A presente dissertação origina-se de uma questão clínica a propósito do consumo de drogas na toxicomania servir de lenitivo para a angústia. Em vista disso, procura-se percorrer as vicissitudes do conceito de angústia nas obras de Freud e Lacan concomitante ao desenvolvimento do que ambos os autores falaram a respeito da função psíquica do recurso tóxico. Questiona-se o protagonismo conferido à substância tóxica na contemporaneidade como determinante para a instauração da toxicomania. Procura-se investigar em que medida a herança da psicanálise com a neurologia poderia oferecer dificuldades ao pesquisador psicanalítico na construção de suas elaborações a propósito da toxicomania. Logo em seguida, desenvolve-se a noção freudiana da indissociabilidade entre sensação e associação de forma que a interferência da droga sobre as condições de sensibilidade ultrapassa em grande medida sua influência, apenas, sobre um corpo-organismo.Busca-se apresentar e tecer alguns questionamentos acerca de elaborações de autores psicanalíticos a propósito da toxicomania. Para, por conseguinte, introduzir uma primeira articulação para a hipótese a respeito da qual o elemento de toxidade inerente à prática da droga produz um efeito de rasura sobre uma escrita composta de traços, a escrita psíquica. Escrita essa passível de leitura através das formações do inconsciente, todavia, não sem se opor ou oferecer resistência a sua decifração, a ponto de tornar impossível uma interpretação definitiva ou inequívoca. / The dissertation hereby arises from a clinic question regarding the drug usage in toxicomania used as a lenitive to anguish. With this is mind, it is intended to show the vicissitues of the concept of anguish in the work of Freud and Lacan, concurrent to what the both authors developed about the psychic function of the toxic. It is also questioned the role given to the toxic in contemporary society as the determinant to the establishment of addiction. It seeks to investigate to which extent the neurological psychoanalytic heritage can offer difficulties to the psychoanalytic researcher in the construction of addiction knowledge. After that, it is developed the Freudian notion of inseparability between feeling and association, in which the drug effect goes significantly beyond its influence on the body-organism. It seeks to present and to formulate some questions about the elaborations on addiction made by some psychoanalytic authors. With this, it is introduced one first articulation to the hypothesis on which the toxic element of the drug usage produces an effect of deletion on the writing composed by traces, the psychic writing. This writing is readable through the unconcious formation, however, not without opposition or resistance to its decipherment, to a level of becoming impossible an definitive or unequivocal interpretation.

A presente dissertação origina-se de uma questão clínica a propósito do consumo de drogas na toxicomania servir de lenitivo para a angústia. Em vista disso, procura-se percorrer as vicissitudes do conceito de angústia nas obras de Freud e Lacan concomitante ao desenvolvimento do que ambos os autores falaram a respeito da função psíquica do recurso tóxico. Questiona-se o protagonismo conferido à substância tóxica na contemporaneidade como determinante para a instauração da toxicomania. Procura-se investigar em que medida a herança da psicanálise com a neurologia poderia oferecer dificuldades ao pesquisador psicanalítico na construção de suas elaborações a propósito da toxicomania. Logo em seguida, desenvolve-se a noção freudiana da indissociabilidade entre sensação e associação de forma que a interferência da droga sobre as condições de sensibilidade ultrapassa em grande medida sua influência, apenas, sobre um corpo-organismo.Busca-se apresentar e tecer alguns questionamentos acerca de elaborações de autores psicanalíticos a propósito da toxicomania. Para, por conseguinte, introduzir uma primeira articulação para a hipótese a respeito da qual o elemento de toxidade inerente à prática da droga produz um efeito de rasura sobre uma escrita composta de traços, a escrita psíquica. Escrita essa passível de leitura através das formações do inconsciente, todavia, não sem se opor ou oferecer resistência a sua decifração, a ponto de tornar impossível uma interpretação definitiva ou inequívoca. / The dissertation hereby arises from a clinic question regarding the drug usage in toxicomania used as a lenitive to anguish. With this is mind, it is intended to show the vicissitues of the concept of anguish in the work of Freud and Lacan, concurrent to what the both authors developed about the psychic function of the toxic. It is also questioned the role given to the toxic in contemporary society as the determinant to the establishment of addiction. It seeks to investigate to which extent the neurological psychoanalytic heritage can offer difficulties to the psychoanalytic researcher in the construction of addiction knowledge. After that, it is developed the Freudian notion of inseparability between feeling and association, in which the drug effect goes significantly beyond its influence on the body-organism. It seeks to present and to formulate some questions about the elaborations on addiction made by some psychoanalytic authors. With this, it is introduced one first articulation to the hypothesis on which the toxic element of the drug usage produces an effect of deletion on the writing composed by traces, the psychic writing. This writing is readable through the unconcious formation, however, not without opposition or resistance to its decipherment, to a level of becoming impossible an definitive or unequivocal interpretation.

The main goal of this thesis is to investigate the nature of an optional consonant deletion process, through an articulatory and acoustic study of word-final consonant clusters in Persian. Persian word-final coronal stops are optionally deleted when they are preceded by obstruents or the homorganic nasal /n/. For example, the final clusters in the words /næft/ “oil”, /suχt/ “burnt” and /qæsd/ “intention” are optionally simplified in fast/casual speech, resulting in: [næf], [suχ], and [qæs]. What is not clear from this traditional description is whether the coronal stop is truly deleted, or if a coronal gesture is produced, but not heard, because it is obscured by the adjacent consonants. According to Articulatory Phonology (Browman & Goldstein 1986, 1988, 1989, 1990a, 1990b, 1992, 2001), the articulatory gestures of the deleted segments can still exist even if the segments are not heard. In this dissertation, ultrasound imaging was used to determine whether coronal consonant deletion in Persian is categorical or gradient, and the acoustic consequences of cluster simplification were investigated through duration and spectral measures. This phonetic study enables an account for the optional nature of the cluster simplification process. A general phonological account is provided for the simplification of coda clusters with rising sonority, and the acoustic and articulatory investigation focuses on the simplification of clusters with coronal stops. Ten Persian-speaking graduate students from the University of Ottawa and Carleton University, five male and five female, aged 25-38 participated in the articulatory and acoustic study. Audio and real time ultrasound video recordings were made while subjects had a guided conversation with a native speaker of Persian. 662 tokens of word-final coronal clusters were auditorily classified into unsimplified and simplified according to whether they contained an audible [t]. Singleton coda consonants and singleton /t/s were also captured as controls. The end of the constriction plateau of C1 and beginning of constriction plateau of C3 were used to define a time interval in which to measure the coronal gesture as the vertical distance between the tongue blade and the palate. Smoothing Splines ANOVA was used in a novel way to compare tongue blade height over time across the three conditions. The articulatory results of this study showed that the gestures of the deleted segments are often still present. More specifically, the findings showed that of the clusters that sounded simplified, some truly had no [t] gesture, some had gestural overlap, and some had reduced gestures. In order to explain the optional nature of the simplification process, it is argued that the simplified tokens are the result of two independent mechanisms. Inevitable mechanical and physiological effects generate gesturally reduced and overlapped tokens whereas planned language-specific behaviors driven by phonological rules or abstract cognitive representations result in no [t]-gesture output. The findings of this study support the main arguments presented in Articulatory Phonology regarding the underlying reasons for sound patterns and sound change. The results of this study are further used to examine different sound change models. It is argued that the simplified tokens with totally deleted [t] gesture could be the result of speakers changing their representations based on other people’s gestural overlap. This would be instances of the Choice and Chance categories in Blevins’ (2004) CCC sound change model. The acoustic results did not find any major cues which could distinguish simplified tokens from controls. It is argued that articulatory data should form an integral part of phonetic studies.

KIF1A is a molecular motor for membrane-bound cargo important to the development and survival of sensory neurons. KIF1A dysfunction has been associated with several Mendelian disorders with a spectrum of overlapping phenotypes, ranging from spastic paraplegia to intellectual disability. We present a novel pathogenic in-frame deletion in the KIF1A molecular motor domain inherited by two affected siblings from an unaffected mother with apparent germline mosaicism. We identified eight additional cases with heterozygous, pathogenic KIF1A variants ascertained from a local data lake. Our data provide evidence for the expansion of KIF1A-associated phenotypes to include hip subluxation and dystonia as well as phenotypes observed in only a single case: gelastic cataplexy, coxa valga, and double collecting system. We review the literature and suggest that KIF1A dysfunction is better understood as a single neuromuscular disorder with variable involvement of other organ systems than a set of discrete disorders converging at a single locus. / National Institutes of Health / Revisión por pares

Iron is extremely important for many organisms. Despite its abundancy, it exists in insoluble forms that makes its usability difficult. Some organisms secrete siderophores, low molecular weight compounds, that can chelate iron and convert it into usable forms for cells. One such organism, Rhizobium leguminosarum, is a nitrogen fixing symbiont proteobacteria that infects leguminous plants. The genome of Rhizobium leguminosarum ATCC 14479, which infects the red clover, Trifoli pratense, has previously been completely sequenced in our lab. Our lab has identified several genes in this strain involved in the biosynthesis of a siderophore, vicibactin. The protein product of one of those genes, VbsS, is hypothesized to be a non-ribosomal peptide synthase. It has been attempted to knockout the VbsS gene utilizing the ‘splicing by overlap extension’ method. Additionally, an in-silico analysis of the genome revealed the Vbs genes in R. leguminosarum ATCC 14479 strain were similar to genes in found in the proteobacterium Phyllobacterium sp. 628 and the fungi Aspergillus fumigatus Af293.

Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon. © 2011 Song et al; licensee BioMed Central Ltd.

Speech-language impairment is one of the most common clinical features in velocardiofacial syndrome (VCFS). This report describes the speech and language development of four children with VCFS studied longitudinally from 6 to 30 months of age and compares their performance with three groups of children: (1) normally developing children, (2) children with cleft lip and palate, and (3) children with isolated cleft palate. The data show that young children with VCFS show a receptive-expressive language impairment from the onset of language. Further, speech and expressive language development were severely delayed beyond a level predicted by their other developmental or receptive language performance. The children with VCFS showed severe limitations in speech sound inventories and early vocabulary development that far exceeded those shown by the children with cleft lip and palate and children with isolated cleft palate. This study indicates that young children with VCFS emerge from a critical speech and language learning period with severe limitations in their communicative abilities. Further studies are required to describe the later course of these early speech and language impairments and to explore the relationship to learning disabilities described for older children with VCFS.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18181号 / 医博第3901号 / 新制||医||1004(附属図書館) / 31039 / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩田 想, 教授 松田 道行, 教授 楠見 明弘 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Edwardsiella ictaluri is the causative agent of enteric septicemia of catfish (ESC), which is the most economically important disease of farm-raised channel catfish. E. ictaluri is considered a facultative intracellular pathogen like other well-known species in the Enterobacteriaceae, and it is capable of surviving inside channel catfish neutrophils and macrophages. Its ability to survive inside neutrophils and macrophages has made the development of an effective vaccine against ESC particularly challenging. The goal is to develop a safe, efficacious live attenuated ESC vaccine that is practical and economically beneficial to catfish producers. In this study, single and combination of mutations in genes encoding TCA cycle enzyme and C-1 metabolism proteins were constructed using inrame mutagenesis. The virulence, vaccine efficacy, and tissue persistence of the constructed single and combination mutants were determined in channel catfish. The constructed mutants EideltasdhC, Eideltamdh, EideltafrdA, EideltaglyA, EideltasdhCdeltamdh, EideltasdhCdeltafrdA, and EideltasdhCdeltagcvP were significantly attenuated and showed 100% protection against E. ictaluri 93-146 infection in juvenile channel catfish. However, when tested in 15-d old catfish fry, mutant EideltasdhCdeltagcvP and EideltafrdA were found to provide good protection (99% and 60%, respectively) against E. ictaluri 93-146 infection. The tissue persistence study indicated higher tissue concentration in mutants EideltasdhCdeltagcvP and EideltafrdA relative to the tissue concentration in EideltasdhC and EideltasdhCdeltafrdA mutants.