Master of Science in Medicine / Saccadic and vestibular-evoked eye movements are similar in that their three-dimensional kinematic properties show eye position-dependence. When the line of sight is directed towards an eccentric target, the eye velocity axis tilts in a manner that depends on the instantaneous position of the eye in the head, with the magnitude of tilt also depending on whether the eye movement is saccadic or vestibular-evoked. The mechanism responsible for producing eye velocity axis tilting phenomena is not well understood. Some authorities have suggested that muscle pulleys in the orbit are critical for implementing eye velocity axis tilting, while others have suggested that the cerebellum plays an important role. In the current study, three-dimensional eye and head rotation data were acquired, using the magnetic search coil technique, to confirm the presence of eye position-dependent eye velocity axis tilting during saccadic eye movements. Both normal humans and humans with cerebellar atrophy were studied. While the humans with cerebellar atrophy were noted to have abnormalities in the two-dimensional metrics and consistency of their saccadic eye movements, the eye position-dependent eye velocity axis tilts were similar to those observed in the normal subjects. A mathematical model of the human saccadic and vestibular systems was utilized to investigate the means by which these eye position-dependent properties may arise for both types of eye movement. The predictions of the saccadic model were compared with the saccadic data obtained in the current study, while the predictions of the vestibular model were compared with vestibular-evoked eye movement data obtained in a previous study. The results from the model simulations suggest that the muscle pulleys are responsible for bringing about eye position-dependent eye velocity axis tilting for both saccadic and vestibular-evoked eye movements, and that these phenomena are not centrally programmed.

Master of Science in Medicine / Saccadic and vestibular-evoked eye movements are similar in that their three-dimensional kinematic properties show eye position-dependence. When the line of sight is directed towards an eccentric target, the eye velocity axis tilts in a manner that depends on the instantaneous position of the eye in the head, with the magnitude of tilt also depending on whether the eye movement is saccadic or vestibular-evoked. The mechanism responsible for producing eye velocity axis tilting phenomena is not well understood. Some authorities have suggested that muscle pulleys in the orbit are critical for implementing eye velocity axis tilting, while others have suggested that the cerebellum plays an important role. In the current study, three-dimensional eye and head rotation data were acquired, using the magnetic search coil technique, to confirm the presence of eye position-dependent eye velocity axis tilting during saccadic eye movements. Both normal humans and humans with cerebellar atrophy were studied. While the humans with cerebellar atrophy were noted to have abnormalities in the two-dimensional metrics and consistency of their saccadic eye movements, the eye position-dependent eye velocity axis tilts were similar to those observed in the normal subjects. A mathematical model of the human saccadic and vestibular systems was utilized to investigate the means by which these eye position-dependent properties may arise for both types of eye movement. The predictions of the saccadic model were compared with the saccadic data obtained in the current study, while the predictions of the vestibular model were compared with vestibular-evoked eye movement data obtained in a previous study. The results from the model simulations suggest that the muscle pulleys are responsible for bringing about eye position-dependent eye velocity axis tilting for both saccadic and vestibular-evoked eye movements, and that these phenomena are not centrally programmed.

As ataxias hereditárias autossômicas recessivas compõem um grupo de doenças heterogêneas, que necessitam de criteriosa avaliação clínica, de exames complementares e, algumas vezes, de testes genéticos para o diagnóstico. A partir da revisão da literatura, foi elaborado um algoritmo para auxiliar a investigação diagnóstica deste grupo. Esta tese tem como objetivo apresentar os resultados da investigação de três formas de ataxias recessivas: 1. Síndrome de Joubert, caracterizada por hipotonia precoce, atraso do desenvolvimento neuropsicomotor, ataxia e padrão respiratório irregular no período neonatal ou anormalidades na motricidade ocular extrínseca. Apresenta amplo espectro clínico, assim como heterogeneidade genética. Alterações renal, hepática e da retina são freqüentes. A presença de hipoplasia do vermis cerebelar, alongamento dos pedúnculos cerebelares superiores e aumento da fossa interpeduncular, aos cortes axiais da ressonância magnética (RM) do encéfalo, constituem o sinal do dente molar, considerado critério radiológico obrigatório para o diagnóstico. Aqui é apresentada uma série de cinco pacientes que preenchem critérios clínicos e radiológico de síndrome de Joubert e tem grande variabilidade fenotípica: duas crianças têm a forma pura (subtipo 1), uma tem associadamente retinopatia (subtipo 3), uma tem amaurose congênita de Leber e alteração renal (subtipo 4) e a outra apresenta associadamente coloboma corioretiniano e alterações hepáticas (subtipo 5); 2. Ataxia com Deficiência de Vitamina E, que apresenta fenótipo semelhante ao da ataxia de Friedreich, progressão mais lenta, baixo nível sérico de -tocoferol e é tratável com reposição da vitamina E. Frequente no sul da Itália e norte da África, sem relatos no Brasil. Foram investigados quatro pacientes pertencentes a duas famílias: três apresentavam o quadro clínico típico acompanhado de distonia em mãos, manifestação pouco relatada, mas que pode contribuir para a diferenciação clínica com ataxia de Friedreich. O outro paciente foi identificado em fase pré-sintomática, após o diagnóstico ser estabelecido em dois irmãos, e permanece com sinais sutis de alteração do equilíbrio após de 5 anos de reposição de vitamina E. Nos demais, a reposição de vitamina E promoveu melhora dos sintomas e impediu que a doença se agravasse; 3. Xantomatose Cerebrotendínea, que está relacionada à alteração no metabolismo do colesterol, com redução na produção dos ácidos biliares e acúmulo de colestanol, um metabólito tóxico. Catarata congênita ou juvenil e diarréia crônica são manifestações precoces. Ataxia cerebelar, paraparesia espástica, declínio cognitivo e xantomas tendíneos completam o quadro clínico. Na RM do encéfalo, a presença de hipersinal nos núcleos denteados, nas sequências T2-pesada e FLAIR, é sugestiva da doença. Três pacientes, pertencentes a duas famílias, com alterações clínicas e radiológica foram investigados. Em todos, o colestanol sérico encontravase elevado. A espectrocopia por RM detectou no cerebelo pico em 1,2-1,4 ppm, sugestivo de lipídio, achado até o momento não descrito. Após início do tratamento com ácido quenodeoxicólico, observou-se melhora da marcha. / Autosomal recessive hereditary ataxias belong to a group of heterogeneous disorders, for which detailed clinical evaluation, ancillary exams, and sometimes, genetic tests, are required for diagnosis. After literature review, an algorithm was built to help the investigation of this group. The objective of this thesis is to present the results of investigation of three forms of recessive ataxias: 1. Joubert syndrome is a condition characterized by early hypotonia, developmental delay, ataxia and neonatal respiratory disturbances or abnormal eye movement. It has a wide clinical spectrum and is genetically heterogeneous. Renal, hepatic and retina abnormalities are often seen. A combination of midline cerebellar vermis hypoplasia, deepened interpenducular fossa, and thick, elongated superior cerebellar penduncles gives to the axial view of the midbrain an appearance of a molar tooth at brain magnetic ressonance image (MRI) study. Molar tooth sign is considered as obligatory radiologic criteria to diagnosis. In this study we present a series of five patients that have clinical and radiologic criteria to Joubert syndrome and a large phenotypic variability: Two children have a pure form (subgroup 1), one child has an associated retinopathy (subgroup 3), the other has Leber congenital amaurosis and kidney abnormalitties (subgroup 4), and another has chorioretinal coloboma and hepatic abnormalities (subgroup 5); 2. Ataxia with vitamin E deficiency, which has a phenotype similar to Friederich ataxia but slowest progression, is characterized by low levels of serum -tocopherol and is treatable with vitamin E. This ataxia is common in South Italy and North Africa, but was not reported in Brazil. Four patients from two different families were studied. Three of them have typical clinical features and hands dystonia, a probably underreported feature which might helps its distinction from Friedreich ataxia. The other case was identified in a presymptomatic stage, after family investigation. After five years of treatment with vitamin E, subtle balance disturbance was still present. The remaing three patientes improved with vitamin E supplementation and disease progression stopped; 3. Cerebrotendinous xantomathosis (CTX) is a disorder of cholesterol metabolism, characterized by reduction of bile acid synthesis and accumulation of cholestanol, a toxic metabolic. Congenital or juvenile cataract and chronic diarrhea are early manifestations. Cerebellar ataxia, spastic paraplegia, cognitive impairment and tendinous xanthomas are also seen. Brain MRI T2-weighted and FLAIR sequences disclosed dentate nucleus hypersignal, a quite feature in CTX. Three patients from two different families, with clinical and radiologic features were studied. In all, serum cholestanol was elevated. MRI spectroscopy demonstrated in cerebellum a peak in 1,2-1,4 ppm, which is an possibly a lipid, not previously described. Treatment with chenodeoxycholic acid improved their gait.

As distrofias musculares doenças genéticas ou congênitas de caráter irreversível e progressivo são caracterizadas por degenerações da musculatura esquelética capazes de induzir anomalias ósseas como resultado da perda de função do músculo. Osteopenia, fraturas por fragilidade, escoliose, além de danos nos processos de crescimento e remodelação que levam a diferenças de forma e de tamanho são modificações ósseas decorrentes desse conjunto de doenças musculares. Os músculos da cabeça e pescoço são também afetados em vários tipos de distrofias, alterando a morfologia craniofacial e a oclusão dentária. Por sua vez, a cartilagem do processo condilar da mandíbula (PC), uma das estruturas responsáveis pelo crescimento facial, por estar sob a influência direta de fatores intrínsecos (genéticos, epigenéticos) e extrínsecos (estimulação mecânica, tipo de alimentação etc), pode ter a sua morfologia prejudicada já que os músculos faciais e da mastigação são, frequentemente, afetados nos distúrbios degenerativos neuromusculares. Assim, o objetivo do presente estudo foi avaliar as repercussões morfológicas das distrofias musculares na cartilagem do PC de dois modelos murinos distintos de distrofia (dmdmdx e largemyd) e de seus respectivos controles: os camundongos C57BL/10. Os grupos animais (n=5) foram organizados de acordo com as idades (04 e 10 semanas), constituindo: C4, M4, L4, C10, M10 e L10 (camundongos controle, dmdmdx e largemyd de 04 e de 10 semanas, respectivamente). Após a eutanásia, os espécimes foram processados através de técnicas histológicas rotineiras e, posteriormente, submetidos às colorações de HE, Picrossírius e Safranina-O, para a evidenciação dos componentes celular e colágeno e imuno-histoquímica para a marcação de células reativas ao IGF-1 e IGF-1R. Os aspectos ultraestruturais também foram analisados através de microscopia eletrônica de transmissão. Os resultados mostraram que a cartilagem apresentou-se debilitada sob os efeitos da distrofia muscular, acarretando em modificações no padrão morfológico geral do tecido, na secreção das fibrilas colágenas e no acúmulo de proteoglicanas na MEC, as quais variaram de acordo com a idade e tipo de distrofia. Qualitativamente, a maior expressão de IGF-I e de seu receptor (IGF-IR) foi encontrada nos animais do grupo controle (C4 e C10), sendo observadas alterações do padrão de expressão dos mesmos no tecido cartilagíneo dos animais distróficos (dmdmdx e largemyd). Tais resultados sugerem prejuízos na maturação da cartilagem e formação óssea precoce e deficiente. / Muscular dystrophies are irreversible progressive diseases, genetic or congenital, characterized by degeneration of the skeletal muscles which can induce bone abnormalities as result of muscle function loss. Osteopeny, fragility fractures and scoliosis are bone modifications belonging to that set of muscular diseases. In addition, damages in the processes of growth and remodeling lead to skeletal differences in shape and size. Head and neck muscles are also affected in various types of dystrophies and may cause changes in both craniofacial morphology and dental occlusion. In turn, mandibular condylar cartilage (MCC) is one of the structures responsible for facial growth that is directly influenced by intrinsic (genetic, epigenetic) and extrinsic factors (mechanical stimulation, type of feeding, etc.). The morphology of MCC can be impaired since the facial and chewing muscles are often affected in the neuromuscular degenerative disorders. Thus, the present study aimed to evaluate the effects of the muscular dystrophies on the growth of the MCC of murine models (dmdmdx and largemyd) and their respective controls the C57BL/10 mice. For that purpose, animal groups were formed (n = 5) divided according to their ages (04 and 10 weeks), into the following experimental groups: C4, M4, L4, C10, M10 and L10 (control mice, dmdmdx and largemyd of 04 and 10 weeks, respectively). After euthanasia, the specimens were processed through routine histological techniques, and then subjected to HE, Sirius red and Safranin-O staining for the disclosure of cellular components and collagen and immunohistochemistry for marking cells responsive to IGF-I and IGF-IR. The ultrastructural aspects were also analyzed by transmission electron microscopy. The results showed that the cartilage turned out to be impaired in the context of muscular dystrophy, leading to changes in general morphological pattern of the tissue, in the secretion of collagen fibrils and in proteoglycans accumulation on ECM. These findings varied to according age and type of dystrophy. Qualitatively, the major expression of IGF-I and its receptor (IGF-IR) occurred in the animals of the control group (C4 and C10), showing alterations of their expression pattern in cartilage of the dystrophic animals (dmdmdx and largemyd). These results suggest early cartilage maturation and poor bone formation.

As distrofias musculares doenças genéticas ou congênitas de caráter irreversível e progressivo são caracterizadas por degenerações da musculatura esquelética capazes de induzir anomalias ósseas como resultado da perda de função do músculo. Osteopenia, fraturas por fragilidade, escoliose, além de danos nos processos de crescimento e remodelação que levam a diferenças de forma e de tamanho são modificações ósseas decorrentes desse conjunto de doenças musculares. Os músculos da cabeça e pescoço são também afetados em vários tipos de distrofias, alterando a morfologia craniofacial e a oclusão dentária. Por sua vez, a cartilagem do processo condilar da mandíbula (PC), uma das estruturas responsáveis pelo crescimento facial, por estar sob a influência direta de fatores intrínsecos (genéticos, epigenéticos) e extrínsecos (estimulação mecânica, tipo de alimentação etc), pode ter a sua morfologia prejudicada já que os músculos faciais e da mastigação são, frequentemente, afetados nos distúrbios degenerativos neuromusculares. Assim, o objetivo do presente estudo foi avaliar as repercussões morfológicas das distrofias musculares na cartilagem do PC de dois modelos murinos distintos de distrofia (dmdmdx e largemyd) e de seus respectivos controles: os camundongos C57BL/10. Os grupos animais (n=5) foram organizados de acordo com as idades (04 e 10 semanas), constituindo: C4, M4, L4, C10, M10 e L10 (camundongos controle, dmdmdx e largemyd de 04 e de 10 semanas, respectivamente). Após a eutanásia, os espécimes foram processados através de técnicas histológicas rotineiras e, posteriormente, submetidos às colorações de HE, Picrossírius e Safranina-O, para a evidenciação dos componentes celular e colágeno e imuno-histoquímica para a marcação de células reativas ao IGF-1 e IGF-1R. Os aspectos ultraestruturais também foram analisados através de microscopia eletrônica de transmissão. Os resultados mostraram que a cartilagem apresentou-se debilitada sob os efeitos da distrofia muscular, acarretando em modificações no padrão morfológico geral do tecido, na secreção das fibrilas colágenas e no acúmulo de proteoglicanas na MEC, as quais variaram de acordo com a idade e tipo de distrofia. Qualitativamente, a maior expressão de IGF-I e de seu receptor (IGF-IR) foi encontrada nos animais do grupo controle (C4 e C10), sendo observadas alterações do padrão de expressão dos mesmos no tecido cartilagíneo dos animais distróficos (dmdmdx e largemyd). Tais resultados sugerem prejuízos na maturação da cartilagem e formação óssea precoce e deficiente. / Muscular dystrophies are irreversible progressive diseases, genetic or congenital, characterized by degeneration of the skeletal muscles which can induce bone abnormalities as result of muscle function loss. Osteopeny, fragility fractures and scoliosis are bone modifications belonging to that set of muscular diseases. In addition, damages in the processes of growth and remodeling lead to skeletal differences in shape and size. Head and neck muscles are also affected in various types of dystrophies and may cause changes in both craniofacial morphology and dental occlusion. In turn, mandibular condylar cartilage (MCC) is one of the structures responsible for facial growth that is directly influenced by intrinsic (genetic, epigenetic) and extrinsic factors (mechanical stimulation, type of feeding, etc.). The morphology of MCC can be impaired since the facial and chewing muscles are often affected in the neuromuscular degenerative disorders. Thus, the present study aimed to evaluate the effects of the muscular dystrophies on the growth of the MCC of murine models (dmdmdx and largemyd) and their respective controls the C57BL/10 mice. For that purpose, animal groups were formed (n = 5) divided according to their ages (04 and 10 weeks), into the following experimental groups: C4, M4, L4, C10, M10 and L10 (control mice, dmdmdx and largemyd of 04 and 10 weeks, respectively). After euthanasia, the specimens were processed through routine histological techniques, and then subjected to HE, Sirius red and Safranin-O staining for the disclosure of cellular components and collagen and immunohistochemistry for marking cells responsive to IGF-I and IGF-IR. The ultrastructural aspects were also analyzed by transmission electron microscopy. The results showed that the cartilage turned out to be impaired in the context of muscular dystrophy, leading to changes in general morphological pattern of the tissue, in the secretion of collagen fibrils and in proteoglycans accumulation on ECM. These findings varied to according age and type of dystrophy. Qualitatively, the major expression of IGF-I and its receptor (IGF-IR) occurred in the animals of the control group (C4 and C10), showing alterations of their expression pattern in cartilage of the dystrophic animals (dmdmdx and largemyd). These results suggest early cartilage maturation and poor bone formation.

As ataxias hereditárias autossômicas recessivas compõem um grupo de doenças heterogêneas, que necessitam de criteriosa avaliação clínica, de exames complementares e, algumas vezes, de testes genéticos para o diagnóstico. A partir da revisão da literatura, foi elaborado um algoritmo para auxiliar a investigação diagnóstica deste grupo. Esta tese tem como objetivo apresentar os resultados da investigação de três formas de ataxias recessivas: 1. Síndrome de Joubert, caracterizada por hipotonia precoce, atraso do desenvolvimento neuropsicomotor, ataxia e padrão respiratório irregular no período neonatal ou anormalidades na motricidade ocular extrínseca. Apresenta amplo espectro clínico, assim como heterogeneidade genética. Alterações renal, hepática e da retina são freqüentes. A presença de hipoplasia do vermis cerebelar, alongamento dos pedúnculos cerebelares superiores e aumento da fossa interpeduncular, aos cortes axiais da ressonância magnética (RM) do encéfalo, constituem o sinal do dente molar, considerado critério radiológico obrigatório para o diagnóstico. Aqui é apresentada uma série de cinco pacientes que preenchem critérios clínicos e radiológico de síndrome de Joubert e tem grande variabilidade fenotípica: duas crianças têm a forma pura (subtipo 1), uma tem associadamente retinopatia (subtipo 3), uma tem amaurose congênita de Leber e alteração renal (subtipo 4) e a outra apresenta associadamente coloboma corioretiniano e alterações hepáticas (subtipo 5); 2. Ataxia com Deficiência de Vitamina E, que apresenta fenótipo semelhante ao da ataxia de Friedreich, progressão mais lenta, baixo nível sérico de -tocoferol e é tratável com reposição da vitamina E. Frequente no sul da Itália e norte da África, sem relatos no Brasil. Foram investigados quatro pacientes pertencentes a duas famílias: três apresentavam o quadro clínico típico acompanhado de distonia em mãos, manifestação pouco relatada, mas que pode contribuir para a diferenciação clínica com ataxia de Friedreich. O outro paciente foi identificado em fase pré-sintomática, após o diagnóstico ser estabelecido em dois irmãos, e permanece com sinais sutis de alteração do equilíbrio após de 5 anos de reposição de vitamina E. Nos demais, a reposição de vitamina E promoveu melhora dos sintomas e impediu que a doença se agravasse; 3. Xantomatose Cerebrotendínea, que está relacionada à alteração no metabolismo do colesterol, com redução na produção dos ácidos biliares e acúmulo de colestanol, um metabólito tóxico. Catarata congênita ou juvenil e diarréia crônica são manifestações precoces. Ataxia cerebelar, paraparesia espástica, declínio cognitivo e xantomas tendíneos completam o quadro clínico. Na RM do encéfalo, a presença de hipersinal nos núcleos denteados, nas sequências T2-pesada e FLAIR, é sugestiva da doença. Três pacientes, pertencentes a duas famílias, com alterações clínicas e radiológica foram investigados. Em todos, o colestanol sérico encontravase elevado. A espectrocopia por RM detectou no cerebelo pico em 1,2-1,4 ppm, sugestivo de lipídio, achado até o momento não descrito. Após início do tratamento com ácido quenodeoxicólico, observou-se melhora da marcha. / Autosomal recessive hereditary ataxias belong to a group of heterogeneous disorders, for which detailed clinical evaluation, ancillary exams, and sometimes, genetic tests, are required for diagnosis. After literature review, an algorithm was built to help the investigation of this group. The objective of this thesis is to present the results of investigation of three forms of recessive ataxias: 1. Joubert syndrome is a condition characterized by early hypotonia, developmental delay, ataxia and neonatal respiratory disturbances or abnormal eye movement. It has a wide clinical spectrum and is genetically heterogeneous. Renal, hepatic and retina abnormalities are often seen. A combination of midline cerebellar vermis hypoplasia, deepened interpenducular fossa, and thick, elongated superior cerebellar penduncles gives to the axial view of the midbrain an appearance of a molar tooth at brain magnetic ressonance image (MRI) study. Molar tooth sign is considered as obligatory radiologic criteria to diagnosis. In this study we present a series of five patients that have clinical and radiologic criteria to Joubert syndrome and a large phenotypic variability: Two children have a pure form (subgroup 1), one child has an associated retinopathy (subgroup 3), the other has Leber congenital amaurosis and kidney abnormalitties (subgroup 4), and another has chorioretinal coloboma and hepatic abnormalities (subgroup 5); 2. Ataxia with vitamin E deficiency, which has a phenotype similar to Friederich ataxia but slowest progression, is characterized by low levels of serum -tocopherol and is treatable with vitamin E. This ataxia is common in South Italy and North Africa, but was not reported in Brazil. Four patients from two different families were studied. Three of them have typical clinical features and hands dystonia, a probably underreported feature which might helps its distinction from Friedreich ataxia. The other case was identified in a presymptomatic stage, after family investigation. After five years of treatment with vitamin E, subtle balance disturbance was still present. The remaing three patientes improved with vitamin E supplementation and disease progression stopped; 3. Cerebrotendinous xantomathosis (CTX) is a disorder of cholesterol metabolism, characterized by reduction of bile acid synthesis and accumulation of cholestanol, a toxic metabolic. Congenital or juvenile cataract and chronic diarrhea are early manifestations. Cerebellar ataxia, spastic paraplegia, cognitive impairment and tendinous xanthomas are also seen. Brain MRI T2-weighted and FLAIR sequences disclosed dentate nucleus hypersignal, a quite feature in CTX. Three patients from two different families, with clinical and radiologic features were studied. In all, serum cholestanol was elevated. MRI spectroscopy demonstrated in cerebellum a peak in 1,2-1,4 ppm, which is an possibly a lipid, not previously described. Treatment with chenodeoxycholic acid improved their gait.

No description available.

Diese Arbeit widmet sich der Untersuchung von zwei Problemen der abzählenden Geometrie im Zusammenhang mit linearen Systemen auf algebraischen Kurven. Das erste Problem besteht darin, die Frage der Gültigkeit der Jonquières-Formeln zu klären. Diese Formeln berechnen die Anzahl von Divisoren mit vorgeschriebener Multiplizität, genannt de Jonquières-Divisoren, die in einem linearen System auf einer glatten projektiven Kurve enthalten sind. Um dies zu tun, konstruieren wir den Raum der de Jonquières-Divisoren als einen Determinantenzyklus des symmetrischen Produkts der Kurve und beweisen, dass er für eine allgemeine Kurve die erwartete Dimension hat. Dabei beschreiben wir die Degenerationen der Jonquières-Divisoren zu den Knotenkurven sowohl mit linearen Systemen als auch mit kompaktifizierten Picard-Schemata. Das zweite Problem behandelt Zyklen von Untergeordneten-, oder allgemeiner, Sekanten-Divisoren zu einem gegebenen linearen System auf einer Kurve. Wir betrachten den Durchschnitt zweier solcher Zyklen, die Sekanten-Divisoren von zwei verschiedenen linearen Systemen auf der gleichen Kurve entsprechen, und untersuchen die Gültigkeit der enumerativen Formeln, die die Anzahl der Teiler im Durchschnitt zählen. Wir untersuchen einige interessante Fälle mit unerwarteten Transversalitätseigenschaften und etablieren eine allgemeine Methode, um zu überprüfen, wann dieser Durchschnitt leer ist. / This thesis is dedicated to the study of two enumerative geometry problems in the context of linear series on algebraic curves. The first problem is that of settling the issue of the validity of the de Jonquières formulas. These formulas compute the number of divisors with prescribed multiplicity, or de Jonquières divisors, contained in a linear series on a smooth projective curve. To do so, we construct the space of de Jonquières divisors as a determinantal cycle of the symmetric product of the curve and prove that, for a general curve with a general linear series, it is of expected dimension. In doing so, we describe the degenerations of de Jonquières divisors to nodal curves using both limit linear series and compactified Picard schemes. The second problem deals with cycles of subordinate or, more generally, secant divisors to a given linear series on a curve. We consider the intersection of two such cycles corresponding to secant divisors of two different linear series on the same curve and investigate the validity of the enumerative formulas counting the number of divisors in the intersection. We study some interesting cases, with unexpected transversality properties, and establish a general method to verify when this intersection is empty.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-27T13:27:24Z No. of bitstreams: 2 Dissertação - Marilda Aparecida do Nascimento Souza - 2016.pdf: 2356436 bytes, checksum: a957e23bb1a3bdd13c4601abcd76f854 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-27T13:28:08Z (GMT) No. of bitstreams: 2 Dissertação - Marilda Aparecida do Nascimento Souza - 2016.pdf: 2356436 bytes, checksum: a957e23bb1a3bdd13c4601abcd76f854 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-03-27T13:28:08Z (GMT). No. of bitstreams: 2 Dissertação - Marilda Aparecida do Nascimento Souza - 2016.pdf: 2356436 bytes, checksum: a957e23bb1a3bdd13c4601abcd76f854 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-08-12 / INTRODUCTION: The main risks factors of dementia are: aging, medical comorbidities and genetic risk. Genetic factors are very important in the investigation of dementia. A positive family history and genetic factors associated can influence the age of onset of the disease. OBJECTIVES: To investigate the prevalence of family history in dementiating degenerative syndromes. To analyze the cognitive and functional performance of these patients to determine whether the positive FH is related to the early onset of the disease, to assess the prevalence of positive FH by dementia subtype, to compare the profile sociodemographic patients with degenerative dementia with family history and no family history and observe which group had more severe dementia. METHODS: This is a cross-sectional study, conducted in the memory clinic of a university hospital in Central Brazil . Were assigned 483 patients with a diagnosis of dementia, from May 2015 to May 2016. This study evaluated the sociodemographic variables, pre- existing diseases and FH of dementia, through a semi-structured interview. To analyze the cognitive level and functional capacity was used the Mini-mental state examination - MMSE and Pfeffer Questionnaire. The Clinical Dementia Rating - CDR was used to assess the severity of dementia. RESULTS: Of the 483 selected participants, 63.8% were women; the average age at evaluation was 74 years, most with low education (32.7%). We found that 45.5% of patients have an affected relative, mostly among simblings, and the age of onset of dementia is lower in people who have positive HF. Positive FH was greater in Huntington's disease 88.8%, followed by Semantic Dementia (66.7%) and primary progressive aphasia (66.7%). CONCLUSION: Family history proved very common in all types of dementia in our sample, mainly in Huntington's disease, followed by frontotemporal lobar degenerations. / INTRODUÇÃO: Entre os riscos para o surgimento das demências estão o envelhecimento, as comorbidades médicas e o risco genético. Fatores genéticos são muito relevantes na investigação das síndromes demenciais. História familiar (HF) positiva e fatores genéticos associados podem influenciar a idade de início da demência. OBJETIVOS: Investigar a prevalência de história familiar em síndromes degenerativas demenciantes; analisar o desempenho cognitivo e funcional desses pacientes; verificar se a HF positiva está relacionada com o inicio precoce da doença; avaliar a prevalência de HF positiva por subtipo de demência; comparar o perfil sociodemográfico de pacientes com demência degenerativa com HF e sem HF e verificar em qual grupo a demência foi mais grave. MÉTODOS: Trata-se de um estudo transversal, realizado no ambulatório de transtornos cognitivos de um hospital universitário, no Brasil Central, realizado em 483 pacientes com o diagnóstico de Demência, no período de maio de 2015 a maio de 2016. Foram avaliadas as variáveis sociodemográficas, as doenças pré-existentes e HF de demência, através de uma entrevista semiestruturada. Para análise do estado cognitivo e da capacidade funcional foram utilizados o Mini Exame do Estado Mental – MEEM e o questionário de atividades funcionais de Pfeffer. O Clinical Dementia Rating – CDR foi utilizado para verificar a gravidade da demência. RESULTADOS: Dos 483 participantes selecionados, 63,8% eram mulheres, com aproximadamente 74 anos, a maioria (32,7%) com baixíssima escolaridade. Do total de pacientes entrevistados, 45,5% possuem um familiar com a mesma doença, sendo o irmão o que mais apresentou alterações cognitivas semelhantes às do entrevistado. A idade de início da demência é menor em pessoas que possuem HF positiva. Entre os tipos de demências mais prevalentes, relacionadas à HF, foram identificadas a doença de Huntington (88,8%), seguida pela Demência Semântica (66,7%) e Afasia Primária Progressiva (66,7%). CONCLUSÃO: A HF positiva mostrou-se frequente nos casos de demência nesta amostra. O tipo de demência que mais apresentou essa herdabilidade foi a Doença de Huntington, seguida pelas degenerações lobares frontotemporais.

In dieser Dissertation konstruieren wir neue Beispiele von koassoziativen Untermannigfaltigkeiten und G2-Instantonen in kompakten G2-Mannigfaltigkeiten, die aus Joyces verallgemeinerter Kummer Konstruktion hervorgehen. Die besondere Eigenschaft der in dieser Arbeit gefundenen koassoziativen Untermannigfaltigkeiten ist, dass ihr (topologisch bestimmtes) Volumen gegen Null geht, wenn die umgebende Mannigfaltigkeit sich ihrem Orbifaltigkeits-Limes annähert. Dies ist im Sinne eines Vorschlags von Halverson und Morrison, der darauf hinweist, dass bestimmte Entartungen (oder, allgemeiner, die Perioden) von G2-Strukturen durch das Verhalten von G2-topologischen Größen wie dem Volumen von assoziativen und koassoziativen Untermannigfaltigkeiten nachweisbar sein könnten. Die Konstruktion dieser koassoziativen Untermannigfaltigkeiten ist Inhalt von Kapitel 3 und basiert auf der Deformation von „Modell-Untermannigfaltigkeiten“. Diese Untermannigfaltigkeiten liegen innerhalb des kritischen Bereiches der umgebenden Mannigfaltigkeit, in welchem die Metrik entartet. Abschnitt 3.3 beinhaltet zahlreiche Beispiele von koassoziativen Untermannigfaltigkeiten, die wir durch diese Methode konstruieren. Des Weiteren beschreiben wir die Deformationsfamilie dieser koassoziativen Untermannigfaltigkeiten. In Kapitel 4 konstruieren wir neue Beispiele von G2-Instantonen über verallgemeinerten Kummer Konstruktionen. Wir konzentrieren uns hierbei hauptsächlich auf Auflösungen von Orbifaltigkeiten, deren singuläre Strata von Kodimension 6 sind. Wie im vorherigen Kapitel basiert die Konstruktion dieser Instantonen auf einem Klebesatz, welcher einen Zusammenhang deformiert, der (im quantifizierten Sinne) fast ein G2-Instanton ist. Außerdem benutzen wir Gruppenwirkungen um die Obstruktionen zu reduzieren. Mithilfe dieser Methode konstruieren wir in Abschnitt 4.4 eine unendliche Familie von G2-Instantonen auf einem Bündel über einer bestimmten Kummer Konstruktion. / In this thesis we construct new examples of coassociative submanifolds and G2-instantons in compact G2-manifolds arising from Joyce’s generalised Kummer construction. The special feature of the coassociative submanifolds found in this thesis is that their (topologically determined) volume shrinks to zero as the ambient manifold approaches its orbifold limit. This is in the spirit of a proposal by Halverson and Morrison which indicates that certain degenerations (or, more general, the periods) of G2-structures may be detectable by the behaviour of G2-topological quantities such as the volume of associative and coassociative submanifolds. The construction of these coassociative submanifolds is the content of Chapter 3. It is based on the deformation of ‘model-submanfiolds’. These submanifolds lie within the critical locus of the ambient manifold in which the metric degenerates. Section 3.3 contains numerous examples of coassociative submanifolds which we construct via this method. Furthermore, we give a description of the deformation family of these coassociative submanifolds. In Chapter 4 we construct new examples of G2-instantons over generalised Kummer constructions. We focus mainly on resolutions of orbifolds whose singular strata are of codimension 6. As in the previous chapter, the construction of these instantons is based on a gluing theorem which deforms a connection that is (in a quantified sense) close to being a G2-instanton. Furthermore, we use group actions to reduce the obstructions. Using this method, we construct in Section 4.4 an infinite family of G2-instantons on a bundle over one particular Kummer construction.