Diversity in excitatory synaptic transmission by cortical pyramidal neurons give rise to the possibility of different neuronal networks that mediate distinct cortical function. Understanding heterogeneity of excitatory input to pyramidal neurons across distinct cortical areas and species will provide insight into cortical specialization and, ultimately, selective vulnerability of cortical areas to neuropathology in humans. In a previous study in our laboratory (Medalla and Luebke, 2015), significant differences in the ultrastructural features of excitatory asymmetric synapses in layers 2-3 (L2-3) neuropil were found between two distinct cortical areas in the rhesus monkey – primary sensory visual (V1) versus higher-order lateral prefrontal (LPFC) cortices. Here, we used serial sectioning electron microscopy to determine whether these differences in synaptic elements also exist in the corresponding visual (V1) and frontal (FC) cortices in the mouse. Multiple analyses of L2-3 neuropil of FC and V1 in mouse revealed three fundamental principles. First, in contrast to the diverse synapses in monkey LPFC and V1, asymmetric axospinous synapses in L2-3 neuropil of mouse FC and V1 are remarkably homogenous with regard to presynaptic and postsynaptic entities. Second, asymmetric axospinous synapses in L2-3 neuropil of mouse V1 resemble that of monkey V1 in postsynaptic entities, but differ in presynaptic entity. Third, asymmetric axospinous synapses in L2-3 neuropil of mouse FC and monkey LPFC differ substantially in both presynaptic and postsynaptic entities. These findings have broad implications for extrapolation of excitatory synaptic transmission data from one cortical area to another, and also from one species to another.

Over the last two centuries, mass-produced serial narratives, especially those created for women, have been vilified or ignored by literary and cultural critics. Serial narratives, which include continuing stories published in installments and independent tales that form part of an overarching plot, have been maligned for their content, for the material realities of their mass production, and most simply for their popularity. Serial texts aimed at female audiences have been subjected to further criticisms: they have been judged as being trivial or insipid in content and as lacking aesthetic merit or cultural weight. Despite these criticisms, serial narratives were exceedingly popular with audiences in the late nineteenth and early twentieth centuries and by the end of the twentieth century became the dominant mode of storytelling across nearly all media. Popularity, far from being a reason to disparage these works, suggests the enormous power serial narratives have to both reflect and shape the culture that produces and consumes them. This cultural agency has long been overlooked, and this study hopes to change that. Serial narratives, it will be argued, train readers and viewers in various ways to actively participate in the narrative and in parallel ways in real life, an outcome especially noteworthy for modern female audiences. Ongoing and repetitive, serial narratives invite long-term engagement that enables audiences to participate imaginatively in the story itself and to embody the attitudes and behaviors of the serial protagonists in their own lives. In addition, because they are published on a potentially infinite basis, serial narratives are a medium through which modern audiences come to understand themselves and the world they inhabit. This connection between the reading and viewing choices of the modern citizen and their lived experiences, what I call serial modernism, provides a way of understanding how serial texts enact this connection particularly in relation to the modern woman’s increasing sense of agency and her continually evolving identity. Several serial texts from different eras and in different media that powerfully engage with evolving expectations of American women over the last 150 years will crystallize this connection: Louisa May Alcott’s Little Women series (1868-1886) and her serialized novel Work (1873); two silent film serials, The Perils of Pauline (1914) and The Hazards of Helen (1914-1917); two teenage sleuth series, Carolyn Keene’s Nancy Drew (1930-2003) and Margaret Sutton’s Judy Bolton (1930-1967); and Sara Paretsky’s adult detective series V.I. Warshawski (1982-present).

Made available in DSpace on 2016-03-28T12:39:38Z (GMT). No. of bitstreams: 2 carolina_aquino_ioc_mest_2013.pdf: 3546414 bytes, checksum: 50b9e1b7b83e8026e691cf54a5cbe6d8 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2016-01-13 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / A leptospirose é uma doença zoonótica causada por bactérias do gênero Leptospira sp. A ausência de um teste diagnóstico rápido e confiável dificulta o diagnóstico precoce e o acesso ao impacto da leptospirose na saúde pública. O Teste de Microaglutinação, considerado padrão-ouro pela Organização Mundial de Saúde, é realizado em poucos laboratórios de referência no mundo e, apesar de altamente específico, apresenta baixa sensibilidade na fase inicial da doença. O objetivo do presente estudo foi identificar novos alvos proteicos a serem empregados como marcadores diagnósticos para leptospirose. Para tal, foi construído um microarranjo de proteínas compreendendo 61% do genoma codificante de Leptospira interrogans sorovar Copenhageni e investigou-se a resposta por anticorpos IgG de 274 indivíduos, sendo 80 pacientes em fase aguda da doença, 80 em fase convalescente e 114 indivíduos saudáveis provenientes de área com transmissão endêmica e não endêmica para doença Foram encontrados 16 antígenos capazes de identificar casos agudos de leptospirose e 18 capazes identificar casos convalescentes. Entre estes, antígenos como LipL32 e os domínios das proteínas Lig já foram previamente descritos como sendo reconhecidos por soros de pacientes humanos, atuando como prova de conceito para a plataforma de microarranjo proteico. Novos antígenos também foram identificados no estudo, como a proteína hipotética LIC10215, que mostrou alta acurácia na identificação de casos agudos e convalescentes de leptospirose. Os antígenos imunodominantes identificados demonstram potencial uso no desenvolvimento de novos ensaios diagnósticos e no melhoramento dos testes diagnósticos disponíveis no mercado. Estudos complementares serão realizados para avaliar o desempenho desses antígenos nos formatos de ELISA e/ou de teste rápido / Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira sp. The lack of a rapid and reliable point-of-care diagnostic test is a major barrier not only to assess the global burden of the disease but also to provide an ear ly diagnosis. Despite the high specificity of the microaglutination test, which is the gold standard test for di agnosing leptospirosis according to the World Health Organization, it presents low sensitivity and is performed in few reference laboratories worldwide. Therefore, the aim of this work was to identify new protein targets to be used as diagnostic markers for leptospirosis. Accordingly, we developed a protein microarray chip comprising 61% of the Leptospira interrogans serovar Copenhageni coding genome and investigated the IgG response of 274 individuals, including 80 convalescent- and 80 acute-ph ase patients and 114 healthy i ndividuals from areas with endemic and non-endemic transmission of the dis ease. We found 16 antigens that identified acute leptospirosis cases and 18 antigens that identified convalescent cases. Among these antigens are LipL32 and the unique domains of the Lig proteins, which have already been described as seroreactive antigens among leptos pirosis patients, thus acting as a proof-of- concept for the protein microarray platform. Nove l antigens were also identified in this study, such as the hypothetical protein LIC10215, that showed high diagnostic accuracy for both acute and convalescent cases. The imunodominant antigens identified here are potential candidates for the development of new diagnosti c assays as well as for the improvement of currently available tests. Further studies are needed to evaluate their performance in ELISA and rapid test platforms

Orientadores: Fernando Ferreira Costa, Anderson Ferreira da Cunha / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T20:38:21Z (GMT). No. of bitstreams: 1 Brugnerotto_AnaFlavia_M.pdf: 5508751 bytes, checksum: b177c8643fd6a6d948194049324253a1 (MD5) Previous issue date: 2010 / Resumo: As síndromes talassêmicas compreendem um grupo heterogêneo de doenças hereditárias em que existe uma redução no ritmo de síntese de uma ou mais cadeias polipeptídicas da hemoglobina. Nas talassemias ß ocorre a supressão total ou parcial da produção de cadeias ß. O estado homozigótico da maioria das variantes genéticas da talassemia ß produz o quadro clínico da talassemia maior. Esses pacientes apresentam acentuada anemia e necessitam de transfusões sanguíneas regulares para sobreviverem. Os indivíduos heterozigotos para a talassemia ß apresentam, com raras exceções, apenas discreta anemia. Existem ainda alguns quadros clínicos não tão graves quanto à forma homozigótica clássica, geralmente não dependem de transfusões, que são denominados de talassemia intermediária. Os genes responsáveis pela síntese das cadeias da ß globina estão organizados em um cluster localizado no braço curto do cromossomo 11. Quase 200 alelos de talassemia ß já foram caracaterizados. Destes, 125 representam mutações pontuais em regiões funcionalmente importantes do gene, uma de particular interesse ao nosso estudo, é a mutação Cd 39 (C--T). Este trabalho teve como objetivo analisar o perfil global de expressão gênica de células CD 34+ de pacientes com talassemia ß, portadores da mesma mutação genética (Cd 39), mas com evoluções clínicas distintas, maior e intermediária, pelo método de SAGE (Serial Analysis of Gene Expression). Foram gerados 2718 trancritos únicos para o perfil de talassemia ß intermediária e 3052 para o perfil de talassemia ß maior, os quais foram classificados como genes identifcados, no matches, ESTs e outras sequências preditas e anotadas. As expressões de 14 genes foram quantificadas pela reação em cadeia da polimerase em tempo real nas amostras de células CD34+ dos pacientes talassêmicos intermediário e maior, com intuito de validar os resultados obtidos pelo SAGE. As expressões foram concordantes em 57,14% dos genes (ABCB10, APEX1, APOC1, EYA3, HMBS, OAZ1, SRGN, TAGLN2) e discordantes nos demais 42,85% (EIF5a, GRIN2C, HMGB1, NAE1, PCBP2, RAD23B). Quando ambos os perfis foram comparados entre si, 42 transcritos foram ditos como diferencialmente expresso (p<0,05). A análise funcional comparativa dos 42 transcritos diferencialmente expressos foi realizada de acordo com o Gene Ontology Consortium afim de obtermos a classificação funcional destes transcritos. Em conjunto, os resultados podem colaborar na identificação de transcritos importantes, que possam auxiliar na melhor compreensão da fisiopatologia desta doença e desempenhar papéis moduladores no fenótipo em talassemia ß / Abstract: Thalassemia syndromes are a heterogeneous group of hereditary diseases in which there is a reduction in the synthesis of one or more hemoglobin chains. In ß-thalassemia there is a reduction or total suppression of the expression of ß globin genes. The homozygous state of most ß-thalassemia genetic variants produces the clinical evolution of thalassemia major. These patients present severe anemia and require regular blood transfusions in order to survive. Heterozygous individuals present, with exceptions, discret anemia. There are some clinical evolutions that are not as severe as the classic homozygous form, which are often blood transfusion independent, named ß-thalassemia intemedia. The gene responsible for the synthesis of ß the globin chain is arranged in a cluster located on the short arm of cromossome 11. Nearly 200 ß-thalassemia alleles have been characterized. Of these, 125 represent mutations in functionally-important regions of the gene. A nonsense mutation, ie base substitution, which introduces a premature stop codon, destroying the normal reading and interfering in mRNA translation, is of particular interest to our study, especially the Cd 39 mutations (C--T). The aim of this study was to evaluate the global gene expression pattern of CD34+ culture cells from patients with ß-thalassemia, carrying the same genetic mutation (Cd 39) but with different phenotypes (major and intermedia), using Serial Analysis of Gene Expression (SAGE). Two SAGE profiles were gerated: INT and MAIOR. Comparison of the 2718 an 3052 distinct tags from the INT and MAIOR profiles, represented by identified trnacripts and novel tags, 42 tags demonstrated with a differential expression at a statistically significant level (p<0,05) and corresponded to known genes, ESTs or no matches. The expression of 14 genes was further investigated by the real-time polymerase chain reaction in cells cultured from patients with ß-thalassemia intermedia and major, with the purpose of to validating the results obtained by the SAGE method. Similar expressions were seen in 57.14% (ABCB10, APEX1, APOC1, EYA3, HMBS, OAZ1, SRGN, TAGLN2) and discordant expressions were seen in 42.85% (EIF5a, GRIN2C, HMGB1, NAE1, PCBP2, RAD23B). The functional classification was performed according to the Gene Ontology Consortium and a total of a 42 transcripts were submitted to functional classification. Together, our results may contribute to identify important transcripts that may play roles in modulating phenotype in ß-thalassemia and to better understand the pathophysiology of this disease / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

This study identifies two syntactically distinguishable types of Serial Verb Constructions (SVCs) in Mandarin Chinese (MC) and Jinjiang Southern Min (JSM), corresponding to the nuclear and core distinction made in Role and Reference Grammar (Foley and Van Valin 1984, Foley and Olson 1985, Van Valin and LaPolla 1997). This distinction is also made on the basis of a general consensus of the cross-linguistic classifications of the processes of monoclausal multi-verb construction formation (e.g., Butt 1993, 1997, Baker and Harvey 2010): namely, predicate fusion and argument fusion. In this study, I propose two sets of diagnostics to establish the distinction; these go beyond the range covered in previous studies (e.g., Olson 1981, Foley and Olson 1985, Crowley 2002, Chang 2007). In the first set of diagnostics in this study, seven inter-clausal diagnostics are considered as the threshold where the behaviours of bi-clausal structures and SVCs split. These diagnostics include independent negation, passivisation of the object of V2, independent modification by temporal adverbial, independent marking of viewpoint aspect, independent modification by manner adverbial, prosodic structure and the Coordinate Structure Constraint (Ross 1967) that is employed in a more restricted manner. In the second set of diagnostics, four intra-clausal diagnostics are adopted to make the distinction between nuclear and core SVCs, which include passivisation of O1, insertion of intervening material, coordination within the SVC, and obligatory topicalisation of undergoer argument. Of particular interest is the possibility that the same string of verbs may occur in superficially similar, but structurally different, SVCs: for example, the Cause-Effect SVC and the Excessive SVC. The diagnostics employed in this study are proposed as a novel method to establish the distinction between the SVCs and the bi-clausal structures, and more importantly, between core and nuclear types of SVC. Contributing to the originality of the new method of diagnosing the status of the SVCs proposed in this study, I add five novel diagnostics, such as passivisation of the object of V2, independent marking of viewpoint aspect, tone sandhi between adjacent verbs, coordination within the SVC and obligatory topicalisation of the undergoer argument, in addition to those that have been employed in the literature. I restrict myself to data of MC and JSM in discussing the rationale of the diagnostics. However, this novel method of identifying SVCs is expected to be cross-linguistically applicable with consistent results, while at the same time allowing for the possibility of cross-linguistic differences in the semantic sub-types of SVCs identified in each language.

This study is the first of its kind to explore the phenomenon of serial rape from a behavioural profiling perspective within the South African context. The dearth of scientific research on serial rape in South Africa has impacted negatively on the recognition and investigation of such cases. The data set for the study consisted of police dockets, victim statements, court transcripts, detectives’ reports, and correctional services reports on nine serial rapists who assaulted and/or raped a total of seventy five victims. A behavioural profiling framework that was developed from existing literature was used to systematically analyse the victim and offender data using both qualitative and quantitative data analysis techniques. Initial victim and offender profiles were constructed using key elements such as age, population group, modus operandi, and sexual behaviour of the offenders. The initial results showed that the South African serial rapists typically exhibit the same behavioural elements reported in international literature with respect to aspects such as the methods of approach utilised, average age of the victims, ages of the offenders, offender – victim relationship, and sexual acts. However, the research also illustrated that South African serial rapists also displayed some behavioural aspects that have not been reported in international literature. In particular, South African serial rapists approach and attack their victims at two different locations. The research also showed that South African serial rapists are more willing to target victims outside their own populations groups. Young children also appear to be targeted more frequently by the South African serial rapists. The South African offenders also employed a new method of approaching the intended victim (i.e. the delayed-con approach). The results are discussed in terms of the extent to which the behavioural patterns, similarities and differences with observations made in international literature, and current police practices with respect to the investigation of serial rape in South Africa could be utilised to enhance investigative processes. Also, specific areas in need of further examination are identified, as are strategies that could assist in decreasing the occurrence of ‘linkage blindness’ in serial rape investigations in South Africa. / Thesis (DPhil)--University of Pretoria, 2009. / Psychology / unrestricted

Serial Analysis of Gene Expression (SAGE) on Caenorhabditis elegans RNA from FACS sorted embryonic body wall muscle cells has identified nearly 8000 genes expressed in nematode body wall muscle. Approximately 60% of these are genes are expressed at low levels (<5 tags/~50,000-100,000 tag library). Low-abundance transcripts have typically been overlooked since most are considered experimental or contamination errors. Consequently, research has been focused on transcripts that are most enriched in the particular tissue of interest. Here I focus on the analysis of low-expressed transcripts in the muscle SAGE libraries in order to investigate what percentage of these are in fact expressed in muscle and are not false positives. Most well characterized C. elegans body wall muscle genes are not expressed at low levels, therefore I anticipate that focusing on these rarely expressed genes will allow for the identification of muscle components that have been previously unrecognized. RT-PCR was performed on RNA isolated from purified body wall muscle cells to initially estimate what fraction of these low abundance transcripts present in the SAGE data are indeed expressed in muscle. I examined 128 genes, of which 84 were represented by a single SAGE tag. From this initial list, 38% of the low-expressed transcripts were verified for their presence in body wall muscle. Subsequently, reporter GFP fusions were used to deduce if these low-expressed transcripts are indeed expressed in vivo within muscle. Of the low-expressed genes that tested positive via RT-PCR, 42% showed in vivo expression in body wall muscle. When the results from the RT-PCR and in vivo expression experiments are combined, I can extrapolate that at least 16% of low-expressed genes identified by the SAGE libraries are in fact expressed in muscle and are not false positives. RNAi and knockout analysis were performed in order to investigate the role of low-expressed muscle genes in myofilament structure. RNAi results show that 14/34 (41%) of the genes screened had mild defects in myofilament organization. The SAGE libraries identified 6388 low-expressed transcripts, this work suggests that at least 16% (1022 genes) of these are in fact expressed in muscle and may reveal new components previously overlooked by other approaches. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

This thesis explores text-music relationships in Dallapiccola’s Goethe Lieder. Though the cycle is based on Goethe’s West-östlicher divan, it was Mann’s novel Joseph und seine Brüder that spurred its inception. This seven-song cycle revolves around Suleika, a character from the biblical love story of Joseph and Potiphar’s Wife. Dallapiccola set this text upon reading Mann’s novel, which stems from the same story; however, Mann portrayed the character of Suleika as a sympathetic lover rather than the traditional evil seductress. By conducting a thorough pitch structure analysis of each song, focusing in particular on motives, symmetry and aggregates, this thesis examines text-music relationships to demonstrate how Mann’s Suleika is musically represented. This thesis illustrates that Dallapiccola’s setting is a musical composite of both Goethe and Mann’s Suleikas and thus sheds new analytical and hermeneutic light on an important work by one of the twentieth-century’s most prominent serial composers.

The 1961 Hammer horror film, The Curse of the Werewolf, paired innovative make-up and set design with the avant-garde music of Benjamin Frankel (1906-1973). Frankel’s concert works had by this time embraced serialism, but The Curse of the Werewolf was his sole attempt at composing an almost entirely serial film score. This music more fully bridged the divide between the continental modernist practices found in his concert works with more conventional film music techniques. Thus, The Curse of the Werewolf’s score represents a crucial point in Frankel’s broader creative development as a composer who increasingly embraced twelve-tone methods in his concert works. Drawing from historical surveys, analytical scholarship, journal articles, and Frankel’s own writings, this thesis provides historical context surrounding Frankel’s life and involvement with the film. Most importantly, this study examines Frankel’s implementation of serialism in The Curse of the Werewolf’s score and its relation to the film’s visual and narrative components. I examine three pivotal scenes through traditional film music analysis combined with twelve-tone analysis. These analyses show how Frankel pairs motives with onscreen characters and situations while still embracing serial methods. This study sheds light on serialism’s application in film through the work of an overlooked British composer.

In 1924, Herbert Eimert’s Atonale Musiklehre was the first published text to describe a systematic approach to composing atonal music. It contains significant contributions to the discourse on the early development of twelve-tone composition. While Eimert uses the term “atonal” to describe his compositional approach, his definition of atonality demands that all twelve tones be present with none repeated, and that they present as complexes not ordered rows. Eimert’s discussion of atonality differs from others of the same period because he focuses on vertical sonorities and introduces “interlocking complexes”, wherein two separate statements of the aggregate can overlap by one pitch or by a set of pitches. Interlocking complexes are an important feature of Eimert’s string quartet Fünf Stücke für Streichquartett, which was published in 1925 and composed at the same time as Atonale Musiklehre was written. In the foreword to Atonale Musiklehre, Eimert clarifies that he is not the originator of the concept of atonality, rather that he absorbed the ideas of Josef Matthias Hauer and Jefim Golyscheff. Twelve-tone complexes appear first in Golyscheff’s 1914 String Trio. He refers to them as “twelve-tone duration complexes” and labels them in the score. As the name “duration complexes” implies, there are examples of serial rotation of rhythm in the Trio, a technique that is not developed further until the 1950s. Combined with the text of Atonale Musiklehre, the compositions of Golyscheff and Eimert from the year immediately following the book’s publication provide insight into the early development of “atonality” and twelve-tone compositional methods. Investigation of these documents that have not been thoroughly discussed in print provides a broader perspective of the development of these methods of composition.