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1
Burgess, Vanessa Anne, i n/a. "Toxicology Investigations With The Pectenotoxin-2 Seco Acids". Griffith University. School of Public Health, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030905.090222.
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Pectenotoxins (PTXs) are a group of large cyclic polyether compounds associated with diarrhetic shellfish poisoning (DSP) as they are often found in combination with other DSPs such as okadaic acid (OA) and dinophysis toxins (DTXs) in shellfish. Although classified and regulated with the DSPs, there is debate over whether these toxins should be classified with DSP toxins. To date, ten different analogues of PTXs have been identified from shellfish and algae, and of these, the pectenotoxin-2 seco acids (PTX2-SAs) are of particular interest as they have previously been implicated in a shellfish poisoning incident in Australia, but relatively little was known of their toxicology. One such incident occurred in December 1997, when approximately 200 people were reported with severe diarrhoetic shellfish poisoning in Northern New South Wales (NSW). Analysis of the shellfish associated with this incident revealed relatively high PTX2-SA concentrations (approx. 300 micrograms/kg shellfish meat), with only trace amounts of pectenotoxin-2 (PTX2) and OA. Following this incident, PTX2-SAs were considered a health threat and guidelines were implemented in the absence of toxicological data, which has caused a great economic burden to shellfish industries around the globe, in particular to Australia, New Zealand and Ireland. Such regulation created in the absence of scientific data demonstrated the need to determine the toxicology of PTX2-SAs in commercial shellfish. Thus a comprehensive study on the toxicology and possible health implications of the PTX2-SAs in Australian shellfish was conducted. PTX2-SAs were isolated in different batches from shellfish (pipis, oysters and mussels) and from algal bloom samples of Dinophysis caudata. Toxin extraction was conducted with several purification stages and chemical analysis was performed with high-performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). The chemical stability of the PTX2-SAs was investigated to ensure consistency of doses between toxicology experiments. Acute dosing studies with mice were then performed and included toxicopathology investigations with light microscopy and electron microscopy, in addition to toxin distribution studies and investigation of in vivo lipid peroxidation. In vitro studies with HepG2 cells included cytotoxicity assays, cell cycle investigations using flow cytometry and gene expression profiling of cells exposed to PTX2-SAs employing cDNA microarray technology. Acute pathology studies demonstrated that the PTX2-SAs do not cause the characteristic symptoms or lesions associated with DSP toxins. No diarrhoea was observed at any dose level in mice and no deaths occurred up to the maximum dosing level of 1.6mg/kg PTX2-SA. Only one batch of PTX2-SA extract produced toxic lesions characteristic of a DSP toxin (batch 1-pilot study) but after follow up studies, it was determined that this first batch of shellfish most likely contained an additional unidentified shellfish toxin or contaminant that co-extracted with PTX2-SAs during toxin isolation and purification procedures. This finding highlighted the importance of supporting the inclusion of the mice bioassay in procedures for shellfish toxin testing to enable detection of new toxins, and also highlighted the importance of toxin purification for toxicology studies. A significant rise in malondialdehyde excretion was observed within 24 hours of dosing mice, indicating that the PTX2-SAs may cause damage by lipid peroxidation in vivo. In vitro studies showed HepG2 cells to have cell cycle and gene expression changes within 24 hours of a dose of 800ng/mL PTX2-SAs. Cell cycle arrest was observed at the G2/M checkpoint and gene expression changes included alterations in genes involved in cell cycle control, lipid metabolism and transport, lipid genesis and trace metal transport. Many genes involved in DNA repair processes were moderated at the 24 hour point, but as no apoptosis was observed up to 72 hours post dosing it is a promising indication that any DNA damage that may have been caused by the administration of PTX2-SAs was not lethal, and was able to be repaired. In light of the information provided by toxicology investigations in this PhD, with particular reference to evidence of in vivo lipid peroxidation by raised levels of MDA in mouse urine, and changes in cell cycle distribution and gene expression in a cultured human cell line, it is concluded that there is potential for these toxins to induce biological changes in mammalian cells in vivo and in vitro, and hence potential for PTX2-SAs to cause health effects in humans. During the course of this three-year study, developments in techniques for shellfish toxin identification within our laboratories have revealed that the shellfish responsible for the 1997 NSW poisoning incident contained significant concentrations of okadaic acid acyl esters that were not detected at the time of the NSW incident. Although reportedly less toxic than okadaic acid itself, the OA ester concentrations present may have been sufficient to cause the observed symptoms. It is also theorized that these esters could be hydrolyzed in the human gastro-intestinal tract to release okadaic acid. In the light of this new evidence and with no pathology lesions or symptoms of diarrhoea being observed in PTX2-SA dosing studies with mice, we now believe these OA acyl esters to be the causative agent in the 1997 NSW DSP incident and not the PTX2-SAs. Nothing is currently known of the chronic toxicology of PTX2-SAs and thus their potential implications to public health in the long term cannot determined. The toxicology investigations in this thesis were acute studies, and it has not been established if the observed changes could be repaired or returned within normal limits without the manifestation of illness or disease occurring. Utilizing the acute toxicology information in this thesis, a health risk assessment for consumption of PTX2-SA contaminated shellfish was performed. This risk assessment, employing numerous safety factors essential for an incomplete data set, produced guideline values that are lower than the current recommend concentrations. To date, there has been no solid evidence that PTX2-SAs cause illness in humans all documented incidents involving the PTX2-SAs have also included other DSP contaminants that are known to cause human illness. Pathology has not unequivocally been demonstrated in animal studies and thus, in consideration of the epidemiological evidence, PTX2-SAs cannot be considered as high a risk to public health as was previously thought. For the reasons discussed above, and weighing up risk-benefit considerations of the economic burden the current guideline values are causing to shellfish industries around the globe, it is recommended that levels of PTX2-SAs be monitored in recognition of the precautionary principle, but no longer regulated as tightly with other DSPs until such a time that toxicological or epidemiological evidence can prove that the PTX2-SAs are a DSP and are a more considerable threat to human health than has been indicated by toxicology studies in this thesis. This study has produced a substantial amount of acute toxicology data and has provided a good basis for future chronic toxicology investigations with the PTX2-SAs for regulatory purposes.
2
Burgess, Vanessa Anne. "Toxicology Investigations With The Pectenotoxin-2 Seco Acids". Thesis, Griffith University, 2003. http://hdl.handle.net/10072/365382.
Pełny tekst źródłaStreszczenie:
Pectenotoxins (PTXs) are a group of large cyclic polyether compounds associated with diarrhetic shellfish poisoning (DSP) as they are often found in combination with other DSPs such as okadaic acid (OA) and dinophysis toxins (DTXs) in shellfish. Although classified and regulated with the DSPs, there is debate over whether these toxins should be classified with DSP toxins. To date, ten different analogues of PTXs have been identified from shellfish and algae, and of these, the pectenotoxin-2 seco acids (PTX2-SAs) are of particular interest as they have previously been implicated in a shellfish poisoning incident in Australia, but relatively little was known of their toxicology. One such incident occurred in December 1997, when approximately 200 people were reported with severe diarrhoetic shellfish poisoning in Northern New South Wales (NSW). Analysis of the shellfish associated with this incident revealed relatively high PTX2-SA concentrations (approx. 300 micrograms/kg shellfish meat), with only trace amounts of pectenotoxin-2 (PTX2) and OA. Following this incident, PTX2-SAs were considered a health threat and guidelines were implemented in the absence of toxicological data, which has caused a great economic burden to shellfish industries around the globe, in particular to Australia, New Zealand and Ireland. Such regulation created in the absence of scientific data demonstrated the need to determine the toxicology of PTX2-SAs in commercial shellfish. Thus a comprehensive study on the toxicology and possible health implications of the PTX2-SAs in Australian shellfish was conducted. PTX2-SAs were isolated in different batches from shellfish (pipis, oysters and mussels) and from algal bloom samples of Dinophysis caudata. Toxin extraction was conducted with several purification stages and chemical analysis was performed with high-performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). The chemical stability of the PTX2-SAs was investigated to ensure consistency of doses between toxicology experiments. Acute dosing studies with mice were then performed and included toxicopathology investigations with light microscopy and electron microscopy, in addition to toxin distribution studies and investigation of in vivo lipid peroxidation. In vitro studies with HepG2 cells included cytotoxicity assays, cell cycle investigations using flow cytometry and gene expression profiling of cells exposed to PTX2-SAs employing cDNA microarray technology. Acute pathology studies demonstrated that the PTX2-SAs do not cause the characteristic symptoms or lesions associated with DSP toxins. No diarrhoea was observed at any dose level in mice and no deaths occurred up to the maximum dosing level of 1.6mg/kg PTX2-SA. Only one batch of PTX2-SA extract produced toxic lesions characteristic of a DSP toxin (batch 1-pilot study) but after follow up studies, it was determined that this first batch of shellfish most likely contained an additional unidentified shellfish toxin or contaminant that co-extracted with PTX2-SAs during toxin isolation and purification procedures. This finding highlighted the importance of supporting the inclusion of the mice bioassay in procedures for shellfish toxin testing to enable detection of new toxins, and also highlighted the importance of toxin purification for toxicology studies. A significant rise in malondialdehyde excretion was observed within 24 hours of dosing mice, indicating that the PTX2-SAs may cause damage by lipid peroxidation in vivo. In vitro studies showed HepG2 cells to have cell cycle and gene expression changes within 24 hours of a dose of 800ng/mL PTX2-SAs. Cell cycle arrest was observed at the G2/M checkpoint and gene expression changes included alterations in genes involved in cell cycle control, lipid metabolism and transport, lipid genesis and trace metal transport. Many genes involved in DNA repair processes were moderated at the 24 hour point, but as no apoptosis was observed up to 72 hours post dosing it is a promising indication that any DNA damage that may have been caused by the administration of PTX2-SAs was not lethal, and was able to be repaired. In light of the information provided by toxicology investigations in this PhD, with particular reference to evidence of in vivo lipid peroxidation by raised levels of MDA in mouse urine, and changes in cell cycle distribution and gene expression in a cultured human cell line, it is concluded that there is potential for these toxins to induce biological changes in mammalian cells in vivo and in vitro, and hence potential for PTX2-SAs to cause health effects in humans. During the course of this three-year study, developments in techniques for shellfish toxin identification within our laboratories have revealed that the shellfish responsible for the 1997 NSW poisoning incident contained significant concentrations of okadaic acid acyl esters that were not detected at the time of the NSW incident. Although reportedly less toxic than okadaic acid itself, the OA ester concentrations present may have been sufficient to cause the observed symptoms. It is also theorized that these esters could be hydrolyzed in the human gastro-intestinal tract to release okadaic acid. In the light of this new evidence and with no pathology lesions or symptoms of diarrhoea being observed in PTX2-SA dosing studies with mice, we now believe these OA acyl esters to be the causative agent in the 1997 NSW DSP incident and not the PTX2-SAs. Nothing is currently known of the chronic toxicology of PTX2-SAs and thus their potential implications to public health in the long term cannot determined. The toxicology investigations in this thesis were acute studies, and it has not been established if the observed changes could be repaired or returned within normal limits without the manifestation of illness or disease occurring. Utilizing the acute toxicology information in this thesis, a health risk assessment for consumption of PTX2-SA contaminated shellfish was performed. This risk assessment, employing numerous safety factors essential for an incomplete data set, produced guideline values that are lower than the current recommend concentrations. To date, there has been no solid evidence that PTX2-SAs cause illness in humans – all documented incidents involving the PTX2-SAs have also included other DSP contaminants that are known to cause human illness. Pathology has not unequivocally been demonstrated in animal studies and thus, in consideration of the epidemiological evidence, PTX2-SAs cannot be considered as high a risk to public health as was previously thought. For the reasons discussed above, and weighing up risk-benefit considerations of the economic burden the current guideline values are causing to shellfish industries around the globe, it is recommended that levels of PTX2-SAs be monitored in recognition of the precautionary principle, but no longer regulated as tightly with other DSPs until such a time that toxicological or epidemiological evidence can prove that the PTX2-SAs are a DSP and are a more considerable threat to human health than has been indicated by toxicology studies in this thesis. This study has produced a substantial amount of acute toxicology data and has provided a good basis for future chronic toxicology investigations with the PTX2-SAs for regulatory purposes.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Public Health
Faculty of Health Sciences
Full Text
3
Rodriguez, Grande Beatriz. "The role of PTX3 in brain inflammation and repair". Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-ptx3-in-brain-inflammation-and-repair(b80f9c46-f81b-44a0-af27-efc932a6bd38).html.
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Pentraxin 3 (PTX3) is an acute phase protein which regulates peripheral inflammationand it has been suggested to have neuroprotective properties. Inflammation iscommonly associated with poor outcome during diverse central nervous system (CNS)disorders, but the role of PTX3 in brain inflammation is completely unknown. Westudied the role of PTX3 in brain inflammation and repair after stroke, a CNS disorderwhich is the third cause of death worldwide. To induce ischaemic stroke, we used themiddle cerebral artery occlusion (MCAo) model and found that the pro-inflammatorycytokine interleukin (IL)-1 was the inducer of PTX3 expression in the brain. Theanalysis of markers of inflammation and repair up to 14 days after MCAo in wild typeand PTX3 knockout (KO) mice revealed that, in general, lack of PTX3 has a negativeeffect on recovery after MCAo. PTX3 KO mice had delayed oedema resolution,defective glial scar, impaired microglial proliferation and reduced angiogenesis andneurogenesis. Therefore, PTX3 emerges as a target for stroke recovery and possiblyother CNS inflammatory diseases. PTX3 was, however, not involved in remoteneurodegeneration in the substantia nigra (SN) (an area of the brain remote butconnected with the area affected by the stroke), but we observed that remoteinflammation preceded remote neuronal death in the SN. Therefore, prevention ofremote inflammation may help prevent remote neurodegeneration in the SN afterstroke. This could have long term implications in SN neurodegeneration, which is akey pathological feature of Parkinson´s disease.
4
Izuogu, Ginikachukwu Osagie. "Mechanisms and impact of Post-transcriptional Exon Shuffling (PTES)". Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3738.
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Most eukaryotic genes undergo splicing to remove introns and join exons sequentially to produce protein-coding or non-coding transcripts. Post-transcriptional Exon Shuffling (PTES) describes a new class of RNA molecules, characterized by exon order different from the underlying genomic context. PTES can result in linear and circular RNA (circRNA) molecules and enhance the complexity of transcriptomes. Prior to my studies, I developed PTESFinder, a computational tool for PTES identification from high-throughput RNAseq data. As various sources of artefacts (including pseudogenes, template-switching and others) can confound PTES identification, I first assessed the effectiveness of filters within PTESFinder devised to systematically exclude artefacts. When compared to 4 published methods, PTESFinder achieves the highest specificity (~0.99) and comparable sensitivity (~0.85). To define sub-cellular distribution of PTES, I performed in silico analyses of data from various cellular compartments and revealed diverse populations of PTES in nuclei and enrichment in cytosol of various cell lines. Identification of PTES from chromatin-associated RNAseq data and an assessment of co-transcriptional splicing, established that PTES may occur during transcription. To assess if PTES contribute to the proteome, I analyzed sucrose-gradient fractionated data from HEK293, treated with arsenite to induce translational arrest and dislodge ribosomes. My results showed no effect of arsenite treatment on ribosome occupancy within PTES transcripts, indicating that these transcripts are not generally bound by polysomes and do not contribute to the proteome. To investigate the impact of differential degradation on expression levels of linear and circRNAs, I analyzed the PTES population within RNAseq data of anucleate cells and established that most PTES transcripts are circular and are enriched in platelets 17-to-188-fold relative to nucleated tissues. For some genes, only reads from circRNA exons were detectable, suggesting that platelets have lost >90% of their progenitor mRNAs, consistent with timedependent degradation of platelets transcriptomes. However, some circRNAs exhibit read density patterns suggestive of miRNA induced degradation. Finally, a linear PTES from RMST locus has been implicated in pluripotency maintenance using limited RNAseq data from human embryonic stem cells (hESC). To identify other PTES transcripts with similar expression patterns, I analyzed RNAseq data from H9 ESC differentiation series. Statistical analyses of PTES transcripts identified during cellular differentiation established that PTES expression changes track with that of cognate linear transcripts and accumulate upon differentiation. Contrary to previous reports, the dominant transcript from RMST is circular and increases in abundance during differentiation. Functional Abstract iii analyses demonstrating the role of RMST in pluripotency maintenance had targeted exons within the predicted circRNA, suggesting previously unreported functional relevance for circRNAs.
5
Slusher, Aaron L. "COUNTERREGULATORY EFFECTS OF PTX3 ON INFLAMMATION AND CELLULAR AGING". VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5287.
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Pentraxin 3 (PTX3) is a vital regulator of innate immune function that has been shown to counterregulate pro-inflammatory signaling and protect against the development of cardiovascular disease (CVD). Less is known about how PTX3 may mitigate against CVD risk by regulating the pro-inflammatory response at the cellular level. Therefore, this dissertation details four manuscripts which aimed to examine the capacity of PTX3 to regulate the innate immune response of peripheral blood mononuclear cells (PBMCs) isolated from healthy adults. Manuscript 1 examined the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of isolated PBMCs with the pro-inflammatory lipid palmitate. In addition, Manuscript 2 sought to examine how participation in acute exercise, a powerful anti-inflammatory behavior that reduces CVD risk, alters the inflammatory phenotype and response of mononuclear cells following ex vivo stimulation with lipopolysaccharide (LPS). Manuscript 3 aimed to further elucidate the potential impact of cardiorespiratory fitness on the capacity of PTX3 to stimulate an innate immune response prior to and immediately following acute exercise in aerobically trained and untrained individuals. Finally, Manuscript 4 investigated the impact of healthy aging on plasma PTX3 concentrations and its relationship with telomere length in middle-aged compared to young adults. The capacity of isolated PBMCs to express a key cellular mechanism involved in maintaining longer telomere lengths, human telomerase reverse transcriptase (hTERT), following cellular stimulation with LPS, PTX3, and PTX3+LPS was also examined to address a mechanism that might explain how persistent exposure of circulating immune cells to the age-related pro-inflammatory milieu contributes to the shortening of telomere lengths.
6
Harvey, Thomas Grierson. "Nonlinear optics of the polydiacetylene pTS". Thesis, Heriot-Watt University, 1991. http://hdl.handle.net/10399/874.
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Oliveira, Mirian Maria de. "O SONHO DA MORADIA DIGNA – PROGRAMA MINHA CASA MINHA VIDA - ENTIDADES GOIÂNIA DE 2009 A 2015". Pontifícia Universidade Católica de Goiás, 2017. http://tede2.pucgoias.edu.br:8080/handle/tede/3819.
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This paper analyzes the Housing Policy in Brazil, in particular Social Interest Housing, focusing on the My House My Life Entities Program in the city of Goiânia from 2009 to 2015. How was the work of the social worker performed in the Technical Work Projects (PTTS) of the Harmonia, Jardim Botânico I and Eldorado Oeste IV Housing Settlements, built by Associations attached to Movements of Housing Movements of the State of Goiás. Families moving to their homes begin to face problems such as distance, lack of Public equipment , security and others. The struggle of entities seeking to provide decent housing for the homeless has been working according to the criteria required by the Minha Casa Minha Vida - Entities Program (PMCMV-E)
Este trabalho analisa a Política de Habitação no Brasil em especial a Habitação de Interesse Social, com foco no Programa Minha Casa Minha Vida Entidades na cidade de Goiânia nos anos de 2009 á 2015. Como foi realizado o trabalho do assistente social nos Projetos de Trabalho Técnico Social (PTTS) dos Conjuntos Habitacionais Harmonia, Jardim Botânico I e Eldorado Oeste IV construídos por Associações ligadas a Entidades dos Movimentos de Moradia do Estado de Goiás. As famílias ao mudarem para suas casas,começam a enfrentar problemas como a distância, a falta de equipamentos públicos, segurança e outros. A luta das entidades em busca de propiciar moradia digna aos sem teto, tem trabalhado de acordo com os critérios exigidos pelo Programa Minha Casa Minha Vida – Entidades (PMCMV-E).
8
Tremblay, Jacques. "Mécanisme d'action de PTX1, un facteur de transcription à homéodomaine". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq43040.pdf.
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Mishra, Gaurav. "Development of Person-Person Network and Interacting PTTS in EpiSimdemics". Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/64160.
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Communications over social media, telephone, email, text etc have emerged as an integral part of modern society and they are popularly used for the expression of anger, anxiety, fear, agitation and opinion by the people. People's social interaction tend to increase dramatically during periods of epidemics, protest and calamities. Therefore, above mentioned communication channels plays an important role in the spread of infectious phenomenon, like rumors, fads and effects. These infectious phenomena alters people's behavior during disease epidemic [1][2].
Social contact networks and epidemics co-evolve [1][2]. The spread of a disease influences people's behavior which in turn changes their social contact network, thereby altering the disease spread itself. As a result, there is a need for modeling the spread of these infectious phenomena that lead to changes in behavior. Their propagation among population primarily depends on the social contact network. The nature of social contagion spread is very similar to the spread of any infectious disease as they are contagious in nature. To spread contagious disease requires direct exposure to an infectious agent, whereas social contagions can be spread using various communications media like social networking forums, phones, emails and tweets.
EpiSimdemics is an individual-based modeling environment. It uses a people-location bipartite graph as the underlying network [3]. In its current form, EpiSimdemics requires two people to interact at a location to model simulations. Thus, it cannot simulate the spread of social contagions that do not necessarily require the meeting of two agents at a location.
We enhance EpiSimdemics by incorporating Person-Person network, which can model communications between people that are not contact based such as communications over email, phone, text and tweet. This Person-Person network is used to model effects (social contagion) which induce behavioral changes in population and thus impacting the disease spread. The disease spread is modeled on Person-Location network. This leads to the scenario of two interacting networks: Person-Person network modeling social contagion and Person-Location modeling disease. Theoretically, there can be multiple such networks modeling various interacting phenomena.
We demonstrate the usefulness of this network by modeling and simulating two interacting PTTSs (probabilistic timed transition systems). To model disease epidemics, we have defined Disease Model and to model effects (social contagion), we have defined Fear Model. We show how these models influence each other by performing simulations on EpiSimdemics with interacting Disease and Fear Model. Therefore a model that does not include the affect adaptations on disease epidemics and vice-versa, fails to reflect the actual behavior of a society during disease epidemic spread. The addition of Person-Person network to EpiSimdemics will allow for a better understanding of the affect adaptions, which can include behavior changes in society during an epidemic outbreak. This would lead to effective interventions and help to better understand the dynamics of disease epidemic.Master of Science
10
Padrão, Ana Isabel Martins Novais. "Estudo das PTMs do citocromo c cardíaco: efeitos do envelhecimento". Master's thesis, Universidade de Aveiro, 2009. http://hdl.handle.net/10773/3126.
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Mestrado em Métodos BiomolecularesOs mecanismos celulares e bioquímicos subjacentes à disfunção cardíaca associada ao envelhecimento encontram-se pouco esclarecidos e, menos compreendido é o papel do estilo de vida neste processo. No sentido de avaliar a influência do estilo de vida ao longo da vida na potencial perda de funcionalidade das proteínas cardíacas, em particular do citocromo c, utilizaram-se ratinhos C57BL/6 machos que foram sujeitos a um protocolo experimental para simular o envelhecimento sedentário e activo. Os animais foram depois sacrificados, isolaram-se as mitocôndrias do coração e procedeu-se à análise de vários parâmetros bioquímicos com o intuito de (i) avaliar a funcionalidade da cadeia respiratória mitocondrial, (ii) identificar as proteínas susceptíveis à carbonilação e/ou nitração, (iii) caracterizar as PTMs do citocromo c de coração. Os resultados obtidos sugerem a existência de uma relação entre a perda de funcionalidade mitocondrial associada ao envelhecimento e o aumento do teor de proteínas carboniladas e/ou nitradas. Como proteínas alvo destas modificações pós-traducionais (PTMs) foram identificadas várias subunidades dos complexos da fosforilação oxidativa. Pela sua importância neste sistema metabólico, analisou-se mais exaustivamente a susceptibilidade do citocromo c a PTMs resultantes de processos oxidativos e de que forma o estilo de vida regula este processo. Apesar de se ter verificado um aumento da expressão do citocromo c com o envelhecimento, o número e o tipo de PTMs identificadas por LC-MS/MS não seguiu a mesma tendência. Efectivamente, identificou-se um maior número de PTMs no citocromo c do homogeneizado total dos ratinhos jovens (12 PTMs) do que nos ratinhos velhos. Considerando o efeito do estilo de vida, verificou-se a existência nos animais activos de um maior número de resíduos de aminoácidos modificados (10 PTMs) do que nos sedentários (6 PTMs). Curiosamente, a oxidação da Met65 foi a única modificação oxidativa identificada no citocromo c da fracção mitocondrial, tendo sido observada nos ratinhos velhos sedentários. ABSTRACT: Cellular and biochemical mechanisms underlying the age-related cardiac dysfunction are not fully understood and, even less clarified is the influence of lifestyle in this process. In order to evaluate the role of lifelong lifestyle in the mitochondrial plasticity and in the potential functionality loss of cardiac proteins, in particular cytochrome c, to post-translational modifications (PTMs), C57BL/6 male mice were subjected to an experimental protocol simulating sedentary and active aging. After animal sacrifice, mitochondria from cardiac muscle were isolated and several biochemical parameters were measured (i) to evaluate the mitochondrial respiratory chain functionality, (ii) to identify the susceptible proteins to carbonylation and/or nitration, (iii) to characterize the PTMs of cardiac cytochrome c. The results suggest a link between the age-related decrease in mitochondrial functionality and the higher susceptibility of cardiac muscle proteins to oxidative damage. Indeed, we observed a significant increase in the content of carbonylated and/or nitrated proteins in old mice, being the oxidative phosphorylation subunits the most affected. Given the importance of cytochrome c as the final mobile electron carrier in this metabolic process, its susceptibility to PTMs induced by oxidative stress was characterized more exhaustively. Despite the age-induced upregulation of cytochrome c, the number of oxidative PTMs identified by LC-MS/MS was not increased. Indeed, a higher number of PTMs was identified in citochrome c from young mice total homogenate (12 PTMs) compared to old mice. Regarding the effect of lifestyle, old active mice presented more PTMs (10 PTMs) than their sedentary counterparts (6 PTMs). Interestingly, the Met65 oxidation was the only PTM identified in mitochondrial cytochrome c and only in old sedentary mice.
11
Larbret, Frédéric. "Impact des modifications post-traductionnelles sur la dynamique du cytosquelette". Thesis, Université Côte d'Azur (ComUE), 2017. http://www.theses.fr/2017AZUR4044.
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Le cytosquelette représente un élément crucial dans les processus cellulaires essentiels des cellules lymphoïdes. Les différents filaments du cytosquelette et leurs modes de régulation représentent donc des cibles thérapeutiques majeures pour le développement de nouveaux composés pharmacologiques. Au cours de ce travail de thèse, nous avons mis au point une nouvelle méthode d’analyse par cytométrie en flux (CytoFRET) permettant de visualiser simultanément la dynamique de polymérisation des filaments d’actine, des microtubules et des filaments intermédiaires de vimentine dans la lignée leucémique T Jurkat. Cette méthode a été utilisée pour le criblage d’une mini-chimiothèque composée d’inhibiteurs d’enzymes impliquées dans les modifications post-traductionnelles des protéines. Nous avons ainsi identifié deux composés, le WP1130 et le b-AP15, des inhibiteurs d’enzymes de déubiquitination (DUBs), comme puissants inducteurs de la polymérisation/nucléation de l’actine. Nous avons montré que l’effet de ces inhibiteurs sur les microfilaments d’actine est consécutif à une poly-ubiquitination de la Destrine, une protéine de liaison à l’actine. Nous avons également identifié des inhibiteurs des déacétylases HDAC6 et SIRT2 comme inducteurs de la polymérisation des microtubules et de l’assemblage de la vimentine. L’effet de ces inhibiteurs a été corrélé à une acétylation directe de la tubuline mais pas de la vimentine. Ces résultats ouvrent ainsi de nouvelles perspectives à la fois fondamentale et thérapeutique sur la physiopathologie du cytosquelette des cellules lymphoïdesActin, microtubules, and intermediate filaments compose three major cytoskeletal structures of vertebrate cells that are characterized by highly dynamic balances between assembly and de-assembly, underlying critical cellular processes such as mitosis, architecture and movement. Consequently, cytoskeleton dysfunctions have been implicated in several pathological situations including cell transformation and metastasis. Thus, cytoskeletal networks represent major targets for the development of novel anti-cancer and anti-metastatic therapies. However, drug development is currently limited by the availability of high-throughput screening systems allowing the simultaneous monitoring of actin, microtubules and intermediate filaments dynamics in living cells. In this work, we have developed a novel screening assay of cytoskeleton dynamics based on the simultaneous recording by flow cytometry of FRET signals produced by the variation of actin, tubulin and vimentin filaments dynamics in living cells. Our novel method was employed to screen a mini-library of drugs known for their ability to interfere with post-translationnal modifications of proteins. Interestingly, our approach revealed that compounds interfering with lysine acetylation have a dramatic impact on vimentin filaments assembly and microtubules polymerization. In addition, two inhibitors (WP1130 and b-AP15) of deubiquitinating enzymes showed increase of actin polymerization. This effect was attributed to poly-ubiquitnation of Destrin, an actin binding protein. In conclusion, our FRET multiplex flow cytometry assay represents a novel effective method for the future development of new anti-cancer therapies
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Hambruch, Eva. "Lipidinteraktion des peroxisomalen PTS-1 Importrezeptors Pex5p". [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=982341806.
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Hanson, Eleanor. "The epigenetics (histone PTMs) of therapeutic protein production in CHO cells". Thesis, University of Sheffield, 2019. http://etheses.whiterose.ac.uk/22945/.
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Chinese hamster ovary (CHO) cells are an important host cell system for the manufacturing of biopharmaceuticals. Epigenetics have been shown to have an important role in controlling gene expression in CHO cells, and thus affect the rate of protein production. It is hoped that by understanding the role of epigenetics in CHO cells improvements can be made in the production of biopharmaceuticals. In this work we have studied how histone PTMs differ between cell lines and throughout culture. These changes have then been correlated with growth rate, cell size and specific productivity. Mass spectrometry (MS) has been used as an unbiased quantitative technique to study how histone PTMs differ between four cell lines and throughout cell culture. The data generated in this study is the first global analysis of histone PTMs in CHO cells to date. The relative abundances of histone PTM were compared across different CHO-S and CHO-K1 cell lines with different productivities. Similar patterns of histone PTMs were observed. The most abundant modifications identified included H3K9me3, H4K20me2 and H3K27me1. Furthermore the results show no significant differences between different clones within a lineage, but the abundance of H3K23ac differed between lineages. In addition, the relative abundances of histone PTM for the different cell lines were compared throughout batch culture. Over 20 proteoforms were identified having different abundances at different stages of culture. The most prominent change was on H4K20 where methylation was progressive. The majority of the modifications that changed were associated with quiescence such as H3K9me3K14ac and H3K27me3 which increased through culture. Given that changes occurred through culture these were then correlated with the cellular phenotypes of growth rate, cell size and specific productivity. H3K27me3 and acetylation of H4 which correlated with growth rate were identified as possible engineering targets. Finally alterations to the epigenetic profile of CHO cells were made by small molecule inhibitors targeting methyltransferases and Histone deacetylases with the aim of improving specific productivity and growth rates of CHO cells. The results showed that addition of the small molecules inhibitors affected the growth rate through altering the epigenetic profile but in an unpredictable manner as multiple modification need to be altered to successfully alter the phenotype.
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Hackbusch, Daniel [Verfasser]. "Protein-Tyrosin-Phosphatasen (PTPs) als interventionelle Zielstrukturen der Arteriogenese / Daniel Hackbusch". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1071088882/34.
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Lang, Bradley Thomas. "THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY". Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755.
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Fernando, Alberto de Jesus. "Desenvolvimento e implementação de um novo sistema pneumático de transferência para irradiação de materiais no reator IEA-R1". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-01062011-152554/.
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Sistemas Pneumáticos de Transferência - \"Pneumatic Transfer Systems\" (PTS) são equipamentos mecânicos amplamente e mundialmente utilizados para o transporte, movimentação e transferência de diversos tipos de materiais, objetos e cargas entre dois ou mais terminais localizados em locais próximos ou distantes um do outro. Devido à sua versatilidade e rapidez, a aplicabilidade do sistema se faz presente em diversas áreas da sociedade tais como medicina (hospitais e laboratórios de análises clínicas); indústria (civil, automobilística, siderúrgica, metalúrgica, mineração, química, de alimentos); comércio (postos de gasolina, cinemas, supermercados, bancos, pedágios, empresas de venda de produtos por internet, cassinos); serviços públicos (repartições públicas, cortes de justiça, correios e telégrafos). Na área nuclear o PTS também tem uma vasta aplicabilidade nas diversas instalações nucleares, destacando-se a sua utilização como parte do processo de produção de radioisótopos e radiofármacos de meia vida curta tais como 67Ga, 201Tl, 18F e 123I-ultra puro, instalações de eliminação e estocagem de resíduos radioativos e áreas de pesquisa que utilizam o método analítico de Análise por Ativação Neutrônica (AAN). O desenvolvimento deste trabalho foi direcionado para o projeto, construção, instalação e implementação de um novo Sistema de Transferência Pneumático para transporte e transferência de materiais que são irradiados no núcleo do reator IEA-R1, localizado no Instituto de Pesquisas Energéticas e Nucleares (IPEN), para aplicação da técnica de AAN. Para sua instalação foi calculado a carga sobre a placa matriz do núcleo do reator e os testes de envio e retorno da amostra em análise. O fluxo neutrônico na posição de irradiação foi determinado utilizando a técnica de folhas de Au (ativação) apresentando um valor de 3,70±0,26.1012 n cm-2 s-1.Pneumatic Transfer Systems (PTS) are classified as mechanical equipment largely operated all over the world for transport of a huge sort of objects, samples and materials located at nearly terminals or even at separated ones. System applicability is often recognized in many activities, such as medicine (hospital settings, clinical analysis labs), industry (steel, automobiles, mining, chemical, food, construction), trading (gas station, movies, supermarkets, banks, e-commerce) and federal agencies (post services, federal courts, public enterprises). In the nuclear settings, PTS shows also a vast array of applications, being a part of radioisotope production, as well as short-lived radiopharmaceuticals, including 67 Ga, 201 Tl, 18 F and 123 I-ultra pure. Besides, PTS are also used at radioactive waste management plants and research institutes that apply neutron activation analysis (NAA). This work was directed toward the design and operation of a new PTS for the IEA-R1 nuclear research reactor settled at Instituto de Pesquisas Energéticas e Nucleares (IPEN) for NAA application. With this aim, it was calculated the charge of reactor core grid plate and sample transport testing. Neutron flux at irradiating position was determined as 3,70 ± 0,26 1012 n cm-2 s-1.
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Bollard, Niall. "Characterisation of phosphotransferase systems (PTS) in Clostridium difficile". Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/52179/.
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Phosphotransferase systems (PTS) represent an important method of sugar uptake in bacteria and have been well described in the past. However, research into PTS within the genus Clostridium has been mainly restricted to the non-pathogens. Analysis of the genome of Clostridium difficile 630 revealed over 40 intact PTS; this is over three times as many as in other pathogenic Clostridia, such as Clostridium perfringens and Clostridium botulinum. Previously, carbon catabolite repression has been shown to affect toxin production in C. difficile. Being capable of utilising different carbohydrates efficiently could be important for C. difficile to adapt to, grow, and survive in the human gut. So far, little work has been done to corroborate the role of individual PTS in carbohydrate uptake, sensing of environmental stimuli and regulation of virulence, i.e. toxin expression. A deeper understanding of the PTS in C. difficile, and their importance in virulence, could lead to the development of new drug targets. The aim of this study is to characterise the main PTS of C. difficile, determine their role in carbohydrate uptake, and their effect on regulation of virulence. To date, we have chosen the main candidates thought to be involved in mannitol and sorbitol uptake, and have inactivated these PTS using the ClosTron and in-frame deletion methods. Phenotypic characterisation of these mutants was undertaken to prove their role in uptake of the relevant sugar and to determine their role in virulence regulation. This study has demonstrated, by growth assays and HPLC, that the operons at CD630_0762-8 and CD630_2331-4 respectively encode PTS specific for sorbitol and mannitol uptake. In the case of the mannitol operon, it has been proved (through the use of cytotoxicity assays, which showed reduced bacterial toxicity in the presence of the sugar) that the suppression of toxin synthesis in the presence of mannitol is dependent upon uptake of the substrate via this operon. With sorbitol, toxin levels are, seemingly, not directly reliant upon uptake of the sugar, resulting in, mainly, an increase of toxin in sorbitol. Presently, it is not possible to say whether these systems have a distinct role or not in the motility of the organism.
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Gabanyi, Ilana. "Produção e uso da proteína de fusão VP22.Pax4 na diferenciação de células-tronco em células produtoras de insulina". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-01032011-141401/.
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O Diabetes Mellitus tipo I (DM1) é causado pela destruição auto-imune das células β pancreáticas, encontradas na porção endócrina do pâncreas, constituída pelas ilhotas pancreáticas. As células β são responsáveis pela produção e liberação de insulina, um hormônio que promove a internalização da glicose pelas células. Junto com outros hormônios, a insulina é um dos principais reguladores do nível de glicose sanguinea (glicemia). Uma das terapias utilizadas para o tratamento do DM1 é o transplante de ilhotas pancreáticas. Entretanto, um dos maiores problemas em relação a esta terapia é a falta de massa celular adequada para ser infundida no paciente. Uma tentativa para solucionar este problema, é o desenvolvimento de fontes alternativas de células produtoras de insulina, como as células-tronco, que possuem a capacidade de se diferenciarem em diversos tipos de células, inclusive nas produtoras de insulina. Pax4 é um dos fatores de transcrição responsáveis pela diferenciação de células β , sendo essencial para o apropriado desenvolvimento e maturação destas, constitui um bom candidato para induzir a diferenciação de células-tronco em células produtoras de insulina in vitro. Para introduzir o Pax4 nas células-tronco, sem provocar alterações no genoma das células diferenciadas, em virtude dos potenciais efeitos indesejáveis de vetores que se integram ao genoma celular, recorreu-se às proteínas contendo domínio de transdução (PTDs), que são capazes de carregar a proteína Pax4, através da membrana, diretamente para o interior das células. As PTDs são pequenas sequências peptídicas que permitem a translocação de proteínas através de membranas celulares e sua internalização em células-alvo. Uma das PTDs mais comumente estudadas é a VP22, produto do gene UL49 do Herpes Simplex vírus tipo I. Portanto, a proteína de fusão VP22.Pax4 permitiria que o Pax4 fosse inserido em células-tronco, possibilitando que este fator de transcrição ative a transcrição de certos genes que aumentariam a eficiência de diferenciação das células-tronco em células produtoras de insulina. Para tal, amplificamos e clonamos o cDNA do Pax4 a partir do RNA das células RINm5f de insulinoma murino, construímos o vetor pVP22.Pax4, o qual foi transfectado em células CHO, que passaram a produzir a proteína de fusão VP22.Pax4. Após o tratamento de células-tronco com a proteína de fusão VP22.eGFP e análise por microscopia confocal, comprovamos que a VP22 é capaz de tranduzir a proteína de fusão também neste tipo celular. Portanto, incorporamos a um dos passos do protocolo de diferenciação de células-tronco em células produtoras de insulina, utilizado em nosso laboratório, a co-cultura com células CHO produtoras de VP22.Pax4. Observamos que a introdução do Pax4 leva a formação de um número maior de agregados celulares (clusters) produtores de insulina. Concluímos, então, que a utilização da VP22 como ferramenta para internalização de proteínas em células-tronco é viável e que a adição do Pax4 pode trazer melhorias para protocolos que busquem a produção de células produtoras de insulina.Diabetes Mellitus type 1 (DM1) is caused by an auto-imunne destruction of the pancreatic β cells, found in the endocrine portion of the pancreas, known as pancreatic islets. These β cells are responsible production and release of insulin, a hormone which promotes glucose internalization by cells. Along with other hormones, insulin is a major regulator of blood glucose levels (glycemia). One of the therapeutical strategies used to treat DM1 is pancreatic islet transplantation. One of the major problem related to this therapy is the lack of adequate cell mass to be infused into the pacients. An attempt to solve this problem is the development of an alternative source of insulin-producing cells by differentiation of stem cells, which display this differentiating potential. Pax4 is one of the transcription factors responsibles for β cell differentiation, being essential for its proper development and maturation, therefore being a good candidate to induce stem cell differentiation into insulin producing cells in vitro. A promising alternative to avoid the alterations of the differentiated cells genome due to its undesirable effects of integrating vectors, but yet allowing the Pax4 to act in diferentiation within the cells are the proteins with a transduction domain (PTDs), which would have the ability to lead the Pax4 protein directly into the cells. The Pax4 could thus act in the nucleus and generate specific transcriptional responses. The PTDs are small peptide sequences which allow translocation of proteins across cell membranes and their internalization into target cells. One of the most commonly studied PTDs is the VP22, a product of the UL49 gene from Herpes Simplex vírus type I. Therefore, the VP22.Pax4 fusion protein would transduce Pax4 into the stem cells, thus allowing the transcription activation of certain genes by Pax4, leading to improvement in the process of stem cells differentiation into insulin-producing cells. To this end, we cloned the Pax4 cDNA from RINm5f murine insulinoma cells, constructed the pVP22.Pax4 vector and transfected this construct into CHO cells, which then produced the VP22.Pax4 fusion protein. Upon verifying that VP22 was also able to transduce proteins into stem cells, by confocal microscopy analysis, after the treatment of these cells with the fusion protein VP22.eGFP, we incorporated the fusion protein VP22.Pax4 to one of the steps of the protocol used for stem cells diferentiation into insulin producing cells in our lab, by co-culturing with CHO cells producing VP22.Pax4. We observed that the addition of Pax4 led to the formation of a higher number of insulin producing cell clusters, therefore we conclude that VP22 may be used as a tool to internalize proteins into stem cells, and that the addition of Pax4 may improves protocols seeking the production of insulin-producing cell
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出口, 亜由美. "黒色系ダリアにおける花弁の黒色化機構". Kyoto University, 2016. http://hdl.handle.net/2433/215583.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第19757号
農博第2153号
新制||農||1038(附属図書館)
学位論文||H28||N4973(農学部図書室)
32793
京都大学大学院農学研究科農学専攻
(主査)教授 土井 元章, 教授 奥本 裕, 准教授 田尾 龍太郎
学位規則第4条第1項該当
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Schuler, Chryssa [Verfasser], i Ingo [Akademischer Betreuer] Schäfer. "Behandlung der Posttraumatischen Belastungsstörung (PTBS) bei Patienten mit Substanzabhängigkeit : Effekte eines integrativen Behandlungsprogramms in der stationären Suchtrehabilitation auf PTBS-Symptomatik, Selbstfürsorge und Lebensqualität / Chryssa Schuler ; Betreuer: Ingo Schäfer". Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://d-nb.info/1208002627/34.
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Butel, Nicolas. "Caractérisation d'un complexe chromatinien impliqué dans l'inactivation post-transcriptionnelle des ARNs". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS302/document.
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Le PTGS (post-transcriptional gene silencing) est un mécanisme de défense qui cible les acides nucléiques invasifs d’origines endogènes (transposons) ou exogènes (pathogènes, transgènes). Des mutations dans les gènes JMJ14 et NAC52 ont été isolées lors d’un crible génétique visant à identifier des mutants déficients en PTGS. JMJ14 code une histone déméthylase ciblant la lysine 4 bi- ou tri-méthylée de l’histone H3, tandis que NAC52 code un facteur de transcription. Ces deux protéines forment un complexe qui régule la transcription de centaines de gènes endogènes. Toutefois, le rôle de ce complexe chromatinien dans l’expression des transgènes et surtout dans le PTGS reste incompris. JMJ14 interagit avec NAC52 mais aussi avec une protéine de type guanine exchange factor de la famille RCC1. Des mutations dans l’un ou l’autre des membres du complexe RCC1-JMJ14-NAC52 réduisent la transcription des transgènes. JMJ14 se fixe au promoteur de façon indépendante de NAC52, tandis que NAC52 a besoin de JMJ14 pour se fixer à la région transcrite. Toutefois, JMJ14 et NAC52 ne semblent pas requis pour la transcription proprement dite. En effet, un niveau normal de transcription est restauré chez le double mutant jmj14 drm2, indiquant que le rôle du complexe RCC1-JMJ14-NAC52 semble être d’empêcher la méthylation de novo du promoteur par DRM2.L’effet des mutations jmj14 et nac52 sur la transcription des transgènes ne peut expliquer leur effet sur certaines formes de PTGS. En effet, les mutations jmj14 et nac52 n’affectent pas le PTGS induit constitutivement. Par contre, elles empêchent la systémie du PTGS induit localement. Des mutations dans le gène SPCL45 codant une Serine Carboxy Peptidase-Like qui interagit avec NAC52, mais pas JMJ14, ont le même effet. En revanche, la mutation rcc1 n’affecte pas la systémie du PTGS, suggérant que c’est au sein d’un complexe JMJ14-NAC2-SPCL45 que JMJ14 et NAC52 contrôlent le PTGS systémique. Ce complexe pourrait agir directement sur la chromatine du transgène pour permettre d’enclencher le PTGS en réponse à la perception du signal systémique, ou indirectement en contrôlant l’expression d’un gène endogène codant une protéine régulant la systémie du PTGS. Afin de mieux comprendre le rôle de JMJ14 dans la systémie du PTGS, un crible génétique visant à isoler des suppresseurs de la mutation jmj14 a été réalisé. Seize mutants correspondants à sept gènes codant des protéines ayant un rapport avec la chromatine et une action antagoniste à JMJ14 ont été caractérisés. Les mutations dans ces sept gènes pourraient supprimer l’effet de jmj14 en augmentant la transcription du transgène cible et donc la quantité du signal systémique de PTGS. Un 17ème mutant pourrait quant à lui affecter qualitativement le signal systémique de PTGS ou la perception du signal dans les cellules qui le reçoivent. Le gène correspondant reste à identifierPost-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) origins. Mutations in JMJ14 and NAC52 have been retrieved from a genetic screen aiming to identify PTGS deficient mutants. JMJ14 encodes an histone demethylase targeting the bi- or tri-methylated lysine 4 of histone H3, while NAC52 encodes a transcription factor. Both act in a complex that regulates the transcription of hundreds endogenous genes. However, the function of this chromatin complex in transgene expression and in PTGS is not known. JMJ14 interacts with NAC52 but also with a guanine exchange factor of the RCC1 family. Mutations in any member of the RCC1-JMJ14-NAC52 complex reduce transgene transcription. JMJ14 binds to the transgene promoter independently of NAC52, whereas NAC52 requires JMJ14 to bind on the transcribed region. However, JMJ14 and NAC52 do not seem to be required for transcription itself. Indeed, a wild-type level of transcription is restored in the jmj14 drm2 double mutant, suggesting that the complex RCC1-JMJ14-NAC52 prevents de novo DNA methylation of the promoter by DRM2. The effects of jmj14 and nac52 mutations on transgene transcription cannot explain their specific effect on some forms of PTGS. Indeed, jmj14 and nac52 do not affect constitutively-induced PTGS, but prevent the systemic spreading of locally-induced PTGS. Mutations in SCPL45, encoding a Serine-Carboxy Peptidase-Like that interacts with NAC52, but not JMJ14, have the same effect. In contrast, rcc1 does not affect the systemic PTGS, suggesting that a JMJ14-NAC52-SCPL45 complex is involved in the control of systemic PTGS. This complex could act directly on transgene chromatin to trigger PTGS in response to the PTGS signal, or indirectly by controlling the expression of an endogenous gene encoding a protein regulating systemic PTGS. To better understand the function of JMJ14 in systemic PTGS, a genetic screen aiming to identify suppressors of jmj14 have been performed. Sixteen mutants corresponding to seven genes encoding proteins related to chromatin and having an antagonist function to JMJ14, have been characterized. Mutations in theses seven genes could suppress jmj14 by increasing transgene transcription and consequently the quantity of the PTGS systemic signal. A seventeenth mutant could have a qualitative effect on the PTGS systemic signal or could affect the perception of this signal in recipient cells. The corresponding gene remains to identify
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Prasad, Dipti. "The role of the TAM family of receptor PTKs in retinal homeostasis". Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3204580.
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Thesis (Ph. D.)--University of California, San Diego, 2006.Title from first page of PDF file (viewed April 4, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 110-125).
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Staudt, Anke [Verfasser], i Bernd [Akademischer Betreuer] Kaspers. "Charakterisierung des langen Pentraxins PTX3 beim Huhn / Anke Staudt ; Betreuer: Bernd Kaspers". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1141053748/34.
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Dehlawi, Saad Mohammad Abid. "Application of CaSx for the complexation of PTEs in soils and waters". Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=202756.
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Elom, Nwabueze. "Human health risk assessment of potentially toxic elements (PTEs) from environmental matrices". Thesis, Northumbria University, 2012. http://nrl.northumbria.ac.uk/15594/.
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In assessing human health risk of potentially toxic elements (PTEs), it is not the concentration of PTEs in the environmental matrices that is of greatest concern but the fraction that is absorbed into the body via the exposure pathways. The determination of this fraction (i.e. the bioaccessible fraction) through the application of bioaccessibility protocols is the focus of this work. The study investigated human health risk of PTEs (As, Cd, Cr, Cu, Pb, Mn, Ni and Zn) from oral ingestion of soil / dust, inhalation of urban street dust and air-borne dust (PM10). To assess health risk via oral ingestion of soil and dust, total PTEs were determined in twenty nine soil samples collected from children’s playing fields and ninety urban street dusts collected from six cities. Analysis of total PTE content in these samples via ICP-MS revealed high Pb concentrations (> 450 mg/kg) in 3 playground soils and 32 urban street dusts. Detailed quantitative risk assessment (DQRA) carried out in the playgrounds showed that no significant possibility of significant harm exist in the playgrounds. The concentration of Pb from a particular dust sample based on 50 mg/day ingestion rate that a child might possibly ingest to reach the estimated tolerable daily intake was calculated and it exceeded the tolerable daily intake for oral ingestion in 4 cities. The bioaccessible PTEs were determined both in the soil and dust samples using the Unified BARGE method and the result showed that in all the samples, the PTEs solubilised more in the gastric phase than in the intestinal phase. A new method has been developed; simulated epithelial lung fluid (SELF) and was used to assess the respiratory bioaccessibility of Pb from inhalable urban dust (<10 µm). Low bioaccessibility (<10 %) was recorded in all the samples analysed.
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Pierson, Alison. "Rôle des Pioneer Translation Products (PTPs) dans la réponse immunitaire anti-tumorale". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS446/document.
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Les vaccins thérapeutiques anti-tumoraux reposent sur l’activation du système immunitaire adaptatif et sont basés sur la reconnaissance des antigènes tumoraux (AT) par les lymphocytes T auxiliaires et cytotoxiques spécifiques. Leur efficacité nécessite une sélection méticuleuse des antigènes cibles ainsi qu’une présentation antigéniques par le CMH de classe I (CMH-I) dans les tumeurs non modifiée. Alors que l’attention s’est d’abord portées uniquement sur les AT dérivés de séquences exoniques, ceux dérivés d’évènements de traduction alternatifs ont été montrés comme ayant un fort potentiel en tant que cibles. Ces derniers peuvent dérivés d’une traduction de séquences dîtes « non traduites », initiée par des codons alternatifs ou dans un cadre de lecture non canonique. Une telle traduction alternative des ARN épissés dans le noyau et donnant naissance aux Pioneer Translation Products (PTPs) a été décrite. Ces derniers ont été montrés comme source de peptides pour la voie de présentation des antigènes par le CMH-I. Récemment, nous avons montré que les antigènes dérivés des PTPs et présentés par les tumeurs sont capables d’entrainer une réponse lymphocytaire T cytotoxique in vivo et de contrôler la croissance tumorale. Lors de ma thèse, nous avons identifié la molécule inhibitrice de l’épissage isoginkgetin comme modulateur positif de cette présentation dans les cellules cancéreuses. De plus, nous avons observé qu’un de ses dérivées, l’IP2, qui est soluble dans l’eau et moins toxique que l’isoginkgetin, est de même capable d’augmenter la présentation des antigènes dérivés des PTPs dans les tumeurs in vitro, ainsi que de réduire la croissance tumorale in vivo de manière dépendante de la réponse immunitaire. Ainsi, le composé IP2 se révèle être un immunomodulateur de la réponse anti-tumorale efficace et prometteur pour le développement de nouvelles stratégies thérapeutiquesAnti-tumoral therapeutic vaccines rely on the activation of the adaptative immune system and are based on the recognition of tumor antigens (TA) by specific helper and cytotoxic T lymphocytes (CTL). Their efficacy requires a careful selection of the targeted antigens as well as an unaltered MHC class I (MHC-I) antigenic presentation in tumors. While the focus was first put on exome-derived TA, evidences highlighted the ones derived from alternative translations as having a high potential as T-cells targets. These can be derived from translation of allegedly non coding sequences, initiated at alternative codons or performed in non-canonical open reading frames. Such an alternative translation occurring from pre-spliced mRNAs in the nucleus has been described as giving rise to the Pioneer Translation Products (PTPs), which constitute a source of polypeptides for the MHC-I pathway. Recently, we showed that PTPs-derived antigens presented by tumors are able to elicit a CTL response in vivo that controls tumor growth. Here, we identified one positive modulator of PTPs-derived antigenic presentation in cancer cells: the splicing inhibitor isoginkgetin. Then, we provided one of its derivatives, the IP2, which is water soluble and less toxic than the isoginkgetin, and showed that IP2 treatment increases PTPs-derived antigenic presentation of cancer cells in vitro and reduces tumor growth in vivo in an immune-dependent manner. Hence we describe here the IP2 as a new efficient immunomodulator of the antitumor response, promising for the development of innovative therapeutic strategies
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Brokx, Stephen John. "Structure and function of enzyme I of the PTS". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0029/NQ63848.pdf.
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Atkinson, Allen Bradley Jr. "A Model for the PTX Properties of H2O-NaCl". Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/34376.
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In many geologic environments, fluids have compositions that are approximated by the H2O-NaCl system. When minerals grow in the presence of such fluids, some of the solution is trapped in the growing mineral as fluid inclusions. The salinity, temperature of homogenization, and pressure of homogenization are required to predict the trapping conditions of the fluid inclusion. In the laboratory the salinity and the temperature of homogenization of the trapped fluid are easily determined however, the pressure of homogenization cannot be determined directly, and must be calculated from an equation of state.A statistical model that relates the vapor pressure of H2O-NaCl to the fluid temperature and composition has been developed. The model consists of equations that predict the vapor pressure of H2O-NaCl from the eutectic temperature (-21.2°C) to 1500°C and for all compositions between the pure end-members. The model calculates the vapor pressure based on the composition (wt% NaCl) and the temperature of homogenization, which can be directly obtained from laboratory studies of fluid inclusions. This information in turn can be used to construct the isochore, or line of constant volume, along which the fluid inclusion was trapped. Finally the isochore can be used to determine the temperature and pressure at which the host mineral of the fluid inclusion was trapped.
Master of Science
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Goletto, Valérie. "Synthèse et caractérisation d'organosilices mésostructurées à porosité périodique". Paris 6, 2002. http://www.theses.fr/2002PA066490.
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Roemmele, Christoph Frieder. "Zur Rolle des langen Pentraxins PTX3 in der Pathogenese des Systemischen Lupus Erythematodes". Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-170024.
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Der SLE ist eine Autoimmunerkrankung aus der Gruppe der Kollagenosen, in deren Verlauf es durch einen Toleranzverlust zu einer fälschlichen Antwort des Immunsystems auf körpereigene Strukturen kommt. Das lange Pentraxin PTX3 ist ein inflammatorisches Akut-Phase-Protein und hat zahlreiche Funktionen im angeborenen Immunsystem. Um den Einfluss von PTX3 auf den SLE zu untersuchen, wurden B6lpr Mäuse verwendet, welche unter einem mit dem SLE vergleichbaren milden Autoimmunsyndrom leiden. In diese Mäuse wurde eine Ptx3-Defizienz eingekreuzt. Es wurde die Hypothese aufgestellt, dass PTX3 die systemische Autoimmunität entscheidend beeinflusst: Entweder führt PTX3 zu einer Aggravation der Klinik durch seine proinflammatorische Wirkung oder PTX3 hemmt die Krankheitsintensität über seine Steigerung der Phagozytose sowie die Hemmung der Selectin-P vermittelten Leukozyteninfiltration.
Überraschenderweise beeinflusste das Fehlen von PTX3 die systemische Autoimmunität in B6lpr Mäusen kaum. So waren die Autoantikörper-produzierenden Plasmazellen sowie die Autoantikörper zwischen beiden Genotypen kaum verändert. Lediglich die Anzahl an „autoreaktiven“ CD4 und CD8 doppelnegativen T-Lymphozyten war in den Ptx3-defizienten B6lpr Mäusen signifikant erhöht. Es konnte gezeigt werden, dass PTX3 eine rasche Clearance apoptotischer T-Zellen intraperitoneal fördert und dass dies einen entscheidenden Beitrag für den Verlust der Immuntoleranz darstellen könnte. Umgekehrt könnte der Anstieg der „autoreaktiven“ T-Zellen durch die verschlechterte Clearance apoptotischer Zellen bedingt sein. Der Mangel an PTX3 zeigte auf Organ-spezifischer Ebene eine entscheidende Rolle bei der Ausprägung des SLE. Während die Lupusnephritis in den Mäusen unverändert blieb zeigte sich eine signifikant verstärkte Lungenschädigung in den Ptx3 knockout-Tieren. Ursächlich hierfür könnte die Anbindung von PTX3 an Selectin-P sein, durch die eine über dieses Adhäsionsmolekül vermittelte Leukozyteninfiltration an den Ort der Entzündung limitiert wird. Somit stellt PTX3 ein negativer Rückkopplungsmechanismus bei Entzündungen dar, da PTX3 vermehrt bei Inflammation gebildet wird, gleichzeitig aber die Leukozytenrekrutierung limitiert und somit das Ausmaß der entzündlich infiltrativ bedingten Lungenschädigung eindämmt. Defekte des Ptx3-Gens könnten ein genetischer Risikofaktor für die SLE bedingte Ausprägung von Lungenschädigungen des Menschen darstellen und so eine Behandlung mit rekombinanten PTX3 oder anderen PTX3-Agonisten eine mögliche spezifische Behandlungsstrategie darstellen.
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Scholbach, Johanna. "Induktion einer Endotoxämie in der humanisierten Maus". Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-197083.
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Die Sepsis ist ein gefürchtetes Krankheitsbild, das in hochentwickelten Industrienationen mit einer hohen Mortalität verknüpft ist und damit zu den häufigsten Todesursachen gehört. Die Pathomechanismen dieses komplexen und heterogenen Krankheitsbildes zu entdecken, gehört momentan zu den Hauptinteressengebieten der Sepsisforschung. Da die Interpretation klinischer Studien aufgrund der Heterogenität des Patientenguts schwierig ist, kommt der Entwicklung adäquater Tiermodelle eine entscheidende Bedeutung zu. Die hierbei gängigen Tiermodelle in Mäusen weisen jedoch Unzulänglichkeiten auf, die die Übertragung der in Tierexperimenten gewonnen Daten auf den klinischen Kontext nur teilweise ermöglichen. Eine Brücke kann hierbei das Tiermodell der humanisierten Maus schlagen, in der, durch Transplantation mit humanen hämatopoetischen Stammzellen, ein humanes Immunsystem reift. Die vorliegende Arbeit beschäftigt sich mit der Fragestellung, inwieweit die humanen Immunzellen in der humanisierten Maus in der Lage sind, auf LPS als Stimmulus zu reagieren. Darüberhinaus wird die Nutzung der Endotoxämie in der humanisierten Maus als alternatives Sepsismodell im Bezug zum klinischen Kontext untersucht. Hierbei ergab sich eine mögliche Nutzung des Endotoxämiemodells in der humanisierten Maus zur genaueren Erforschung des Zytokinmilieus, sowie neuer Surrogatmarker wie Pentraxin 3. Bezüglich der Reaktion einzelner immunologischer Subpopulationen und deren Bedeutung für die Klinik scheint eine Untersuchung an Modellen, die eine B- und T-Zell-Reifung nachvollziehen können und in der murine Residualzellen möglichst gering vorhanden sind, als sinnvoll.
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Winterhagen, Patrick. "Entwicklung von "screening"-Methoden zur Analyse von PTGS-basierter Resistenz gegen Nepoviren in Pflanzen". [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:100-opus-1609.
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Mazin, Asim Mohamed. "REDUCING THE PEAK TO AVERAGE POWER RATIO OF MIMO-OFDM USING Particle SWARM OPTIMIZATION BASED PTS". OpenSIUC, 2013. https://opensiuc.lib.siu.edu/theses/1130.
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Asim M. Mazin, for the Master of Science degree in Electrical and Computer Engineering, presented on Mar 27, 2013, at Southern Illinois University Carbondale. TITLE: REDUCING THE PEAK TO AVERAGE POWER RATIO OF MIMO-OFDM USING PSO BASED PTS. MAJOR PROFESSOR: Dr. Garth V. Crosby, In this thesis we proposed PSO based PTS to accomplish the lowest Peak-to-Average Power Ratio of MIMO-OFDM system. We applied the PSO based PTS on each antenna of the system in order to find the optimal phase factors which is a straightforward method to get the minimum PAPR in such a system. The performance of PSO based PTS algorithm in MIMO-OFDM with a wide range of phase factor tends to give a high performance according to the simulation results. In addition, there is no need to increase the number of particles of the PSO algorithm to enhance the performance of the system, which keeps the complexity of finding the minimum PAPR reasonable.
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Bourque, Kyle P. "Combat-Related Stress, Cohesion, Coping, and Perceived Threat: Predictors and Moderators of Posttraumatic Symptomatology Among Deployed U.S. Army Soldiers". Thesis, Boston College, 2012. http://hdl.handle.net/2345/2974.
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Thesis advisor: James E. LubbenThis study examined the roles cohesion, coping, and perceived threat have in buffering the effect of war-zone stress on mental health symptoms. Specifically, six factors were tested as potential moderators of the relationship between combat-related stressors and posttraumatic stress symptomatology (PTSS), including horizontal (peer) cohesion, vertical (NCO) cohesion, vertical (officer) cohesion, problem-focused coping, emotion-focused coping, and perceived threat. In addition, direct effects and curvilinear interaction effects were examined. This study was a secondary analysis of Mental Health Advisory Team (MHAT) VI data collected by military researchers as part of an ongoing effort to assess soldiers' behavioral health. This study analyzed data from a total of 1,824 male and female U.S. Army soldiers from 15 active-duty brigades who anonymously completed the Walter Reed Army Institute of Research (WRAIR) Deployment Well-Being Survey during their deployment to Iraq in support of Operation Iraqi Freedom (OIF). PTSS, combat-related stressors, horizontal (peer) cohesion, vertical (NCO) cohesion, vertical (officer) cohesion, problem-focused coping, emotion-focused coping, and perceived threat were measured. Hierarchical multiple regression analysis was used to identify both risk factors and protective factors for PTSS. The analysis revealed three risk factors and four protective factors. During a war-zone deployment, higher levels of combat-related stressors, problem-focused coping, and perceived threat (i.e., risk factors) were independently associated with greater report of PTSS. Higher levels of horizontal (peer) cohesion, vertical (NCO) cohesion, vertical (officer) cohesion, and emotion-focused coping (i.e., protective factors) were independently associated with decreased levels of PTSS. Hierarchical moderated multiple regression analysis indicated that vertical (NCO) cohesion, vertical (officer) cohesion, and emotion-focused coping buffered the effect of combat-related stressors on PTSS; soldiers higher in vertical (NCO) cohesion, vertical (officer) cohesion, and emotion-focused coping showed weaker relationships between combat-related stressors and PTSS. No support for curvilinear interaction effects were found, suggesting that for this population of soldiers deployed to Iraq, the moderating effect of vertical cohesion and emotion-focused coping on the relationship between combat-related stressors and PTSS is linear in nature
Thesis (PhD) — Boston College, 2012
Submitted to: Boston College. Graduate School of Social Work
Discipline: Social Work
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Fischer, Beth Ann. "A PROSPECTIVE EXAMINATION OF URINARY STRESS HORMONES AND PTSD SYMPTOMS FROM MOTOR VEHICLE ACCIDENT TO POST-TRAUMA RECOVERY". Kent State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=kent1194966805.
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Schmitz, Benjamin P. Schmitz. "Post Translational Modifications and How to Use Them". Miami University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=miami1524585691186704.
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Facemire, Vanessa Caitlynn Facemire. "Understanding the Insidious Trauma of Racism: An Exploration of the Impact of Racial Socialization, Gender, and Type of Racist Experiences". University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1525285448114384.
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COSTA, Elias Cardoso da. "Caracterização do material particulado inalável na atmosfera e na vegetação urbana na cidade de Goiânia". Universidade Federal de Goiás, 2011. http://repositorio.bc.ufg.br/tede/handle/tde/614.
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Previous issue date: 2011-09-08This work had as objective to study the thin particulate material (PM2;5), thick (PM10) suspended in the atmosphere and the PTS adsorved in the vegetation s foliage of the Goiânia city and also study the metals associated with these particulates, especially Pb and Cd, giving subsidies to the city s air quality avaliation. The samples were studied between june of 2010 to june of 2011, using samplers of the type stacker which collects the thin and thick particulate simultaneously in polycarbonate membranes of 47 mm of diameter and pores of 0.4 and 8µm of diameter. The particulates masses were determinated by gravimetria and the metals analysis were done by the Atomic Espectrometry of Absortion(AEA). The thin and thick particulates concentrations showed seasonal variation with a reduction of 80% in the rainy season. The primary standard in the CONAMA resolution, of 150µg.m-³,was not exceeded in any sampled day.The ideal annual average, of 50µg.m-³, was exceeded sometimes during this period and the air quality ranged between goot to regular during the drought season and good during the rainy season. The thin particulate concentrations were above the USEPA s recommended limit in the drought season.The concentrations of the metals associated to the particulate, like Pb, Cu, Cr, Mn and Ni were below the USEPA s and WHO s concentrations. The Cd concentrations, in some samples, were above the WHO s recommended limit. The studied vegetation showed a great adsortion capacity of PTS on their foliage and reached the maximum concentration of 16,97 mg.mm-² on the Monguba s foliage and contributed to the air quality.The species which showed the biggest particulate adsorption capacity per unit of area was Oiti, followed by Monguba.OBS: Estão subscritos 2,5 e 10 em PM. O programa não copia algumas formatações.
Este trabalho teve como objetivo estudar o material particulado fino (MP2,5), grosso (MP10) em suspensão na atmosfera e o PTS adsorvidos em folhagem de vegetação da cidade de Goiânia e bem como os metais associados a esses particulados, principalmente Pb e Cd, dando subsídios para a avaliação da qualidade do ar na cidade. As amostragens foram realizadas entre Junho de 2010 e Junho de 2011, utilizandose amostrador tipo stacker que coleta o particulado fino e grosso simultaneamente em membranas de policarbonato de 47mmde diâmetro e com diâmetros de poros de 0.4 e 8µm. As massas de particulados foram determinadas por gravimetria e as análises de metais foram realizadas empregando-se a técnica da Espectrometria de Absorção Atômica (AAS). As concentrações de particulados finos e grossos apresentaram variação sazonal com uma redução de 80% no período chuvoso. O padrão primário previsto na resolução CONAMA, de 150 µg.m-³, não foi ultrapassado em nenhum dia amostrado. O valor médio anual ideal, de 50 µg.m-³, foi ultrapassado algumas vezes nesse período e a qualidade do ar variou de boa a regular no período de seca e boa durante o período chuvoso. As concentrações de particulado fino ficaram acima do limite recomendado pelo USEPA no período seco. As concentrações de metais associados ao particulado, tais como, Pb, Cu, Cr, Mn e Ni ficaram abaixo do limite recomendado pela USEPA e OMS. As concentrações de Cd, em algumas amostras, ficaram acima do limite recomendado pela OMS. A vegetação estudada apresentou grande capacidade de adsorção de PTS em suas folhagens e alcançou uma concentração máxima de 16,97 mg.mm-² em folha de Monguba e contribui na melhoria da qualidade do ar. A espécie que apresentou maior capacidade de adsorção de particulado por unidade de área foi o Oiti, seguido pela Monguba. OBS: Estão subscritos 2,5 e 10 em PM. O programa não copia algumas formatações.
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Semer, Maryssa. "Le facteur de réparation XPC est un cofacteur de l'ARN polymérase II régulant les modifications post-traductionnelles des histones lors de la transcription". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ040/document.
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La voie de réparation NER implique une cascade de complexes protéiques dont le senseur des dommages de l’ADN (XPC/HR23B). Des mutations dans les gènes de la NER (TTD-A, XPA-G, XPV, CSA et CSB), sont associées à des maladies génétiques humaines dont le Xeroderma Pigmentosum (XP), la Trichothiodystrophie (TTD) et le syndrome de Cockayne (CS). L’ensemble des symptômes des patients ne peut être expliqué seulement par un défaut de la réparation de l’ADN. Or depuis quelques années, il a été prouvé que les facteurs de la NER sont aussi impliqués lors de la transcription. Dans le cadre de ma thèse, je me suis particulièrement intéressé à la protéines XPC en déterminant son rôle transcriptionnel à l’échelle génomique afin de mieux comprendre les conséquences de sa dérégulation dans un contexte pathologique. En ce sens, mon second objectif a été de caractériser au niveau moléculaire l’étiologie de nouveaux patients XP en analysant de manière combinée les évènements moléculaires de la NER et la transcription associés à XPC. Nos différentes approches expérimentales ont permis d’identifier au niveau génomique un ensemble de gènes sont les promoteurs sont régulés aussi bien positivement que négativement par XPC dans un contexte RAR dépendant. De plus, nous montrons que XPC interagit avec KAT2A contenu dans le complexe ATAC, ainsi que qu’avec le facteur de transcription E2F1, le facteur de remodelage de la chromatine BRD2 et le variant d’histone H2A.Z. Via KAT2A, ce complexe va acétyler non seulement H2A.Z mais également H3K9 au niveau des promoteurs ciblés par E2F1NER involves a cascade of protein complexes including the DNA damage sensor (XPC/HR23B). Mutations in NER genes (TTD-A, XPA-G, XPV, CSA and CSB) are associated with human genetic diseases including Xeroderma pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS). All the symptoms can only be explained by a defect of the DNA repair. However all the symptoms can only be explained by a defect of the DNA repair. However, it has been proven that NER factors are also involved in transcription. As the genomic scale to better understand the consequences of its deregulation in a pathological context. In this sense, my second goal has been to characterize at the molecular level the etiology of new XP patients by analyzing in a combined way the molecular events of the NER and the transcription associated with XPC. Our different experimental approaches have made it possible to identify at genomic level a set of gene whose promoters are regulated both positively and negatively by XPC in a dependent RAR context. In addition, we show that XPC interacts with KAT2A contained in the ATAC complex, as well as with the transcription factor E2F1, the chromatin remodeling factor BRD2, and the histone variant H2A.Z. Via KAT2A, this complex will acetylate not only H2A.Z but also H3K9 at promoters targeted by E2F1
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Koch, Sandro. "Electrical and optical properties of hydrogen-related complexes and their interplay in ZnO". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-187905.
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The commercial breakthrough of ZnO-based devices is hampered mainly by the unipolar n-type conductivity of this material. Hydrogen, which is known to form both electrically active and inactive complexes in ZnO, is considered as a main cause of this behavior. However, the existing literature is incomplete and partly contradictory. The object of the present thesis is a comprehensive investigation of the properties of two hydrogen-induced shallow donors HBC and HO, the hydrogen molecule H2, and a hydrogen-related defect, which gives rise to local vibrational modes (LVMs) at 3303 and 3320 cm-1, in ZnO and their interaction. The defects are characterized by Raman spectroscopy, infrared absorption spectroscopy, photoconductivtity (PC) and photoluminescence measurements. Based on the PC technique, a novel and highly sensitive spectroscopic approach is established, which is applicable for probing LVMs in strongly absorbing spectral regions. This technique enables the detection of the local modes of HO at 742 and 792 cm-1 in the neutral charge state. In consequence, earlier theoretical predictions regarding the microscopic structure of this shallow donor can be verified. In Raman measurements the electronic 1s→2s transition of HO is identified at 273 cm-1. This quantity is found to blue-shift with the HO defect concentration. A similar blue-shift of the 1s→2s(2p) donor transition of HBC is assigned to local lattice strain which was generated during high temperature processes. A Raman study of the H2 molecule covers its formation, stability, lattice position and interplay with the ZnO host. In particular, the role of H2 for the continuous generation of HO and HBC and the related n-type behavior is elaborated. The analysis unambiguously confirms that the so-called “hidden hydrogen” species is indeed H2. Moreover, the observation of the ortho-para-conversion process and the coupling to the host phonons contribute to a general understanding of H2 in semiconductors. Experimental results of the LVMs of 3303 and 3320 cm-1 in conjunction with model calculations yield an underlying defect containing three hydrogen atoms. This complex Y–H3 exhibits two configurations, which differ only in the orientation of one chemical bond. The findings are consistent equally with a zinc vacancy decorated with three hydrogen atoms and an ammonia molecule, respectively. Earlier models proposed in the literature are discarded. Measurements of concentration profiles by using Raman spectroscopy reveal the local distribution of the hydrogen-related defects as well as lattice imperfections. At the surface, where oxygen vacancies are present, HO is identified as the dominant shallow donor. Below, in parts of the crystal with low damage, HBC is the prevalent defect. In the sample center, characterized by a significant amount of zinc vacancies, the concentrations of H2 and Y–H3 show their maxima. By recording concentration profiles after thermal treatments a spatially resolved investigation of the interplay of these hydrogen-related defects is possibleDer kommerzielle Durchbruch von ZnO-basierten Bauelementen ist hauptsächlich durch die beständige n-Typ Leitung des Materials eingeschränkt. Wasserstoff, der sowohl elektrisch aktive als auch inaktive Komplexe in ZnO formt, gilt als ein Hauptverursacher dieses Verhaltens. Jedoch ist die bestehende Literatur zu derartigen Defekten unvollständig, teils auch widersprüchlich. Gegenstand der vorliegenden Arbeit sind umfassende Untersuchungen der beiden wasserstoffinduzierten Donatoren HBC und HO, des Wasserstoffmoleküls H2 und eines Wasserstoffdefekts mit lokalen Schwingungsmoden (LSMn) bei 3303 und 3320 cm-1 in ZnO hinsichtlich ihrer Eigenschaften und gegenseitigen Wechselwirkung. Die Charakterisierung der Komplexe erfolgt mit Hilfe von Raman-Spektroskopie, Infrarot-Absorptionsspektroskopie, Photoleitfähigkeits- (PC) und Photolumineszenzmessungen. Basierend auf der PC Technik wird eine neuartige, hochsensitive Spektroskopiemethode etabliert, welche auch in stark absorbierenden Spektralbereichen anwendbar ist. Diese Technik ermöglicht erstmals die Detektion der LSMn von HO bei 742 und 792 cm-1 im neutralen Ladungszustand. Das experimentelle Ergebnis verifiziert theoretische Vorhersagen zur mikroskopischen Struktur dieses flachen Donators. In Raman-Messungen wird der elektrische 1s→2s Übergang von HO bei 273 cm-1 identifiziert und eine Blauverschiebung dieser Größe mit zunehmender HO-Konzentration beobachtet. Der Donator HBC zeigt ebenfalls eine Blauverschiebung des elektrischen 1s→2s(2p) Übergangs, welche durch lokale Gitterverzerrungen nach Hochtemperaturbehandlungen bedingt ist. Eine Raman-Studie charakterisiert das H2-Molekül in Bezug auf seine Bildung, Stabilität, Gitterposition und die Wechselwirkung mit dem ZnO-Kristall. Insbesondere wird seine Rolle für die fortwährende Bildung der Donatoren HO und HBC und des damit verbundenen n-Typ Verhaltens herausgearbeitet. Die Analyse ergibt die eindeutige Identifizierung der in der Literatur mit „hidden hydrogen“ bezeichneten Spezies als H2. Darüber hinaus tragen die beobachteten Umwandlungsprozesse zwischen ortho-H2 und para-H2 sowie die Kopplung an das Phononenspektrum zu einem generellen Verständnis von Wasserstoffmolekülen in Halbleitern bei. Die experimentellen Ergebnisse der LSMn bei 3303 und 3320 cm-1 in Kombination mit Modellrechnungen ergeben einen zugrundeliegenden Defekt mit drei Wasserstoffatomen. Dieser Komplex Y–H3 weist zwei Konfigurationen auf, welche sich durch die Orientierung von nur einer chemischen Bindung unterscheiden. Die Beobachtungen sind mit einer Zinkvakanz besetzt mit drei Wasserstoffatomen bzw. einem Ammoniakmolekül als mikroskopische Struktur gleichermaßen erklärbar. Bisherige Modelle aus der Literatur können damit widerlegt werden. Messungen von Konzentrationsprofilen mit Raman-Spektroskopie offenbaren die lokale Verteilung der Wasserstoffdefekte sowie von Gitterstörungen. An der Oberfläche, im Beisein von Sauerstoffvakanzen, ist HO der dominante flache Donator. In dem sich anschließenden ungestörten Kristallverbund ist hingegen der Donator HBC vorherrschend. In Zentrum, welches von Zinkvakanzen geprägt ist, sind die Konzentrationen von H2 und Y–H3 maximal. In Verbindung mit Temperaturbehandlungen ist eine räumlich aufgelöste Untersuchung der Wechselwirkung möglich
41
Young, Chris 1981. "NMR studies if the Galactitol-specific PTS proteins IIA and IIB". Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98525.
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The phosphoenolpyruvate-dependant carbohydrate transport system (PTS) couples uptake of a variety of carbohydrates with phosphorylation in prokaryotes. In this system, a phosphoryl group is sequentially transferred through two general phosphoryl carrier proteins, enzyme I (EI) and HPr, and a carbohydrate-specific permease enzyme II (EII). EII is constituted of two cytoplasmic domains IIA and IIB, and a transmembrane channel IIC domain. The galactitol-specific transporter (IIgat) belongs to the glucitol family and is structurally the least well-known. Nuclear Magnetic Resonance (NMR) spectroscopy was used to solve the three-dimensional structure of IIBGat. IIB Gat is composed of a central four-stranded parallel beta sheet flanked by alpha helices on both sides. NMR titrations and isothermal titration calorimetry (ITC) with IIAGat allowed the identification of the binding interface and preliminary modeling of the structure of the IIB Gat - IIAGat heterodimer. IIAGat was also phosphorylated in-vitro, producing several large chemical shift changes, but no changes to the overall structure.
42
Bara, Mourad. "Etude par spectroscopie et Diffusion des neutrons du pFBS et pTS". Paris 7, 1985. http://www.theses.fr/1985PA07F127.
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L'origine de ce travail résulte de la volonté de mieux comprendre le phénomène de polymérisation à l'état solide dans les diacétylènes à l'échelle microscopique. Pour cette raison, nous avons substitué dans les groupes latéraux du pTS le groupe méthyle par un fluor. Le composé ainsi obtenu, le pFBS, devait nous permettre de tester l'influence des propiétés des groupes latéraux sur le phénomène de polymérisation et sur la phase incommensurable, réservée pour l'instant au seul pTS. Les résultats ne donnent pas lieu à des conclusions définitives. Les points que nous avons retenu de cette étude sont, d'une part l'importance de la répartition des dipôles dans le groupe latéral et, d'autre part, l'influence des déformations intramoléculaires, lorsque le taux de polymère augmente, sur le comportement élastique du matériau. . .
43
Dias, Mara Regina [UNESP]. "A atuação do assistente social como educador ambiental nos Projetos de Trabalho Técnico Social (PTTS)". Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/98602.
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dias_mr_me_fran.pdf: 842435 bytes, checksum: 08974fe197c67176b5e620a2dadb11a9 (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
As questões ambientais vem conquistando cada vez mais espaço na agenda pública e é mais visível nos diversos setores da sociedade civil. Os desafios propostos pela globalização provocam a necessidade de se ampliar as reflexões multidisciplinares, exigindo maior atenção à problemática socioambiental. Percebemos que a preocupação pela preservação do meio ambiente vem aumentando e já atinge diversos setores da sociedade, embora sejam limitadas, tendo muito a ser feito. Dentro destas reflexões e atuações multidisciplinares, encontramos a oportunidade de atuação do Serviço Social, pois preservação do meio ambiente é um tema relacionado ao trabalho do Assistente Social, uma vez que a garantia da qualidade de vida e dos direitos básicos das populações depende diretamente da qualidade do meio ambiente em que elas estão inseridas. A partir desse pressuposto apresentamos a educação ambiental como uma nova demanda ocupacional para o Assistente Social, procurando refletir acerca da intervenção deste profissional. Desta forma abordamos na dissertação a pertinência e necessária atuação dos profissionais de Serviço Social no espaço criado pelo Governo Federal, e operacionalizado pela Caixa Econômica Federal, através dos Projetos de Trabalho Técnico Social (PTTS), onde paralelo as obras físicas dos programas de desenvolvimento urbano, contam com a prestação de serviços dos assistentes sociais, que em suas atividades trabalham diversos ações como: mobilização e organização comunitária, por meio de processo educativo trabalham temas de educação ambiental e sanitária, e de geração de trabalho e renda. Enfocaremos as experiências dos trabalhos dos assistentes sociais realizados em cidades na região de Piracicaba/SP
Environmental issues have been gaining more space on the public agenda and have become more visible in the various sectors of civil society. The challenges posed by globalization cause the need to broaden the multidisciplinary reflections thus, requiring greater attention to the socio-environmental problems. We noticed that the concern for preserving the environment is increasing and already affects many sectors of society. Within these reflections and disciplinary actions we found the opportunity for the work of Social Services. Preserving the environment is an issue related to the work of the social worker, this is because the guarantee of quality of life and basic rights of the population depends on the quality the population’s environment. From this assumption we introduce environmental education as a new demand from the occupational social worker, trying to reflect on this professional intervention. Therefore we discuss the relevance of the dissertation and the necessary work of professional social work in the space created by the Federal Government and operated by the Caixa Economica Federal, through the Technical Working Projects Social – PTTs. This program, which parallels the physical work of urban development programs, relies on the services of social workers who work on various activities such as: mobilization and community organization, educational process promoting themes of environmental education and health, and employment and income generation. We focus on the experiences of work done by social workers in cities located in the region of Piracicaba/SP
44
Haas, Julienne [Verfasser]. "Wirksamkeit psychotherapeutischer und pharmakologischer Verfahren bei Patienten mit PTBS und komorbider psychischer Erkrankung / Julienne Haas". Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/122628907X/34.
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Nagy, Jeffrey Howard. "The relationship between military training, combat exposure, PTSS and functioning in post-9/11 veterans". Thesis, Trident University International, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10239371.
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The Global War on Terror has routinely exposed military personnel to PTSD qualifying traumatic events. Scant research has included a military training and occupational context among combat Veteran populations who leave military service. This retrospective cohort study explored the influence of pre-exposure training on the relationship between combat exposure, posttraumatic stress symptoms (PTSS) and functioning impairments after discharge from military service. The results confirmed an occupational associated exposure risk for approximately 15% of the US military. Despite the combative specialty Veteran experiencing more combat in frequency and intensity, there were no differences in PTSS or functioning impairment any time after discharge or within the last thirty days between occupational cohorts. The study concluded that combative occupational training is protective against the effects of battle exposure experiences, but not post battle experiences. The study results suggest that military organizational resilience training is not effective in bolstering hardiness after discharge and transitioning into the civilian population. These findings support the creation of a military occupational mental health model for future PTSD diagnosis and treatment for combat Veteran populations.
46
Gifoni, Markus Andret Cavalcante. "Envolvimento da pentraxina 3 (PTX3) na patogÃnese da cistite hemorrÃgica induzida por ifosfamida em camundongos". Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1245.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorA cistite hemorrÃgica (CH) à um fenÃmeno inflamatÃrio frequentemente associado à quimioterapia com oxazafosforinas. Trata-se de uma resposta inflamatÃria inata à aÃÃo da AcroleÃna (ACR), metabÃlito hepÃtico comum à Ifosfamida (IFO) e à ciclofosfamida (CTX). O papel da resposta ao recrutamento de receptores toll-like (TLR) e do estÃmulo por TNF-α e IL-1β com envolvimentto de iNOS e COX-2 tem sido demonstrado neste fenÃmeno. Estudos recentes demonstram que a Pentraxina 3 (PTX3) assume papel de mediador inflamatÃrio em modelos de resposta inflamatÃria inata in vivo, sobretudo relacionada ao recrutamento de TLR. Desta forma, o presente estudo pretende investigar o possÃvel envolvimento de PTX3 na patogÃnese da CH induzida por ifosfamida em camundongos. Para isso, foi realizada quantificaÃÃo de RNAm por RT-PCR para PTX3 e IL-1β em camundongos C57/ BL6 tratados com ifosfamida e salina. Em seguida, o modelo experimental da CH induzida por ifosfamida foi reproduzido em grupos de camundongos com hiperexpressÃo e nocauteados para PTX3 em comparaÃÃo com os respectivos controles do tipo selvagem e com grupos controle tratados com salina para posterior obtenÃÃo dos pesos vesicais Ãmidos (PVU), realizaÃÃo de anÃlise histomorfomÃtrica, imunohistoquÃmica e quantificaÃÃo de RNAm por RT-PCR para PTX3, IL-1β, TNF-α e iNOS. Os animais transgÃnicos e seus controles foram sacrificados com tempos de 3h e 12h apÃs o tratamento, enquanto os nocauteados e seus controles foram sacrificados com 12 horas do tratamento. Finalmente, a CH em animais C57/ BL6 foi modulada com o prÃ-tratamento com Talidomida, Pentoxifilina, MESNA, Amifostina e Aminoguanidina para a posterior marcaÃÃo imunohistoquÃmica com PTX3, IL-1β, TNF-α e iNOS. Observou-se que o RNAm de PTX3 està cerca de 70 vezes mais expresso em animais com CH, contra uma razÃo de expressÃo de 10 para IL-1β. Animais trangÃnicos para PTX3 tÃm reduÃÃo inicial da resposta inflamatÃria com expressÃo inferior de PTX3 e TNF-α e expressÃo aumentada de iNOS e intensificaÃÃo da inflamaÃÃo ao tempo de 12 horas, com expressÃo superior dos mediadores. NÃo houve diferenÃas significativas de intensidade da CH em animais KO em relaÃÃo aos controles. A modulaÃÃo da CH por talidomida e MESNA produziu reduÃÃo importante sobre a expressÃo de PTX3, enquanto a inibiÃÃo da CH por amifostina nÃo teve reduÃÃo expressiva da pentraxina. Em conjunto, estes dados apontam para um envolvimento inequÃvoco de PTX3 na fisiopatologia da inflamaÃÃo inata em modelo de CH murino com Ãntima relaÃÃo coma expressÃo de TNF-α
The Hemorrhagic Cystitis (HC) is an inflammatory reaction usually associated with Cancer Chemotherapy with Oxazaphosphorines. It is an innate inflammatory response to vesical irritation by Acrolein, an hepatic metabolite of the treatment with Iphosphamide and Cyclophosphamide. The role of toll-like receptor (TLR) engagement and TNF-α and IL-1β expression and the involvement of iNOS and COX-2 in the pathogenesis has been well demonstrated in a murine model of HC. Recent data configure pentraxin 3 (PTX3) as an inflammatory mediator in several experimental models of innate immune response in vivo, with a straight relation with TLR engagement. Because of that, this study looks at the involvement of PTX3 in the pathogenesis of iphosphamideâinduced HC in mice. For this purpose, the mRNA to PTX3 and IL-1β t was quantified by RT-PCR in groups of C57BL6 mice treated with Iphosphamide or Saline. After that, groups of transgenic and Knock-Out mice to PTX3 and its respectives wild-type controls were treated with Iphosphamide or saline with intention to measure the Bladder Wet Weight (BWW), histomorphometric scores and Immunohistochemistry and RT-PCR to PTX3, IL-1β, TNF-α e iNOS analysis. The transgenic mice and its controls were killed in 3h and 12h after the treatment, while the PTX3 KO and its controls were killed after 12 hours. Finally, the experimental HC was modulated by pretreatment with Talidomide, Pentoxiphiline, MESNA, Amifostine and Aminoguanidine and the bladders submitted to immunohistochemistry assay (PTX3, TNF-α, IL-1β and iNOS). By RT-PCR quantification, mRNA for PTX3 was expressed 70 times more in mice treated with iphosphamide than in controls, while IL-1β RNAm had an expression rate of 10 times. PTX3 transgenic mice had initial reduction of the inflammatory response with less expression of PTX3 and TNF-α and greater expression of iNOS. In the other hand, after 12 hours, the PTX3 transgenic mice had more inflammatory signs with superior expression of all the mediators. There was no difference between the PTX3 KO mice and its controls in the HC intensity although differences between groups were seen in cytokines expression. Talidomide and MESNA produced substantial reduction on the PTX3 expression, the same was seen to TNF-α, while the amifostine marked inhibition of HC had low effect on PTX3 expression. These data as a whole, point to an unequivocal involvement of PTX3 in the pathogenesis of innate inflammatory response of HC in mice with close relation with TNF-α engagement
47
Dias, Mara Regina. "A atuação do assistente social como educador ambiental nos Projetos de Trabalho Técnico Social (PTTS) /". Franca, 2012. http://hdl.handle.net/11449/98602.
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Orientador: Analúcia Bueno dos Reis GiomettiBanca: Ana Tereza Caceres Cortez
Banca: Helen Barbosa Raiz Engler
Resumo: As questões ambientais vem conquistando cada vez mais espaço na agenda pública e é mais visível nos diversos setores da sociedade civil. Os desafios propostos pela globalização provocam a necessidade de se ampliar as reflexões multidisciplinares, exigindo maior atenção à problemática socioambiental. Percebemos que a preocupação pela preservação do meio ambiente vem aumentando e já atinge diversos setores da sociedade, embora sejam limitadas, tendo muito a ser feito. Dentro destas reflexões e atuações multidisciplinares, encontramos a oportunidade de atuação do Serviço Social, pois preservação do meio ambiente é um tema relacionado ao trabalho do Assistente Social, uma vez que a garantia da qualidade de vida e dos direitos básicos das populações depende diretamente da qualidade do meio ambiente em que elas estão inseridas. A partir desse pressuposto apresentamos a educação ambiental como uma nova demanda ocupacional para o Assistente Social, procurando refletir acerca da intervenção deste profissional. Desta forma abordamos na dissertação a pertinência e necessária atuação dos profissionais de Serviço Social no espaço criado pelo Governo Federal, e operacionalizado pela Caixa Econômica Federal, através dos Projetos de Trabalho Técnico Social (PTTS), onde paralelo as obras físicas dos programas de desenvolvimento urbano, contam com a prestação de serviços dos assistentes sociais, que em suas atividades trabalham diversos ações como: mobilização e organização comunitária, por meio de processo educativo trabalham temas de educação ambiental e sanitária, e de geração de trabalho e renda. Enfocaremos as experiências dos trabalhos dos assistentes sociais realizados em cidades na região de Piracicaba/SP
Abstract: Environmental issues have been gaining more space on the public agenda and have become more visible in the various sectors of civil society. The challenges posed by globalization cause the need to broaden the multidisciplinary reflections thus, requiring greater attention to the socio-environmental problems. We noticed that the concern for preserving the environment is increasing and already affects many sectors of society. Within these reflections and disciplinary actions we found the opportunity for the work of Social Services. Preserving the environment is an issue related to the work of the social worker, this is because the guarantee of quality of life and basic rights of the population depends on the quality the population's environment. From this assumption we introduce environmental education as a new demand from the occupational social worker, trying to reflect on this professional intervention. Therefore we discuss the relevance of the dissertation and the necessary work of professional social work in the space created by the Federal Government and operated by the Caixa Economica Federal, through the Technical Working Projects Social - PTTs. This program, which parallels the physical work of urban development programs, relies on the services of social workers who work on various activities such as: mobilization and community organization, educational process promoting themes of environmental education and health, and employment and income generation. We focus on the experiences of work done by social workers in cities located in the region of Piracicaba/SP
Mestre
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Gifoni, Markus Andret Cavalcante. "Envolvimento da pentraxina 3 (PTX3) na patogênese da cistite hemorrágica induzida por ifosfamida em camundongos". reponame:Repositório Institucional da UFC, 2008. http://www.repositorio.ufc.br/handle/riufc/2592.
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GIFONI, Markus Andret Cavalcante. Envolvimento da pentraxina 3 (PTX3) na patogênese da cistite hemorrágica induzida por ifosfamida em camundongos. 130 f. 2008. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2008.Submitted by denise santos (denise.santos@ufc.br) on 2012-05-04T16:36:22Z No. of bitstreams: 1 2008_dis_macgifoni.pdf: 3631477 bytes, checksum: 2a13693f0c54b428c60eea4f01db4b4f (MD5)
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The Hemorrhagic Cystitis (HC) is an inflammatory reaction usually associated with Cancer Chemotherapy with Oxazaphosphorines. It is an innate inflammatory response to vesical irritation by Acrolein, an hepatic metabolite of the treatment with Iphosphamide and Cyclophosphamide. The role of toll-like receptor (TLR) engagement and TNF-α and IL-1β expression and the involvement of iNOS and COX-2 in the pathogenesis has been well demonstrated in a murine model of HC. Recent data configure pentraxin 3 (PTX3) as an inflammatory mediator in several experimental models of innate immune response in vivo, with a straight relation with TLR engagement. Because of that, this study looks at the involvement of PTX3 in the pathogenesis of iphosphamide–induced HC in mice. For this purpose, the mRNA to PTX3 and IL-1β t was quantified by RT-PCR in groups of C57BL6 mice treated with Iphosphamide or Saline. After that, groups of transgenic and Knock-Out mice to PTX3 and its respectives wild-type controls were treated with Iphosphamide or saline with intention to measure the Bladder Wet Weight (BWW), histomorphometric scores and Immunohistochemistry and RT-PCR to PTX3, IL-1β, TNF-α e iNOS analysis. The transgenic mice and its controls were killed in 3h and 12h after the treatment, while the PTX3 KO and its controls were killed after 12 hours. Finally, the experimental HC was modulated by pretreatment with Talidomide, Pentoxiphiline, MESNA, Amifostine and Aminoguanidine and the bladders submitted to immunohistochemistry assay (PTX3, TNF-α, IL-1β and iNOS). By RT-PCR quantification, mRNA for PTX3 was expressed 70 times more in mice treated with iphosphamide than in controls, while IL-1β RNAm had an expression rate of 10 times. PTX3 transgenic mice had initial reduction of the inflammatory response with less expression of PTX3 and TNF-α and greater expression of iNOS. In the other hand, after 12 hours, the PTX3 transgenic mice had more inflammatory signs with superior expression of all the mediators. There was no difference between the PTX3 KO mice and its controls in the HC intensity although differences between groups were seen in cytokines expression. Talidomide and MESNA produced substantial reduction on the PTX3 expression, the same was seen to TNF-α, while the amifostine marked inhibition of HC had low effect on PTX3 expression. These data as a whole, point to an unequivocal involvement of PTX3 in the pathogenesis of innate inflammatory response of HC in mice with close relation with TNF-α engagement.
A cistite hemorrágica (CH) é um fenômeno inflamatório frequentemente associado à quimioterapia com oxazafosforinas. Trata-se de uma resposta inflamatória inata à ação da Acroleína (ACR), metabólito hepático comum à Ifosfamida (IFO) e à ciclofosfamida (CTX). O papel da resposta ao recrutamento de receptores toll-like (TLR) e do estímulo por TNF-α e IL-1β com envolvimentto de iNOS e COX-2 tem sido demonstrado neste fenômeno. Estudos recentes demonstram que a Pentraxina 3 (PTX3) assume papel de mediador inflamatório em modelos de resposta inflamatória inata in vivo, sobretudo relacionada ao recrutamento de TLR. Desta forma, o presente estudo pretende investigar o possível envolvimento de PTX3 na patogênese da CH induzida por ifosfamida em camundongos. Para isso, foi realizada quantificação de RNAm por RT-PCR para PTX3 e IL-1β em camundongos C57/ BL6 tratados com ifosfamida e salina. Em seguida, o modelo experimental da CH induzida por ifosfamida foi reproduzido em grupos de camundongos com hiperexpressão e nocauteados para PTX3 em comparação com os respectivos controles do tipo selvagem e com grupos controle tratados com salina para posterior obtenção dos pesos vesicais úmidos (PVU), realização de análise histomorfométrica, imunohistoquímica e quantificação de RNAm por RT-PCR para PTX3, IL-1β, TNF-α e iNOS. Os animais transgênicos e seus controles foram sacrificados com tempos de 3h e 12h após o tratamento, enquanto os nocauteados e seus controles foram sacrificados com 12 horas do tratamento. Finalmente, a CH em animais C57/ BL6 foi modulada com o pré-tratamento com Talidomida, Pentoxifilina, MESNA, Amifostina e Aminoguanidina para a posterior marcação imunohistoquímica com PTX3, IL-1β, TNF-α e iNOS. Observou-se que o RNAm de PTX3 está cerca de 70 vezes mais expresso em animais com CH, contra uma razão de expressão de 10 para IL-1β. Animais trangênicos para PTX3 têm redução inicial da resposta inflamatória com expressão inferior de PTX3 e TNF-α e expressão aumentada de iNOS e intensificação da inflamação ao tempo de 12 horas, com expressão superior dos mediadores. Não houve diferenças significativas de intensidade da CH em animais KO em relação aos controles. A modulação da CH por talidomida e MESNA produziu redução importante sobre a expressão de PTX3, enquanto a inibição da CH por amifostina não teve redução expressiva da pentraxina. Em conjunto, estes dados apontam para um envolvimento inequívoco de PTX3 na fisiopatologia da inflamação inata em modelo de CH murino com íntima relação coma expressão de TNF-α.
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Ismail, Ihab. "Function and Regulation of Xylem Cysteine Protease 1 and Xylem Cysteine Protease 2 in Arabidopsis". Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/11243.
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A functional water-conducting system, the tracheary elements of the xylem, is required to sustain plant growth and development. Tracheary element formation is dependent on many biological processes terminated by programmed cell death and cellular autolysis. The final two processes are probably dependent on the activity of hydrolytic enzymes such as XCP1 and XCP2 known to be expressed in tracheary elements during these final two processes. Thus, the transcriptional regulation of XCP1 and the function of XCP2 were investigated. Qualitative and quantitative assessments of GUS activity as directed by various fragments of the XCP1 promoter showed that a 237-bp internal region was able to drive GUS expression in a tracheary element-specific manner in Arabidopsis. A 25-bp deletion at the 3' end of this region abolished GUS expression. The 237-bp region served as bait in a yeast one-hybrid analysis. Screening of yeast colonies retrieved 109 putative positive interactions, which included a potential transcriptional regulator, indole acetic acid-induced protein 8 (IAA8). An auxin responsive element that potentially binds auxin responsive transcription factors was found within the 25-bp deletion. Cis-elements were predicted by Genomatix and Athamap computer programs. The cis-elements form pyrimidine and gibberellic acid responsive elements that can potentially bind Dof and Myb transcription factors, respectively. In an independent effort, attempts to develop a mapping population to isolate upstream regulators of XCP1 expression did not succeed. Functionally, tracheary element-specific expression of XCP2 in Arabidopsis suggested a specialized role for XCP2 in final phases of tracheary element differentiation. The function of XCP2 was assessed using T-DNA insertional mutants, post-transcriptional gene silencing, and through tracheary element-specific expression of the cysteine protease inhibitor, soyacystatin N in Arabidopsis. Our findings revealed that the absence of XCP2 expression due to T-DNA insertional mutagenesis did not affect plant growth and development in the laboratory. Soyacystatin N was an effective in vitro inhibitor of cysteine proteases. Plants expressing 35S-driven cytosolic form of soyacystatin exhibited stunting and reduced apical dominance. Plants expressing pXCP1-driven cytosolic soyacystatin did not differ from wild type plants. Additionally, transgenic plants expressing pXCP1- and 35S-directed XCP2-double-stranded RNA for the silencing of XCP2 showed no unusual phenotypes compared to their wild type counterpartsPh. D.
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Åslund, Hannah. "Posttraumatiska stressymptom hos förskolebarn". Thesis, Malmö högskola, Fakulteten för lärande och samhälle (LS), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-31198.
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Posttraumatiska stressyndrom (PTSS) är en diagnos som hittills har omfattat vuxna, men på senare år även kommit att gälla barn som upplevt traumatiska händelser. Syftet med studien är att belysa PTSS och ge en förklaring av vad diagnosen innebär. Jag vill också dra relevanta slutsatser för förskolan. Det teoretiska underlaget är hämtat från forskning kring ämnet och har analyserats i ett förskoleperspektiv. Studiens empiriska underlag är en enkätstudie. Resultatet av enkätstudien omfattar uttalanden som till viss del stärker forskarnas påpekanden.