem that habitats many of the world’s freshwater species. The flood pulse which seasonally inundates the flooded forests creates dynamic environments with varied degrees of adaptations within fauna species. River dolphins in the Amazon are facing different threats, although their abundance and encounter rates seem to be at a high level still. There is a large difference in preferences for distribution between Inia geoffrensis and Sotalia fluviatilis, where encounter rates of I. geoffrensis is higher than S. fluviatilis, but group sizes show an opposite distribution. The environmental variable confluence has a high effect on the encounter rates of both dolphin species, where the presence of this habitat on a transect line, leads to an increase in encounter rates. The anthropogenic variables tested for this thesis showed little effect on encounter rates, although the distance from a community showed a negative effect on encounter rates on I. geoffrensis, and motor traffic had a positive effect on S. fluviatilis. The psychological traits of these river dolphins show that the riverine habitat preference of these species is also different, where Inia prefer habitat along the river margins, and Sotalia prefers to be in the center of the river

Norse expansion and sami counterpower in Sør-Salten c. 600-1350

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Numerical and analytical studies of ship deckhouse impact with steel and RC bridge girders

Bridges crossing navigable waterways are under the threat of accidental collisions from passing ships. However, previous research focus was mainly placed on ship collision with bridge substructures while ship-bridge superstructure collisions were largely ignored. In fact, superstructure collision accidents between bridge girders and ship deckhouses have occurred with increasing frequency in the past decade. Therefore, it is important to evaluate the bridge girder capacity against ship superstructure collisions in the design phase. In this paper, finite element models of a ship deckhouse and three types of bridge girders are established. Numerical simulations are conducted to investigate the response of the bridge girders under ship deckhouse collisions. The application and validity of the commonly adopted rigid body assumption of bridge girders are investigated. The results are compared with integrated collision simulations where both the striking deckhouse and the struck bridge girder are modelled as deformable bodies. The impact force, structural failure mode, and energy dissipation during the collision process are discussed. The effects of girder material and structural configuration are also discussed. Based on the numerically obtained failure mode of the ship deckhouse, an efficient analytical design approach for bridge girders against ship deckhouse impacts is proposed.publishedVersio

Det norske skyldeie - et særnorsk fænomen?

Land Rent Ownership In Norway - A Peculiarity of the Norwegians?There seems to be a wide-spread conception among Nordic agrarian historians that the right to land property in the form it existed in Norway from the thirteenth to the eighteenth century, namely land-rent ownership (skyldeie), i.e., ownership of the right to receive rent from landed property rather than ownership of the land as such, was a peculiarly Norwegian phenomenon. An outstanding exponent of this idea was the Norwegian agrarian historian Andreas Holmsen. The author of the present study has nevertheless found a number of examples, especially in Danish sources, that justify a rejection of Holmsen's construction of the property system as uniquely Norwegian. For in Denmark as well, the annual land rent (skylden) of the Late Middle Ages and Early Modern Period functioned as a measure of land ownership in purchase, sale, and not the least, inheritance. The landowner could likewise possess a partial rent right or shares in the farm's rent right, an arrangement that merely entailed a right to a portion of the farm's income, but not the right of physical disposal. Like Norwegian land-rent ownership, the Danish annual land rent was the direct consequence of a predominant property and rent structure in the Late Middle Ages. The ownership of land functioned first and foremost as a source of rents; the landowners at that time rarely conceived of subdividing farms and plots or demanding the use of certain areas of a farm. Moreover, many of the tenant leases were tied into a complicated system of commons, some of them inhibiting the physical division of the farms involved; and in some forms of inheritance the cultivation systems would require a subdivision of rents and shared rent ownership. Furthermore, since the principle of justice was frequently applied in inheritance cases among the nobility, noble families seeking to divide the inheritance of farms with the greatest possible justice to the heirs could resort to a division of the annual land rents. On the other hand, Danish letters from the Late Middle Ages bear witness to the rarity of donating, bequeathing, selling, or panting rent shares to ecclesiastical institutions as well as other kinds of transactions involving rent shares. The Zealand Ecclesiastical Land Record (Sjællands Stifts Landebog) from 1567 shows quite clearly that the kind of donations made by the peasants to the parish churches and the clergy were small single plots, fields, crofts, cattle enclosures, or a house. A cursory examination of the tax record of 1662 shows with great clarity that cases of rent division in Denmark were modest in number compared, for instance, with those recorded in Norway in 1647. For the dominant pattern in Denmark was that one or more entire farms or even villages were owned by one person, while in central parts of Norway it was generally the rule that two or more persons held shares in one and the same farm.In the course of the sixteenth and seventeenth centuries interest in the form of ownership underwent a change in Denmark. The right of disposal of landed property and its potential as a source of income increasingly became a motive in property transactions. Parallel with the growth of demesne production, the acquisition of surrounding properties, and the development of manorial rights (primarily tenant labour), manorial status acquired greater attraction as an object of ownership. Compared to the older rent-owner the manorial owner (herlighetseieren) personified sovereign landownership - in possession of far greater rights than his predecessor. In Norway the right of bygsel, like manorial rights (herlighetsrettigheter) in Denmark, replaced rent ownership as the real object of ownership from around the middle of the seventeenth century. The right of bygsel gave the owner of the largest share of land rent the right to determine the successor of the tenant and to ensure the collection of the rent. In Norway, too, it was new owner interests that brought about the changes in the concept of property. This is seen in the way the right of rent ceded in importance to the right of disposal of the farm, its prerogatives and its appurtenances. We have seen that there were many similarities between the Danish and the Norwegian property systems, although agrarian society in the two countries was obviously very different in many ways. The fact remains that a system of land-rent rights existed in both countries. In Sweden, too, examples can be found of rent ownership, e.g., in the Skara Ecclesiastical Land Record for 1540. It is also likely that similar forms of ownership can be found in other countries such as England, France, and Germany.Translated by Michael Wolf

Solid strukturhistorie om kvinner, uten særlig mange menn

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Substrate specificity of transglutaminases for gluten peptides

The human immune system has developed intricate mechanisms to protect the body by discriminating between infectious agents and self. Unfortunately, in some cases these mechanisms can be bypassed and immune responses may be elicited by antigens derived from self. The loss of tolerance to autoantigens may lead to the development of autoimmune diseases. Autoimmune diseases are chronic inflammatory diseases of unknown etiology where both genetic and environmental factors play a role. Human leukocyte antigens (HLA) have been shown to be the most important susceptibility factor for several of the autoimmune diseases, what strongly suggests the involvement of T cells. In many autoimmune diseases the self antigen causing the disease is not known. This is the case for rheumatoid arthritis, multiple sclerosis and type 1 diabetes. For celiac disease however, the trigger of the disease is known to be gluten. Interestingly, although gluten was known to be the environmental factor for years, it was not until a decade ago that a posttranslational modification of gluten mediated by an enzyme called tissue transglutaminase 2 (TG2) was discovered to be critical for the disease. The posttranslationally modified gluten peptides bind the disease associated HLA-molecules with a higher affinity than the unmodified gluten peptides, what results in a multifaceted T-cell response. Thus, posttranslational modifications of self-antigens, or in this case; of food antigens normally tolerated by the body, is one way in which novel epitopes are created that are not tolerated by the immune system. Interestingly, immune responses directed towards enzymatically modified self-antigens were also reported for other autoimmune diseases, e.g. against citrullinated proteins in rheumatoid arthritis and methylated and phosphorylated proteins in systemic lupus erythematosus. As the importance of posttranslational modifications of gluten peptides is acknowledged in celiac disease, further research in this field may be relevant also for other autoimmune diseases. In this thesis, we have used mass spectrometry-based strategies to investigate the posttranslational gluten modifications catalyzed by the transglutaminase enzymes implicated in gluten sensitive diseases. The main focus has been on TG2 and its important role in T-cell epitope selection in celiac disease

Likestilling i barnehagen

I denne oppgaven skriver jeg om likestilling i barnehagen. Jeg har tatt utgangspunkt i en semesteroppgave jeg skrev tidligere i år som handlet om hvordan personalet i barnehagen kan jobbe for å fremme likestilling mellom kjønnene, og i denne oppgaven ser jeg på likestilling i forhold til gutters og jenters utviklingsmuligheter. Jeg har valgt å se på voksenrollen, og jeg ønsker å finne ut om personalet i barnehagen gjennom sine holdninger og handlinger forskjellsbehandler jenter og gutter. Jeg kom frem til følgende problemstilling: Det er ulike ”regler” for gutter og jenter i barnehagen

Source level interpretation of mixed biological stains using coding region SNPs

The association of body fluids/cell types and donors in mixed biological traces is an important, but challenging task required to evaluate the value of evidence given forensic propositions concerning the source of the DNA. The linking of a DNA profile with evidence from presumptive tests or RNA analysis is not straightforward. Coding region SNPs (cSNPs) are a novel type of evidential markers that are both cell type specific and individual specific. They thereby provide a direct link between a donor and a body fluid in mixed biological stains. In this proof-of-concept paper we consider the evaluation of cSNP profiles given source level propositions and explore the use of the open-source software EuroForMix to compute likelihood ratios. The discrimination power of the cSNPs for various body fluids is investigated with simulations. We provide case examples where the type of biological material is questioned and where cSNP profiles can be used to assign a donor to a body fluid, and discuss how the results can be reported in court. Keywords: Body fluid identification; Body fluid mixtures; Coding region SNP (cSNP); Forensic Science; Likelihood ratio; Source level propositions; mRN