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Immune genes of the major histocompatibility complex (MHC) constitute a central component of the adaptive immune system and play an essential role in parasite resistance and associated life-history strategies. In addition to pathogen-mediated selection also sexual selection mechanisms have been identified as the main drivers of the typically-observed high levels of polymorphism in functionally important parts of the MHC. The recognition of the individual MHC constitution is presumed to be mediated through olfactory cues. Indeed, MHC genes are in physical linkage with olfactory receptor genes and alter the individual body odour. Moreover, they are expressed on sperm and trophoplast cells. Thus, MHC-mediated sexual selection processes might not only act in direct mate choice decisions, but also through cryptic processes during reproduction. Bats (Chiroptera) represent the second largest mammalian order and have been identified as important vectors of newly emerging infectious diseases affecting humans and wildlife. In addition, they are interesting study subjects in evolutionary ecology in the context of olfactory communication, mate choice and associated fitness benefits. Thus, it is surprising that Chiroptera belong to the least studied mammalian taxa in terms of their MHC evolution. In my doctoral thesis I aimed to gain insights in the evolution and diversity pattern of functional MHC genes in some of the major New World bat families by establishing species-specific primers through genome-walking into unknown flanking parts of familiar sites. Further, I took a free-ranging population of the lesser bulldog bat (Noctilio albiventris) in Panama as an example to understand the functional importance of the individual MHC constitution in parasite resistance and reproduction as well as the possible underlying selective forces shaping the observed diversity. My studies indicated that the typical MHC characteristics observed in other mammalian orders, like evidence for balancing and positive selection as well as recombination and gene conversion events, are also present in bats shaping their MHC diversity. I found a wide range of copy number variation of expressed DRB loci in the investigated species. In Saccopteryx bilineata, a species with a highly developed olfactory communication system, I found an exceptionally high number of MHC loci duplications generating high levels of variability at the individual level, which has never been described for any other mammalian species so far. My studies included for the first time phylogenetic relationships of MHC genes in bats and I found signs for a family-specific independent mode of evolution of duplicated genes, regardless whether the highly variable exon 2 (coding for the antigen binding region of the molecule) or more conserved exons (3, 4; encoding protein stabilizing parts) were considered indicating a monophyletic origin of duplicated loci within families. This result questions the general assumed pattern of MHC evolution in mammals where duplicated genes of different families usually cluster together suggesting that duplication occurred before speciation took place, which implies a trans-species mode of evolution. However, I found a trans-species mode of evolution within genera (Noctilio, Myotis) based on exon 2 signified by an intermingled clustering of DRB alleles. The gained knowledge on MHC sequence evolution in major New World bat families will facilitate future MHC investigations in this order. In the N. albiventris study population, the single expressed MHC class II DRB gene showed high sequence polymorphism, moderate allelic variability and high levels of population-wide heterozygosity. Whereas demographic processes had minor relevance in shaping the diversity pattern, I found clear evidence for parasite-mediated selection. This was evident by historical positive Darwinian selection maintaining diversity in the functionally important antigen binding sites, and by specific MHC alleles which were associated with low and high ectoparasite burden according to predictions of the ‘frequency dependent selection hypothesis’. Parasite resistance has been suggested to play an important role in mediating costly life history trade-offs leading to e.g. MHC- mediated benefits in sexual selection. The ‘good genes model’ predicts that males with a genetically well-adapted immune system in defending harmful parasites have the ability to allocate more resources to reproductive effort. I found support for this prediction since non-reproductive adult N. albiventris males carried more often an allele associated with high parasite loads, which differentiated them genetically from reproductively active males as well as from subadults, indicating a reduced transmission of this allele in subsequent generations. In addition, they suffered from increased ectoparasite burden which presumably reduced resources to invest in reproduction. Another sign for sexual selection was the observation of gender-specific difference in heterozygosity, with females showing lower levels of heterozygosity than males. This signifies that the sexes differ in their selection pressures, presumably through MHC-mediated molecular processes during reproduction resulting in a male specific heterozygosity advantage. My data make clear that parasite-mediated selection and sexual selection are interactive and operate together to form diversity at the MHC. Furthermore, my thesis is one of the rare studies contributing to fill the gap between MHC-mediated effects on co-evolutionary processes in parasite-host-interactions and on aspects of life-history evolution.
Background: For heterogeneous tissues, such as blood, measurements of gene expression are confounded by relative proportions of cell types involved. Conclusions have to rely on estimation of gene expression signals for homogeneous cell populations, e.g. by applying micro-dissection, fluorescence activated cell sorting, or in-silico deconfounding. We studied feasibility and validity of a non-negative matrix decomposition algorithm using experimental gene expression data for blood and sorted cells from the same donor samples. Our objective was to optimize the algorithm regarding detection of differentially expressed genes and to enable its use for classification in the difficult scenario of reversely regulated genes. This would be of importance for the identification of candidate biomarkers in heterogeneous tissues.
Results: Experimental data and simulation studies involving noise parameters estimated from these data revealed that for valid detection of differential gene expression, quantile normalization and use of non-log data are optimal. We demonstrate the feasibility of predicting proportions of constituting cell types from gene expression data of single samples, as a prerequisite for a deconfounding-based classification approach. Classification cross-validation errors with and without using deconfounding results are reported as well as sample-size dependencies. Implementation of the algorithm, simulation and analysis scripts are available.
Conclusions: The deconfounding algorithm without decorrelation using quantile normalization on non-log data is proposed for biomarkers that are difficult to detect, and for cases where confounding by varying proportions of cell types is the suspected reason. In this case, a deconfounding ranking approach can be used as a powerful alternative to, or complement of, other statistical learning approaches to define candidate biomarkers for molecular diagnosis and prediction in biomedicine, in realistically noisy conditions and with moderate sample sizes.
This study aimed to determine the specific physical and basic gymnastics skills considered critical in gymnastics talent identification and selection as well as in promoting men’s artistic gymnastics performances. Fifty-one boys from a provincial gymnastics team (age 11.03 ± 0.95 years; height 1.33 ± 0.05 m; body mass 30.01 ± 5.53 kg; body mass index [BMI] 16.89 ± 3.93 kg/m²) regularly competing at national level voluntarily participated in this study. Anthropometric measures as well as the men’s artistic gymnastics physical test battery (i.e., International Gymnastics Federation [FIG] age group development programme) were used to assess the somatic and physical fitness profile of participants, respectively. The physical characteristics assessed were: muscle strength, flexibility, speed, endurance, and muscle power. Test outcomes were subjected to a principal components analysis to identify the most representative factors. The main findings revealed that power speed, isometric and explosive strength, strength endurance, and dynamic and static flexibility are the most determinant physical fitness aspects of the talent selection process in young male artistic gymnasts. These findings are of utmost importance for talent identification, selection, and development.
This document presents a formula selection system for classical first order theorem proving based on the relevance of formulae for the proof of a conjecture. It is based on unifiability of predicates and is also able to use a linguistic approach for the selection. The scope of the technique is the reduction of the set of formulae and the increase of the amount of provable conjectures in a given time. Since the technique generates a subset of the formula set, it can be used as a preprocessor for automated theorem proving. The document contains the conception, implementation and evaluation of both selection concepts. While the one concept generates a search graph over the negation normal forms or Skolem normal forms of the given formulae, the linguistic concept analyses the formulae and determines frequencies of lexemes and uses a tf-idf weighting algorithm to determine the relevance of the formulae. Though the concept is built for first order logic, it is not limited to it. The concept can be used for higher order and modal logik, too, with minimal adoptions. The system was also evaluated at the world championship of automated theorem provers (CADE ATP Systems Competition, CASC-24) in combination with the leanCoP theorem prover and the evaluation of the results of the CASC and the benchmarks with the problems of the CASC of the year 2012 (CASC-J6) show that the concept of the system has positive impact to the performance of automated theorem provers. Also, the benchmarks with two different theorem provers which use different calculi have shown that the selection is independent from the calculus. Moreover, the concept of TEMPLAR has shown to be competitive to some extent with the concept of SinE and even helped one of the theorem provers to solve problems that were not (or slower) solved with SinE selection in the CASC. Finally, the evaluation implies that the combination of the unification based and linguistic selection yields more improved results though no optimisation was done for the problems.
The present study aimed to integrate findings from technology acceptance research with research on applicant reactions to new technology for the emerging selection procedure of asynchronous video interviewing. One hundred six volunteers experienced asynchronous video interviewing and filled out several questionnaires including one on the applicants' personalities. In line with previous technology acceptance research, the data revealed that perceived usefulness and perceived ease of use predicted attitudes toward asynchronous video interviewing. Furthermore, openness revealed to moderate the relation between perceived usefulness and attitudes toward this particular selection technology. No significant effects emerged for computer self-efficacy, job interview self efficacy, extraversion, neuroticism, and conscientiousness. Theoretical and practical implications are discussed.