Syftet med studien är att utöka kunskapen om i vilken omfattning samhällsfaktorer kan ha påverkat Charles Darwin vid utformandet av teorin om det naturliga urvalet. Studien vill på så sätt, utifrån ett sociologiskt perspektiv, bidra till kunskapen om hur den nya synen på naturens evolutionsprocesser kunde växa fram, genom abstraktioner som centrala verktyg i kunskapens produktionsprocess. Utgångspunkten för analysen är Herbert Spencers antagande att samma lagbundna utveckling som gäller för samhällen också gäller för levande organismer. Analysen av Darwins avhandling Om arternas uppkomst begränsas till två centrala kapitel. Dessa kapitel har valts då de bedömts vara centrala för en positionering av sociologin inom evolutionsbiologin. I dessa kapitel utvecklas Darwins syn på det naturliga urvalet och variationen, nämligen kapitel IV ”Det naturliga urvalet” och kapitel V ”Lagarna för variationen”. I studien undersöks vilka nödvändiga egenskaper den verklighet bör ha haft som utgjort grunden för den nya evolutionsbiologins världsbild, och vilka underliggande generativa mekanismer i samhället, som bidragit till att forma Darwins teori om det naturliga urvalet. Sammanfattningsvis måste studien anses ha funnit stöd för att anta hypotesen att ett samband kan påvisas mellan å ena sidan Darwins teori om det naturliga urvalet och å andra sidan sociala mekanismer i det dåtida samhället.

Diss. Lund : Lunds universitet, 2006.

Augsburg, Univ., Diss., 2008.

Diss. Univ. St. Gallen, 2001.

Regensburg, Univ., Diss., 2008.

Idrott intar en stark position i vårt västerländska samhälle och idrottsprestationer är av stort nationellt intresse. Att välja ut talangfulla elever till Nationella idrottsutbildningar är inte helt lätt och kunskapen om urvalsprocessen är bristfällig. Syftet med denna studie var att generera kunskap om talang-identifikationsprocessen till de Nationella Idrottsutbildningar(NIU) inom ramen för utbildnings-reformen GY-11. Genom intervjuer med idrottsinstruktörer inom 10 olika idrotter besvarades frågor om hur de definierade och identifierade talang och hur de valde ut de elever som skulle bli antagna till NIU. Mer specifikt studerades instruktörernas beslutsfattande i urvalsprocessen. Studien visade på att instruktörerna hade svårt att definiera talang och ge en entydig bild av talangbegreppet. Urvalsprocessen och i den talangidentifikationen, processen att välja ut talanger, var relativt omfattande och väl utarbetad gemensamt av specialidrottsförbunden(SF) och skolorna. Dock såg den olika ut i en del SF. Informationen om ungdomarna hanterades samtidigt av instruktörerna under talangidentifikationsprocessen, vilken senare låg till grund för en slutgiltig bedömning av ungdomarnas fysiska, tekniska och personliga kvalitéer. Det gick att identifiera tre olika sammanvävda mönster som användes i talangidentifikationsprocessen. För det första kunde talang tolkas som ett socialt konstruerat fenomen utifrån instruktörernas tycke och smak. För det andra kunde valen förstås utifrån klassifikationsscheman som karaktäriserades utifrån instruktörernas sammanlagda erfarenhet, som över tid format deras preferenser för idrottsspecifik talang och/eller talang som personlighet. För det tredje så använde de sig av sitt praktiska förnuft och sin visuella erfarenhet för att identifiera och särskilja den talangfulle idrottaren från den mediokra utifrån kunskap om rörelsemönster i respektive idrott. En slutsats som gick att dra är att talangidentifikationsprocessen är komplex och inte alltid så objektiv och rationell som man vill tro.Nyckelord:

This is a critical theoretical inspired study of the centralized talent development within Swedish football. Prior research from mainly Tomas Peterson and Rolf Carlsson shows how difficult it is to anticipate which players that have best prerequisites to reach the elite level in football, and how individuals born in the first months of the year in early national youth elite selections are substantial overrepresented compared to individuals born late in the year because of further physical, intellectual and social development. These are factors that will be equally divided in adult age, and the dividing up in birth quarters of the players at the elite level also is quite equal which shows that the former imbalance were unjustified in terms of which players that have the best prerequisites for success.In my C-essay, a comparative study of IFK Göteborgs and Malmö FF´s respectively football academy, my comprehensive conclusion were to abolish the youngest youth national teams and divide the resources to an increased quantity deliberated training for as many youth players as possible through a diffusion of football academies in Sweden. This underlies my question at issue in this study and for a critical interview with the former director of player education at the Swedish Football Association, Thomas Lyth. Interviews on the subject have also been done with three big football district associations in the south, which are compared with each other and the National Football Association.It appears that it has been made important changes of the centralized talent development due to the research results. The individual education of players is emphasized to a greater extent than before, every year a larger age group of players to be stimulated is chosen, and the system of youth national teams (age 13-19) isn’t excluded for players that on an early stage in the system have been redacted (which was pretty much the case before). In spite of this I think a discussion of more changes to be done can be interesting. Interviews with the football districts show that within Swedish football there also are some critics. Representatives from the districts Skåne, Småland and Göteborg have more or less critic to have the youngest youth national teams. Most of the players’ training take place at the local level; therefore it is important to have strong football district associations that can give many players a deliberate education in a good environment just like football academies potentially can supply. I think that stimulation activities and ability groupings favourably can be done at district and club level. I think youth national teams are motivated from about the age of 18 years, when the dividing up of players in birth quarters is pretty equal and it’s easier to anticipate which players that have best prerequisites for success at the senior elite level. Earlier youth national teams send wrong signals to both the players who are chosen and mostly to all the players who are redacted. I think that a diffusion of resources and competence in Sweden according to talent development is important.

Die mangelnde Wasserlöslichkeit von Wirkstoffen ist eines der größten Probleme in der pharmazeutischen Medikamentenentwicklung, welches durch das Scheitern zahlloser vielversprechender Leitstrukturen immense Kosten verursacht. Es wird eine Methode vorgestellt, um spezifische Löslichkeitsvermittler für schwerlösliche, niedermolekulare Verbindungen zu entwickeln. Dafür wurden Partner für die nichtkovalente Bindung von Wirkstoffen aus Peptidbibliotheken identifiziert. Als Testsubstanzen wurden Sensibilisatoren für die photodynamische Krebstherapie gewählt. Über die Fluoreszenz der Photosensibilisatoren konnte die Anreicherung an Polymerpartikeln verfolgt werden, deren Peptidsequenzen eine hohe Affinität zu den Wirkstoffen besaßen. Positive Treffer wurden isoliert und deren Aminosäuresequenz mittels Tandem-Massenspektrometrie bestimmt. Diese Informationen wurden verwendet, um Löslichkeitsvermittler für die Sensibilisatoren zu synthetisieren. Dafür wurden die Sequenzen an einen hydrophilen Polyethylenoxid-Block (PEO) konjugiert, wobei das Peptidsegment die Bindung des Gastmoleküls vermittelt, während der Polymerblock die Wasserlöslichkeit des Komplexes garantiert. Mit diesen Konjugaten wurden die Sensibilisatoren erfolgreich in wässrige Lösung gebracht. Die Eigenschaften der Solubilisatoren bezüglich Beladungsgrad, Aggregation und Freisetzung der Gastmoleküle wurde untersucht, sowie die Aktivität der solubilisierten Sensibilisatoren bezüglich der Erzeugung von Singulett-Sauerstoff. Die Anpassung der Screening-Bedingungen, der Konjugat-Architektur und den Einbau eines schaltbaren Bausteins erlaubte die zusätzlich Feinjustierung. Durch einen Vergleich der verschiedenen Sensibilisatoren wurde die Sensibilität der Methode für strukturelle Unterschiede der Testsubstanzen und die Spezifität der gewonnenen Solubilisatoren für ihr Zielmolekül überprüft. Zuletzt wurden die Aufnahme und der Aufnahmemechanismus der solubilisierten Sensibilisatoren in Krebszellen studiert. / Insufficient water solubility of small molecule compounds is one of the major issues in pharmaceutical drug development causing tremendous costs due to failure of numerous high potential lead structures. Herein, a generic method to develop specific solubilizers for insoluble, small molecules is presented. Suitable binding partners for a set of sensitizers for photodynamic cancer therapy (m THPC, Pheophorbide A und Chlorin E6) were selected from a split&mix peptide library. The enrichment of sensitizer molecules at high affinity peptide sequences was followed by monitoring their intrinsic fluorescence via fluorescence microscopy. Positive hits were isolated and amino acid sequences were identified by tandem mass spectrometry (MALDI-Tof-MS/MS). The information gained about the requirement for non-covalent binding on a molecular level was used to synthesize specific solubilizers for small molecule drug entities. Therefore, identified peptide sequences were conjugated to a polyethylene oxide block to obtain water solubility, whereas peptide segments provide non-covalent binding of drug molecules. Insoluble photosensitizers were successfully rendered water soluble by peptide-PEO conjugates. Key parameters like drug payload capacity, aggregation behavior and guest molecule release, as well as activity regarding singlet oxygen generation, were studied. By adaptation and variation of screening conditions, conjugate architecture and incorporation of a switchable building block, properties of conjugate solubilizers were fine-tuned further. To evaluate screening sensitivity towards structural aspects of screened small molecules and specify of resulting solubilizers, screening results of different sensitizers and peptide-PEO solubilizers performance were compared. Finally, cellular uptake of solubilized photosensitizer in cancer cells and uptake pathways was studied in vitro using confocal laser-scanning microscopy and fluorescence lifetime imaging.

Modern humans originated in Africa around 200,000 years ago and today have settled in nearly every corner of earth. During migrations humans became exposed to new pathogens, food sources and have encountered vastly different environments. Natural selection likely contributed to the survival under such diverse conditions by promoting the raise in frequency of advantageous alleles. Thereby natural selection leaves genetic footprints that we can identify. The thesis at hand is about understanding how natural selection has shaped different human populations by analyzing these genetic footprints. In the first study, I infer the evolutionary history of an insertion-substitution variant using present-day human genomic data. This variant is interesting because the ancestral allele encodes a previously unannotated open-reading frame for a gene with antiviral ac- tivity (IFNL4 ), while the derived allele truncates this open-reading frame and is strongly associated with improved clearance of Hepatitis C, a major health care problem. Using an approximate bayesian computation approach I infer a complex evolutionary history, where the derived, truncating allele evolved under weak positive selection in Africa, with selection strength increasing in non-African populations, especially in East Asian popu- lations where the truncating allele is nearly fixed today. Hence, the changes in selection and resulting population differences in allele frequency contribute to the variation in Hep- atitis C clearance observed across human populations today. In the second study, I use ancient human genomes to estimate genome-wide allele frequencies in the past to understand present-day population differentiation. I develop a new statistic and incorporate the genome of Ust’-Ishim, a modern human that lived 45,000 year ago in Siberia, to study to what extent natural selection and drift have contributed to human population differentiation. The results suggest that European populations carry high frequency alleles in protein-coding (genic) regions that evolved under strong, recent positive selection. Further, the genic alleles that rose in frequency recently in Europeans were already present in ancient hunter-gatherers more often than in ancient farmers. This suggests that during the colonization of Europe local, positive selection changed the frequency of advantageous alleles in hunter-gatherer populations prior to the influx of farming individuals and those alleles remained beneficial also in the later admixed populations.

In this thesis, we address the identification of biomarkers in high-dimensional omics data. The identification of valid biomarkers is especially relevant for personalized medicine that depends on accurate prediction rules. Moreover, biomarkers elucidate the provenance of disease, or molecular changes related to disease. From a statistical point of view the identification of biomarkers is best cast as variable selection. In particular, we refer to variables as the molecular attributes under investigation, e.g. genes, genetic variation, or metabolites; and we refer to observations as the specific samples whose attributes we investigate, e.g. patients and controls. Variable selection in high-dimensional omics data is a complicated challenge due to the characteristic structure of omics data. For one, omics data is high-dimensional, comprising cellular information in unprecedented details. Moreover, there is an intricate correlation structure among the variables due to e.g internal cellular regulation, or external, latent factors. Variable selection for uncorrelated data is well established. In contrast, there is no consensus on how to approach variable selection under correlation. Here, we introduce a multivariate framework for variable selection that explicitly accounts for the correlation among markers. In particular, we present two novel quantities for variable importance: the correlation-adjusted t (CAT) score for classification, and the correlation-adjusted (marginal) correlation (CAR) score for regression. The CAT score is defined as the Mahalanobis-decorrelated t-score vector, and the CAR score as the Mahalanobis-decorrelated correlation between the predictor variables and the outcome. We derive the CAT and CAR score from a predictive point of view in linear discriminant analysis and regression; both quantities assess the weight of a decorrelated and standardized variable on the prediction rule. Furthermore, we discuss properties of both scores and relations to established quantities. Above all, the CAT score decomposes Hotelling’s T 2 and the CAR score the proportion of variance explained. Notably, the decomposition of total variance into explained and unexplained variance in the linear model can be rewritten in terms of CAR scores. To render our approach applicable on high-dimensional omics data we devise an efficient algorithm for shrinkage estimates of the CAT and CAR score. Subsequently, we conduct extensive simulation studies to investigate the performance of our novel approaches in ranking and prediction under correlation. Here, CAT and CAR scores consistently improve over marginal approaches in terms of more true positives selected and a lower model error. Finally, we illustrate the application of CAT and CAR score on real omics data. In particular, we analyze genomics, transcriptomics, and metabolomics data. We ascertain that CAT and CAR score are competitive or outperform state of the art techniques in terms of true positives detected and prediction error.