Analysis of staff knowledge of client rights in West Virginia institutions for the developmentally disabled was undertaken in this study. Even with the identification of guaranteed rights for institutionalized individuals through federal and state legislation, standards, policies, and judicial decisions, whose findings have shown that violation of client rights continues to occur in most institutions. A review of the literature indicated that one possible cause for the continuation of rights violations may be the staff limited understanding of client rights. The literature also has revealed few studies have attempted an investigation in this area. This study involved 644 full-time staff who were representative of one of six different job categories. The staff were employed in one of three West Virginia institutions for the developmentally disabled. It was hypothesized that if differences in staff knowledge of client rights were identified, this information could be used to direct staff training and policy-making decisions and perhaps minimize the continuous violations of client rights. That significant differences in knowledge of client rights did exist when different job categories of staff were compared within each institution as well as across institutions. It was found that significant relationships in knowledge of client rights exist between staff with different job longevity rates, but the correlation was too low to be considered a reliable predictor of limited value. No significant differences in staff knowledge of client rights were found between the three institutions. The implication of these research findings and the future need for research in this area are discussed. / Ed. D.

This thesis consists of two projects in which various machine learning approaches and statistical analysis for the integration of biomedical data analysis were explored, developed and tested. Integration of different biomedical data sources allows us to get a better understating of human body from a bigger picture. If we can get a more complete view of the data, we not only get a more complete view of the molecule basis of phenotype, but also possibly can identify abnormality in diseases which were not found when using only one type of biomedical data. The objective of the first project is to find biological pathways which are related to Duechenne Muscular Dystrophy(DMD) and Lamin A/C(LMNA) using the integration of multi-omics data. We proposed a novel method which allows us to integrate proteins, mRNAs and miRNAs to find disease related pathways. The goal of the second project is to develop a personalized recommendation system which recommend cancer treatments to patients. Compared to the traditional way of using only users' rating to impute missing values, we proposed a method to incorporate users' profile to help enhance the accuracy of the prediction. / Master of Science / There are two existing major problems in the biomedical field. Previously, researchers only used one data type for analysis. However, one measurement does not fully capture the processes at work and can lead to inaccurate result with low sensitivity and specificity. Moreover, there are too many missing values in the biomedical data. This left us with many questions unanswered and can lead us to draw wrong conclusions from the data. To overcome these problems, we would like to integrate multiple data types which not only better captures the complex biological processes but also leads to a more comprehensive characterization. Moreover, utilizing the correlation among various data structures also help us impute missing values in the biomedical datasets. For my two research projects, we are interested in integrating multiple biological data to identify disease specific pathways and predict unknown treatment responses for cancer patients. In this thesis, we propose a novel approach for pathways identification using the integration of multi-omics data. Secondly, we also develop a recommendation system which combines different types of patients’ medical information for missing treatment responses’ prediction. Our goal is that we would find disease related pathways for the first project and enhance missing treatment response’s prediction for the second project with the methods we develop. The findings of my studies show that it is possible to find pathways related to muscular dystrophies using the integration of multi-omics data. Moreover, we also demonstrate that incorporating patient’s genetic profile can improve the prediction accuracy compared to using the treatment responses matrix alone for imputation.

Pathway analysis is an important task for gaining novel insights into the molecular architecture of many complex diseases. With the advancement of new sequencing technologies, a large amount of quantitative gene expression data have been continuously acquired. The springing up omics data sets such as proteomics has facilitated the investigation on disease relevant pathways. Although much work has previously been done to explore the single omics data, little work has been reported using multi-omics data integration, mainly due to methodological and technological limitations. While a single omic data can provide useful information about the underlying biological processes, multi-omics data integration would be much more comprehensive about the cause-effect processes responsible for diseases and their subtypes. This project investigates the combination of miRNAseq, proteomics, and RNAseq data on seven types of muscular dystrophies and control group. These unique multi-omics data sets provide us with the opportunity to identify disease-specific and most relevant biological pathways. We first perform t-test and OVEPUG test separately to define the differential expressed genes in protein and mRNA data sets. In multi-omics data sets, miRNA also plays a significant role in muscle development by regulating their target genes in mRNA dataset. To exploit the relationship between miRNA and gene expression, we consult with the commonly used gene library - Targetscan to collect all paired miRNA-mRNA and miRNA-protein co-expression pairs. Next, by conducting statistical analysis such as Pearson's correlation coefficient or t-test, we measured the biologically expected correlation of each gene with its upstream miRNAs and identify those showing negative correlation between the aforementioned miRNA-mRNA and miRNA-protein pairs. Furthermore, we identify and assess the most relevant disease-specific pathways by inputting the differential expressed genes and negative correlated genes into the gene-set libraries respectively, and further characterize these prioritized marker subsets using IPA (Ingenuity Pathway Analysis) or KEGG. We will then use Fisher method to combine all these p-values derived from separate gene sets into a joint significance test assessing common pathway relevance. In conclusion, we will find all negative correlated paired miRNA-mRNA and miRNA-protein, and identifying several pathophysiological pathways related to muscular dystrophies by gene set enrichment analysis. This novel multi-omics data integration study and subsequent pathway identification will shed new light on pathophysiological processes in muscular dystrophies and improve our understanding on the molecular pathophysiology of muscle disorders, preventing and treating disease, and make people become healthier in the long term. / Master of Science / Identification of biological pathways play a central role in understanding both human health and diseases. A biological pathway is a series of information processing steps via interactions among molecules in a cell that partially determines the phenotype of a cell. Specifically, identifying disease-specific pathway will guide focused studies on complex diseases, thus potentially improve the prevention and treatment of diseases. To identify disease-specific pathways, it is crucial to develop computational methods and statistical tests that can integrate multi-omics (multiple omes such as genome, proteome, etc) data. Compared to single omics data, multi-omics data will help gaining a more comprehensive understanding on the molecular architecture of disease processes. In this thesis, we propose a novel data analytics pipeline for multi-omics data integration. We test and apply our method on/to the real proteomics data sets on muscular dystrophy subtypes, and identify several biologically plausible pathways related to muscular dystrophies.

Over the past few decades it has become evident that the work/family interface is a much broader concept that does not only stress the negative side of the relationship, but also include a positive side. This refers to the process by which participation in one role (e.g. work role) is made better or easier by virtue of participation in the other role (e.g. family role). South Africa is a multicultural society, which consists of four groups (i.e. Black, White, Coloured and Indian), speaking eleven official languages. All of these groups are faced with unique and different circumstances. Apart from cultural, ethnic and linguistic differences, other divergent elements may exist (i.e. values and norms). Therefore South African employees may experience the positive side of the work/family interface differently from employees within other countries. To add to the problem, it is not clear how South African employees‟ experiences of enrichment between work and family domains compare to the experiences of employees in other countries. Furthermore, to date no measuring instrument to assess the enrichment between work and family domains in both directions (work-to-family and family-to-work) exists, that is unique to the South African context. This could pose potential problems for organisations and for future studies on the positive side of work/family in South Africa. The objectives of this research were 1) to determine how the positive side of the work/family interface, particularly work-family enrichment, is conceptualised according to the literature; 2) to develop a new work-family enrichment instrument that is suitable for the South African context and that addresses conceptual and measurement issues relating to previous positive measurements of the work/family interface; 3) to investigate the psychometric properties of the newly developed work-family enrichment instrument; and 4) to assess antecedents and outcomes of work-family enrichment among employees within the South African context. The study consisted of four phases. During the first phase, following an extensive review of literature covering the positive side of the work/family interface, a theoretical framework was proposed for the study. Thereafter, a new instrument that measures work-family enrichment was developed based on the proposed theoretical framework. The instrument was tested via Rasch modelling with a pre-limenary study (N = 527), in order to overcome some of the measurement limitations from the previous positive work-family instruments. This test was followed by investigating the psychometric properties (i.e. construct validity, discriminant validity, convergent validity and external validity; N = 627) of the newly developed MACE Work-Family Enrichment Instrument. During the final phase, antecedents, work-family enrichment and outcomes were assessed in the South African context. In both phases 3 and 4, the following instruments (accompanied by the new instrument) were utilised, namely the Work Resources Scale, Home Resources Scale, Utrecht Work Engagement Scale, Family Engagement Scale, Job Satisfaction Scale, Career Satisfaction Scale, Life Satisfaction Scale, Family Satisfaction Scale and the Work-family Enrichment Scale. During the first phase, the literature revealed that the positive side of the work-family interface is presented by various concepts (i.e. work-family enhancement, work-family facilitation, work-family positive spillover and work-family enrichment). The review also revealed that, to date, the work-family enrichment concept has been the only concept in literature on the positive work/family interface that is grounded in a properly developed conceptualised theoretical model. The fundamental thinking behind the work-family enrichment model is that work and family each provides individuals with resources (i.e. skills and perspectives, psychological and physical, social-capital, flexibility, material) in the one domain, that may help the individual improve the quality of his/her performance in the other domain. These resources thus enable improved performance in the other role either directly (i.e. instrumental path) or indirectly (i.e. affective path). During the second phase a new work-family enrichment instrument was developed, namely the MACE Work-Family Enrichment Instrument. This instrument was based on the proposed work-family enrichment theoretical model for both directions (i.e. work-to-family and family-to-work). Initially 133 items were developed that the researcher obtained from the existing literature, and 161 items were self-developed. During the evaluation study, various problematic items were eliminated by using the Rasch measurement model. The third phase included the validation study in which the psychometric properties of the new MACE instrument was investigated. The results provided evidence for construct validity, discriminant validity and convergent validity, and showed significant relations with external variables. Adequate internal consistency was also found for the proposed scales. The final number of items retained after this phase in the development and pilot study of the MACE Work-Family Enrichment Instrument were 34. During the final phase, various relationships were pointed out between antecedents (i.e. various work resources and home resources), work-family enrichment dimensions, as well as dimensions and outcomes of this type of enrichment. These included work-engagement dimensions, family engagement dimensions, as well as satisfaction-dimensions for work, career, life and the family environment. The results of these relationships were found to be in accordance with other literature on the positive side of the work/family interface. The present study provided evidence for the psychometric properties of the new MACE instrument, which researchers and managers can use to investigate the specific enrichment between work and family domains of employees in a South African context. The results give researchers and managers insight into the specific antecedents (e.g. work resources) and outcomes (e.g. job satisfaction) that play a role in work-family enrichment. This insight can be used as basis on which interventions can be developed to deal with these issues currently. Recommendations were also made for future research. / PhD (Industrial Psychology), North-West University, Potchefstroom Campus, 2014

The roles of females have changed significantly over the past years as females increasingly are entering the labour market in South Africa. This resulted in females having to fulfil multiple roles simultaneously, for example being mother, wife and employee. Therefore the statement can be made that females have a work life and a family life to contend with. This can be enriching, seeing that these domains can generate experiences and resources, which females can use in other domains to enhance the quality. The general objective of this study was to explore various relationships that females experience between work resources, home resources, work engagement, family engagement and work-family enrichment. A cross-sectional survey design was used in this study. A combined purposive and convenience non-probability sample of female workers (N = 420) was taken across the spectrum of several industries in South Africa. Measuring instruments were used for biographical characteristics, work resources (self-developed), home resources (self-developed), work-family enrichment (MACE Work-Family Enrichment Instrument), work engagement (Utrecht Engagement Scale) and family engagement (adapted Utrecht Work Engagement Scale). Omegas and Cronbach’s alpha coefficients were used to determine the reliability of the findings, while correlations were employed to identify significant relationships between the constructs. The dual work-family enrichment models and the mediating effect of the various dimensions of work-to-family enrichment, as well as family-to-work enrichment, were also tested by the Mplus statistical programme. Two models in which work-family enrichment and family-work enrichment act as mediators were also tested. The results indicated a positive statistical significant relationship between work resources, and work-family enrichment; also between home resources, and family-work enrichment; and between work-family enrichment and work engagement. However, a very small, but statistical significant, relationship was shown to exist between family-work enrichment and family engagement. Work-family enrichment also mediated the relationship, with a large effect, between work resources, with work engagement as outcome and family-work enrichment mediated the relationship, with a small effect, between home resources, with family engagement as outcome. Recommendations were made for organisations to follow up and for future research on the topic. / MCom (Industrial Psychology), North-West University, Potchefstroom Campus, 2014

Over the past few decades it has become evident that the work/family interface is a much broader concept that does not only stress the negative side of the relationship, but also include a positive side. This refers to the process by which participation in one role (e.g. work role) is made better or easier by virtue of participation in the other role (e.g. family role). South Africa is a multicultural society, which consists of four groups (i.e. Black, White, Coloured and Indian), speaking eleven official languages. All of these groups are faced with unique and different circumstances. Apart from cultural, ethnic and linguistic differences, other divergent elements may exist (i.e. values and norms). Therefore South African employees may experience the positive side of the work/family interface differently from employees within other countries. To add to the problem, it is not clear how South African employees‟ experiences of enrichment between work and family domains compare to the experiences of employees in other countries. Furthermore, to date no measuring instrument to assess the enrichment between work and family domains in both directions (work-to-family and family-to-work) exists, that is unique to the South African context. This could pose potential problems for organisations and for future studies on the positive side of work/family in South Africa. The objectives of this research were 1) to determine how the positive side of the work/family interface, particularly work-family enrichment, is conceptualised according to the literature; 2) to develop a new work-family enrichment instrument that is suitable for the South African context and that addresses conceptual and measurement issues relating to previous positive measurements of the work/family interface; 3) to investigate the psychometric properties of the newly developed work-family enrichment instrument; and 4) to assess antecedents and outcomes of work-family enrichment among employees within the South African context. The study consisted of four phases. During the first phase, following an extensive review of literature covering the positive side of the work/family interface, a theoretical framework was proposed for the study. Thereafter, a new instrument that measures work-family enrichment was developed based on the proposed theoretical framework. The instrument was tested via Rasch modelling with a pre-limenary study (N = 527), in order to overcome some of the measurement limitations from the previous positive work-family instruments. This test was followed by investigating the psychometric properties (i.e. construct validity, discriminant validity, convergent validity and external validity; N = 627) of the newly developed MACE Work-Family Enrichment Instrument. During the final phase, antecedents, work-family enrichment and outcomes were assessed in the South African context. In both phases 3 and 4, the following instruments (accompanied by the new instrument) were utilised, namely the Work Resources Scale, Home Resources Scale, Utrecht Work Engagement Scale, Family Engagement Scale, Job Satisfaction Scale, Career Satisfaction Scale, Life Satisfaction Scale, Family Satisfaction Scale and the Work-family Enrichment Scale. During the first phase, the literature revealed that the positive side of the work-family interface is presented by various concepts (i.e. work-family enhancement, work-family facilitation, work-family positive spillover and work-family enrichment). The review also revealed that, to date, the work-family enrichment concept has been the only concept in literature on the positive work/family interface that is grounded in a properly developed conceptualised theoretical model. The fundamental thinking behind the work-family enrichment model is that work and family each provides individuals with resources (i.e. skills and perspectives, psychological and physical, social-capital, flexibility, material) in the one domain, that may help the individual improve the quality of his/her performance in the other domain. These resources thus enable improved performance in the other role either directly (i.e. instrumental path) or indirectly (i.e. affective path). During the second phase a new work-family enrichment instrument was developed, namely the MACE Work-Family Enrichment Instrument. This instrument was based on the proposed work-family enrichment theoretical model for both directions (i.e. work-to-family and family-to-work). Initially 133 items were developed that the researcher obtained from the existing literature, and 161 items were self-developed. During the evaluation study, various problematic items were eliminated by using the Rasch measurement model. The third phase included the validation study in which the psychometric properties of the new MACE instrument was investigated. The results provided evidence for construct validity, discriminant validity and convergent validity, and showed significant relations with external variables. Adequate internal consistency was also found for the proposed scales. The final number of items retained after this phase in the development and pilot study of the MACE Work-Family Enrichment Instrument were 34. During the final phase, various relationships were pointed out between antecedents (i.e. various work resources and home resources), work-family enrichment dimensions, as well as dimensions and outcomes of this type of enrichment. These included work-engagement dimensions, family engagement dimensions, as well as satisfaction-dimensions for work, career, life and the family environment. The results of these relationships were found to be in accordance with other literature on the positive side of the work/family interface. The present study provided evidence for the psychometric properties of the new MACE instrument, which researchers and managers can use to investigate the specific enrichment between work and family domains of employees in a South African context. The results give researchers and managers insight into the specific antecedents (e.g. work resources) and outcomes (e.g. job satisfaction) that play a role in work-family enrichment. This insight can be used as basis on which interventions can be developed to deal with these issues currently. Recommendations were also made for future research. / PhD (Industrial Psychology), North-West University, Potchefstroom Campus, 2014

The roles of females have changed significantly over the past years as females increasingly are entering the labour market in South Africa. This resulted in females having to fulfil multiple roles simultaneously, for example being mother, wife and employee. Therefore the statement can be made that females have a work life and a family life to contend with. This can be enriching, seeing that these domains can generate experiences and resources, which females can use in other domains to enhance the quality. The general objective of this study was to explore various relationships that females experience between work resources, home resources, work engagement, family engagement and work-family enrichment. A cross-sectional survey design was used in this study. A combined purposive and convenience non-probability sample of female workers (N = 420) was taken across the spectrum of several industries in South Africa. Measuring instruments were used for biographical characteristics, work resources (self-developed), home resources (self-developed), work-family enrichment (MACE Work-Family Enrichment Instrument), work engagement (Utrecht Engagement Scale) and family engagement (adapted Utrecht Work Engagement Scale). Omegas and Cronbach’s alpha coefficients were used to determine the reliability of the findings, while correlations were employed to identify significant relationships between the constructs. The dual work-family enrichment models and the mediating effect of the various dimensions of work-to-family enrichment, as well as family-to-work enrichment, were also tested by the Mplus statistical programme. Two models in which work-family enrichment and family-work enrichment act as mediators were also tested. The results indicated a positive statistical significant relationship between work resources, and work-family enrichment; also between home resources, and family-work enrichment; and between work-family enrichment and work engagement. However, a very small, but statistical significant, relationship was shown to exist between family-work enrichment and family engagement. Work-family enrichment also mediated the relationship, with a large effect, between work resources, with work engagement as outcome and family-work enrichment mediated the relationship, with a small effect, between home resources, with family engagement as outcome. Recommendations were made for organisations to follow up and for future research on the topic. / MCom (Industrial Psychology), North-West University, Potchefstroom Campus, 2014

In the majority of schools gifted learners are given the same quantity and quality of academic work as their non-gifted classmates. In some cases gifted learners are left to look after themselves when they are done with class work or worse still, asked to teach their non-gifted classmates. Some educationists advocate for a differentiated curriculum between gifted and non-gifted learners. This study sought to establish the impact of enrichment programs to gifted Science learners. Forty gifted learners were identified and drawn equally into one of the two groups — experimental or control. These learners wrote a pre-test after which the twenty learners in the experimental group received enrichment. The forty learners then wrote the same post-test to assess their understanding of the concepts learnt. The cycle was repeated but with a different topic. Learners’ marks were compared and it emerged all twenty learners in the experimental group performed better than those in the control group. Gifted learners should therefore be given enrichment as it deepens, broadens, and sharpens their understanding of concepts. / Science and Technology Education / M. Ed. (Natural Science Education)

Die Supply Chain von Algen in Indonesien, insbesondere Karrageen und Agarprodukte, ist mit Störungen innerhalb der Unternehmen und in externen Netzwerken konfrontiert wie z. B. Quantität, Qualität, Preis und Infrastruktur. Sobald eine Störung in einem Teil der Supply Chain auftritt, kann diese die gesamte Wertschöpfungskette beeinflussen. Um eine nachhaltige Algenindustrie sicher zu stellen, bedarf es einer langzeitigen Planung. Hierbei kann das Supply Chain Risk Management (SCRM) helfen. SCRM umfasst vier kritische Stufen: Identifikation der Algen-Supply Chains, Identifikation und Kategorisierung der Risiken, Einschätzen der Risiken und Vermeidung der Risiken. Um die Algen-Supply Chains zu identifizieren, wurden Feldforschung, Tiefeninterviews und Literaturrecherchen durchgeführt. Die Feldstudie wurde in den Provinzen Süd-Sulawesi, West-Java, Ost-Java, Banten und West-Nusa Tenggara durchgeführt. Anschließend wurden die Algen-Supply Chains mit der Software Umberto NXT Universal 7.0 modelliert, um ein besseres Verständnis von den Material- und Energieflüssen zwischen den Hauptakteuren zu erhalten. Um die Risiken zu identifizieren und zu kategorisieren wurden Literaturrecherchen durchgeführt und die Delphi Methode angewandt, um potentielle Quellen der Risiken, ihre Gründe und ihre Effekte zu analysieren. Zur Einschätzung der Risiken wurde ein semi-quantitativer Ansatz gewählt, welcher auf Face-to-face Interviews zurückgreift. Dementsprechend wurde eine Risikokarte erstellt, welche die Wahrscheinlichkeiten und Effekte von ungünstigen Ereignissen widerspiegelt. Basierend auf den vorherigen Ergebnissen wurde die Intensität der Risiken in die folgenden fünf Kategorien unterteilt: vernachlässigbare, geringe, kritische, sehr kritische und katastrophale Risiken. Drei alternative Strategien zur Vermeidung der Risiken werden vorgeschlagen: der Bau einer kleinen Algen-Fabrik, große Algen-Herstellung und industrielle Algen-Cluster, welche direkt am Algenanbau angegliedert sein müssen. Um die Strategien zu bewerten wurde die Preference Ranking Organization Method for Enrichment Evaluation (PROMETHEE) angewandt, welche der multikriteriellen Entscheidungsanalyse zuzurechnen ist. Die Vermeidungsstrategien berücksichtigen  Nachhaltigkeitskriterien (Ökologie, Wirtschaft, Soziales) und Risikokriterien. Die Ergebnisse zeigen, dass Algen-Supply Chains mit vertikaler Kooperation, aus Algen-Lieferanten (Farmer, lokale Händler, Großhändler und Exporteure) und Algen-Herstellern (Carrageen- und Agarunternehmen) bestehen. Die meisten Algen-Farmer sind unabhängige Farmer, die die Möglichkeit haben die Algen entweder an lokale Händler oder andere je nach Präferenz verkaufen können. Lokale Händler spielen eine entscheidende Rolle hinsichtlich der finanziellen Unterstützung der Farmer, der technischen Informationen und des Marktzugangs. Indonesische Carrageen- und Agarhersteller weisen ein kontinuierliches Marktwachstum auf, insbesondere als Familienunternehmen. Die Risiken der Algen-Supply Chain werden in zwei Hauptkategorien unterteilt: interne und externe Risiken. Interne Risiken werden weiterhin in zwei Gruppen untergliedert: interne Unternehmensrisiken, welche aus Prozess- und Steuerungsrisiken bestehen, sowie externe Unternehmensrisiken, die Supply- und Nachfragerisiken umfassen. Externe Supply Chain Risiken, die aus externen Netzwerkketten resultieren, sind Risiken hinsichtlich regulatorischer Fragen, der Finanzierung, Infrastruktur als auch soziale und umweltbezogene Risiken. Als kritischstes Risiko für die Carrageen-Supply Chain wurde die mangelnde Qualität von E.cottonii rohgetrockneten Algen identifiziert. Weitere kritische Risiken der Agar-Supply Chain sind Quantitätsunsicherheiten, die Knappheit von Gracilaria roh getrockneten Algen sowie negative Umweltauswirkungen des Abwassers. Aus  der Fallstudie zu halb-raffinierten Karrageen resultierte das Clustern von Algen-Verarbeitungsbetrieben als ist die beste Risikovermeidungsstrategie sowohl für große als auch kleine Unternehmen. Nichtsdestotrotz kann sich das Clustern negativ auf die lokale Umwelt auswirken.

Durante o desenvolvimento do sistema nervoso, as oscilações da concentração de cálcio intracelular livre resultam na proliferação celular, migração e diferenciação neuronal. Nesta tese foram investigadas a participação dos receptores ionotrópicos purinérgicos dos tipos P2X2 e P2X4 seletivos ao influxo de cálcio durante a diferenciação neuronal in vitro das células de carcinoma embrionário murino P19. Identificamos o padrão diferencial de expressão de receptores purinérgicos nas células indiferenciadas e neurônios P19. O receptor P2X4 é expresso durante toda a diferenciação neuronal e o receptor P2X2 é detectado na fase tardia da diferenciação em neurônios. Através de ensaios farmacológicos, foi possível identificar a participação dos receptores metabotropicos P2Y e do receptor P2X4 na formação dos corpos embriônicos, na proliferação celular e ou na determinação do fenótipo de progenitor neural. Durante a maturação neuronal os receptores P2X2 e P2Y1 participam da determinação do fenótipo neuronal glutamatérgico NMDA e os receptores P2X2 e P2Y2 no fenótipo neuronal colinérgico. A ausência de inibidores específicos e seletivos aos receptores purinérgicos levou-nos a empregar a técnica SELEX (Systematic Evolution of Ligands by EXponential enrichment) a fim de identificar inibidores seletivos aos receptores P2X2 e P2X4. A técnica envolve a utilização da biblioteca combinatória randômica de RNA 2\'- F pirimidina modificadas resistentes a nucleases. Após 9 ciclos de seleção in vitro de SELEX (ciclo 9-P2X4), as sequências selecionadas mostraram-se seletivas a ligação somente ao receptor P2X4 e não aos receptores P2X2 ou P2X7 através de ensaios de ligação radioligante-receptor. Por patch clamping na configuração whole cell recording identificou-se que além de seletividade ao receptor, que a aplicação do RNA ciclo 9- P2X4 promoveu inibição da corrente ativada pelo ATP somente nos receptores P2X4 e não em P2X2 em celulas 1321N1 astrocitoma transfectadas. A incubação do RNA ciclo 9-P2X4 na concentração de 200 nM com as células no estágio indiferenciado inibiu a formação dos corpos embriônicos. Já utilização de 25 nM, resultou em mudanças morfológicas nas células diferenciadas. Estes dados corroboram com os dados farmacológicos que identificaram a participação do receptor P2X4 na diferenciação precoce. Após 11 ciclos P2X2 de seleção, identificou-se sequências com especificidade de ligação aos receptores P2X2. Aptâmeros, moleculas de RNA com sequência identificada e com alta afinidade ao alvo da seleção, foram isolados de ambas as bibliotecas, ciclo 9 P2X4 e ciclo 11 P2X2. A co-aplicação destes aptâmeros e ATP em ensaios de whole-cell recording resultou na inibição de 30 a 80% da corrente ativada pelo ATP nos receptores P2X2 ou P2X4. Estes testes em células PC12 de rato, que expressa os receptores endógenos, resultou em inibição da corrente ativada pelo ATP de modo semelhante. Além de termos desenvolvido aptâmeros como ferramentas para elucidar as funções dos receptores P2X2 e P2X4 durante o desenvolvimento, diferenciação, em processos fisiológicos e patológicos, estas moléculas resistentes a nucleases são as primeiras identificadas capazes de reconhecer, discernir e inibir dois subtipos de receptores purinérgicos sendo promissores para utilização terapêutica. / During the development of the nervous system, oscillations of intracellular calcium concentrations activate programs of gene expression resulting in proliferation, migration and neuronal differentiation of embryonic cells. In this thesis, the participation of ionotropic P2X2 and P2X4 receptor subtypes, whose receptor channels are highly permeable for calcium influx in the cells, was studied during the process of neuronal differentiation. We have identified differential gene expression of purinergic receptors in undifferentiated and neuronal-differentiated P19 cells. P2X4 receptor expression was present along neuronal differentiation of P19 cells, whereas P2X2 receptor expression was only detected when P19 cells became neurons. Based on purinergic receptor pharmacology we have determined the participation of P2X4 receptors in addition to metabotropic P2Y2 receptors in the formation of embryonic bodies as prerequisites for phenotype determination of P19 neural progenitor cells. Final neuronal maturation of P19 cells in the presence or absence of agonists or antagonists of purinergic receptors implicated the involvement of P2X2, P2Y1, and P2Y2 in the determination of the final neuronal phenotype, such as expression of NMDA-glutamate and cholinergic receptors. In order to further evaluate the functions of these P2X receptors and due to the absence of specific inhibitors for these receptor subtypes, we have used the SELEX technique (Systematic Evolution of Ligands by EXponential enrichment) to select for specific inhibitors for P2X2 and P2X4 receptors. The 2\' -F-pyrimidine modified, nuclease- resistant combinatorial SELEX RNA pool enriched with inhibitors of P2X4 receptors following nine cycles of in vitro selection (cycle 9-P2X4) specifically interacted with P2X4 receptors and not with P2X2 or P2X7 receptors as verified in radioligand-receptor binding studies. Moreover, whole-cell recording measurements using astrocytoma cells expressing recombinant rat P2X2 or P2X4 receptors showed inhibition of P2X4 but not of P2X2 receptors by the selected RNA molecules. RNA molecules selected in vitro in 11 reiterative SELEX cycles using the P2X2 receptor as target specifically bound to membrane extracts containing recombinant P2X2 receptors. From both selected RNA libraries (against P2X4 and P2X2 receptors) aptamers, as RNA molecules with identified sequences and high-affinity binding, were identified by cloning and DNA sequencing. The presence of these aptamers in whole-cell recording experiments resulted in 30-80% inhibition of ATP-induced receptor activity and did not provoke any inhibitory effects on P2X receptors which had not been used as selection target. The activity of the aptamers selected using recombinant receptors as targets in inhibiting wild-type P2X4 or P2X2 receptors was verified in whole-cell recording experiments with PC12 cells which endogenously express both receptor subtypes. In addition of having developed aptamers as tools to elucidate P2X2 and P2X4 receptor functions during neuronal differentiation, these nuclease-resistant aptamers are suitable for in vivo use and may turn into therapeutics in the inhibition of purinergic receptor participation in pathophysiological conditions.