Molecular docking has been extensively applied in virtual screening of small molecule libraries for lead identification and optimization. A necessary prerequisite for successful differentiation between active and non-active ligands is the accurate prediction of their binding affinities in the complex by use of docking scoring functions. However, many studies have shown rather poor correlations between docking scores and experimental binding affinities. Our work aimed to improve this correlation by implementing a multipose binding concept in the docking scoring scheme. Multipose binding, i.e., the property of certain protein-ligand complexes to exhibit different ligand binding modes, has been shown to occur in nature for a variety of molecules. We conducted a high-throughput docking study and implemented multipose binding in the scoring procedure by considering multiple docking solutions in binding affinity prediction. In general, improvement of the agreement between docking scores and experimental data was observed, and this was most pronounced in complexes with large and flexible ligands and high binding affinities. Further developments of the selection criteria for docking solutions for each individual complex are still necessary for a general utilization of the multipose binding concept for accurate binding affinity prediction by molecular docking.

This paper deals with a measure theoretical model for evaluation of e-learning programs. Based on methods of general measure theory an evaluation model is developed which can be used for assessment of complex target structures in context of e-learning programs. With the presented rating function target structures can be evaluated by a scoring value which indicates how the targets in sense of a given logical target structure has been reached. A procedure is developed for the estimation of scoring values for target structures based on adapted assessment checklists.

A variety of tools have been developed to assist in the quantification and analysis of naturalistic language samples. In recent years, computer technology has been employed in language sample analysis. This study compares a new automated index, Scoring Sentences Developmentally (SSD), to two existing measures. Eighty samples from three corpora were manually analyzed using DSS and MLU and the processed by the automated software. Results show all three indices to be highly correlated, with correlations ranging from .62 to .98. The high correlations among scores support further investigation of the psychometric characteristics of the SSD software to determine its clinical validity and reliability. Results of this study suggest that SSD has the potential to compliment other analysis procedures in assessing the language development of young children.

Thesis (MscAgric (Animal Sciences))--University of Stellenbosch, 2006. / The development of basic husbandry techniques and determining basic performance parameters are among the first steps towards culturing a new species. Silver kob, Argyrosomus inodorus, is a large Sciaenid and endemic to South Africa and Namibia and has been selected as a candidate aquaculture species. However, the proposed culture raises many questions, with two of them being the adaptability to captive conditions and product quality in the captive raised fish. To address these, trials were set up with eighty-three silver kob, divided into three ponds and fed three different diets. The effects of the diet on performance and quality were determined over a nine month trial period. The fish fed the pilchard diet adapted faster to the captive conditions than the fish fed the artificial diets. The growth of these fish were also markedly better than that of the fish fed the artificial diets, although after the adaptation period, the growth rate of the fish fed the artificial diets surpassed that of the fish fed the pilchards. Fifteen fish, five from each treatment were sacrificed and compared on a chemical and sensory level to wild-caught fish (control, n=6). Differences (p≤0.05) were noted in the total lipid content and fatty acid composition between the fish fed the different diets and the control. Sensory analysis revealed that the fish fed pilchards differed (p≤0.05) from the other groups by having an undesirable odour and flavour. The body partitioning and the proximate chemical composition of silver kob were determined. The length-weight relationship for silver kob raised in captivity was determined and a b-value of 3.32 was obtained, which indicates allometric growth with the fish becoming more rotund as their length increases. The results of these trials indicates that silver kob, A. inodorus adapts in captive conditions. The final product also compares favourably to wild-caught fish. The use of digital image analysis as a method of determining fish condition was also assessed with promising results for future application in research and production systems.

The rationalisation of drug potency using three-dimensional structures of protein-ligand complexes is a central paradigm in medicinal research. For over two decades, a major goal has been to find the rules that accurately relate the structure of any protein-ligand complex to its affinity. Addressing this problem is of great concern to the pharmaceutical industry, which uses virtual screens to computationally assay up to many millions of compounds against a protein target. A fast and trustworthy affinity estimator could potentially streamline the drug discovery process, reducing reliance on expensive wet lab experiments, speeding up the discovery of new hits and aiding lead optimization. Water plays a critical role in drug-protein interactions. To address the often ambiguous nature of water in binding sites, a water placement method was developed and found to be in good agreement with X-ray crystallography, neutron diffraction data and molecular dynamics simulations. The method is fast and has facilitated a large scale study of the statistics of water in ligand binding sites, as well as the creation of models pertaining to water binding free energies and displacement propensities, which are of particular interest to medicinal chemistry. Structure-based scoring functions employing the explicit water models were developed. Surprisingly, these attempts were no more accurate than the current state of the art, and the models suffered from the same inadequacies which have plagued all previous scoring functions. This suggests a unifying cause behind scoring function inaccuracy. Accordingly, mathematical analyses on the fundamental uncertainties in structure-based modelling were conducted. Using statistical learning theory and information theory, the existence of inherent errors in empirical scoring functions was proven. Among other results, it was found that even the very best generalised structure-based model is significantly limited in its accuracy, and protein-specific models are always likely to be better. The theoretical framework developed herein hints at modelling strategies that operate at the leading edge of achievable accuracy.

The clinical utility of the Intermediate Category Test, a measure of executive functioning in children 9 to 14 years of age, is currently limited by the availability of only a Total Error score for normative interpretation. The Process Scoring System (PSS) was developed to provide a standardized method of assessing specific processing patterns and problem-solving errors. The purpose of this study was to determine the ability of the PSS scores to discriminate between children with and without suspected executive deficits, thereby providing evidence of criterion-related validity.

Antecedentes: La neumonía es una infección grave común en la infancia y principal causa de muerte en niños menores de 5 años. Se sabe poco sobre escalas que evalúen el riesgo de muerte por neumonía. Objetivos: Establecer qué escala tiene mejor desempeño como predictor de muerte por neumonía adquirida en la comunidad (NAC) en niños menores de cinco años. Métodos: Se realizo un estudio observacional, retrospectivo, analítico con un diseño de precisión diagnóstica en una cohorte de registros clínicos de pacientes con NAC entre 2013 y 2015 en las primeras 24 horas de ingreso al hospital. El desempeño de las tres escalas se evaluó comparando el área bajo la curva (ABC) como medida de capacidad discriminativa. Resultados: La escala PIRO modificada (Predisposition, Insult, Response and Organic dysfunction) tiene mayor capacidad discriminatoria con un ABC de 0,93 (IC del 95%: 0,89 a 0,96), siendo la mejor de las tres escalas evaluados. En segundo lugar, la escala RISC (Respiratory Index of Severity in Children) con ABC 0,83 (IC 95%: 0.79-0.87) y, finalmente, la escala PRESS (Pediatric Respiratory Severity Score) ABC 0.67 (IC 95% 0.61 - 0.74). Conclusión: Las escalas PIROm y RISC son buenos predictores de muerte en niños menores de 59 meses, basados en criterios clínicos, radiológicos y laboratoriales. La primera escala podría ser utilizada en centros de salud de mayor complejidad. La segunda escala netamente clínica podría ser utilizada en centros de atención primaria de salud. Se sugiere realizar más estudios en poblaciones con diversas características clínicas, demográficas y ambientales. / Background: Pneumonia is a common serious infection in childhood, being the major cause of death in children under 5 years. Little is kwon about clinical scales predicting risk of death owing to pneumonia Objectives: Establish which scale has better performance as a predictor of death due to community-acquired pneumonia (CAP) in children under five years. Methods: An observational, retrospective, analytical study with a diagnostic precision design was conducted in a cohort of clinical records of patients with CAP between 2013 and 2015 that were review in the first 24 hours of admission to the hospital. The performance of the three scales were evaluated by the comparison of the area under the curve (AUC) as a measure of discriminative capacity. Results: The PIRO modified scale (Predisposition, Insult, Response and Organic dysfunction) has greater discrimination capacity AUC of 0.93 (95% CI 0.89 - 0.96) being the best of the three evaluated. Secondly, the RISC scale (Respiratory Severity Index in children) with AUC 0.83 (95% CI: 0.79-0.87) and, finally, the PRESS scale (Pediatric Respiratory Severity Score) AUC 0.67 (95% CI 0.61 - 0.74). Conclusion: The PIROm and RISC scales are good predictors of death in children under 59 months, based on clinical, radiological and laboratory criteria. The first scale could be used in healthcare centers of higher complexity. The second scale purely clinical could be used in centers of primary health care attention. It is suggested to carry out more studies in diverse populations with different clinical, demographical and environmental characteristics. / Tesis

Med hjälp av den här undersökningen i svenska med didaktisk inriktning skapas en uppgiftspecifik lärandematris utifrån en bedömningsmatris med hjälp av Johan Alms femstegsmodell. Avsikten med lärandematrisen är att synliggöra lärandet för eleven och baseras på de styrdokument som Skolverket tillhandahåller. Den har ett elevperspektiv, vilket skiljer den från den mer vedertagna bedömningsmatrisen, som har ett bedömningsperspektiv ur pedagogens vinkel. Lärandematrisens uppbyggnad med tydlig layout och lättillgängligt språk underlättar för elevens förståelse för uppgiften och dess progression vilket bör bidra till ökat kunskapsintag. Litteraturstudiens resultat bekräftar att femstegsmodellen är användbar i skapandet av lärandematrisen, och bekräftar därmed syfte och frågeställning. / With the help of this research in Swedish with didactic focus, a task-specific learning matrix is created based on an assessment matrix using Johan Alm's five-step model. The intention of the learning matrix is to make the learning visible to the student and is based on the steering documents provided by the National Agency for Education. It has a student perspective, which distinguishes it from the more accepted assessment matrix, which has an assessment perspective from the educator´s aspect. The structure of the learning matrix with clear layout and easily accessible language facilitates the student's understanding of the task and its progression, which should contribute to increased knowledge intake. The result of the literature study confirms that the five-step model is useful in the creation of the learning matrix, thereby confirming the purpose and research question.

TITLE The Choice of the swimming method, the most common mistakes when swimming with applicants for study at the Faculty of Education of Charles University AUTHOR Šárka Papežová DEPARTMENT Department of physical education SUPERVISOR PaedDr. Irena Svobodová ABSTRACT This thesis deals with the choice of swimming strokes in entrance examinations for a study at the College of Education, Charles University, and it also analyses the most common mistakes in individual swimming strokes with reference to accepted swimming rules. The problem is approached from the perspective of academic field of Physical Education and Teaching for Kindergartens and it is analysed with view of sex and age of the candidates. The thesis also turns to the characteristics of individual swimming strokes and mistakes in swimming. Statistical analysis of 5 years of records of entrance examinations were used in preparation of this thesis. KEYWORDS Swimming method, the front crawl, the breaststroke, the backstroke, respiration during swimming, statistic, physical education, teaching for infant school

Studies are focused on methods for better recognition of internet shop customers. General this method is called Customer Intelligence. It contains means of increase of customers valuation for a society. It is based on exploitation of accumulated data about customer which helps to get necessary information. A main target of Studies is to create system of Customer Intelligence addapted to society needs. For internet seller it is necessary to include a web analytics into the system too. In a theoretical part there is an explanation of attitude and significance of Customer Intelligence in terms of informational company system. Furthermore there is taken a customer value. It is proceeded from basic means of customer valuation assesment via customers lifelong value for society to means of customer scoring A practical part of Studies is devoted to performed analyses of customer data which are the main details for execution of Customer Intelligence. There is explained how this obtained information will be used. In a conclusion there is descirbed a technical realization and problems which had to be necessarily solved during the implementation.