Biased immunoglobulin heavy variable (IGHV) gene usage and distinctive B-cell receptor (BCR) features have been reported in chronic lymphocytic leukaemia (CLL), which may reflect clonal selection by antigens during disease development. Furthermore, the IGHV gene mutation status distinguishes two clinical entities of CLL, where patients with unmutated IGHV genes have an inferior prognosis compared to those with mutated IGHV genes. Recently, one subgroup of CLL patients expressing the IGHV3-21 gene was found to display highly similar immunoglobulin (IG) gene features, even within the heavy chain complementarity-determining region 3 (HCDR3). Patients in this subgroup typically had a poor prognosis. In paper I, we aimed to identify further subgroups with restricted BCR features among 346 CLL cases. Six subsets were defined which carried virtually identical BCRs in terms of rearranged heavy and light chain (LC) IG genes and CDR3 length and composition. In paper II, we investigated 90 IGHV3-21 cases from diverse geographical locations. We confirmed the highly restricted HCDR3 characteristics in 56% of patients and a biased usage of the IGLV3-21 gene in 72% of cases. Survival analysis also confirmed the poor outcome of this group, irrespective of IGHV gene mutation status and geographical origin. Papers III and IV involved a large-scale analysis of IGH and IG kappa and lambda (IGK/L) gene rearrangements, to define subsets with ‘stereotyped’ BCRs and also to systematically examine the somatic hypermutation (SHM) features of the IG genes in CLL. We studied a cohort of 1967 IGH and 891 IGK/L gene sequences from 1939 patients from 6 European institutions. Over 5300 IGH and ~4700 IGK/L sequences from non-CLL B cells were used as a control data set. In total, 110 CLL stereotyped subsets were defined according to HCDR3 homology. Striking IGK/L gene biases were also evident within subsets, along with distinctive K/LCDR3 features, such as length and amino acid composition. At cohort level, the patterns of mutation appeared to be consistent with that of a canonical SHM mechanism. However, at a subgroup level, certain stereotyped subsets, e.g. IGHV3-21/IGLV3-21 and IGHV4-34/IGKV2-30 CLL, deviated from this pattern. Furthermore, recurrent ‘stereotyped’ mutations occurred in cases belonging to subsets with restricted HCDR3s, in both IGHV and IGK/LV genes, which were subset- and CLL-biased when compared to non-CLL B cells. In conclusion, our findings implicate antigen selection as a significant factor in the pathogenesis of CLL, particularly in cases carrying stereotyped BCRs. The presence of stereotyped mutations throughout the VH and VL domain also indicates involvement of IG regions other than the CDR3 in antigen recognition. Finally, biased IGK/L gene usage and specific K/LCDR3 features are strong indications that LCs are crucial in shaping the specificity of leukemic BCRs, in association with defined heavy chains.

Läroplanen är föränderlig över tid och har kunnat återspegla sin samtid samhällets rådande grundintentioner. Piaget, Dewey och Vygotskij har alla påverkat den svenska läroplanens utformning på olika sätt och skapat olika förutsättningar och svårigheter för individen och dennes utveckling. En undersökning som byggde på 15 lärares upplevelser fokuserade på huruvida den senaste läroplanen skapade problem för eleverna och hur de i så fall uttrycktes. Resultaten visade att läroplanen i sig inte var den avgörande, utan att yttre faktorer såsom media, samhällets struktur och föräldrar hade en större betydelse för hur eleverna fungerade i skolan. Flera lärare kommenterade nya fenomen som råare attityder mellan flickor, lustbarn och starkt präglad individualism vilka alla kan ses som vidare underlag för framtida forskning.

¡@¡@By applying ¡§Case Study¡¨ as a research method, this essay is to explore the risk types derived from ¡§The Standardized Contract for Online Game¡¨ for the game operator to analyze the level of risks, as well as to know the implementing way for dealing with the risk. By interpreting these processes which may caused the impact on stakeholders, the study eventually makes a conclusion and suggestions for reducing the risk and settling the disputes. ¡@¡@The research result in the study has shown that the customers are protected effectively along with the implementation of ¡§The Standardized Contract for Online Game ¡¨ through rebuilding format and functions of contract itself. Reduce the consumer complaints such as account hack successfully. Relatively, government takes advantage of it; instead, the risk to the corporation management is increasing. As a result, it takes methodology, negotiation capability, business process to prevent, shift or take the risk at one¡¦s own risk. In this study, the stakeholders like consumers, employees and government are impacted the most, following with suppliers and distributors. Because of ¡§The Standardized Contract for Online Game ¡¨, each party undertakes the circumstance of risk transfer with others.

The purpose of the present study is to explore six-year-old children&amp / #8217 / s understanding of the superhero phenomenon, through cartoon superhero figures. Particularly Spiderman was chosen as a typical symbol of the superhero genre, futhermore Spiderman is found to be the favorite cartoon character in Turkey.The study was conducted in the preschool of Middle East Technical University in Spring 2007. Ten children / five girls and five boys, attending to the preschoolprogram participated in the study. The main emphasis in the present study is given to children&#039 / s own expressionsvia drawings, play and interviews, to understand their ways to make sense of the superheroscenarios. Therefore selecting qualitative methods and aphenomenological approach in particular was considered to be a valid form of nquiry. At the end of the analysis procedure the total number of meaning units (MUs)was 40. In order to verify the results of the study, randomly selected 30 MUs were presented to completely independent and separate reviewers. The feedback from the reviewers indicated a high rate concordance of established at 86.6 %. After the results of this auditing process, confirmability of the present study is maintained. The results indicated that superhero theme was enjoyable for participant children, as it provided a sense of well-being. Aggressive behavior, which is generally linked to superhero issue, was hardly ever observed. However, gender is found to be a central factor on children&#039 / s understanding of superheroes, and stereotypical thinking was perpetuated via superhero animations.

The Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) published by the American Psychiatric Association (APA) in 1987 is currently the primary tool used by counselors in clinical settings for diagnosing clients' psychological and behavioral problems. Beginning with the third edition of the manual (DSM-III; APA, 1968) a multiaxial process for diagnosis was introduced to encourage a biopsychosocial perspective of client's problems.This study was designed to investigate if alterations in diagnosis on Axis IV and V could further encourage a biopsychosocial perspective. It was designed to imitate the rapid diagnostic process that takes place in many clinical settings. In the present study, the criterion for a biopsychosocial perspective was the maintenance of neutral perceptions and unbiased hypothesis-testing strategies following diagnosis of a client.Twenty-four counseling psychology trainees participated in the study. The counselor trainees diagnosed a client after listening to approximately 20 minutes of an audio-tape of an initial assessment interview. The 12 counselor trainees in the control group diagnosed the client using the standard multiaxial format for diagnosis. The 12 counselor trainees in the experimental group diagnosed the client using an alternative format which encouraged a focus on positive aspects of the client and the client's environment.The counselor trainees completed the Impression Formation Questionnaire to assess their perceptions of the client. They then wrote 12 questions they would ask the client in the next counseling session. These questions constituted their hypothesis-testing strategies for their diagnoses on Axis I and Axis II.The counselor trainees in both groups maintained primarily neutral perceptions of the client as measured by the IFQ. The counselor trainees in both groups favored confirmatory hypothesis-testing strategies when assigned to groups based on their hypothesis-testing strategy score (p < .05).The results of this study indicated that the standard and alternative multiaxial formats for diagnosis may encourage neutral perceptions of a client when counselors must diagnose the client based on very little information. Neither format for diagnosis was successful, however, in discouraging a biased, confirmatory search for information. / Department of Counseling Psychology and Guidance Services

Abnormal behaviour of horses is a problematic behaviour that occurs mainly in horses domesticated or held in captivity due to the effect of incorrect breeding methods or improper handling with these animals. A part of abnormal behaviour is also stereotyped behaviour which is main target of this thesis. There are many causes of stereotyped behaviour. It could be a trauma during early weaning, lack of physical activity, an impact of nutrition, genetics and other factors. It is difficult to find out the true cause of stereotyped behaviour and it is even harder to remove these stereotypes. However the reduction of symptoms is almost always possible. The aim of the thesis was explanation, based on literature review, of the concept of stereotyped behaviour of horses, describe its symptoms, causes and suggest possible ways of removing. Another aim of the thesis was monitoring of stereotyped behaviour using a questionnaire survey within the Czech Republic. The information gathered from survey consisted of causes of stereotyped behaviour ? e.g. age, rearing, use (work, riding etc.), breed, temperament, attendance of other horses etc. The aim was not only the evaluation of occurrences of horse?s stereotyped behaviour, but with the help of gathered information in the literature review, propose the possibilities of reducing unwanted behaviour and suggest precautions in horses who do not have evident manifestations of unwanted behaviour yet.

Submitted by Gabriela Cortellini Ferreira (g.cortelliniferreira@gmail.com) on 2018-05-03T10:27:22Z No. of bitstreams: 1 Dissertação revisada.pdf: 889795 bytes, checksum: 3360d05887915c18ad67a29eb27195cf (MD5) / Approved for entry into archive by Ederson Vasconcelos Pereira null (edersonpereira@fmva.unesp.br) on 2018-05-03T20:51:10Z (GMT) No. of bitstreams: 1 ferreira_gc_me_araca_int.pdf: 889795 bytes, checksum: 3360d05887915c18ad67a29eb27195cf (MD5) / Made available in DSpace on 2018-05-03T20:51:10Z (GMT). No. of bitstreams: 1 ferreira_gc_me_araca_int.pdf: 889795 bytes, checksum: 3360d05887915c18ad67a29eb27195cf (MD5) Previous issue date: 2018-03-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Atualmente, os animais selvagens estão tendo seus hábitats destruídos, e com isso, várias espécies estão se extinguindo. O primeiro zoológico público foi fundado no século XVIII, onde os animais expostos eram apreendidos em circos e outros eventos. Em 1826 foi fundado o primeiro zoológico com objetivo de ser uma instituição científica para estudo, porém com a falta de verba foi aberto para visitação. O primeiro zoológico com preocupação de bem-estar dos animais foi fundado em 1900, e somente no século XX houve uma mudança do enfoque da função dos zoológicos, que passaram a desenvolver atividades e funções voltadas para a conservação da fauna. Hoje os zoológicos tem papel importante para reserva genética, desenvolvimento de pesquisas e educação ambiental. A adaptação dos animais em cativeiro é fundamental para que não apresentem problemas de saúde e bem-estar, o que reflete em seu comportamento normal. Desde 1967 um conjunto de “estados” ideias, denominado “cinco liberdades” dos animais deve ser respeitado. O tráfico de animais silvestre no Brasil fica atrás somente do tráfico de narcóticos e armas, sendo em sua maioria, o tráfico de aves, devido à beleza de suas plumagens, canto, inteligência, docilidade e habilidade de imitar a voz humana. O Brasil possui a maior diversidade de Psitacidae do mundo, sendo a Aratinga leucophthalma uma espécie representante dessa ordem, com porte médio e plumagem predominante verde e reluzente, que faz com que seja muito visada para criação. A compreensão dos seus comportamentos naturais e padrões sociais têm implicações para a prevenção e tratamento de vários comportamentos indesejáveis, que podem surgir quando mantidas em cativeiro, como arrancamento de penas e automutilação, gritos, agressividade e fobias. E nesse momento é que o enriquecimento ambiental desempenha o seu papel, sendo a chave para uma manutenção equilibrada, permitindo que a ave satisfaça suas necessidades e manifeste seu potencial. O enriquecimento ambiental é um processo dinâmico no qual, mudanças na estrutura e implantações de práticas de manejo com estratégias temporais, físicas, sociais e sensoriais visam oferecer uma série de estímulos que possam aumentar o conforto e a capacidade de adaptação do animal ao cativeiro. As medidas de enriquecimento ambiental para psitacídeos visam providenciar às aves a simulação de hábitos e comportamentos normais, focando em três aspectos essenciais: procura de alimento; alteração no espaço e exercícios e interação social. / Today, wild animals are having their habitats destroyed, and with that, several species are becoming extinct. The first public zoo was founded in the 18th century, where exposed animals were seized in circuses and other events. In 1826 the first zoo was founded with the objective of being a scientific institution for study, but with the lack of money was opened for visitation. The first zoo with concern for animal welfare was founded in 1900, and it was only in the twentieth century that there was a shift in focus from the function of zoos to activities and functions aimed at wildlife conservation. Today, zoos play an important role in gene pooling, research development and environmental education. The adaptation of captive animals is essential so that they do not present problems of health and well-being, which reflects in their normal behavior. Since 1967 a set of "states" ideas, called "five freedoms" of animals must be respected. The trafficking of wild animals in Brazil is behind only narcotics and arms trafficking, most of which are the traffic of birds, due to the beauty of their plumage, singing, intelligence, docility and the ability to imitate the human voice. Brazil has the greatest diversity of Psitacidae in the world, being the Aratinga leucophthalma a representative species of this order, with medium size and predominant green and gleaming plumage, which makes it very targeted for breeding. Understanding their natural behaviors and social patterns have implications for the prevention and treatment of various undesirable behaviors that may arise when held in captivity, such as feathering and self-mutilation, shouting, aggression, and phobias. And at that time, environmental enrichment plays its part, being the key to balanced maintenance, allowing the bird to meet its needs and manifest its potential. Environmental enrichment is a dynamic process in which changes in the structure and implantation of management practices with temporal, physical, social and sensorial strategies aim to offer a series of stimuli that can increase the comfort and adaptability of the animal to captivity. Environmental enrichment measures for psittacines aim to provide birds with the simulation of normal habits and behaviors, focusing on three essential aspects: food demand; alteration in space and exercises and social interaction.

In recent years, great progress has been achieved towards identifying novel biomarkers in lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), at the genomic, transcriptomic and epigenomic level for accurate risk-stratification and prediction of treatment response. In paper I, we validated the prognostic relevance of a recently proposed RNA-based marker in CLL, UGT2B17, and analyzed its expression levels in 253 early-stage patients. Besides confirming its prognostic impact in multivariate analysis, we could identify 30% of IGHV-mutated CLL (M-CLL) cases with high expression and poor outcome, which otherwise lacked any other poor-prognostic marker. In paper II, we investigated the prognostic impact of a previously reported 5 CpG signature that divides CLL patients into three clinico-biological subgroups, namely naive B-cell-like CLL (n-CLL), memory B-cell-like CLL (m-CLL) and intermediate CLL (i-CLL), in 135 CLL patients using pyrosequencing. We validated the signature as an independent marker in multivariate analysis and further reported that subset #2 cases were predominantly classified as i-CLL, although displaying a similar outcome as n-CLL. In paper III, we investigated the methylation status and expression level of miR26A1 in both CLL (n=70) and MCL (n=65) cohorts. High miR26A1 methylation was associated with IGHV-unmutated (U-CLL) and shorter overall survival (OS) in CLL, while it was uniformly hypermethylated in MCL. Furthermore, overexpression of miR26A1 resulted in significant downregulation of EZH2 that in turn led to increased apoptosis. In paper IV, we performed DNA methylation profiling in 176 CLL cases assigned to one of 8 major stereotyped subsets (#1-8) in relation to non-subset CLL (n=325) and different normal B-cell subpopulations. Principal component analysis of subset vs. non-subset CLL revealed that U-CLL and M-CLL subsets generally clustered with n-CLL and m-CLL, respectively, indicating common cellular origins. In contrast, subset #2 emerged as the first defined member of the i-CLL subgroup, which in turn alludes to a distinct cellular origin for subset #2 and i-CLL patients. Altogether, this thesis confirms the prognostic significance of RNA and epigenetic-based markers in CLL, provides insight into the mechanism of miRNA deregulation in lymphoid malignancies and further unravels the DNA methylation landscape in stereotyped subsets of CLL.

Nitric oxide (NO) is a neurotransmitter which is synthesized on demand from L-arginine by the enzyme nitric-oxide-oxidase, and is implicated in a variety of physiological functions, including release and uptake of dopamine. Amphetamine induces stereotyped behavior via release of dopamine from dopaminergic neurons in the striatum and related structures, while apomorphine induces such behavior via activation of central dopaminergic receptors. Recently we have demonstrated that a NO donors and a NO-synthase inhibitor modify the response of some central dopaminergic receptors to their agonists and antagonists. In the present study we examined the effect of two NO donors and one NO-synthase inhibitor on stereotyped behavior induced in rats by amphetamine and apomorphine, and the sex-selectivity of this effect. A highly significant dose-dependent sexual differentiation was recorded in the stereotyped behavior of amphetamine, as the duration and intensity of this effect was shortened by L-NAME but not by L-arginine and Molsidomine. Differences in the stereotyped behavior between female and male rats administered apomorphine were dose-dependent, but were not affected by any of the three drugs tested. It is concluded that while nitric oxide is involved in the reactivity of central dopamine receptors, the intensity and duration of this effect is drug- and sex-dependent.

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