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Background: The lack of knowledge regarding preschool children's mental health prompted Uppsala University, in collaboration with Uppsala Kommun, to start a study in which children aged 3, 4, and 5 years are screened using the "Strength and Difficulties Questionnaire" (SDQ). This screening method has been introduced into the majority of Uppsala County child care centers (BVC), and the nurses' experience of working with this method is examined in this paper. Method: A qualitative approach with semi-structured questions was used to interview ten nurses who pioneered the SDQ Method. The interviews where recorded, transcribed and analyzed using content analysis. Results: Three themes and nine categories were identified from the interviews. The themes were: "Attitude and motivation are important when working with the form", "Clearer overall picture with preschool answer", and "A tool to identify difficulties". The results show that the nurses were satisfied with the form. They felt that their assessment of the child became more extensive, and that the parents were to a large extent able to describe their child. The method was experienced to facilitate communication between nurses and parents regarding sensitive issues. No extra time was needed for the visit itself, but more time was needed to send out the forms. Conclusion: The nurses welcomed a new assessment tool for children's visits to the BVC. A shorter version of the form was requested, primarily for parents who felt they didn’t have time to respond. Furthermore, they believed that using a structured questionnaire increased the value of the visit and reduced the risk of failing to identify children with adverse behavior, without using more time than before.

Polycomb Group (PcG) proteins are responsible for post-transcriptional modifications in histone tails leading to chromatin condensation and changes in gene expression. In Arabidopsis thaliana, curly leaf (CLF) is a member of the Polycomb Reporssive Complex 2 (PRC2), which cnfers a repressive epigenetic mark, namely trimethylation of histone H3 at lysine 27 (H3K27me3). In the clf mutant, the expression of the floral organ identity gene AGAMOUS (AG) is derepressed in vegetative stages and coincides with loss of H3K27me3 at the AG locus. Recent whole genome prfiling studies have suggested that PcG genes regulate mang more developmental regulators than AG (about 15% of Arabidopis genes). However, it remains unclear what the relevance of PcG regulation of these targets is for plant development; in addition, it is not known how changes in J3K27me3 casue gene repression in plants. To unravel the role of CLFcin A. thaliana, a T-DNA mutagenesis in the clf background was performed to identify mutations enhancing or suppressing the Clf- phenotype, as these may identify additional PcG genes and targets. Firstly, I screened an A. thaliana T-DNA mutagenized population and identified four mutations suppressing the Clf- phenotype: suppressor of polycomb 1 to 4 (sop1, sop2, sop3 and sop4). Secondly, I characterized these four mutants. The sop1 mutant had normal flowering time and the suppressed phenotype is due to a loss of function mutation in SEPALLATA3 (SEP3). I establied the SEP3 is an activator and a co-factor of AG. Also, I found that SEP3 is stronlgy mis-expressed in clf mutants and SEP3 chromatin is enriched the H3K27me3, which stronly suggests that SEP3 is a direct target of CLF. In addition, I showed that a mutation in Flowering Locus T (FT), which is a positive regulator of SEP3, suppreesed the Clf- phenotype suggesting the FT is also a target of CLF. Suppressors sop3, sop3 and sop4 are late flowering, unlike sop1, and show increased expression of Flowering Locus C (FLC), a MADS-box transcription factor gene that represses flowering. I found that the sop4 mutation in likely casued by disruption of FPA, a predicted RNA binding protein that promotes flowering time by repressing FLC. Consistent with this, sop4 mutants show hight levels of FLC. Unexpectedly, fpa clf (sop4) mutatns are much later flowering than clf FRI mutants, which have similarly high levels of FLC. This suggests that FPA may regulate other genes controlling flowering thant FLC. The genes involved in sop2 and sop3 mutants remain to be identified. In this thesis I brought genetic and molecular evidence showing that CLF, though the PRC2, control floral induction (FLC), floral integration (FT) and floral organ formation (SEP3 and AG) in A. thaliana.

This thesis presents new spherical harmonic (SH) approaches for ligand-based high-throughput virtual screening (HTVS). If it is assumed that small drug molecules may be adequately superposed and distinguished by co-locating their centers of mass and by performing rotational correlations of their shapes, then to a good approximation each molecule may be represented very compactly using a two dimensional (2D) SH surface envelope. Of course, this assumes that the true molecular surface is star-like, or single-valued, with respect to radial rays projecting from the selected origin. However, this often holds to a very good approximation for small globular molecules. Even when this is not the case, it is nonetheless reasonable to suppose that similar molecules should give similar radial projections and, therefore, that they should share very similar SH representations. Following this premise, a new program called “SpotLight” was developed. The results obtained with this software show that SH-based global shape matching provides a powerful new way to perform HTVS. SH surface representations are increasingly being applied to a broad range of object recognition and registration tasks, and have also been used to model protein-ligand shape complementarity. Most current shape similarity techniques search for global similarities, and may therefore miss finding active compounds with different overall shapes and sizes but which share similar substructures or surface features. Existing molecular fragment matching algorithms can identify common covalent substructures but they are not well suited for performing scaffold-hopping shape-based database searches. This thesis introduces a novel SH fragment-based shape matching approach that can exploit knowledge of structures of existing protein-ligand complexes to perform virtual screening using as queries SH surface fragments derived from crystallographic ligand binding surfaces.