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Characterisation of the mechanism of human serum resistance in Trypanosoma brucei gambiense.Felu, Cécile 15 September 2006 (has links)
The two human pathogenic sub-species T.b.gambiense and T.b.rhodesiense can be distinguished from the morphologically identical T.b.brucei by their ability to infect humans, enabling them to cause sleeping sickness. This is because they are resistant to lysis by the lytic factor (APOL-I) present in normal human serum (NHS). In T.b.rhodesiense resistance to this lytic factor is due to a truncated VSG gene termed SRA which blocks lysis by interacting with APOL-I in the lysosome. SRA does not exist in T.b.gambiense. The search for a similar truncated VSG gene lead to the identification of a T.b.gambiense specific glycoprotein termed TGSGP. TGSGP transfected alone into the sensitive T.b.brucei is unable to confer resistance to this sub-species. This is either due to incorrect processing of this gene is this sub-species or because TGSGP requires a partner to confer resistance.
In the search for a partner, the genomic locus of TGSGP was cloned and sequenced. We found that TGSGP is linked to a truncated gene homologous to the S.cerevisiae AUT1 gene, a gene implicated in autophagy and more specifically in membrane expansion. Southern blot hybridization and PCR analysis on genomic DNA from several isolates demonstrated that this feature was a specific to T.b.gambiense. In addition, we observed a correlation between the aut1 allele size and the geographical origin of the isolate.
Since in trypanosomes lysis by NHS is due to an uncontrolled expansion of the lysosome, we speculated that the truncation of the aut1 allele could be implication in the resistance to human serum. We characterized the genomic organisation of the AUT1 locus. T.b.brucei possesses two native AUT1 alleles whilst T.b.gambiense possesses a truncated aut1 allele, as well as a native AUT1 allele. We showed that in the T.b.gambiense LiTAR isolate (aut1/AUT1), despite the presence of a wild-type allele this gene is no longer expressed at the mRNA and protein level. Our complimentary results by run-on transcription assay showed that the AUT1 region is transcribed but that the messenger is unstable. LiTAR is a functional knock-out for AUT1, but Northern blot analysis on several T.b.gambiense isolates showed that this is not a generalised T.b.gambiense characteristic.
We explored the role of AUT1 in trypanosomes by invalidation of the AUT1 gene in T.b.brucei and by the over-expression of the AUT1 and aut1 alleles in T.b.brucei. By functional analysis of AUT1 knocked-down cells we showed that AUT1 is not essential in trypanosomes. By recreating in T.b.brucei the T.b.gambiense AUT1/aut1 genotype we were able to show that the expression of the aut1 UTR down-regulated the expression of the wild-type AUT1 allele. We speculated that this may be due to a natural RNAi mechanism. Par northern blot, using probes covering the potential target region of AUT1, we detected a 50nt small RNA specific to T.b.gambiense. In addition, we showed that in a LiTAR strain in which the RNAi pathway was abolished AUT1 expression is restored.
We continued to investigate TGSGP’s role in the resistance to human serum by invalidation of TGSGP in T.b.gambiense and by expressing TGSGP in the NHS-sensitive T.b.brucei. Because T.b.gambiense cannot be cultured in vitro we established a new in vivo transfection technique and as the knock-out of TGSGP is most probably lethal, we created an inducible RNAi T.b.gambiense cell strain. These indispensable tools will be used to test whether invalidation TGSGP is sufficient to confer resistance to NHS. Many strategies were tested in order to correctly expressing TGSGP in T.b.brucei; in none of these transfectants was TGSGP correctly located in the flagellar pocket as is the case in T.b.gambiense and only partial resistance was ever obtained. In order to identify the factors in human serum that could interacts with TGSGP, we subjected NHS to affinity chromatography using TGSGP as bait. We showed that TGSGP interacts with APOA-I, a major component of HDLs.
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The role of sensory history and stimulus context in human time perception : adaptive and integrative distortions of perceived durationFulcher, Corinne January 2017 (has links)
This thesis documents a series of experiments designed to investigate the mechanisms subserving sub-second duration processing in humans. Firstly, duration aftereffects were generated by adapting to consistent duration information. If duration aftereffects represent encoding by neurons selective for both stimulus duration and non-temporal stimulus features, adapt-test changes in these features should prevent duration aftereffect generation. Stimulus characteristics were chosen which selectively target differing stages of the visual processing hierarchy. The duration aftereffect showed robust interocular transfer and could be generated using a stimulus whose duration was defined by stimuli invisible to monocular mechanisms, ruling out a pre-cortical locus. The aftereffects transferred across luminance-defined visual orientation and facial identity. Conversely, the duration encoding mechanism was selective for changes in the contrast-defined envelope size of a Gabor and showed broad spatial selectivity which scaled proportionally with adapting stimulus size. These findings are consistent with a second stage visual spatial mechanism that pools input across proportionally smaller, spatially abutting filters. A final series of experiments investigated the pattern of interaction between concurrently presented cross-modal durations. When duration discrepancies were small, multisensory judgements were biased towards the modality with higher precision. However, when duration discrepancies were large, perceived duration was compressed by both longer and shorter durations from the opposite modality, irrespective of unimodal temporal reliability. Taken together, these experiments provide support for a duration encoding mechanism that is tied to mid-level visual spatial processing. Following this localised encoding, supramodal mechanisms then dictate the combination of duration information across the senses.
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The Chronology of Abrupt Climate Change and Late Upper Palaeolithic Human Adaptation in EuropeBlockley, S.P.E., Blockley, S.M., Donahue, Randolph E., Lane, C.S., Lowe, J.J., Pollard, A. Mark January 2006 (has links)
No / his paper addresses the possible connections between the onset of human expansion in Europe following the Last Glacial Maximum, and the timing of abrupt climate warming at the onset of the Lateglacial (Bölling/Allerød) Interstadial. There are opposing views as to whether or not human populations and activities were directly forced by climate change, based on different comparisons between archaeological and environmental data. We review the geochronological assumptions and approaches on which data comparisons have been attempted in the past, and argue that the uncertainties presently associated with age models based on calibrated radiocarbon dates preclude robust testing of the competing models, particularly when comparing the data to non-radiocarbon-based timescales such as the Greenland ice core records. The paper concludes with some suggestions as to the steps that will be necessary if more robust tests of the models are to be developed in the future.
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Characterisation of the mechanism of human serum resistance in T.b.gambienseFelu, Cécile 15 September 2006 (has links)
The two human pathogenic sub-species T.b.gambiense and T.b.rhodesiense can be distinguished from the morphologically identical T.b.brucei by their ability to infect humans, enabling them to cause sleeping sickness. This is because they are resistant to lysis by the lytic factor (APOL-I) present in normal human serum (NHS). In T.b.rhodesiense resistance to this lytic factor is due to a truncated VSG gene termed SRA which blocks lysis by interacting with APOL-I in the lysosome. SRA does not exist in T.b.gambiense. The search for a similar truncated VSG gene lead to the identification of a T.b.gambiense specific glycoprotein termed TGSGP. TGSGP transfected alone into the sensitive T.b.brucei is unable to confer resistance to this sub-species. This is either due to incorrect processing of this gene is this sub-species or because TGSGP requires a partner to confer resistance.<p><p>In the search for a partner, the genomic locus of TGSGP was cloned and sequenced. We found that TGSGP is linked to a truncated gene homologous to the S.cerevisiae AUT1 gene, a gene implicated in autophagy and more specifically in membrane expansion. Southern blot hybridization and PCR analysis on genomic DNA from several isolates demonstrated that this feature was a specific to T.b.gambiense. In addition, we observed a correlation between the aut1 allele size and the geographical origin of the isolate.<p><p>Since in trypanosomes lysis by NHS is due to an uncontrolled expansion of the lysosome, we speculated that the truncation of the aut1 allele could be implication in the resistance to human serum. We characterized the genomic organisation of the AUT1 locus. T.b.brucei possesses two native AUT1 alleles whilst T.b.gambiense possesses a truncated aut1 allele, as well as a native AUT1 allele. We showed that in the T.b.gambiense LiTAR isolate (aut1/AUT1), despite the presence of a wild-type allele this gene is no longer expressed at the mRNA and protein level. Our complimentary results by run-on transcription assay showed that the AUT1 region is transcribed but that the messenger is unstable. LiTAR is a functional knock-out for AUT1, but Northern blot analysis on several T.b.gambiense isolates showed that this is not a generalised T.b.gambiense characteristic. <p><p>We explored the role of AUT1 in trypanosomes by invalidation of the AUT1 gene in T.b.brucei and by the over-expression of the AUT1 and aut1 alleles in T.b.brucei. By functional analysis of AUT1 knocked-down cells we showed that AUT1 is not essential in trypanosomes. By recreating in T.b.brucei the T.b.gambiense AUT1/aut1 genotype we were able to show that the expression of the aut1 UTR down-regulated the expression of the wild-type AUT1 allele. We speculated that this may be due to a natural RNAi mechanism. Par northern blot, using probes covering the potential target region of AUT1, we detected a 50nt small RNA specific to T.b.gambiense. In addition, we showed that in a LiTAR strain in which the RNAi pathway was abolished AUT1 expression is restored. <p><p>We continued to investigate TGSGP’s role in the resistance to human serum by invalidation of TGSGP in T.b.gambiense and by expressing TGSGP in the NHS-sensitive T.b.brucei. Because T.b.gambiense cannot be cultured in vitro we established a new in vivo transfection technique and as the knock-out of TGSGP is most probably lethal, we created an inducible RNAi T.b.gambiense cell strain. These indispensable tools will be used to test whether invalidation TGSGP is sufficient to confer resistance to NHS. Many strategies were tested in order to correctly expressing TGSGP in T.b.brucei; in none of these transfectants was TGSGP correctly located in the flagellar pocket as is the case in T.b.gambiense and only partial resistance was ever obtained. In order to identify the factors in human serum that could interacts with TGSGP, we subjected NHS to affinity chromatography using TGSGP as bait. We showed that TGSGP interacts with APOA-I, a major component of HDLs.<p> / Doctorat en sciences, Spécialisation biologie moléculaire / info:eu-repo/semantics/nonPublished
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An exploratory study of psychological resilience factors associated with climate change adaptation by subsistence farmers in a rural community in Maruleng, Limpopo ProvinceKgopa, Bontle Patience January 2022 (has links)
Thesis (Ph.D. (Psychology)) -- University of Limpopo, 2022 / Climate change poses a major threat to both the well-being of people and the
environment. Subsistence farmers are particularly affected because they rely on local
supply systems that are sensitive to climate variation. The aim of the study was to
explore psychological resilience factors associated with climate change adaptation by
subsistence farmers in a rural farming community in Maruleng Municipality in Limpopo
Province (South Africa). The objectives of the study were to: investigate subsistence
farmers' notions of climate change and adaptation; determine the psychological resilience
factors influencing the farmers’ adaptation the climate change; determine strategies that
the farmers use to cope with climate change; and, based on the farmers’ notions of
climate change and adaptation, and the associated resilience factors, develop a
psychological explanatory model on climate change adaptation by subsistence farmers.
Data were collected through direct interactions with participants using a grounded theory
research design. An open-ended interview guide was used to collect data with a sample
of 15 participants selected through theoretical sampling within the Maruleng Municipality.
The research findings indicate that farmers have limited conceptual knowledge relating
to climate change and its causes. The results further indicated that participants have
become resilient to climate change through mitigation strategies including mulching,
adaptive irrigation techniques and being innovative. From a psychological perspective,
the subsistence farmers’ resilience factors that emerged included passion for farming,
hope, enthusiasm, courage, acceptance or tolerance, livelihood and a coherent belief
system. Based on the findings of the study, a psychological explanatory model in climate
change adaptation by subsistence farmers was developed. The explanatory model
suggests that resilience factors are influenced by notions and adaptations of climate
change. The study is concluded by, among others, recommending that counseling
services be made available to farmers to help them deal with the stress associated with
the negative impact of climate change.
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Urban Space Recreation for Pedestrians through Smart Lighting Control SystemsKaragöz, Hande January 2018 (has links)
Connected public lighting for more sustainable and liveable cities is highly demanding research in lighting design field through human centred design approach. While following this understanding, this thesis aims to answer the question “How a networked public lighting can be created in order to enhance the needs of the pedestrians in Fredhällspark?”. To investigate this study, a background research was studied in the relevant topics of urban lighting, followed by the study of human safety regarding to this topic and lastly the possible new lighting technologies. The main study is involved in a pedestrian path at Fredhällspark in Stockholm, Sweden, in two months duration in the spring time of 2018 by conducting user surveys and taking the lighting measurements. Based on the results the study showed, a lighting design proposal is developed with a site-specific approach in order to make it up-to date and sustainable for future urban environments while complying with the requirements of the users.
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Pittsburgh's Identity: Investigating the Relationship between Geography, Geology and the City's Social DevelopmentKirsch, Alexandra N. 07 May 2020 (has links)
No description available.
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Co-adaptive myoelectric control for upper limb prosthesesIgual Bañó, Carles 21 June 2021 (has links)
[ES] Mucha gente en el mundo se ve afectada por la pérdida de una extremidad (las predicciones estiman que en 2050 habrá más de 3 millones de personas afectadas únicamente en los Estados Unidos de América). A pesar de la continua mejora en las técnicas de amputación y la prostética, vivir sin una extremidad sigue limitando las actividades de los afectados en su vida diaria, provocando una disminución en su calidad de vida. En este trabajo nos centramos en los casos de amputaciones de extremidades superiores, entendiendo por ello la pérdida de cualquier parte del brazo o antebrazo.
Esta tesis trata sobre el control mioeléctrico (potenciales eléctricos superficiales generados por la contracción de los músculos) de prótesis de extremidades superiores. Los estudios en este campo han crecido exponencialmente en las últimas décadas intentando reducir el hueco entre la parte investigadora más dinámica y propensa a los cambios e innovación (por ejemplo, usando técnicas como la inteligencia artificial) y la industria prostética, con una gran inercia y poco propensa a introducir cambios en sus controladores y dispositivos. El principal objetivo de esta tesis es desarrollar un nuevo controlador implementable basado en filtros adaptativos que supere los principales problemas del estado del arte.
Desde el punto de vista teórico, podríamos considerar dos contribuciones principales. Primero, proponemos un nuevo sistema para modelar la relación entre los patrones de la señales mioélectricas y los movimientos deseados; este nuevo modelo tiene en cuenta a la hora de estimar la posición actual el valor de los estados pasados generando una nueva sinergia entre máquina y ser humano. En segundo lugar, introducimos un nuevo paradigma de entrenamiento más eficiente y personalizado autónomamente, el cual puede aplicarse no sólo a nuestro nuevo controlador, sino a otros regresores disponibles en la literatura. Como consecuencia de este nuevo protocolo, la estructura humano-máquina difiere con respecto del actual estado del arte en dos características: el proceso de aprendizaje del controlador y la estrategia para la generación de las señales de entrada.
Como consecuencia directa de todo esto, el diseño de la fase experimental resulta mucho más complejo que con los controladores tradicionales. La dependencia de la posición actual de la prótesis con respecto a estados pasados fuerza a la realización de todos los experimentos de validación del nuevo controlador en tiempo real, algo costoso en recursos tanto humanos como de tiempo. Por lo tanto, una gran parte de esta tesis está dedicada al trabajo de campo necesario para validar el nuevo modelo y estrategia de entrenamiento. Como el objetivo final es proveer un nuevo controlador implementable, la última parte de la tesis está destinada a testear los métodos propuestos en casos reales, tanto en entornos simulados para validar su robustez ante rutinas diarias, como su uso en dispositivos prostéticos comerciales.
Como conclusión, este trabajo propone un nuevo paradigma de control mioélectrico para prótesis que puede ser implementado en una prótesis real. Una vez se ha demostrado la viabilidad del sistema, la tesis propone futuras líneas de investigación, mostrando algunos resultados iniciales. / [CA] Molta gent en el món es veu afectada per la pèrdua d'una extremitat (les prediccions estimen que en 2050 hi haurà més de 3 milions de persones afectades únicament als Estats Units d'Amèrica). Malgrat la contínua millora en les tècniques d'amputació i la prostètica, viure sense una extremitat continua limitant les activitats dels afectats en la seua vida diària, provocant una disminució en la seua qualitat de vida. En aquest treball ens centrem en els casos d'amputacions d'extremitats superiors, entenent per això la pèrdua de qualsevol part del braç o avantbraç.
Aquesta tesi tracta sobre el control mioelèctric (potencials elèctrics superficials generats per la contracció dels músculs) de pròtesis d'extremitats superiors. Els estudis en aquest camp han crescut exponencialment en les últimes dècades intentant reduir el buit entre la part investigadora més dinàmica i propensa als canvis i innovació (per exemple, usant tècniques com la intel·ligència artificial) i la indústria prostètica, amb una gran inèrcia i poc propensa a introduir canvis en els seus controladors i dispositius. Aquesta tesi contribueix a la investigació des de diversos punts de vista. El principal objectiu és desenvolupar un nou controlador basat en filtres adaptatius que supere els principals problemes de l'estat de l'art.
Des del punt de vista teòric, podríem considerar dues contribucions principals. Primer, proposem un nou sistema per a modelar la relació entre els patrons de la senyals mioelèctrics i els moviments desitjats; aquest nou model té en compte a l'hora d'estimar la posició actual el valor dels estats passats generant una nova sinergia entre màquina i ésser humà. En segon lloc, introduïm un nou paradigma d'entrenament més eficient i personalitzat autònomament, el qual pot aplicar-se no sols al nostre nou controlador, sinó a uns altres regresors disponibles en la literatura. Com a conseqüència d'aquest nou protocol, l'estructura humà-màquina difereix respecte a l'actual estat de l'art en dues característiques: el procés d'aprenentatge del controlador i l'estratègia per a la generació dels senyals d'entrada.
Com a conseqüència directa de tot això, el disseny de la fase experimental resulta molt més complex que amb els controladors tradicionals. La dependència de la posició actual de la pròtesi respecte a estats passats força a la realització de tots els experiments de validació del nou controlador en temps real, una cosa costosa en recursos tant humans com de temps. Per tant, una gran part d'aquesta tesi està dedicada al treball de camp necessari per a validar el nou model i estratègia d'entrenament. Com l'objectiu final és proveir un nou controlador implementable, l'última part de la tesi està destinada a testar els mètodes proposats en casos reals, tant en entorns simulats per a validar la seua robustesa davant rutines diàries, com el seu ús en dispositius prostètics comercials.
Com a conclusió, aquest treball proposa un nou paradigma de control mioelèctric per a pròtesi que pot ser implementat en una pròtesi real. Una vegada s'ha demostrat la viabilitat del sistema, la tesi proposa futures línies d'investigació, mostrant alguns resultats inicials. / [EN] Many people in the world suffer from the loss of a limb (predictions estimate more than 3 million people by 2050 only in the USA). In spite of the continuous improvement in the amputation rehabilitation and prosthetic restoration, living without a limb keeps limiting the daily life activities leading to a lower quality of life. In this work, we focus in the upper limb amputation case, i.e., the removal of any part of the arm or forearm.
This thesis is about upper limb prosthesis control using electromyographic signals (the superficial electric potentials generated during muscle contractions). Studies in this field have grown exponentially in the past decades trying to reduce the gap between a fast growing prosthetic research field, with the introduction of machine learning, and a slower prosthetic industry and limited manufacturing innovation. This thesis contributes to the field from different perspectives. The main goal is to provide and implementable new controller based on adaptive filtering that overcomes the most common state of the art concerns.
From the theoretical point of view, there are two main contributions. First, we propose a new system to model the relationship between electromyographic signals and the desired prosthesis movements; this new model takes into account previous states for the estimation of the current position generating a new human-machine synergy. Second, we introduce a new and more efficient autonomously personalized training paradigm, which can benefit not only to our new proposed controller but also other state of the art regressors. As a consequence of this new protocol, the human-machine structure differs with respect to current state of the art in two features: the controller learning process and the input signal generation strategy.
As a direct aftereffect of all of this, the experimental phase design results more complex than with traditional controllers. The current state dependency on past states forces the experimentation to be in real time, a very high demanding task in human and time resources. Therefore, a major part of this thesis is the associated fieldwork needed to validate the new model and training strategy. Since the final goal is to provide an implementable new controller, the last part of the thesis is devoted to test the proposed methods in real cases, not only analyzing the robustness and reliability of the controller in real life situations but in real prosthetic devices.
As a conclusion, this work provides a new paradigm for the myoelectric prosthetic control that can be implemented in a real device. Once the thesis has proven the system's viability, future work should continue with the development of a physical device where all these ideas are deployed and used by final patients in a daily basis. / The work of Carles Igual Bañó to carry out this research and elaborate this dissertation has been supported by the Ministerio de Educación, Cultura y Deporte under the FPU Grant FPU15/02870. One visiting research fellowships (EST18/00544) was also funded by the Ministerio de Educación, Cultura y Deporte of Spain. / Igual Bañó, C. (2021). Co-adaptive myoelectric control for upper limb prostheses [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/168192
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