No description available.

This master‘s thesis focuses on the issue of trafficking in persons in Thailand in the period of 2002-2017. The thesis answers research questions about the causes, size and consequences of trafficking in the country, as well as the impact of trafficking on the country’s security situation. The work presents approaches to assesing trafficking in persons and explores the most common forms of exploitation. The thesis also focuses on trafficking in persons within the Association of Southeast Asian Nations (ASEAN), of which Thailand is a member. The 3P index will be used to gain some deeper understanding of the situation in Thailand and to compare selected ASEAN countries. Due to the specificity of data collecting the thesis uses among literature particularly the reports about trafficking in persons from the US Department of State and other reports from international organizations dealing with this issues and which regularly monitor the situation.

Doenças cardiovasculares são a principal causa de morte no Brasil. Em contraste a esse cenário, o treinamento físico aeróbio (TFA) figura como importante ferramenta de combate a esse quadro, atuando, dentre diversos mecanismos, na expressão de microRNAs (miRNA) e na hipertrofia cardíaca (HC). Nesse sentido, seria o TFA capaz de reduzir expressão do miR-34c-3p em cardiopatologias, gerando melhora aos danos causados? Na tentativa de elucidar essa lacuna, ratos Wistar machos (2 meses) passaram por oclusão da coronária gerando infarto do miocárdio (IMS; IMT) ou indução de diabetes tipo I por STZ (DS;DT: 45mg/kg). Após a verificação do dano, estes foram submetidos a TFA (10 sem), e os ventrículos esquerdos (VE) foram dissecados a posteriori. Ao analisar a expressão gênica por RT-PCR, o TFA diminuiu (39%; p<0,02) a expressão do miRNA-34c-3p no VE de IMT vs. IMS. Em consonância, houve diminuição (27%; p<0,04) do miRNA em DT vs. DS. Investigando o potencial terapêutico dessa inibição, ao proceder análise in vitro em cultura primária de cardiomiócitos tratados com inibidor do miRNA (amiR-34c-3p), houve diminuição de sua expressão em 71% (50nM; p<0,01) vs. grupo controle (C), enquanto houve aumento de 41000% (50nM; p<0,01) entre o superexpressor (mmiR) e C. Analisando os marcadores de HC patológica entre amiR e C, verificou-se redução na a-actina esquelética (6,1%;p<0,02), aumento no ANF (84,4%; p<0,05) e redução na b-MHC (66%; p<0,007), demonstrando HC fisiológica em cardiomiócitos tratados com amiR. Buscando alvos do miR-34c-3p responsáveis por essas alterações, analisou-se o eIF4E, último fator iniciador de tradução ativado por via não canônica da PI3K-AKTmTOR. Sua direta ativação pode representar importante avanço na busca por terapias que induzam a HC fisiológica. O amiR aumentou o eIF4E (64%; p<0,003), com validação por diminuição da atividade da luciferase (48%; p<0,02) através de ensaio com vetor 3\'UTR do gene e miR-34c-3p. Outro alvo predito analisado, o KLF11, tem homologia com gene da insulina e pode estar relacionado com melhora metabólica do VE. O tratamento com amiR aumentou (192%; p<0,006) a expressão gênica do KLF11, validado com redução de 55% na atividade da luciferase, e aumento da captação de glicose (13%; p<0,04). Com os dados expostos, o TFA foi eficiente em inibir a expressão do miR-34c-3p em VE de animais cardiopatas que, atuando em seus alvos agora validados, foi capaz de promover HC fisiológica e melhora metabólica em cardiomiócitos. Considerando os efeitos cardioprotetores da inibição desse miRNA, vislumbra-se o potencial terapêutico dessa inibição em paciente na perspectiva de atenuação de prejuízos causados por cardiopatias / Cardiovascular diseases are the leading cause of death in Brazil. In contrast to this scenario, aerobic exercise training (AET) is an important tool to combat this condition, acting, among several mechanisms, on the expression of microRNAs (miRNA) and cardiac hypertrophy (CH). In this sense, would AET be able to reduce expression of miR-34c-3p in cardiac pathologies, generating improvement to the damages caused by them? In an attempt to elucidate this knowledge gap, male Wistar rats (2 months) underwent coronary occlusion, causing myocardial infarction (IMS; IMT) or induction of type I diabetes by STZ (DS: DT: 45mg kg). After proof that cardiac damage was caused, they were submitted to AET (10 wk), and left ventricles (LV) were dissected post mortem. Analyzing gene expression by RT-PCR, AET decreased (39%; p <0.02) miRNA-34c-3p expression in the LV of IMT vs. IMS. In agreement, there was a decrease (27%; p <0.04) of the miRNA in DT vs. DS. Investigating the therapeutic potential of this inhibition, through in vitro analysis in primary culture of neonatal rat cardiomyocytes treated with miRNA inhibitor (amiR-34c-3p), expression of miRNA- 34c-3p was decreased in 71% (50nM; p <0.01) vs. (C), whereas there was an increase of 41000% (50nM; p <0.01) between the superexpressor (mmiR) and C. Analyzing the pathologic HC markers between amiR and C, there was a reduction in skeletal a-actin (P <0.05), an increase in ANF (84.4%, p <0.05) and reduction in b-MHC (66%; p <0.007), demonstrating physiological HC in cardiomyocytes treated with amiR. Searching for miRNA-34c-3p targets responsible for these changes, eIF4E, the last non-canonically activated translation initiator of PI3K-AKT-mTOR, was analyzed. Its direct activation may represent an important advance in the search for therapies that induce physiological CH. The amiR increased eIF4E expression (64%, p <0.003), with validation for decreased luciferase activity (48%; p <0.02) by assaying 3\'UTR vector of the gene and miR-34c-3p. Another predicted target analyzed, KLF11, has homology with insulin gene and may be related to LV metabolic improvement. The treatment with amiR increased KLF 11 gene expression (192%; p <0.006), with a 55% reduction in luciferase activity and an increase in glucose uptake (13%; p <0.04). With the data presented, AET was efficient in inhibiting the expression of miRNA-34c-3p in LV of cardiopathic animals that, acting on their now validated targets, was able to promote physiological CH and metabolic improvement in cardiomyocytes. Considering the cardioprotective effects of inhibition of this miRNA, we can speculate a therapeutic potential of the inhibition of miR-34c-3p in patients in prospect of mitigating the damage caused by cardiopathies

Social service Support for independent living provides life for people with disabilities in the common environment. The theoretical part describes the most important topics concerning integration people with disabilities into society. One of the tools of social integration is just the Social service support for independent living. The aim of this work is to map the social service Support for independent living and focus on the scope, focus, form and methods for implementation service. Furthermore, to implement research on a sample of adults with disabilities, users of the Social service support for independent living. I used the tool of social worker "3P - Profile of the necessary support." The practical part was processed through qualitative research. I used the following methods and techniques of data collection: questionnaire survey, on-standardized telephone interviews, secondary data analysis. Research has found that the social service Support for independent living in the Czech Republic is unevenly distributed. This service is unavailable in some regions for certain target groups. This service is suitable for people with disabilities with lower support. This conclusion was achieved by applying an instrument for social worker "3P - Profile of necessary support". Social service support for independent living helps these people to integrate into society and therefore its availability should increase.

This study aimed to explore university undergraduates’ experiences of student involvement in assessment (SIA). Based on Biggs’ 3P model of student learning, this study focused on students’ experiences prior to SIA, during SIA and after SIA in three Business and Management modules. Applying this framework, different practices of involving students in assessment (peer assessment, self assessment or self designed assessment) were studied from the perspectives of the students concerned. Unlike other studies that normally test to what extent the designed outcomes of SIA have been met, the goal of this research was to reveal the inside picture of how students were coping with those SIA tasks and their learning. This picture was outlined from students’ perceptions of SIA, the main factors that might influence students’ engagement with SIA, and students’ reflections on SIA practice in the particular module. This study adopted mixed research methods with sequential explorative design. It employed the ETLA (Environment of Teaching, Learning and Assessment) questionnaire and follow up semi-structured interviews. There were in total 251 valid questionnaire responses from students and 18 valid student interviews. The data were collected from three undergraduate Business and Management degree modules in which different strategies were used to involve students in assessment. The three innovative modules were all from Scottish universities in which assessment practices were being re-engineered by involving students in assessment. Two of the modules had participated in the REAP (Re-engineering Assessment Practice) project. However, they were different from each other in terms of the way in which they involved students in assessment and the level or extent of student involvement in assessment that was entailed. The report and analysis of the findings has taken three main forms. First, the module context including the teaching, learning and assessment environment and student learning approaches and satisfactions in the particular module were compared and analysed using the questionnaire data. The results showed a strong association between the elements in the teaching and learning environment and student learning approaches. They also indicated that the quality of teaching, feedback and learning support played significant roles in the quality of student learning. Secondly, an analysis of the interview data was undertaken to examine why and how students would learn differently in different module contexts with different SIA practices, and how students were coping with their learning in the SIA tasks concerned. In addressing these questions, students’ previous experiences in SIA, and knowledge about SIA, peers’ influence, teachers’ support and training for SIA, interaction between and among students and teachers, the clarity of the module objectives and requirements and learning resources were found to be the major factors that might influence students’ engagement in the SIA. Additionally, the salient learning benefits and challenges of SIA as perceived by students were explored. Thirdly, based on the preceding findings, the analysis of each module aimed to further consider in what way the three modules differed from each other with respect to SIA practices, and how students responded in the three different module contexts in terms of their engagement with SIA. These three forms of analysis made it possible to gain a rich understanding of students’ experiences of SIA that could also feed into a consideration of what kind of support the students might need in order to better engage them into the SIA and better prepare them for life-long learning.

<p>Rho GTPase signaling regulates a wide variety of cellular functions in the developing and adult central nervous system. These molecular switches are in turn spatially and temporally regulated by an over abundance of positive and negative regulatory proteins: the activating guanine nucleotide exchange factors (GEFs) and the deactivating GTPase activating proteins (GAPs). The WAVE-associated Rac GAP (WRP) is thought to regulate key aspects of synapse development and function, and has been implicated in a form of mental retardation in humans called 3p- Syndrome. WRP is a member of the srGAP family of Rho GAP domain containing proteins, which share a characteristic domain organization and are expressed throughout the brain. Recently, one of the members of this family was found to contain a newly described inverse F-BAR (IF-BAR) domain of unknown function and to regulate cortical migration in developing neurons. This study focuses on the regulatory capacity of WRP during the development of neuronal connections in the central nervous system, and what role its loss may have on cognitive functions.</p><p>To assess these roles, biochemical studies were performed to characterize the way in which WRP's novel IF-BAR domain interacted with lipid membranes. Additionally, WRP's role in regulating neuronal function was assessed both in vitro and in vivo through the use of mouse model systems for critical genes in the WAVE complex pathway, including a conditional WRP KO mouse developed in our lab. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated.</p><p>This study shows that WRP's IF-BAR domain senses, or facilitates, outward membrane protrusions through a convex lipid-binding surface of the dimerized WRP IF-BAR domain. WRP localizes to the membranes of dendritic shafts via its IF-BAR domain where it is enriched in filopodia like projections. During dendritic filopodia formation, WRP functions to regulate the WAVE-1 complex and its downstream effectors, including the Arp2/3 complex. Loss of WRP in vivo and in vitro results in a reduction of dendritic spines, and that this is a function of WRP's role in the initiation of dendritic filopodia, not during the maturation of dendritic filopodia into mature dendritic spines. Finally, this study demonstrates that the loss of WRP results in deficits in learning and memory, linking WRP to the cognitive deficits seen in 3p- syndrome.</p> / Dissertation

Prostate cancer is the second most common cancer in the United States that affects men today. To better treat this disease accurate biomarkers and successful therapeutic treatments are needed. A novel approach to understand the mechanisms behind prostate cancer tumor formation lies in identifying dysregulated micro-RNAs (miRNAs), which are a class of small (18-24 nucleotides) non-coding RNAs that regulate gene expression posttranscriptionally by either inhibiting protein synthesis or signaling messenger-RNA for degradation. Multiple miRNAs were discovered in our highly tumorigenic and metastatic prostate cancer progression model M12 cell line compared to its weakly tumorigenic P69 parental cell line. Various analyses such as human panel analyses, single-miR analyses and patient tumor biopsy samples were analyzed to determine dysregulated miRNAs that contributed to the progression and metastasis of prostate cancer. Together with performing experiments to identify miRNAs, a de novo next generation sequencing approach was applied to identify miRNAs naturally present in biological fluids of normal and healthy subjects. Since, these miRNAs are highly dysregulated in many diseases, including cancer, they can act as potential biomarkers or therapeutic targets to improve treatments for prostate cancer. Essential miRNAs studied for this research were miR-17-3p that is known to target the ErbB2 mRNA; miR-299-5p that directly targets osteopontin (OPN) mRNA, and miR-147b that directly targets many mRNAs, such as COL4A2, ALDH5A1, NDUFA4, SDHD, and IER5. A wide range of miRNAs were identified in six biological fluids: venous blood, menstrual blood, vaginal fluid, semen, saliva, and feces. There were some miRNAs that were common to all 6 body fluids, some unique to each body fluid, and some miRNAs that literature suggested could potentially be biomarkers or normalizers for body fluid characterization.

A unique computational approach was undertaken to identify targets of miR-17-3p that impart an oncogenic potential to the cells of the prostate. Utilizing this approach, we identified insulin growth factor receptor 1 (IGF1R) as a potential target of miR-17-3p. IGF1R imparts an oncogenic approach to the cells by helping cells escape apoptosis, become hypertrophic and increase the production of extracellular proteases that allow cells to detach from neighbors. The regulation of insulin growth factor receptor 1 by human microRNA-17-3p was evaluated using a western blot analysis of prostate cancer cell lines. Protein levels were compared in a cell line that expressed a non-targeting control RNA and a cell line that expressed microRNA-17-3p. The cell line that expressed the non-targeting control had significantly higher levels of IGF1R protein than the cell line expressing more of the active microRNA. Based on this experiment, it appears that microRNA-17-3p might regulate the insulin growth factor receptor 1.

The aim of this research programme was to examine the 3P model of learning (Biggs, 1987a, 1999). The first stage necessarily involved an examination of the Study Process Questionnaire (SPQ) (Biggs, 1987a), an instrument developed to measure the process component of the model. The structure of the SPQ was examined utilising exploratory and confirmatory factor analysis of undergraduate responses (n= 260). The results indicated the higher-order factor structure of deep-achieving and surface-achieving-motive provided the most reliability and a better model fit than either the subscales or scales of the SPQ. The construct validity of the two constructs deep and surface was assessed next using a multitrait-multimethod matrix (MTMM) constructed from the three measures of the self-report questionnaire, interview ratings and written assessments from first-year students (n = 50). The results indicated good convergent validity between the deep scale of the SPQ and the interview ratings on the deep scale, between the deep scale on the SPQ and the written assessment ratings, and between the interview ratings and written assessment ratings. The results indicated good convergent validity between the surface scale on the SPQ and the interview ratings on the surface scale, but not between the surface scale on the SPQ and the written assessment ratings, and between the interview ratings and written assessment ratings. The discriminant validity between deep and surface was good for the SPQ, but not for either the interview or the written assessment. The findings indicate the deep and surface scales of the SPQ adequately measure the underlying deep and surface constructs. The retest reliability of the SPQ was then examined utilising Spearman’s Rho to assess the rank-order correlations with a sample of third-year students (n=87). Over a period of three months there were significant correlations for the surface motive, surface strategy, deep strategy, achieving motive and achieving strategy subscales of the SPQ, suggesting good reliability for these subscales. The results at the scale level of the SPQ result in similar conclusions. There was a moderate significant correlation for the surface, deep and achieving scales of the SPQ, suggesting the scales have good reliability over a period of three months. There was also a moderate significant correlation for the surface-achieving-motive and deep-achieving scales over a period of three months. The stability of SPQ scores was also assessed utilising a series of one-way repeated measures MANOVA’s with a sample of third-year undergraduates (n = 64). The results suggest some change occurs in self-reported use of approaches to learning between the first and third-years of an undergraduate degree programme. The role of the teaching-learning environment was next examined. Utilising a within-subjects design, undergraduate students (n=48) concurrently enrolled in traditional (viz. lecture and tutorial) and non-traditional (viz. workshops and group projects) subjects completed the SPQ to describe their approaches to learning in each subject. A series of 2x2 repeated measures MANOVA’s were undertaken. The results indicated students were likely to change their approach to learning based on their perceptions of the learning environment (traditional or non-traditional subject). However, those students identified as predominantly surface learners significantly increased their deep scale scores in the non-traditional subject when compared to deep learners. The next study examined a range of personality (locus of control, sensing function, thinking function, intelligence) and demographic variables (age, gender, year of study) to assess which were good predictors of deep and surface approaches to learning. A series of regression analyses identified age, sensing function and locus of control as significant predictors of the surface, surface-achieving-motive, and deep approaches to learning. Locus of control was found to be a significant predictor of the deep-achieving approach to learning. The final study examined the 3P model of learning. Based on the results of earlier studies in the research programme the situational component of the presage factors was not included. The model was examined using structural equation modelling (n= 394). Two initial models were tested using both the three (deep, surface, achieving) and two (surface-achieving-motive and deep-achieving) process factor models. The three process factor model provided the better model fit. The results suggest deep and surface approaches to learning do not mediate between personal characteristics and learning outcomes (i.e. GPA). The results of this series of studies suggest the need for further research into the SPQ and the 3P model of learning. The implications of the research programme are also discussed.

L’hématopoïèse est un processus actif, ordonné, et hautement régulé faisant intervenir des étapes de prolifération, de différenciation et d’apoptose et permettant la production de toutes les cellules sanguines matures à partir d’un nombre restreint de cellules souches hématopoïétiques. La dérégulation des mécanismes intervenant dans l’hématopoïèse induit le développement d’hémopathies, notamment de leucémies. De nombreux facteurs de transcription et microARN (miARN) ont été identifiés en tant que des régulateurs essentiels à l’établissement des différents lignages hématopoïétiques. Mon travail de thèse a porté sur l’étude du rôle des miARN dans la régulation de la différenciation macrophagique humaine. Nous avons reproduit le processus de différenciation macrophagique in vitro à partir de monocytes issus du sang périphérique traités avec du CSF-1 (colony stimulating factor-1). Suite à l’analyse du profil d’expression des miARN au cours du processus de différenciation, notre projet s’est orienté sur l’étude de miR-142-3p dont le taux d’expression diminue le plus fortement au cours de cette différenciation. Nous avons montré que miR-142-3p forme une boucle d’auto-régulation négative avec EGR2 (early growth response 2), un facteur de transcription connu pour réguler positivement la différenciation macrophagique. Cette boucle est essentielle au bon déroulement de la différenciation. Par ailleurs, nous avons observé une altération de cette boucle de régulation dans les monocytes de patients atteints d’une LMMC (leucémie myélomonocytaire chronique) suggérant que ce mécanisme puisse être impliqué dans la leucémogenèse. Au cours de ce projet, nous avons également initié une étude in vivo via l’utilisation du modèle que représente le Poisson-Zèbre. L’hématopoïèse du Poisson-Zèbre est très similaire à celle des mammifères que ce soit au niveau des populations hématopoïétiques ou des mécanismes de régulation impliqués. L’inhibition de l’expression du miR-142a-3p, homologue du miR-142-3p humain, se traduit par une absence de monocytes et de macrophages au niveau de l’ICM (intermediate cell mass), organe primaire de l’hématopoïèse, ainsi que par une diminution de l’expression de la myéloperoxydase, marqueur des granulocytes chez le Poisson-Zèbre. Ainsi, miR-142-3p semble être un inducteur de la formation des granulocytes et monocytes. / Hematopoiesis is an active process, orderly and highly regulated, involving proliferation, differentiation and apoptosis steps, and allowing the production of mature blood cells from a restricted number of hematopoietic stem cells. Deregulation of mechanisms involved in hematopoiesis leads to the development of leukemias. Many transcription factors and microRNAs (miRNAs) have been identified as essential regulators in the establishment of different hematopoietic lineages. My thesis investigated the role of miRNAs in the regulation of human macrophage differentiation. We examined macrophage differentiation in vitro, from peripheral blood monocytes treated with CSF-1 (colony stimulating factor-1). After the analysis of miRNAs expression profile, our project has focused on the study of miR-142-3p whose expression levels decreased most strongly during macrophage differentiation. We showed that miR-142-3p involved in a negative feedback loop with EGR2 (early growth response 2), a transcription factor known to favor macrophage differentiation. This molecular circuitry is necessary for the normal processus of differentiation. Furthermore, we observed an alteration of this regulation circuitry in monocytes of CMML (chronic myelomonocytic leukemia) patients, suggesting that this mechanism may be involved in leukemogenesis. During this project, we also initiated a study in vivo through the use of the zebrafish model. Zebrafish hematopoiesis is very similar to that in mammals both at the level of hematopoietic populations or regulatory mechanisms involved. The inhibition of miR-142a-3p expression, homolog of the human miR-142-3p, gave rise to an absence of monocytes and macrophages in ICM (intermediate cell mass), the primary organ of hematopoiesis and a decreased expression of myeloperoxidase, a marker of granulocytes in the zebrafish. Thus, miR-142-3p appears to be an inducer of granulocytes and monocytes formation.