928 resultados para spontaneous vesicle
Resumo:
The common focus of the studies brought together in this work is the prosodic segmentation of spontaneous speech. The theoretically most central aspect is the introduction and further development of the IJ-model of intonational chunking. The study consists of a general introduction and five detailed studies that approach prosodic chunking from different perspectives. The data consist of recordings of face-to-face interaction in several spoken varieties of Finnish and Finland Swedish; the methodology is usage-based and qualitative. The term “speech prosody” refers primarily to the melodic and rhythmic characteristics of speech. Both speaking and understanding speech require the ability to segment the flow of speech into suitably sized prosodic chunks. In order to be usage-based, a study of spontaneous speech consequently needs to be based on material that is segmented into prosodic chunks of various sizes. The segmentation is seen to form a hierarchy of chunking. The prosodic models that have so far been developed and employed in Finland have been based on sentences read aloud, which has made it difficult to apply these models in the analysis of spontaneous speech. The prosodic segmentation of spontaneous speech has not previously been studied in detail in Finland. This research focuses mainly on the following three questions: (1) What are the factors that need to be considered when developing a model of prosodic segmentation of speech, so that the model can be employed regardless of the language or dialect under analysis? (2) What are the characteristics of a prosodic chunk, and what are the similarities in the ways chunks of different languages and varieties manifest themselves that will make it possible to analyze different data according to the same criteria? (3) How does the IJ-model of intonational chunking introduced as a solution to question (1) function in practice in the study of different varieties of Finnish and Finland Swedish? The boundaries of the prosodic chunks were manually marked in the material according to context-specific acoustic and auditory criteria. On the basis of the data analyzed, the IJ-model was further elaborated and implemented, thus allowing comparisons between different language varieties. On the basis of the empirical comparisons, a prosodic typology is presented for the dialects of Swedish in Finland. The general contention is that the principles of the IJ-model can readily be used as a methodological tool for prosodic analysis irrespective of language varieties.
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The study investigates actions by recipients in spontaneous Russian conversations by focusing on DA, NU and TAK, when they are used as responses to the main speaker's larger on-going turn. The database for the study consists of some 7 hours of spontaneous conversations. The participants of the conversations come from different parts of Russia. The use of DA, NU and TAK was analyzed by applying the method of ethnomethodological conversation analysis from the point of view of the type of the context, the sequential placement of the response and its manner of production. The particles were analyzed both in contexts in which they responded to an informing and in affective contexts. The particles NU and TAK were used by the speakers almost exclusively in informing contexts, whereas DA was the central response type in affective contexts. DA was also the most common response to information with affective implications. The information, to which the particle NU provided as response, was often unspesific and projected a spesification or explanation by its speaker as the next action. DA and TAK, by contrast, treated the information as one that could be followed and was sufficient in its local context. As a response to parenthetical information NU responded to information that was only loosely connected with the mainline of talk. The particle DA, by contrast, was used as a response to such parenthetical information, which was more crucial for the larger on-going activity. Only NU was used as a response that invited the main speaker to continue a turn that she or he had offered as possibly complete. NU was also used by the recipient after her or his own contribution as a continuer. In affective contexts, DA expressed, depending on its more spesific context, not only agreement but also other functions, such as giving up arguing or prior knowledge on the topic being discussed. In addition DA responses were used to display empathy and identification with the state of affairs expressed by the co-participant. NU, by contrast, was seldom used as a response to a turn that expressed affect. When it was used in affective contexts, it displayed agreement with the co-participant or just registered an assessment by her or him.
Resumo:
This study examines both theoretically an empirically how well the theories of Norman Holland, David Bleich, Wolfgang Iser and Stanley Fish can explain readers' interpretations of literary texts. The theoretical analysis concentrates on their views on language from the point of view of Wittgenstein's Philosophical Investigations. This analysis shows that many of the assumptions related to language in these theories are problematic. The empirical data show that readers often form very similar interpretations. Thus the study challenges the common assumption that literary interpretations tend to be idiosyncratic. The empirical data consists of freely worded written answers to questions on three short stories. The interpretations were made by 27 Finnish university students. Some of the questions addressed issues that were discussed in large parts of the texts, some referred to issues that were mentioned only in passing or implied. The short stories were "The Witch à la Mode" by D. H. Lawrence, "Rain in the Heart" by Peter Taylor and "The Hitchhiking Game" by Milan Kundera. According to Fish, readers create both the formal features of a text and their interpretation of it according to an interpretive strategy. People who agree form an interpretive community. However, a typical answer usually contains ideas repeated by several readers as well as observations not mentioned by anyone else. Therefore it is very difficult to determine which readers belong to the same interpretive community. Moreover, readers with opposing opinions often seem to pay attention to the same textual features and even acknowledge the possibility of an opposing interpretation; therefore they do not seem to create the formal features of the text in different ways. Iser suggests that an interpretation emerges from the interaction between the text and the reader when the reader determines the implications of the text and in this way fills the "gaps" in the text. Iser believes that the text guides the reader, but as he also believes that meaning is on a level beyond words, he cannot explain how the text directs the reader. The similarity in the interpretations and the fact that the agreement is strongest when related to issues that are discussed broadly in the text do, however, support his assumption that readers are guided by the text. In Bleich's view, all interpretations have personal motives and each person has an idiosyncratic language system. The situation where a person learns a word determines the most important meaning it has for that person. In order to uncover the personal etymologies of words, Bleich asks his readers to associate freely on the basis of a text and note down all the personal memories and feelings that the reading experience evokes. Bleich's theory of the idiosyncratic language system seems to rely on a misconceived notion of the role that ostensive definitions have in language use. The readers' responses show that spontaneous associations to personal life seem to colour the readers' interpretations, but such instances are rather rare. According to Holland, an interpretation reflects the reader's identity theme. Language use is regulated by shared rules, but everyone follows the rules in his or her own way. Words mean different things to different people. The problem with this view is that if there is any basis for language use, it seems to be the shared way of following linguistic rules. Wittgenstein suggests that our understanding of words is related to the shared ways of using words and our understanding of human behaviour. This view seems to give better grounds for understanding similarity and differences in literary interpretations than the theories of Holland, Bleich, Fish and Iser.
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Non-linear planar response of a string to planar narrow band random excitation is investigated in this paper. A response equation for the mean square deflection σ2 is obtained under a single mode approximation by using the equivalent linearization technique. It is shown that the response is triple valued, as in the case of harmonic excitation, if the centre frequency of excitation Ω lies in a certain specified range. The triple valued response occurs only if the excitation bandwidth β is smaller than a critical value βcrit which is a monotonically increasing function of the intensity of excitation. An approximate method of investigating the almost sure asymptotic stability of the solution is presented and regions of instability in the Ω-σ2 plane have been charted. It is shown that planar response can become unstable either due to an unbounded growth of the in-plane component of motion or due to a spontaneous appearance of an out-of-plane component.
Resumo:
The basolateral amygdala (BLA) is a complex brain region associated with processing emotional states, such as fear, anxiety, and stress. Some aspects of these emotional states are driven by the network activity of synaptic connections, derived from both local circuitry and projections to the BLA from other regions. Although the synaptic physiology and general morphological characteristics are known for many individual cell types within the BLA, the combination of morphological, electrophysiological, and distribution of neurochemical GABAergic synapses in a three-dimensional neuronal arbor has not been reported for single neurons from this region. The aim of this study was to assess differences in morphological characteristics of BLA principal cells and interneurons, quantify the distribution of GABAergic neurochemical synapses within the entire neuronal arbor of each cell type, and determine whether GABAergic synaptic density correlates with electrophysiological recordings of inhibitory postsynaptic currents. We show that BLA principal neurons form complex dendritic arborizations, with proximal dendrites having fewer spines but higher densities of neurochemical GABAergic synapses compared with distal dendrites. Furthermore, we found that BLA interneurons exhibited reduced dendritic arbor lengths and spine densities but had significantly higher densities of putative GABAergic synapses compared with principal cells, which was correlated with an increased frequency of spontaneous inhibitory postsynaptic currents. The quantification of GABAergic connectivity, in combination with morphological and electrophysiological measurements of the BLA cell types, is the first step toward a greater understanding of how fear and stress lead to changes in morphology, local connectivity, and/or synaptic reorganization of the BLA.
Resumo:
This thesis presents an experimental study of the speech prosody of identical and non-identical twins. Speech fluency, pauses, speech rate, utterance length and speech frequency were examined phonetically, auditorily, semantically and statistically. The methods included both reading tasks (reading the alphabet, numerical lists, sentences with foreign loan words, holiday theme questions as well as 1.5 pages of text with long sentences and complex words) and spontaneous speech tasks (picture description and answering holiday theme questions). The subjects were Finnish-speaking 22-28-year-old female twins: 8 identical (monozygotic) and 10 non-identical (dizygotic) pairs. One pair was male-female. Comparisons were made between twin groups and between sisters. The data was regathered from four twin pairs, to make it possible to investigate some subjects intra-individually. In addition phoneticians, phonetic students and people without knowledge of phonetic science were tested in two listening experiments. The results showed that the dizygotic twins differed more from each other than monozygotic twins and that monozygotic twin sisters shared more similarities than dizygotic twin sisters. For example, between monozygotic twin sisters smaller differences were found between word count, utterance length and speech rate in spontaneous speech tasks. Dizygotic twin sisters made more different kinds of reading mistakes with the same target words than monozygotic twin sisters, while monozygotic twin sisters made more of the same reading mistakes with the same target words than dizygotic twin sisters. The listening experiments showed that only professional phoneticians were able to recognize the twin sisters. Even though the twins had the possibility to freely choose their speech rate, pausing and speech frequency, they used their own speech patterns; these included the same average speech frequency, average speech rate, type of pausing routine or filled pauses, and other speech mannerisms throughout their speech.
Resumo:
The aim was to analyse the growth and compositional development of the receptive and expressive lexicons between the ages 0,9 and 2;0 in the full-term (FT) and the very-low-birth-weight (VLBW) children who are acquiring Finnish. The associations between the expressive lexicon and grammar at 1;6 and 2;0 in the FT children were also studied. In addition, the language skills of the VLBW children at 2;0 were analysed, as well as the predictive value of early lexicon to the later language performance. Four groups took part in the studies: the longitudinal (N = 35) and cross-sectional (N = 146) samples of the FT children, and the longitudinal (N = 32) and cross-sectional (N = 66) samples of VLBW children. The data was gathered by applying of the structured parental rating method (the Finnish version of the Communicative Development Inventory), through analysis of the children´s spontaneous speech and by administering a a formal test (Reynell Developmental Language Scales). The FT children acquired their receptive lexicons earlier, at a faster rate and with larger individual variation than their expressive lexicons. The acquisition rate of the expressive lexicon increased from slow to faster in most children (91%). Highly parallel developmental paths for lexical semantic categories were detected in the receptive and expressive lexicons of the Finnish children when they were analysed in relation to the growth of the lexicon size, as described in the literature for children acquiring other languages. The emergence of grammar was closely associated with expressive lexical growth. The VLBW children acquired their receptive lexicons at a slower rate and had weaker language skills at 2;0 than the full-term children. The compositional development of both lexicons happened at a slower rate in the VLBW children when compared to the FT controls. However, when the compositional development was analysed in relation to the growth of lexicon size, this development occurred qualitatively in a nearly parallel manner in the VLBW children as in the FT children. Early receptive and expressive lexicon sizes were significantly associated with later language skills in both groups. The effect of the background variables (gender, length of the mother s basic education, birth weight) on the language development in the FT and the VLBW children differed. The results provide new information of early language acquisition by the Finnish FT and VLBW children. The results support the view that the early acquisition of the semantic lexical categories is related to lexicon growth. The current findings also propose that the early grammatical acquisition is closely related to the growth of expressive vocabulary size. The language development of the VLBW children should be followed in clinical work.
Resumo:
Spontaneous mutation or chance seedling: discovered in the mid-1990s as a superior plant growing in a commercial field of “Common” Cynodon dactylon on Jimboomba Turf Company’s farm at Jimboomba in south-east Queensland. Selection criteria: vigorous lateral spread, high shoot density and turf quality, low inflorescence numbers, and darker green colour. In 1999 after observing the superior turf performance of this mutant plant as a small patch within a much larger paddock of “Common”, vegetative material was taken and propagated in clean ground elsewhere on the farm for multiplication and further trials in a variety of turf situations in south-east Queensland. Propagation: vegetative. Breeder: Lynn Davidson, Jimboomba, QLD. PBR Certificate Number 2640, Application Number 2002/282, granted 24 February 2005.
Resumo:
Spontaneous mutation: In 1996, vegetative material (later designated ‘TL2’) taken from a disease resistant mutant plant on the fifteenth green at Novotel Palm Cove resort course near Cairns was included an on-going program of selection and testing of promising ‘Tifgreen’ mutants by Tropical Lawns Pty Ltd. Selection criteria: healthy vigorous growth during the tropical wet season, dense fine-textured appearance under close mowing, and dark green leaves. In subsequent trials, ‘TL2’ was identified as the outstanding plant among selections of mutant ‘Tifgreen’ genotypes from other north Queensland sites in terms of colour, texture and density for greens use. Propagation: vegetative. Breeder: Terry Anderlini, Gordonvale, QLD. PBR Certificate Number 2639, Application Number 2002/268, granted 24 February 2005.
Resumo:
Spontaneous mutation or chance seedling: discovered in 2001 as a superior plant growing among “Common” green couch on the breeder’s turf farm at Berries Road, Childers. A selected piece of sod was removed and broken into vegetative sprigs to propagate a larger area of this variety elsewhere on the breeder’s property. The original plant has now been multiplied vegetatively three times without showing any discernible off types. Selection criteria: dense prostrate habit and limited inflorescence production (giving a low mowing requirement), high turf quality, dark green colour. Propagation: vegetative. Breeder: Robert William Morrow, Childers, QLD. PBR Certificate Number 2844, Application Number 2004/035, granted 22 August 2005.
Resumo:
Spontaneous mutation: discovered in February 2001 as a superior plant growing among “Common” buffalo grass growing on the breeder’s property at Saltash in the Hunter Valley (NSW). The selected material has smaller (finer) leaves and showed better growth and colour than the parent variety with minimal inputs (water, fertiliser) under stressful climatic conditions. Subsequently, it also showed better leaf colour retention than the parent variety during winter. A vegetative plug taken from the original plant has now undergone four subsequent vegetative divisions to expand the original material for performance trials in NSW and Queensland without showing any discernible off types. Main selection criteria: winter colour retention, small leaves, low fertiliser requirement. Propagation: vegetative. Breeder: Brent Redman, Maitland North, NSW. PBR Certificate Number 2715, Application Number 2002/283, granted 18 March 2005.
Resumo:
Atherosclerosis is a disease of the arteries; its characteristic features include chronic inflammation, extra- and intracellular lipid accumulation, extracellular matrix remodeling, and an increase in extracellular matrix volume. The underlying mechanisms in the pathogenesis of advanced atherosclerotic plaques, that involve local acidity of the extracellular fluid, are still incompletely understood. In this thesis project, my co-workers and I studied the different mechanisms by which local extracellular acidity could promote accumulation of the atherogenic apolipoprotein B-100 (apoB-100)-containing plasma lipoprotein particles in the inner layer of the arterial wall, the intima. We found that lipolysis of atherogenic apoB-100-containing plasma lipoprotein particles (LDL, IDL, and sVLDL) by the secretory phospholipase A2 group V (sPLA2-V) enzyme, was increased at acidic pH. Also, the binding of apoB-100-containing plasma lipoprotein particles to human aortic proteoglycans was dramatically enhanced at acidic pH. Additionally, lipolysis by sPLA2-V enzyme further increased this binding. Using proteoglycan-affinity chromatography, we found that sVLDL lipoprotein particles consist of populations, differing in their affinities toward proteoglycans. These populations also contained different amounts of apolipoprotein E (apoE) and apolipoprotein C-III (apoC-III); the amounts of apoC-III and apoE per particle were highest in the population with the lowest affinity toward proteoglycans. Since PLA2-modification of LDL particles has been shown to change their aggregation behavior, we also studied the effect of acidic pH on the monolayer structure covering lipoprotein particles after PLA2-induced hydrolysis. Using molecular dynamics simulations, we found that, in acidity, the monolayer is more tightly packed laterally; moreover, its spontaneous curvature is negative, suggesting that acidity may promote lipoprotein particles fusion. In addition to extracellular lipid accumulation, the apoB-100-containing plasma lipoprotein particles can be taken up by inflammatory cells, namely macrophages. Using radiolabeled lipoprotein particles and cell cultures, we showed that sPLA2-V-modification of LDL, IDL, and sVLDL lipoproteins particles, at neutral or acidic pH, increased their uptake by human monocyte-derived macrophages.
Resumo:
The permanent mammalian kidney (metanephros) develops as a result of complex reciprocal tissue interactions between a ureteric epithelium and the renal mesenchyme. The overall goal of the research in this thesis was to gain data that will eventually help in elucidating the formation of congenital renal malformations. The experiments in my thesis aimed to reveal the mechanisms by which Notch, Wnt and GDNF/Ret signalling pathways regulate the development of functional kidney. The function of Notch pathway was studied by a transgenic mouse model, where it was shown that overactivation of Notch signalling disturbs kidney development and alters the expression of Gdnf and Ret/GFRa1. This indicates that Notch signalling interplays with GDNF/Ret in the regulation of the primary ureteric budding and its subsequent branching. The data also suggested that strict spatio-temporal regulation of these two pathways is required for determination of ureteric tip-identity, which appeared to be crucial for the branch formation. The function of Wnt signalling in the ureteric morphogenesis was studied by in vivo and in vitro methods to show that a canonical pathway is required for ureteric branching. Stabilisation and deletion of the canonical pathway mediator, b-catenin specifically in the ureteric epithelium result in renal aplasia/hypodysplasia. These defects originate from severe blockage of ureteric branching due to the disrupted Ret signalling. Consequently, ureteric tip specific markers are lost and ureteric stalk identity is expanded throughout the whole epithelium. Thus, the data demonstrates that the Wnt/b-catenin pathway plays an essential role in the patterning and branching of the ureteric epithelium. A novel in vitro method was generated and utilised in nephron induction studies to reveal the mechanisms through which nephrogenesis is induced. Transient GSK3 inhibition results in stabilisation of b-catenin in the isolated renal mesenchyme, which efficiently triggers nephron formation. Also genetic stabilisation of b-catenin specifically in the mesenchyme results in spontaneous nephrogenesis. The results show that activation of the canonical Wnt pathway is sufficient to initiate nephrogenesis, and suggest that this pathway mediates the nephron induction in murine kidney mesenchymes. Taken together, this thesis demonstrates Notch and Wnt signalling pathways as novel regulators of ureteric branching morphogenesis, and that activation of the canonical Wnt pathway is sufficient for nephron induction. The studies also indicate that the Notch and Wnt pathways cross-talk with GDNF/Ret signalling in the patterning of ureteric epithelium.
Resumo:
Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the causative agent of three human malignancies: Kaposi's sarcoma (KS), Multicentric Castleman's Disease (MCD), and primary effusion lymphoma (PEL). In tumors, KSHV establishes latent infection during which it produces no infectious particles. Latently infected cells can enter the lytic replication cycle, and upon provision of appropriate cellular signals, produce progeny virus. PEL, commonly described in patients with AIDS, represents a diffuse large-cell non-Hodgkin's lymphoma, with median survival time less than six months after diagnosis. As tumor suppressor gene TP53 mutations occur rarely in PEL, the aim of this thesis was to investigate whether non-genotoxic activation of the p53 pathway can eradicate malignant PEL cells. This thesis demonstrates that Nutlin-3, a small-molecule inhibitor of the p53-MDM2 interaction, efficiently restored p53 function in PEL cells, leading to cell cycle arrest and massive apoptosis. Furthermore, we found that KSHV infection activated DNA damage signaling, rendering the cells more sensitive to p53-dependent cell death. We also showed in vivo the therapeutic potential of p53 restoration that led to regression of subcutaneous and intraperitoneal PEL tumor xenografts without adversely affecting normal cells. Importantly, we demonstrated that in a small subset of intraperitoneal PEL tumors, spontaneous induction of viral reactivation dramatically impaired Nutlin-3-induced p53-mediated apoptosis. Accordingly, we found that elevated KSHV lytic transcripts correlated with PEL tumor burden in animals and that inhibition of viral reactivation in vitro restored cytotoxic activity of a small-molecule inhibitor of the p53-MDM2 interaction. Latency provides a unique opportunity for KSHV to escape host immune surveillance and to establish persistent infections. However, to maintain viral reservoirs and spread to other hosts, KSHV must be reactivated from latency and enter into the lytic growth phase. We showed that phosphorylation of nucleolar phosphoprotein nucleophosmin (NPM) by viral cyclin-CDK6 is critical for establishment and maintenance of the KSHV latency. In short, this study provides evidence that the switch between latent phase and lytic replication is a critical step that determines the outcome of viral infection and the pathogenesis of KSHV-induced malignancies. Our data may thus contribute to development of novel targeted therapies for intervention and treatment of KSHV-associated cancers.
Resumo:
The main targets of human immunodeficiency virus (HIV) are CD4 receptors of CD4+ lymphocytes and many other cells such as monocytes/macrophages, megakaryocytes, peripheral blood dendritic cells, follicular dendritic cells (DC), epidermal Langerhans cells, and astrocytes. Infection and killing of CD4+ lymphocytes or false reaction of the body to HIV infection and the spontaneous apoptosis of CD4+ lymphocytes decrease CD4+ lymphocyte counts leading to immunosuppression, further disease progression, and appearance of opportunistic infections and malignancies. Oral manifestations are considered to be among the first signs of HIV infection. Enhanced degradation of extracellular matrix and basement membrane components in oral diseases including periodontitis is caused by Zn-dependent enzymes called matrix metalloproteinases (MMPs). The levels and degrees of activation of MMP-1, -2, -3, -7, -8, -9, -25, -26, tissue inhibitors of MMPs (TIMP)-1 and -2, and myeloperoxidase (MPO) and collagenolytic/gelatinolytic activities, and also Ig A, -G, and -M, total protein, and albumin levels in a two-year follow-up were studied from salivary samples. The expression of MMP-7, -8, -9, -25, and -26 immunoreactivities in gingival tissue specimens were studied. Healthy HIV-negative subjects served as controls. All studied clinical periodontal parameters and microbiological evaluation of the periodontopathogens showed that periodontal health of the HIV-positive patients was moderately decreased in comparison to the healthy controls. The levels of Candida in the periodontal pockets and salivary MPO increased with the severity of HIV infection. Immunoreactivities and levels of MMPs and TIMPs, and MMP activities (collagenase, gelatinase) were enhanced in the HIV-positive patient salivary samples relative to the healthy controls regardless of the phase of HIV infection. However, these parameters did not reflect periodontal status in a similar way as in the generally healthy periodontitis patients. Salivary total protein, albumin, IgA, -G, and -M levels were significantly higher in all phases of HIV infection compared to the controls, and salivary total protein, IgG and IgM levels remained higher after two years follow-up, partly correlating with the disease progression and which may reflect the leakage of serum components into the mouth and thus a decreased mucosal barrier. Salivary analyses of MMPs and TIMPs with immunohistochemical analyses showed that HIV infection could predispose to periodontal destruction when compared with healthy controls or the body s defence reactions associated with HIV infection may have been reflected or mediated by MMPs.