In type 1 diabetes (T1D), an autoimmune disease, autoantibodies are preferentially directed against proteins associated with Golgi and post-Golgi secretory vesicles, including insulin secretory granules and synaptic-like microvesicles. Thus, the study of beta-cell autoantigens with yet unknown function may provide novel insight into the secretory machinery of beta-cells and led to the discovery of novel pathways. Islet cell autoantigen of 69 kDa (ICA69) is a T1D autoantigen. It is a cytosolic protein of still unknown function. An impairment in neurotransmitter release upon mutation of its homologue in C. elegans suggests, however, an involvement of ICA69 in neurosecretion. Interestingly, ICA69 contains a BAR domain, present in several proteins involved in intracellular transport. The BAR domain functions as a dimerization motif, provides a general binding interface for different types of GTPases, and is a membrane binding/bending module. Its presence in ICA69 is a further hint supporting the putative involvement of ICA69 in intracellular membrane trafficking. The first part of this thesis was concerned with the characterization of ICA69, and the elucidation of its role in membrane traffic in pancreatic beta-cells. ICA69 was shown to be enriched in the perinuclear region, where also markers of the Golgi region are found. ICA69 was shown to interact with several membrane lipids, preferentially with PI(4)P, enriched on the Golgi complex. During the course of this thesis a combination of biochemical and imaging techniques were applied to investigate the interaction between ICA69 and Rab2, a small GTPase associated with the intermediate compartment and involved in the trafficking between the ER and the Golgi complex. ICA69 was shown to co-immunoprecipitate with Rab2 from INS-1 cells extracts. GST-pull down assays demonstrated that this interaction is GTP-dependent. Furthermore, confocal microscopy indicated that ICA69 and Rab2 extensively colocalize in particulate structures throughout the cytoplasm. Immunocytochemistry and subcellular fractionation experiments suggested that Rab2 recruits ICA69 to membranes. Functional studies indicated that ICA69 over-expression in INS-1 cells has effects that resemble, and in some cases amplify those observed upon Rab2 over-expression. Specifically, it impairs the trafficking between ER and Golgi, measured through the appearance and the conversion of the pro-form of ICA512 in the mature form of the protein. Moreover, it correlates with a redistribution of the beta-COP subunit of the coatomer, participating in the early secretory pathway, between membrane-bound compartments and the cytosol and it reduces stimulated insulin secretion. The data reported in this thesis conclusively point to ICA69 as a novel Rab2 effector, and may therefore contribute to the elucidation the yet poorly understood mechanism of action of Rab2 in the secretory pathway. The second part of the thesis was devoted to the study of an ICA69 paralogue gene, called ICA69-RP. Similarly to ICA69, ICA69-RP mRNA was shown to be primarily present in tissues such as brain and pancreatic islets, showing the expression pattern of a gene preferentially expressed in neuroendocrine cells. Unlike ICA69, however, and similar to other genes associated with the secretory machinery of beta-cells, ICA69-RP appeared to be glucose regulated, as shown by a 1.55 fold increase in mRNA levels upon stimulation of the cells with 25 mM glucose for two hours.Glucose stimulation of beta-cells prompts the activation of post-transcripional mechanisms which quickly up-regulate the expression of secretory granule genes and consequently renew granule stores. The increased expression of ICA69-RP upon glucose stimulation of cells may be part of this process. Unfortunately, all attempts to elucidate the intracellular localization of endogenous ICA69-RP failed, and it was not possible to obtain significant insights about its localization by over-expressing a fusion protein between ICA69-RP and GFP. Unlike other paralogues containing the BAR domain, such as amphiphysin 1 and 2 or Rvs167p and Rvs161p, ICA69 and ICA69-RP were shown not to form heterodimers. Furthermore, ICA69-RP did not show any interaction with Rab2 or Rab1, involved in the anterograde transport between ER and Golgi. Thus, its physiological role remains to be investigated.

No ano de 2007 foram analisadas representações mentais de alunos do 1º ano do ensino médio, na disciplina de biologia da Escola Estadual Parobé, Porto Alegre, RS. Foi avaliada a influência das figuras do livro didático (LD) no processo de aprendizagem de conceitos biológicos abstratos (bioquímica e biofísica celular), na construção do pensamento complexo e de modelos mentais. São discutidas quais as metodologias adequadas para trabalhar com representações do conhecimento do tipo pictóricas (do LD) e também a relevância do uso de desenhos como ferramenta de pesquisa de modelos mentais, no estudo da biologia. A pesquisa foi desenvolvida em quatro turmas, divididas em dois grupos, de acordo com a utilização ou não do LD. Os alunos produziram 487 desenhos em tarefas instrucionais; são proposições relacionadas aos conhecimentos prévios (pré-teste), ou aos conceitos desenvolvidos em aula (pós-teste). Nas turmas com o LD, o pós-teste também se relacionou com os conceitos das figuras do LD. Categorias indutivas foram produzidas para avaliar as representações complexas, e as representações e modelos mentais foram analisados de acordo com Greca e Moreira (1996, 2000), Moreira e Lagreca (1998) e Moreira (1994). Foi encontrada uma menor frequência de desenhos que indicavam a construção do pensamento complexo, e de modelos mentais no grupo de alunos com o LD. Estes alunos não desenvolveram uma aprendizagem significativa. / In 2007 mental representations of students in the 1st year of secondary education were analysed, in the subject of biology at the Parobé State School, in Porto Alegre, Rio Grande do Sul - RS. The influence of the figures in the didactic book (DB) was assessed, in the process of learning abstract biological concepts (biochemistry and cellular biophysics), in the construction of complex thought and of mental models. Discussions involved which are the adequate methodologies for working with knowledge representations of a pictorial kind (from a DB) as well as the relevance of the use of drawing as a research tool for mental models, in the study of biology. The research was carried out in four teams, divided into two groups, according to the use or not of the DB. Students produced 487 drawings in instructional tasks; they are propositions related to former knowledge (pre-test), or to the concepts developed in the classroom (post-test). In the teams with the DB, the post-test also related to the concepts of the figures in the DB. Inductive categories were produced to assess the complex representations, and the representations and mental models were analysed according to Greca and Moreira (1996 - 2000), Moreira and Lagreca (1998) and Moreira (1994). A lower frequency was found of drawings that indicated the construction of complex thought, and of mental models in the group of students with the DB. These students failed to develop significant learning.

No ano de 2007 foram analisadas representações mentais de alunos do 1º ano do ensino médio, na disciplina de biologia da Escola Estadual Parobé, Porto Alegre, RS. Foi avaliada a influência das figuras do livro didático (LD) no processo de aprendizagem de conceitos biológicos abstratos (bioquímica e biofísica celular), na construção do pensamento complexo e de modelos mentais. São discutidas quais as metodologias adequadas para trabalhar com representações do conhecimento do tipo pictóricas (do LD) e também a relevância do uso de desenhos como ferramenta de pesquisa de modelos mentais, no estudo da biologia. A pesquisa foi desenvolvida em quatro turmas, divididas em dois grupos, de acordo com a utilização ou não do LD. Os alunos produziram 487 desenhos em tarefas instrucionais; são proposições relacionadas aos conhecimentos prévios (pré-teste), ou aos conceitos desenvolvidos em aula (pós-teste). Nas turmas com o LD, o pós-teste também se relacionou com os conceitos das figuras do LD. Categorias indutivas foram produzidas para avaliar as representações complexas, e as representações e modelos mentais foram analisados de acordo com Greca e Moreira (1996, 2000), Moreira e Lagreca (1998) e Moreira (1994). Foi encontrada uma menor frequência de desenhos que indicavam a construção do pensamento complexo, e de modelos mentais no grupo de alunos com o LD. Estes alunos não desenvolveram uma aprendizagem significativa. / In 2007 mental representations of students in the 1st year of secondary education were analysed, in the subject of biology at the Parobé State School, in Porto Alegre, Rio Grande do Sul - RS. The influence of the figures in the didactic book (DB) was assessed, in the process of learning abstract biological concepts (biochemistry and cellular biophysics), in the construction of complex thought and of mental models. Discussions involved which are the adequate methodologies for working with knowledge representations of a pictorial kind (from a DB) as well as the relevance of the use of drawing as a research tool for mental models, in the study of biology. The research was carried out in four teams, divided into two groups, according to the use or not of the DB. Students produced 487 drawings in instructional tasks; they are propositions related to former knowledge (pre-test), or to the concepts developed in the classroom (post-test). In the teams with the DB, the post-test also related to the concepts of the figures in the DB. Inductive categories were produced to assess the complex representations, and the representations and mental models were analysed according to Greca and Moreira (1996 - 2000), Moreira and Lagreca (1998) and Moreira (1994). A lower frequency was found of drawings that indicated the construction of complex thought, and of mental models in the group of students with the DB. These students failed to develop significant learning.

Puerto Chancay Archaeological Rescue Project: Preliminary ResultsThis note presents the preliminary results of the Archaeological Rescue Project Puerto Chancay. (November 1993 to November 1994). The excavations revealed a long occupation sequence lasting from the Early Intermediate to the Late Intermediate Periods. / En el presente artículo se presentan los resultados preliminares del Proyecto de Rescate Arqueológico Puerto Chancay realizado entre noviembre de 1993 y noviembre de 1994. En estas se evidencia una larga ocupación prehispánica de la zona que va desde el Periodo Intermedio Temprano hasta el Intermedio Tardío.

No ano de 2007 foram analisadas representações mentais de alunos do 1º ano do ensino médio, na disciplina de biologia da Escola Estadual Parobé, Porto Alegre, RS. Foi avaliada a influência das figuras do livro didático (LD) no processo de aprendizagem de conceitos biológicos abstratos (bioquímica e biofísica celular), na construção do pensamento complexo e de modelos mentais. São discutidas quais as metodologias adequadas para trabalhar com representações do conhecimento do tipo pictóricas (do LD) e também a relevância do uso de desenhos como ferramenta de pesquisa de modelos mentais, no estudo da biologia. A pesquisa foi desenvolvida em quatro turmas, divididas em dois grupos, de acordo com a utilização ou não do LD. Os alunos produziram 487 desenhos em tarefas instrucionais; são proposições relacionadas aos conhecimentos prévios (pré-teste), ou aos conceitos desenvolvidos em aula (pós-teste). Nas turmas com o LD, o pós-teste também se relacionou com os conceitos das figuras do LD. Categorias indutivas foram produzidas para avaliar as representações complexas, e as representações e modelos mentais foram analisados de acordo com Greca e Moreira (1996, 2000), Moreira e Lagreca (1998) e Moreira (1994). Foi encontrada uma menor frequência de desenhos que indicavam a construção do pensamento complexo, e de modelos mentais no grupo de alunos com o LD. Estes alunos não desenvolveram uma aprendizagem significativa. / In 2007 mental representations of students in the 1st year of secondary education were analysed, in the subject of biology at the Parobé State School, in Porto Alegre, Rio Grande do Sul - RS. The influence of the figures in the didactic book (DB) was assessed, in the process of learning abstract biological concepts (biochemistry and cellular biophysics), in the construction of complex thought and of mental models. Discussions involved which are the adequate methodologies for working with knowledge representations of a pictorial kind (from a DB) as well as the relevance of the use of drawing as a research tool for mental models, in the study of biology. The research was carried out in four teams, divided into two groups, according to the use or not of the DB. Students produced 487 drawings in instructional tasks; they are propositions related to former knowledge (pre-test), or to the concepts developed in the classroom (post-test). In the teams with the DB, the post-test also related to the concepts of the figures in the DB. Inductive categories were produced to assess the complex representations, and the representations and mental models were analysed according to Greca and Moreira (1996 - 2000), Moreira and Lagreca (1998) and Moreira (1994). A lower frequency was found of drawings that indicated the construction of complex thought, and of mental models in the group of students with the DB. These students failed to develop significant learning.

In type 1 diabetes (T1D), an autoimmune disease, autoantibodies are preferentially directed against proteins associated with Golgi and post-Golgi secretory vesicles, including insulin secretory granules and synaptic-like microvesicles. Thus, the study of beta-cell autoantigens with yet unknown function may provide novel insight into the secretory machinery of beta-cells and led to the discovery of novel pathways. Islet cell autoantigen of 69 kDa (ICA69) is a T1D autoantigen. It is a cytosolic protein of still unknown function. An impairment in neurotransmitter release upon mutation of its homologue in C. elegans suggests, however, an involvement of ICA69 in neurosecretion. Interestingly, ICA69 contains a BAR domain, present in several proteins involved in intracellular transport. The BAR domain functions as a dimerization motif, provides a general binding interface for different types of GTPases, and is a membrane binding/bending module. Its presence in ICA69 is a further hint supporting the putative involvement of ICA69 in intracellular membrane trafficking. The first part of this thesis was concerned with the characterization of ICA69, and the elucidation of its role in membrane traffic in pancreatic beta-cells. ICA69 was shown to be enriched in the perinuclear region, where also markers of the Golgi region are found. ICA69 was shown to interact with several membrane lipids, preferentially with PI(4)P, enriched on the Golgi complex. During the course of this thesis a combination of biochemical and imaging techniques were applied to investigate the interaction between ICA69 and Rab2, a small GTPase associated with the intermediate compartment and involved in the trafficking between the ER and the Golgi complex. ICA69 was shown to co-immunoprecipitate with Rab2 from INS-1 cells extracts. GST-pull down assays demonstrated that this interaction is GTP-dependent. Furthermore, confocal microscopy indicated that ICA69 and Rab2 extensively colocalize in particulate structures throughout the cytoplasm. Immunocytochemistry and subcellular fractionation experiments suggested that Rab2 recruits ICA69 to membranes. Functional studies indicated that ICA69 over-expression in INS-1 cells has effects that resemble, and in some cases amplify those observed upon Rab2 over-expression. Specifically, it impairs the trafficking between ER and Golgi, measured through the appearance and the conversion of the pro-form of ICA512 in the mature form of the protein. Moreover, it correlates with a redistribution of the beta-COP subunit of the coatomer, participating in the early secretory pathway, between membrane-bound compartments and the cytosol and it reduces stimulated insulin secretion. The data reported in this thesis conclusively point to ICA69 as a novel Rab2 effector, and may therefore contribute to the elucidation the yet poorly understood mechanism of action of Rab2 in the secretory pathway. The second part of the thesis was devoted to the study of an ICA69 paralogue gene, called ICA69-RP. Similarly to ICA69, ICA69-RP mRNA was shown to be primarily present in tissues such as brain and pancreatic islets, showing the expression pattern of a gene preferentially expressed in neuroendocrine cells. Unlike ICA69, however, and similar to other genes associated with the secretory machinery of beta-cells, ICA69-RP appeared to be glucose regulated, as shown by a 1.55 fold increase in mRNA levels upon stimulation of the cells with 25 mM glucose for two hours.Glucose stimulation of beta-cells prompts the activation of post-transcripional mechanisms which quickly up-regulate the expression of secretory granule genes and consequently renew granule stores. The increased expression of ICA69-RP upon glucose stimulation of cells may be part of this process. Unfortunately, all attempts to elucidate the intracellular localization of endogenous ICA69-RP failed, and it was not possible to obtain significant insights about its localization by over-expressing a fusion protein between ICA69-RP and GFP. Unlike other paralogues containing the BAR domain, such as amphiphysin 1 and 2 or Rvs167p and Rvs161p, ICA69 and ICA69-RP were shown not to form heterodimers. Furthermore, ICA69-RP did not show any interaction with Rab2 or Rab1, involved in the anterograde transport between ER and Golgi. Thus, its physiological role remains to be investigated.

International research on bullying suggests that bullying is pervasive in schools and the workplace. Most researchers concur that bullying behavior is a disruptive factor to the social and educational well-being of students. Previous research, grounded in social and family systems theory, has indicated those who bully tend to be involved in self-destructive and delinquent behaviors. Additionally, in the only-large scale study on bullying behaviors, 29% of the 10th-grade student body admitted to being bullied that school year. Further, in a new study conducted by the Josephson Institute of Ethics, half of all high school students reported that they have bullied another student. In spite of these studies, there remains a paucity of information in the literature regarding what distinguishes bullies from other students in terms of family factors such as family size, family composition, and birth order. Little has been conducted on which variables in the home contribute to being labeled a bully. The purpose of this quantitative study was to examine the relationships that exist between reported middle-school bullying and each of the above-named family variables. This study examined archival data from a standardized bully questionnaire completed by middle school students. A correlational analysis approach of the bully subscale score and family factors indicate that having a small family size and living with both parents are associated with a lower probability of engaging in bullying behavior. This research yields insight on relationships between bullying behaviors and family variables. Implications for social change included better assessment of, identification of risk factors of bullying behaviors which can lead to a more comprehensive model of bullying strategies that includes broadening our understanding of bullies as being part of a family system versus as an isolated individual.

Indiana University-Purdue University Indianapolis (IUPUI) / Giant axonal neuropathy (GAN) is a rare genetic disease that causes progressive damage to the nervous system. Neurons in GAN patients develop an abnormal organization of cytoskeletal proteins called intermediate filaments (IFs), which normally provide strength and support for the overall cell structure. The irregular IF structure in GAN patient neurons leads to a progressive loss of motor skills in children and subsequent death in adolescence. GAN is caused by reduced levels of the gigaxonin (Giga) protein. Giga functions to control the degradation of other cellular proteins, and the loss of Giga in GAN cells results in significantly elevated levels of the galectin-1 (Gal-1) protein. Gal-1 stabilizes the active form of the Ras signaling protein, which functions as a molecular switch to regulate the phosphorylation and subsequent organization of IFs. The connection between these pathways led us to propose that Giga regulates IF phosphorylation and structure by modulating Ras signaling through the degradation of Gal-1. Using GAN patient cells, we demonstrated that restoring Giga reduced Gal-1 protein levels, decreased IF phosphorylation, and reestablished normal IF organization. Similar effects of reduced IF phosphorylation and improved IF structure were also obtained in GAN cells by directly decreasing the protein levels of either Gal-1, or downstream Ras signaling proteins. Taken together, these results demonstrate that the loss of Giga induces Gal-1 mediated activation of Ras signaling, thereby leading to the increased IF phosphorylation and abnormal IF structure observed in GAN cells. Identification of aberrant Ras signaling is significant because it is the first to specify a mechanism by which the loss of Giga leads to the development of GAN and provides targets for novel drug therapies for the treatment of this currently immedicable genetic disease.

Children learn through doing, and using drama in the elementary classroom gets children actively learning in all subjects (Wood, 2000). A large amount of research has been done on the benefits of incorporating drama into the classroom to enhance academic subjects. However, few teachers incorporate drama on a regular basis. The purpose of this project was to investigate the benefits and ways of incorporating drama into the traditional elementary school classroom, specifically intermediate elementary grades. The benefits of this were examined and the means to make incorporating drama possible for every teacher were explored. The outline of the thesis began with a section on the rationale for incorporating drama, focusing on the social and academic benefits for all children. This was followed by information on the basics of theatre and the description of activities that are considered a part of drama in' the classroom. The incorporation of drama in the specific subjects of language arts, mathematics, science, and social studies was covered along with sample lesson plans for each. The goal is that any teacher reading this thesis will gain some of the skills, information, and confidence needed to use drama in his or her elementary classroom.

Master of Science / Department of Electrical and Computer Engineering / William B. Kuhn / Q‐enhanced filtering technologies have been heavily researched, but have not yet been adopted into commercial designs due to tuning complexity, and performance issues such as noise figure and dynamic range. A multi‐pole Q‐enhanced band‐pass filter operating at 450 MHz with tunable bandwidth is developed in this thesis. A noise figure of 14 dB and dynamic range of 140 dB/Hz have been measured, making the filter suitable for operating in the IF subsystem of a radio receiver. The design utilizes off‐chip resonators, created using surface mount components or embedded passives in LTCC processes, to have a reasonably high base‐Q. The equivalent parallel loss resistance of the finite‐Q inductor and connected circuitry at resonance is partially offset by negative resistances, implemented with tunable on‐chip transconductors, as required to reach the needed Q for the targeted bandwidth. Each pole of the filter has binary weighted negative resistance cells for Q‐enhancement and binary weighted capacitances for frequency tuning. Binary weighted capacitive coupling cells allow the filter to achieve the level of coupling appropriate to the targeted bandwidth. To maintain the filter bandwidth, center frequency, and gain over environmental changes a realtime tuning algorithm is needed. A low complexity tuning algorithm has been implemented and found to accurately maintain the bandwidth, center frequency, and gain when operating at bandwidths of 10 or 20 MHz. Flatness of the pass‐band is also maintained, to within 0.5 dB across a temperature range of 25‐55 degrees C. In addition to the implementation of the tuning algorithm, the thesis provides a solution for pass‐band asymmetries spawned from the use of finite‐Q resonators and associated control circuitry.