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TREZZI, ILARIA. "INVESTIGATING GLUTAMATE TOXICITY ASSOCIATED TO PARK2 MUTATIONS IN PRE-CLINICAL MODELS OF PARKINSON¿S DISEASE." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/925250.
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ABSTRACT
Background: Park2 mutations cause Autosomal Recessive Juvenile Parkinsonism (ARJP), characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Park2 encodes for a ubiquitin-ligase protein whose mutation upregulates Gluk2, a subunit of the glutamate kainate receptor (KAR), expressed in SNpc neurons. Park2 is highly expressed also in astrocytes and KARs upregulation may induce excitotoxicity both in DA neurons and glia, leading to an early synaptopathy, neuroinflamation and neurodegeneration.
Aims and Objectives: 1. To generate Park2 induced pluripotent stem cells (iPSCs)-derived in vitro cellular models; 2. To characterize Park2 iPSCs-derived in vitro cellular models; 3. to test glutamate toxicity due to KAR upregulation in Park2 cellular models.
Materials and Methods: Fibroblasts and lymphocytes from Park2 patients and age-matched controls were reprogrammed into iPSCs. The iPSCs were further differentiated into dopaminergic neurons, astrocytes and mesencephalic organoids were generated and differentiated. Protein expression profile was analysed through western blot (WB), qPCR and immunofluorescence (IF). Electrophysiology assessment was performed on dopaminergic neurons and midbrain organoids in order to better functionally profile these models.
Results: Gluk2 levels resulted significantly increased in PARK2 midbrain organoids compared to CTR both at WB (p< 0.001) and qPCR analyses (p< 0.001). Gluk2 levels resulted also significantly enhanced in PARK2 astrocytes both at WB (p< 0.05) and qPCR analyses (p< 0.05). TH mRNA and protein levels were significantly increased both in PARK2 dopaminergic neurons (WB p< 0.01; qPCR p< 0.0001; IF p< 0.0001) and midbrain organoids (WB p< 0.01; qPCR p< 0.0001; IF p< 0.0001) compared to CTR. Glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, resulted enhanced in PARK2 astrocytes and especially in PARK2 midbrain organoids (WB p< 0.001; IF p< 0.01). EAAT2, the astrocytic glutamate transporter resulted reduced in mutated lines (WB p< 0.01). Calcium-imaging and HD-MEAs show an oscillatory augmented reactivity in PARK2 midbrain organoids.
Conclusions and perspectives: Gluk2 expression was enhanced in PARK2 astrocytes and midbrain organoids, confirming the previous finding that Park2 mutations lead to KAR upregulation (Maraschi A, 2014). Neuronal reactivity was also found increased in PARK2 midbrain organoids at electrophysiology assessment, maybe linked to glutamate dysregulation. Two innovative findings emerged from this study. First of all, that TH expression resulted increased in PARK2, supporting previous finding that stated an augmented dopamine turnover and a reduced dopamine re-uptake (Jiang H., 2012). This is an impairment that happens early in the neurodegenerative process and that could consequently lead to an excessive oxidative stress and consequent neurodegeneration. The second original result is that PARK2 is associated to an increased astrocytic reactivity and a possible dysfunction of astrocytic glutamate transporter EAAT2. This finding means that astrocytes play a key role in neurodegeneration although it is not clear whether they contribute to the initiation or propagation of it. Their increased reactivity could be the consequence of a glutamate toxicity or glutamate toxicity could result from reactive astrocytes dysfunction, not able to process the excessive glutamate influx. Further studies are required in order to establish Park2 role in TH expression regulation, in astrocytic reactivity induction and in glutamate toxicity.
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Miele, Gino. "Analyses of gene expression in Prn-p+/+ and Prn-p-/- mice." Thesis, University of Edinburgh, 2000. http://hdl.handle.net/1842/22489.
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The Transmissible Spongiform Encephalopathies (TSEs) are a group of invariably fatal neurodegenerative diseases which manifest in a broad range of species. At present, the causative agent of the TSEs remains unknown. The only disease-specific macromolecule identified to date is a protease-resistant abnormal isoform (PrPSc) of a protease sensitive normal host-encoded glycoprotein (PrPC). Despite the discovery of PrPC more than a decade ago, the precise normal physiological function of this protein remains unknown. PrPC is highly conserved across all species studied to date, and is expressed predominantly in neural tissues, but is also detected in non-neuronal tissues. PrP mRNA is developmentally regulated during embryogenesis, and has been shown to be widespread at E13.5. However, the precise timing of PrP mRNA transcriptional activation during murine embryogenesis has not been examined. Surprisingly, two lines of mice harbouring a null mutation in Prn-p, and which do not express detectable levels of PrPC, are viable and develop and reproduce apparently normally. This thesis describes attempts to obtain clues to the normal physiological function of PrPC by assessing the effect on gene expression of the ablation of PrPC. To identify genes with altered expression profiles as a result of the ablation of PrPC, the technique of Differential Display RT-PCR (DDRT-PCR) was optimised and utilised to undertake a comprehensive analysis of gene expression between Prn-p+/+ and Prn-p-/- postnatal developing brain. Five candidate genes were identified as being differentially expressed between Prn-p+/+ and Prn-p-/- brain. One of these genes was PrP, demonstrating the validity of the approach. The isolation, identification and expression of the remaining candidate transcripts is described. A detailed expression analysis of PrP mRNA expression was also performed and indicated that PrP is transcriptionally activated between E8.5 and E9 in the murine embryo, during neurulation. It was also demonstrated that PrP mRNA is developmentally regulated in the murine postnatal (P) developing brain, increasing in expression level approximately 8-fold from P0 to P42.
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Olivera, Espinoza César Augusto. "PRK: excimer láser experiencia hospitalaria." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2003. https://hdl.handle.net/20.500.12672/2018.
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El presente trabajo tiene por meta realizar un estudio prospectivo de un grupo de pacientes con diversos grados de Ametropia Miopica, protocolizandolos y sometiéndose a cirugía refractiva fotoablativa. PRK; no LASIK por no contar con el Microkeratomo.
El protocolo ha sido diseñado para así uniformizar la elección de los pacientes y poder interpretar fidedignamente los resultados. Como es bien sabido el porcentaje de vicios de refracción. es muy atto en la población en general por lo tanto la necesidad de corregirlos con la tecnología actual es cada vez más imperante.Tesis de segunda especialidad
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Couto, Gustavo de Alvarenga. "Efeito do ângulo da fieira na geometria e propriedades mecânicas de barras trefiladas." Universidade Federal de Minas Gerais, 2011. http://hdl.handle.net/1843/PRCN-8P9GMW.
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In cold drawing of metallic bars most of the plastic flow is caused by compressive forces which arise from the reaction of the metal to the die. Due to the characteristics of the process this flow is not homogeneous along the cross section of the bar and is influenced by the die geometry. This inhomogeneous deformation generates residual stresses in the bars, which can produce a change in size and straightness during subsequent processes of cutting, grinding and heat treatment. This work presents an analysis of the influence of the die geometry and number of drawing passes on the final geometry and mechanical properties of drawn bars of SAE 1045 steel. Eight experiments were performed, with die angles of 12º, 18º, 30º and 40º, bearing lengths from 3,51mm to 7,09mm, and 01 or 02 passes of drawing. Measurements of straightness, roundness and diameter, microhardness and tensile tests were performed on the bars. Also were made measurements of straightness of shock absorbers rods after the induction hardening process. This study has shown that the die angle has a strong influence on the final geometry of the drawn bars; dies with high entry angle (30º and 40º) resulted in better values of straightness than dies with smaller angles (12º and 18º). Dies with high entry angle also resulted in less variation between the bearing diameter and the final diameter of the bar. It was also observed a strong relation between the straightness of the drawn bars and the straightness of the shock absorbers rods after the induction hardening process, where drawn bars with better straightness resulted in a better straightness of the shock absorbers rods after the induction hardening process.Na trefilação a frio de barras metálicas a maior parte da deformação plástica é atribuída às tensões de compressão impostas ao material, devido ao contato entre a barra e a fieira. Devido às características do processo esta deformação não é homogênea ao longo da seção transversal da barra e seu nível é influenciado pela geometria da fieira. Esta deformação não homogênea gera tensões residuais nas barras trefiladas, as quais podem produzir uma mudança nas dimensões e retilineidade das mesmas, durante processos de corte, retífica e tratamento térmico ulteriores. Neste trabalho foi realizada uma análise da influência do ângulo e comprimento do paralelo da fieira, além do número de passes de trefilação, na geometria final e nas propriedades mecânicas das barras trefiladas de aço SAE 1045. Foram realizados oito experimentos, com ângulos de fieira de 12º, 18º, 30º e 40º, com comprimentos de paralelo de 3,51mm a 7,09mm, com 01 e 02 passes de trefilação. Para as barras trefiladas de cada experimento foram realizadas medições de retilineidade, diâmetro e ovalização, além de ensaios de microdureza e ensaios de tração completos. Também foram realizadas medições de retilineidade de hastes de amortecedor após o processo de têmpera superficial por indução. Com este trabalho foi possível verificar que o ângulo da fieira exerce forte influência na geometria final das barras trefiladas, sendo que fieiras com maior ângulo de entrada (30º e 40º) resultaram em melhores valores de retilineidade em comparação às fieiras com ângulos menores (12º e 18º). Fieiras com maior ângulo de entrada também resultaram em menor variação entre o diâmetro do paralelo e o diâmetro final da barra. Também foi observada uma forte relação entre a retilineidade das barras trefiladas e a retilineidade das hastes de amortecedor após o processo de têmpera superficial por indução, sendo que melhor retilineidade das barras trefiladas implicou em melhor retilineidade das hastes de amortecedor após o processo de têmpera.
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Bezerra, Augusto Cesar da Silva. "Concreto com fibras curtas de aço submetido a alta temperatura." Universidade Federal de Minas Gerais, 2012. http://hdl.handle.net/1843/PRCN-8TEFUF.
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This study investigated conventional concrete with the addition of short fibers of steel in normal condition and after have been subjected to high temperature. The fibers were characterized by microscopy and mechanical tensile tests. The constituents of the cementitious composites were characterized. To evaluate the interaction between fibers and the cement matrix, were fabricated prismatic specimen partitioned with 40x40x160mm, the halves were connected by three
fibers in the direction longititudinal and they were tested at flexion. To evaluate the cementitious composites reinforced, was molded 4 prismatic specimens with 150X150X500mm and 20 cylindrical with 100mm in diameter and 200mm in height for each type of model with fiber and without fiber. Half of the specimens was taken to the oven for heating. After heating, the raw samples and submitted high temperatures were mechanically characterized by compressive strength testing, tensile strength in diametral compression testing, tensile strength testing in bending and dynamic modulus of elasticity. The results show that there is a reduction in the mechanical properties after subjection to high temperatures, and smaller losses in fiber reinforced concrete.O presente trabalho estudou concreto convencional com adição de fibras curtas de aço em condição normal e após ser submetido a temperatura elevada. As fibras foram caracterizadas por meio de técnicas de microscopia e ensaios mecânicos de tração. Os compósitos cimentícios tiveram seus constituintes caracterizados. Para avaliação da interação das fibras e matriz cimentícia foram confeccionados corpos-de-prova prismáticos de 40x40x160mm particionados, sendo as metades ligadas por três fibras na direção longititudinal e os mesmos foram ensaiados a flexão. Para a avaliação do compósito cimentício reforçado foram moldados 4 corpos-de-prova prismáticos de 150X150X500mm e 20 cilíndricos de 100mm de diâmetro e 200mm de altura para cada modelo de fibra e sem fibra. A metade dos corpos-de-prova foi levada ao forno para aquecimento. Após o aquecimento, os corpos-de-prova crus e submetidos à altas temperaturas foram caracterizados mecanicamente através dos ensaios de resistência à compressão, resistência à tração na compressão diametral, resistência à tração na flexão e modulo de elasticidade dinâmico. Os resultados demonstram que ocorre redução nas propriedades mecânicas após a submissão a temperaturas elevadas, sendo menores as perdas nos concretos reforçados com fibras.
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Sandgren, Daniel. "Test av brunnslock i komposit enligt standard prEN 124." Thesis, Umeå universitet, Institutionen för tillämpad fysik och elektronik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100025.
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Standarder finns i alla möjliga delar av samhället. De används för att säkerställa kvalité, säkerhet och effektivitet. Standarden för hur brunnslock produceras och designas heter prEN 124. Den har förändrats och det är grunden till detta projekt.Brunnspecialisten AB, ett företag i Holmsund, är projektets beställare och har behov av att godkänna sina brunnslock enligt prEN 124 för fortsatt försäljning.Projektets arbetsmoment kan delas in i tre saker. För det första att tolka vilka tester som behöver utföras för att godkänna brunnslock enligt prEN 124. För det andra definiera hur de ska utföras samt det tredje; att utföra fyra av dessa tester.Det certifierande organet är Svensk maskinprovning. De hade kunnat granska standarden prEN 124 och ta fram alla testmetoder. Med detta projekt hoppas deras granskning och då även Brunnspecialisten ABs kostnad kunna minskas.De definierade testerna ska sammanställas i ett dokument. Dokumentet har till uppgift att hjälpa Brunnspecialisten AB när brunnslocken ska certifieras enligt prEN 124. Tolv tester behöver utföras för certifiering. Åtta av dessa tester definieras och beskrivs i tidigare nämnda dokument. Till dokumentet bifogas också ett flödesschema. Flödesschemat visar i vilken ordning testerna ska utföras. Två av testerna utreds om de ens måste utföras. Anledningen är att prEN 124 beskriver en annan design än brunnslocken som Brunnspecialisten AB har. Utredningen visade att SMP godkänner den alternativa designen. Deformationstestet är endast med i flödesschemat. Halkskyddstestet undersöks inte alls i detta projekt.De fyra testerna som skulle utföras var vattenabsorptionstest, motstånd mot fordonsbränsle, stöttest och test av värmepåverkan. Dessa fyra tester genomfördes som planerat. Däremot blev utförandet något förenklat i vissa delar. Förenklingarna skedde av ekonomiska och tidsmässiga skäl.Resultaten från samtliga tester hamnade inom de krav som ställs utifrån prEN 124.De förenklingar som gjorts under projektet anses som acceptabla. Detta eftersom beställaren har deltagit och kunnat bedöma om mer resurser ska tillföras för att utföra testet noggrannare.De fyra testerna visar att brunnslocken troligen klarar att möta standarden prEN 124 för vattenabsorption, motstånd mot fordonsbränsle, stöttålighet och värmepåverkan.Standards are used in all parts of society to secure quality, safety, and efficiency. Some guiding requirements for design and production as well as the certification methods for manhole covers are specified in standard prEN 124. It is currently undergoing changes and is the reason for this project.Brunnspecialisten AB, a company located in Holmsund, is the project owner. They need to certify their product according to prEN 124 to continue their business.The thesis project was devided into three parts. The first part presents what kind of tests that have to be made to secure that a gully top or manhole top meets the standard according to prEN 124. The second part interprets how these tests should be done and the third part; to carry out four of these tests.The defined tests are collected in a document. The purpose of the document is to help Brunnspecialisten AB when the manhole covers are to be certified according to prEN 124. Twelve tests are defined in the certification standard called prEN 124. Eight of these tests shall be interpreted and described in the previously mentioned document. With the document follows a flow chart. The flow chart shows in which order the tests are carried out. Two of the tests will not be carried out, and a part of this project investigates if they can be removed. SMP (Swedish Machinery Testing Institute) deemed that the tests can be skipped, accepting the alternative design which is the reason why the tests are undoable. The deformation test is only mentioned in the flow chart. Slip/skid resistance test was not included in this project.The certifying institution is the Swedish Machinery Testing Institute. They could read prEN 124 and develop the test methods for the manhole top certification. With this project the hope is to minimize the work that SMP needs to do in preparation for the certifying tests. The less work SMP put in the cheaper the certification will be for Brunnspecialisten AB.The four tests carried out in this project were water absorption, resistance against vehicle fluids, impact resistance and heat resistance. These four tests were carried out as planned, but on some parts the tests were not carried out as defined in prEN 124. The reasons were shortage of time and to save money.The results show that the manhole tops meet the requirements set in the standard prEN 124.The diversions done in the test process are considered acceptable. This is because the project owner has been participating in the tests, giving them the chance to add more resources to get more similarity to the defined test method.The four tests are deemed to make the gully top and manhole covers ready for certifying tests for water absorption, resistance against vehicle fluid, impact resistance, and heat resistance.
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Nejedlý, Zdeněk. "Mechanické a technologické vlastnosti duplexních ocelí v závislosti na hodnotě PREN." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2014. http://www.nusl.cz/ntk/nusl-231634.
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This thesis deals with stainless austenitic-ferritic (duplex) steels and their mechanical and technological properties. The first part focuses on introducing these high-alloy materials. The second part describes the influence of chemical composition on the mechanical properties, technological properties and steel structure. There was also observed the effect of heat treatment and steel melting under reduced pressure.
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Uliniuc, Ancuta. "Modificări chimice ale polizaharidelor şi ale hidrogelurilor lor prin procedeul "click chemistry"." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00834679.
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Ce travail a pour objet l'obtention et la caractérisation de nouveaux copolymères amphiphiles et d'hydrogels à hydrophilie contrôlée, à partir de polymères naturels, avec comme utilisations potentielles la vectorisation de principes actifs. En conséquence, il est donc nécessaire que les polymères utilisés pour l'obtention de ces architectures répondent à un certain nombre de contraintes, notamment être non-toxiques, biocompatibles et biodégradables. Pour ces raisons, on retient le plus souvent comme matériaux de départ des polymères naturels, en particulier les polysaccharides. Quelques polymères synthétiques répondent aussi à ces contraintes, telle que la polycaprolactone. Ainsi, le matériau de base utilisé dans ce travail est l'amidon sur lequel a été greffé soit la poly (ε-caprolactone), soit une chaîne grasse. La thèse est structurée en cinq chapitres consacrés d'une part au greffage de structures hydrophobes sur l'amidon et la formation d'hydrogels à hydrophobie modulable, d'autre part à la vectorisation de la lévofloxacine par ces composés. La première partie traite du greffage de la polycaprolactone sur l'amidon par "click chemistry" (CuAAC) entre l'amidon fonctionnalisé par des fonctions alcynes et des polycaprolactones à fonction azoture en bout de chaîne, ces dernières étant préalablement obtenues par POC de la caprolactone. Les réactions de CuAAC ont été effectuées non seulement selon les protocoles habituels, mais aussi par micro ondes. Par ailleurs, l'amidon a aussi été hydrophobisé par les méthodes usuelles d'estérification par une chaîne grasse via le chlorure de l'acide palmitoique. Les produits ainsi obtenus ont été caractérisés par RMN, IR, XPS et leur comportement dans différents solvants (solubilité, gonflement) a été étudié. Une seconde partie est consacrée à l'élaboration d'hydrogels à base d'amidon et d'amidon modifié avec des chaînes d'acides gras et de PCL par réticulation avec l'acide citrique. Afin d'atteindre les objectifs, une stratégie multifactorielle expérimentale avec deux variables indépendantes a été utilisée. La modélisation mathématique des données expérimentales permet de remonter aux paramètres physico-chimiques pertinents, montre les effets de synergie et établit les conditions d'optimisation. Une dernière partie a permis d'évaluer les cinétiques de libération de la lévofloxacine, un antibiotique de dernière génération, par les hydrogels obtenus. Les matériaux obtenus ont montré des propriétés de libération contrôlée potentiellement intéressantes. Les résultats obtenus au cours de cette thèse ont été évalués par la publication de trois articles et par dissémination des résultats au six conférences internationales.
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Stanciu, Nicoleta Doriana. "Compozite polimer-organice şi polimer-anorganice obţinute prin polimerizare radicalică „in situ”." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10006.
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Ce travail porte sur l'obtention et la caractérisation de composites polymères à charges organiques et inorganiques obtenus par polymérisation radicalaire in situ de monomères dans une matrice organique de type cellulose ou inorganique de type silicate. Avec la cellulose, les monomères retenus sont d'abord des dérivés vinyliques de type acide (méth)acrylique et de comonomères tels que l'anhydride maléique, le styrène et le chlorométhylstyrène. Les produits sont caractérisés notamment par ATG et XRD. La conductivité électrique de ces composites en fonction de leur gonflement a été étudiée. La copolymérisation de l'anhydride maléique avec le dicyclopentadiène est ensuite étudiée dans le toluène et le dioxane. Ce type de copolymère n'avait pas été étudié jusqu'à présent. L'influence du type de solvant sur la conduite de la réaction est étudiée. La caractérisation des composites est effectuée par IR, XRD et microscopie SEM. L'interaction entre les composants est mise en évidence par XRD. Les composites à base de silicate sont obtenus par polymérisation radicalaire contrôlée après greffage de l'amorceur sur le support inorganique. Le greffage est caractérisé par IR. Les analyses XRD et IR mettent en évidence la prédominance du greffage du polymère à la surface du silicate. L'étude de la copolymérisation chlorométhylstyrène - méthacrylate d'hydroxyéthyle a été effectuée qui montre in fine l'influence du support sur la structure des copolymères. De même, les analyses XRD et IR révèlent la modification de la structure du silicate. La microscopie SEM met en évidence des structures homogènes. Une étude complète de dégradation thermique a été menée par ATG qui montre l'influence des différents polymèresThe synthesis of organic-polymer or inorganic-polymer composites was a real challenge within the last decades due to the difficulty of optimally dispersing the reinforcing agent into the polymeric matrix. A method to solve this problem is the "in situ "polymerization. The first part of the experimental study deals with the synthesis of the polymer-cellulose composites. Cellulose-containing composites based on copolymers of acrylic acid with styrene, 4-chloro-methyl-styrene and maleic anhydride or based on copolymers of methacrylic acid with styrene and 4-chloro-methyl-styrene were prepared for proton conducting membranes. Next, cellulose composites with maleic anhydride – dicyclopentadiene copolymer matrix were obtained by “in situ” free-radical polymerization. The syntheses were carried out in two different solvents: toluene and dioxane, aiming to determine their influence upon both the polymerization process and properties of the resulting materials. To the best of our knowledge, studies concerning the preparation of this composite have not been published in the literature until now. The second part of the original contributions section is dedicated to the investigation of some polymer-layered silicates composites, using a commercial layered silicate (Cloisite 30B), modified with OH-containing quaternary ammonium salts. First, a new ATRP-based procedure to synthesize polymer-layered silicate composites involving a simpler method than those published in the literature up to now, was studied. The novelty of the methods consists in the one-step preparation of the ATRP initiating sites anchored onto the layered silicate by reacting the OH groups of the quaternary ammonium salt with chloroacetic anhydride, followed by the "in situ” ATRP of the monomer. This way several intermediate stages are eliminated. The last experimental study concerns the synthesis and characterization of a composite with an inorganic support (Cloisite 30B) and a polymeric matrix synthesized by the copolymerization of two different monomers with high reactivity: 2-hydroxyethyl methacrylate and 4-chloro-methyl-styrene. To our knowledge, there are no studies published in the literature describing the preparation of this composite until now. The obtained composite materials were characterized both structurally by FT-IR, NMR, XRD and SEM, and from the thermal behavior point of view by TGA-DSC-MS
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Netto, Marcelo Vieira. "Efeitos do uso tópico da mitomicina C na prevenção e tratamento da opacidade corneana em coelhos submetidos à ceratectomia fotorrefrativa." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-20022009-132232/.
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Objetivos: Determinar os efeitos celulares e o mecanismo de ação da mitomicina C tópica na prevenção e tratamento da opacidade corneana em coelhos submetidos à ceratectomia fotorrefrativa (PRK). Métodos: Foram submetidos à cirurgia de PRK 224 coelhos para correção de -9 dioptrias esféricas, associada à aplicação de mitomicina C tópica ou solução salina balanceada. O nível de opacidade corneana foi avaliado por meio de análise à lâmpada de fenda. Os animais foram sacrificados quatro horas, 24 horas, quatro semanas e seis meses após a cirurgia. A análise imunohistoquímica foi realizada com as técnicas de TUNEL e foram utilizados os anticorpos Ki67 e alpha-SMA para a análise da apoptose celular, replicação celular e formação de miofibroblastos, respectivamente. Resultados: Todos os grupos submetidos à aplicação de mitomicina C apresentaram um maior número de células positivamente marcadas pelo ensaio com TUNEL (indicando maior taxa de apoptose celular) e um menor número de células positivamente marcadas pelo anticorpo Ki67 (indicando menor taxa de replicação celular). Uma menor quantidade de miofibroblastos (células positivamente marcadas pelo anticorpo alpha-SMA) foi identificada após a aplicação profilática da mitomicina C, comparada com sua aplicação com finalidade terapêutica. Além disso, identificou-se uma zona de acelularidade no estroma anterior de córneas tratadas com mitomicina C, persistente por um período mínimo de seis meses. Conclusões: A aplicação da mitomicina C diminuiu signficativamente a formação de opacidade corneana em coelhos. Apesar da mitomicina C ter induzido uma maior apoptose de ceratócitos e miofibroblastos, seu principal mecanismo de ação, responsável pela prevenção da opacidade corneana, decorreu do bloqueio da replicação dos ceratócitos ou outras linhagens celulares progenitoras dos miofibroblastos. A aplicação da mitomicina C na concentração de 0,002% mostrou-se tão eficiente quanto sua aplicação na concentração de 0,02%. Não obstante, uma persistente diminuição da densidade de ceratócitos no estroma anterior pode representar um sinal de alerta para possíveis complicações a longo prazoPurpose: To determine cellular effects and the mechanism through which topical mitomycin C prevents and treats corneal haze after photorefractive keratectomy (PRK) in rabbits. Methods: Minus nine diopters PRK with mitomycin C or balanced salt solution was performed in two hundred and twenty four New Zealand rabbits. Haze level was graded at the slit lamp. Rabbits were sacrificed at 4 hours, 24 hours, 4 weeks or 6 months after surgery and immunohistochemistry was performed with TUNEL assay, Ki67 and alpha-SMA to analyze keratocyte cells apoptosis, keratocyte cells replication and myofibroblast cells formation, respectively. Results: TUNEL-positive cells increased in all mitomycin C groups (representing more keratocyte cells undergoing apoptosis) while Ki67-positive cells decreased significanlty (representing a decreased keratocyte cells replication) following mitomycin C application. A greater decrease in myofibroblasts was noted with prophylactic mitomycin C treatment than therapeutic mitomycin C treatment. There was, however, an anterior stromal acellular zone in eyes treated with mitomycin C that persisted out to the maximum follow-up of 6 months. Conclusion: Mitomycin C application significantly reduced corneal haze formation in rabbits. Its treatment induces apoptosis of keratocytes and myofibroblasts, but the predominate effect in inhibiting or treating haze appears to be at the level of blocked replication of keratocytes or other progenitor cells of myofibroblasts. Treatment with 0.002% mitomycin C appears to be just as effective as higher concentrations (0.02%) in the rabbit model. However, a persistent decrease in keratocyte cells density in the anterior stroma could be a warning sign for future complications
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Foulquier, Elodie. "Du métabolisme carboné à la morphogenèse : Rôle interprété par YvcK, protéine de Bacillus subtilis." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX22077.
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La protéine de fonction inconnue, YvcK, est vitale chez Staphylococcus aureus mais non essentielle chez les bactéries modèles Bacillus subtilis ou Escherichia coli. Chez B. subtilis, les bactéries délétées du gène yvcK, sont sérieusement affectées dans leur croissance et leur morphologie dans des conditions de croissance gluconéogéniques. Les défauts observés peuvent être compensés par l’ajout de fortes concentrations de magnésium ou par l’inactivation de gènes impliqués dans le métabolisme. Ceci suggère que, les mutants yvcK présentent des altérations au niveau de la paroi bactérienne qui sont probablement dues à un désordre du métabolisme. Le phénotype lié à l’absence d’YvcK est similaire à celui observé chez des souches mutées au niveau de gènes impliqués dans la synthèse du peptidoglycane ou constituant le cytosquelette. La protéine MreB, composant majeur du cytosquelette bactérien, forme une structure hélicoïdale sous la membrane cytoplasmique pour positionner les enzymes de synthèse et la maturation du peptidoglycane. In vivo, la protéine YvcK est également localisée sous la forme d’une hélice. Par ailleurs, la surexpression de YvcK supprime le défaut de morphologie du mutant mreB et vice versa. Il a été montré que, chez B. subtilis, la localisation de la protéine membranaire PBP1 était dépendante de MreB. Une délétion de ponA, gène codant pour PBP1, rétablit la viabilité d’un mutant mreB et celle du mutant yvcK dans des conditions de croissance gluconéogéniques. La protéine de fusion GFP-PBP1 dans une souche délétée du gène yvcK, cultivée en milieu liquide CE-gluconate est délocalisée expliquant le gonflement des cellules. Ce résultat suggère que la localisation normale de PBP1 au septum due à la surproduction de YvcK dans un mutant mreB (et réciproquement) permet la restauration de la croissance et de la morphologie. De plus, nous avons montré que, comme son homologue présent chez Mycobacterium tuberculosis, YvcK est phosphorylée in vitro. Nous avons caractérisé la phosphorylation d’YvcK par la protéine kinase PrkC et nous avons identifié la Thr 304 comme site unique de phosphorylation. Cette phosphorylation semblerait jouer un rôle important dans la complémentation du mutant mreB et du repositionnement de la PBP1The YvcK protein is a bacterial conserved protein of unknown function. It is essential in Staphylococcus aureus but not essential in both Bacillus subtilis and Escherichia coli. In B. subtilis, inactivation of the yvcK gene seriously affects growth and morphology on neoglucogenic carbon sources. The defects observed in a yvcK mutant can be offset by the addition of high concentrations of magnesium or by inactivation of genes involved in metabolism. This suggests that, when grown on some carbon sources, yvcK mutants display alterations in their cell wall probably due to a disorder in this metabolism. The phenotype associated with the absence of YvcK is similar to that observed with strains mutated in genes involved in peptidoglycan synthesis or encoding proteins of the cytoskeleton. The major component of cytoskeleton, MreB, an actin-like protein, together with other proteins, forms a helical structure at the cell membrane that participates in the organization and positioning of the enzymes of peptidoglycan synthesis and maturation. We showed that YvcK is organized as a helical like pattern localized near the inner surface of the membrane, independently of the presence of MreB. Surprisingly and despite that these two proteins do not harbour any similarity of sequence or structure, an overproduction of YvcK restored a normal morphology in an mreB mutant strain and vice versa. Furthermore, as already observed for the mreB mutant, in a yvcK mutant strain, the penicillin-binding protein PBP1 is delocalized and deletion of its gene restores growth of a yvcK mutant on gluconate medium. All these results suggest that YvcK is not only involved in the synthesis of cell wall from gluconeogenic carbon sources but also plays a role in cell morphogenesis. In addition, we have shown that similarily to its Mycobacterium tuberculosis homolog, YvcK is phosphorylated in vitro. We have characterized the phosphorylation of YvcK by the protein kinase PrkC and we identified the Thr 304 as the single phosphorylation site. Furthermore, this phosphorylation appears to play an important role in the complementation of the mreB mutant and repositioning of PBP1
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Vieira, Luiz Rosa. "Uso de termografia para avaliação da temperatura em cirurgias laser PRK." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2006. http://hdl.handle.net/10183/8000.
Full textAbstract:
Hipermetropia e miopia são problemas visuais freqüentes que decorrem de uma conformação inadequada da córnea. Esta inadequação pode ser corrigida com o emprego de métodos cirúrgicos através dos quais a curvatura dessa lente biológica é modificada. A possibilidade de dano na córnea, durante cirurgias refrativas, tem sido uma preocupação constante e um risco sempre presente, independentemente do método cirúrgico utilizado. Um limite de temperatura aceitável, dentro de uma margem de segurança prudente, tem sido buscado, existindo vários artigos sobre o assunto, não tendo sido encontrada, contudo, uma abordagem na forma aqui apresentada. O presente trabalho foi desenvolvido em duas etapas, sendo uma experimental preparatória, quando foram desenvolvidos estudos preliminares para projeto, montagem e teste dos acessórios necessários para pesquisa. Com o emprego destes acessórios foram feitas medições em olhos de suínos ex vivo, no sentido de determinar a emissividade da superfície da córnea usando termômetros de contato, forno corpo negro e termografia. Conhecidos os valores de emissividade da córnea, com e sem a camada epitelial, teve início a segunda etapa, também experimental, do trabalho. Inicialmente foram efetuadas medições, já com a participação de pacientes voluntários, para a elaboração de um protocolo para a análise das imagens infravermelhas, que seriam coletadas durante a realização de cirurgias laser. Estabelecido o protocolo, teve inicio o monitoramento da temperatura, através da gravação dinâmica de imagens, para posterior mapeamento dos campos de temperatura, de procedimentos cirúrgicos para correção de hipermetropia e miopia. Da análise das imagens gravadas, concluiu-se ser a termografia uma técnica eficaz para a medição dos campos de temperatura no olho humano, durante a realização de cirurgias empregando fontes laser e, ainda, que a temperatura final da superfície do globo ocular é baixa, não chegando aos 39 ºC em qualquer dos casos monitorados. Nestas cirurgias, foi empregada uma metodologia, desenvolvida pelo cirurgião, para controle da temperatura, que consistiu no uso de colírio anestésico refrigerado, na fase pré-operatória e após a aplicação do laser, seguido da instalação de lente gelatinosa, também refrigerada e aplicação de mais colírio anestésico refrigerado.Hypermetropia and myopia are frequent visual problems that happen due to an inadequate cornea conformation. This inadequacy may be amended by means of surgical procedures that modify the curvature of this biological lens. The possibility of damage on the cornea during refractive surgery has been a constant concern and an ever-present hazard, independently of the surgical method used. A limit of acceptable temperature, within a prudent safety margin, has been pursued and there are various papers about the subject; however, with an approach different from the one that is introduced here. The present research was developed in two parts: an experimental preparatory one, in which preliminary studies for the project, assemblage and test of the necessary accessories for the research were performed. With the use of these accessories, measurements of swine eyes ex vivo were made in order to determine the emissivity of the cornea ocular region, by using contact thermometers, black body furnace, and thermography. After the cornea emissivity values were found, with and without the epithelial stratum, the second phase of the research, which was also experimental, began. It comprised the measurement of self-conscious volunteers to establish a protocol for the analysis of the infrared images, which would be collected during laser surgeries. After this protocol was established, the monitoring of the temperature was proceeded, through the dynamic recording of images, for mapping the temperature fields throughout surgical procedures to the improvement of myopia and hypermetropia. From the analysis of the images recorded, it was concluded that thermography is an effective instrument for field temperature measuring of the human eye during surgeries involving laser sources. It was also found that the temperature on the eye surface, after the surgery, was below 39 ºC in any of the cases studied. In these surgeries, a methodology developed by surgeon, for the control of the temperature, which consisted in the use of chilled collyrium at the presurgical phase and after the laser application, followed by the implantation of gelatinous lenses, also chilled and the instillation of more chilled collyrium.
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Sánchez-Alvarez, Leticia. "Planar Cell Polarity Genes prkl-1 and dsh-1 Polarize C. Elegans Motorneurons during Organogenesis." Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23513.
Full textAbstract:
The correct polarity of a neuron underlies its ability to integrate precise circuitries in
the nervous system. The goal of my thesis was to investigate the pathways that establish and
maintain neuron polarity/orientation in vivo. To accomplish this, I used bipolar VC4/5 motor
neurons, which innervate the C. elegans egg-laying musculature, as a model system. Vulval
proximal VC4/5 neurons extend axons in the left-right (LR) orientation, around the vulva;
whereas vulval distal VC1-3,6 neurons extend axons along the anterior-posterior (AP) axis.
A previous study showed that vang-1, a core planar cell polarity (PCP) gene, suppresses AP
axon growth in VC4/5 neurons. In order to identify new components of this pathway we
performed genetic screens for mutants with abnormal VC4/5 polarity/morphology. We
isolated and mapped alleles of farnesyl transferase b (fntb-1) and of core PCP genes, prickle-
1 (prkl-1) and dishevelled-1 (dsh-1); all of which display tripolar VC4/5 neurons, similar to
vang-1 lof. In prkl-1 and dsh-1 mutants, primary LR and ectopic AP VC4/5 axons are born
simultaneously, suggesting an early role in establishing polarity. In addition, prkl-1 and dsh-1
act persistently to maintain neuron morphology/orientation. Genetic analysis of double
mutants suggests that prkl-1 interacts with vang-1 in a common PCP pathway to prevent AP
axon growth, while dsh-1 also acts in a parallel pathway. Furthermore, prkl-1 functions cell
autonomously in neurons, whereas dsh-1 acts both cell autonomously and cell nonautonomously
in epithelial cells. Notably, prkl-1 overexpression results in unipolar VC4/5
neurons, in a dose-dependent manner. In contrast, dsh-1 overexpression in VC4/5 neurons
results in a lof phenotype, similar to vang-1 lof and overexpression phenotype. Remarkably,
prkl-1 overexpression restores normal VC4/5 polarity in dsh-1 and vang-1 mutants, which is
suggestive of a downstream role for prkl-1. Both PRKL-1 and DSH-1 are expressed in
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uniformly distributed puncta at the plasma membrane of VC4/5, similar to VANG-1;
suggesting that their asymmetric distribution is not critical for neuron polarity. Furthermore,
we found that the vulva epithelium induces prkl-1 expression in VC4/5; indicating a
functional relationship between the egg-laying organ and neuron morphology. Moreover, a
structure-function analysis of PRKL-1 revealed that the conserved PET domain and the Cterminal
region are crucial to prevent AP axon growth, whereas the three LIM domains are
dispensable for this role. In addition, we showed that dsh-1 also regulates the morphology of
AP-oriented PDE neurons. dsh-1 promotes the formation of PDE posterior axons, contrary to
its function in VC5 neurons; which indicates a context-dependent role for dsh-1 in neuronal
polarity. Altogether, this thesis implicates the PCP signalling pathway in a previously
unknown role, in establishing and maintaining neuronal polarity, by controlling AP axon
growth in response to organ-derived polarizing cues.
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Gros, Pierre-Paul. "The characterization of PrpZ and PrkY, two eukaryotic-type proteins of Salmonella enterica serovar Typhi /." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116030.
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The intracellular human pathogen Salmonella enterica serovar Typhi (S. typhi) causes the systemic disease known as typhoid fever. This disease afflicts approximately 17,000,000 people every year, of which over 600,000 cases are fatal.Sequencing of the S. typhi genome has allowed a better understanding of the pathogenesis caused by this bacterium. In silico research on the genome sequence identified three open reading frames, termed prpZ gene cluster, present in the Ty2 and multi-drug resistant CT18 strains of S. typhi but absent in all other sequenced serovars of S. enterica. Further analysis of this gene cluster revealed that the three genes are transcribed as an operon that encodes two eukaryotic-like Ser/Thr kinases (PrkX and PrkY) and a protein phosphatase 2C (PP2C) (PrpZ).
A previous study has shown that the recombinant His-PrpZ protein has all the hallmarks of a PP2C. Typically, PP2Cs hydrolyze phosphoserine and phosphothreonine residues. In addition, His-PrpZ was found to hydrolyze phosphotyrosine residues, making it a dual specificity phosphatase. A subsequent investigation implicates the prpZ gene cluster in S. typhi virulence as the survival of a prpZ operon deletion mutant is compromised after 48 hours of macrophage infection when compared to wild type bacteria.
It is clear from these results that the prpZ operon plays a role in the pathogenesis of S. typhi. To determine the role of these three genes in virulence, an in vitro characterization of PrkY was carried out as well as an examination of the possible physiological roles of PrpZ.
We have demonstrated that PrkY is an active protein kinase capable of phosphorylating artificial substrates in the presence of Mg2+ and/or Mn2+. Optimal phosphorylation of substrates is achieved in the presence of 5mM Mg2+ at pH 8.0. In addition, we have identified a putative interaction between PrkY and PrpZ, leading to an inhibition of the kinase activity of PrkY. While exploring the possible physiological functions of PrpZ, we have found that this protein is secreted by Ty2 S. typhi in both LB and in the low pH, low phosphate and low Mg 2+ LPM medium.
These findings suggest that PrkY and PrpZ may have antagonistic effects in a S. typhi specific virulence pathway involved in the modulation of host cell signaling by secreted bacterial virulence factors.
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Iacomi, Béatrice Michaela. "Ciuperci din genul Alternaria transmise prin seminte de crucifere : detectie moleculara, variabilitate si activitate patogena." Angers, 2001. http://www.theses.fr/2001ANGE0015.
Full textAbstract:
Alternaria brassicae, A. Brassicicola, et A. Japonica, constituent un complexe d'espèces pathogènes des crucifères et responsable de la maladie des taches noires. Afin de limiter la propagation de cette maladie lors de échanges internationaux, il est nécessaire de garantir la qualité sanitaire des semences par la certification de l'absence de ces trois espèces pathogènes dans les lots de graines commercialisés. La méthode actuelle de détection qui s'appuie sur leur mise en culture et leur identification morphologique est lourde et souvent peu fiable. Une méthode de diagnostic moléculaire utilisant l'amplification par réaction de polymérisation en chaîne (PCR) a été développée. Des amorces spécifiques de chaque espèce ont été synthétisées sur la base des séquences nucléotidiques des espaceurs internes transcrits (ITS) de l'ADN ribosomique. Leur utilisation lors des réactions d'amplification en présence de matrices d'ADN extraites de macérats de graines, a permis de détecter après deux jours d'incubation, la présence d'A. Brassicicola et d'A. Japonica sur des semences contaminées à seulement 10%. A. Brassicae a également pu être détecté en utilisant une méthode similaire à l'aide d'amorces correspondant à un gène codant une cyclique-pepdide synthase. La variabilité génétique des trois espèce a été analysée à trois niveau : polymorphisme de l'ADN, sensibilité à fongicides et niveau d'agressivité. Ceci a permis de montrer que les individus de l'espèce A. Brassicae se propageaient de façon quasi-clonale avec une absence de résistance aux fongicides et une agressivité assez faible. A l'inverse, l'analyse des souches d'A. Brassicicola a révélé l'existence d'un polymorphisme assez important chez cette espèce avec identification d'isolats de terrain resistants aux phenylpyrroles et la mise en évidence d'une agressivité importante.
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Cuenot, Elodie. "Rôle des Sérine/Thréonine kinases PrkC et CD2148 dans la physiologie du pathogène Clostridium difficile." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC286.
Full textAbstract:
C. difficile (CD) est un bacille à gram-positif anaérobie strict et sporulant. Ce pathogène est la principale cause d’infections nosocomiales intestinales après une antibiothérapie. La contamination des patients s’effectue via l’ingestion de spores de CD. Suite à une prise d’antibiotiques, une dysbiose du microbiote conduit à des changements dans les pools de métabolites favorisant la germination des spores et la croissance de CD dans le tube digestif. CD va alors produire deux toxines entrainant des dommages cellulaires et une forte inflammation ce qui va conduire à des diarrhées ou des colites pseudomembraneuses. Une partie des cellules de CD va aussi former des spores conduisant à la transmission de l’infection. Lors de son cycle infectieux, CD doit s’adapter rapidement aux changements dans son environnement via la régulation de ses différents processus physiologiques. La phosphorylation est une modification post-traductionnelle réversible. Elle est très souvent utilisée pour moduler l’activité de protéines impliquées dans des voies de signalisation. Les Ser/Thr kinases (STKs) bactériennes phosphorylent leurs substrats sur des résidus Ser ou Thr et régulent de nombreux processus tels que la traduction, le métabolisme du carbone, la synthèse de l’enveloppe, la résistance aux antibiotiques, la division cellulaire ou la virulence. De manière intéressante, CD possède deux STKs, PrkC et CD2148, qui n’ont jamais été étudiées. Ces deux STKs possèdent un domaine kinase cytoplasmique ainsi qu’un segment transmembranaire. Seule PrkC présente une partie extracellulaire composée de 2 domaines PASTA. L’inactivation de PrkC affecte la morphologie ainsi que la division cellulaire de CD. Les cellules du mutant ∆prkC sont hétérogènes en taille. Certaines cellules très allongées ne possèdent pas de septum, d’autres cellules ont un septum mal localisé ou plusieurs septa rapprochés pour environ 15% des cellules du mutant ∆prkC comme observé en microscopie électronique. Nos résultats ont montré que le mutant ∆prkC était capable de sporuler et de germer de manière similaire à la souche sauvage mais présente cependant une motilité réduite ainsi qu’une plus grande capacité à former des biofilms. De plus, le mutant ∆prkC montre une plus grande sensibilité aux céphalosporines qui sont des antibiotiques qui favorisent les infections à CD, à certains peptides antimicrobiens et au lysozyme qui sont l’une des premières lignes de défense de l’hôte et aux sels biliaires secondaires tels que le déoxycholate qui sont toxiques pour les cellules végétatives. En outre, la sensibilité accrue du mutant ∆prkC à ces stress d’enveloppe que CD rencontre dans l’intestin lors du cycle infectieux, pourrait être la cause du délai de colonisation observé pour ce mutant chez le hamster. L’inactivation de PrkC affecte donc l’homéostasie de l’enveloppe de CD. Nous avons montré que la composition du peptidoglycane n’est pas différente entre la souche sauvage et le mutant ∆prkC. En revanche, nous avons mis en évidence un relargage plus important du glycopolymère de surface, le PSII, dans le milieu de culture du mutant ∆prkC. Des résultats préliminaires suggèrent que cet acide téichoïque est également plus présent à la surface du mutant ∆prkC et nous réalisons actuellement des expériences complémentaires pour le vérifier. La structure du PSII étant la même chez les deux souches, ces résultats suggèrent que PrkC est impliquée dans les mécanismes de contrôle de la synthèse du PSII, de son exportation ou de son ancrage au peptidoglycane de CD. Au cours de ce travail, nous avons également commencé l’analyse du mutant CD2148::erm. Les premiers phénotypes observés pour ce mutant sont nettement différents de ceux de ∆prkC puisque l’inactivation de CD2148 affecte le processus de sporulation et la séparation des cellules après division cellulaireClostridium difficile (CD) is the leading cause of intestinal nosocomial post-antibiotic infections in adults. Exposure to certain antibiotics including cephalosporins induces dysbiosis promoting CD infection. Resistance of CD to these antibiotics is a major concern while resistance mechanisms remain poorly characterized. CD produces two toxins that cause epithelial cell damage and inflammation while additional factors associated to cell surface participate in the colonization process. During infection, CD also encounters several stresses in the gut such as secondary bile salts that are toxic for vegetative cells, antibiotics, antimicrobial peptides released by the host, reactive oxygen and nitrogen species produced during inflammation. Pathogen survival depends on its capacity to rapidly adapt to the host environment. Protein phosphorylation is a reversible post-translational modification employed for signal transduction and regulation. Bacterial Ser/Thr kinases (STKs) regulate numerous physiological processes. In response to specific stimuli, STKs phosphorylate substrates on Ser or Thr residues to trigger the appropriate cellular response. Nothing is known about the role of the two STKs of CD, PrkC and CD2148, in the physiology of this enteropathogen. To investigate their function, we constructed ∆prkC and ∆CD2148 mutants. Cells of the ∆prkC mutant had an increased size and abnormal septa. The ∆prkC mutant also had a reduced motility and formed more biofilms. PrkC inactivation increased sensitivity to antimicrobial compounds that CD may encounter in the gut during infection such as deoxycholate, cephalosporins, cationic antimicrobial peptides and lysozyme. This increased susceptibility was not associated to differences in the structure of peptidoglycan. By contrast, we showed that the ∆prkC mutant released more polysaccharide II (PSII) in the supernatant suggesting a decreased deposition of this glycopolymer to the cell surface in this mutant. Our results also revealed that the ∆prkC mutant had a delay in gut implantation in a hamster model. Finally, we observed that the mutant ∆CD2148 formed chains of cells and sporulated more rapidly than the wild-type strain. Accordingly, key sporulation genes were up-regulated in this mutant. Work is now in progress to detect proteins phosphorylated in vivo using phosphoproteomic approaches and to identify substrates of PrkC and CD2148
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Zhao, Yelin. "Ambitious model, ambiguous artist : three case studies of Victorine Meurent, Suzanne Valadon and Alice Prin." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/21231/.
Full textAbstract:
This thesis is about a singular figure who appeared on the artistic scene in the middle of the nineteenth century. I call this figure the Model-Artist. This term conjugates two facets of the production of art, which links issues of labour, creativity, class and gender. In this thesis, I look specifically into three case studies of the Model-Artist working in Paris from the second half of the nineteenth century to the second decade of the twentieth: Victorine Meurent (1844-1927), Suzanne Valadon (1865-1938) and Alice Prin (1901-1953). By scrutinising the archives of these three individuals and reading critical writings on their work at the time and in subsequent biographies and art historical studies, I advance an argument about the significance of the model’s labour/the labour of modelling, in order to shift the canonical histories of modern art from 1860 to 1930 which privilege the artist. I also challenge, by expanding some of the feminist studies that examine the work of women as artists and as models in this period. I do so by examining three instances of women who worked as both models and artists in artistically and culturally different moments of the histories of modernism. This highlights the specific relations between the shape of each of these three women’s careers. It underscores both the new conditions of artistic production associated with the emerging formation of the avant-garde community and the new modes of art that were generated in terms of both the treatment of old and new subjects and in terms of artistic representation. Through the case studies, I avoid creating exceptional histories, and acknowledge invisibility (other stories yet to be found) as much as re-read known stories. Methodologically, I challenge and expand existing feminist art histories by criticising their continuation of the hierarchy between model and artist and the privileging of the artist. Through close reading of images, I pinpoint the changing aesthetic of art and analyse its impact on the artist’s practice of modelling as well as the modelling labour. The study of Victorine Meurent rests on a fragile and fragmented archive. I draw on Derrida’s theory of the archive and Foucault’s theory of the fold in the discourse to tackle the question of how to study a subject about which the documentary evidence is scarce. With a much more documented and substantial œuvre, Suzanne Valadon’s case enables an investigation into her artistic manoeuvres and avant-garde gambits in relation to her contemporaries. I examine her paintings as traces of an articulation of embodied experience that at the same time solicit different forms of spectatorship. The chapter on Alice Prin is an analysis of the cultural and social dynamics within the Montparnasse circle in Paris in the second and third decades of the twentieth century. From this close-knit community of international artists, the mythological figure of Kiki de Montparnasse emerged. Each case study situates the strategies and practices of three women negotiating a relation to artistic practice determined by the social, cultural, organisational and aesthetic specificities of three different moments in the emergence of modernist artistic practice and its communities. Labour, community and gender are key concepts throughout this study.
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Yao, Sheng. "SiRNA inhibition of PRKC-σ-vb expression abrogates the aggressive phenotype of human prostate cancer cells." Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510949.
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The work performed in this Thesis was aimed to elucidate a possible function of PKC~ in human prostate cancer cell-lines. In particular, the role of gene P RKC-(-vb, the predominat isoform expressed in these cells, playing in human prostate tumorigenesis and metastasis, was investigated. The Introduction gIves general information about prostate cancer, PKCs families, particularly PKC-~ and its role in prostate cancer. The Thesis includes six main chapters, presenting data as follows: The gene expression of PRKC-( (PRKC-(-vb, PRKC-(-vn) was determined in prostate malignant and non-malignant cell-lines. Overexpression of both variants of PRKC-(was detected in prostate cancer when compared to non-malignant cell-lines, indicating P RKC-( to be a potential biomarker of prostate cancer. Overexpression of P RKC-l was also detetected in prostate cancer in comparison to non-malignant cell-lines. This result indicated these two PKCs may play similar functions in prostate cancer through phosphorylation of different substrates. To further determine the function of PRKC-(-vb in prostate cancer, gene knockdown cell-lines PRKC-(-vb-Tl-6 and PRKC-(-vb-Tl-2 were established using vector-based RNAi. Reduced gene expression of PRKC-(-vb was confirmed in these two cell-lines when compared to PC3-M parental and scrambles control cell-lines. The transfected cell-lines PRKC-(-vb-Tl-6 and PRKC-(-vb-Tl-2 were further investigated by in-vitro and in-vivo assays. Altered morphology indicated the changed phenotype of the transfectant cells. Reduced proliferation, invasion and anchor-independent growth in transfectant cells indicated reduced malignancy and then suggested the role of PRKC-(-vb in promoting prostate cancer tumorigenesis and metastasis. Reduced tumorigenesis in gene knockdown cells was confirmed by in-vivo assays. Thereafter, potential oncogenic signalling pathways in the gene knockdown cells were investigated by oligonucleotide based micro array. A down-regulated canonical NF-Kl3 pathway was identified in the gene knockdown cell-lines. Moreover, several molecules involved in prostate cancer were detected, indicating that crosstalk of these molecules may exist in prostate cancer. In previously work, a novel sequence was detected to be expressed as extention of 5' primer of "vn". Based on expressed sequences, up-and down-stream of "vn" were determined using RT-PCR. An expressed sequence was detected as an extention of 3' down stream of "vn". However, the method need to be revised to detect the 5' up-stream sequence because Alu blocks were identified at 5' up stream "vn" within 1500bp disturbing further sequencing. Based on the original sequence confirmed previously, a new monoclonal antibody was generated according to the epitope that is different to that of PKC-s. A novel protein specific to prostate cancer was also detected, indicating that a new potential splice variant of PKC-s may be present in prostate cancer. In conclusion, the current study suggests the original hypothesis that expression of P RKC-( is not only a biomarker of prostate cancer but that it plays an important role in promoting prostate cancer tumorigenesis and enhancing tumour metastasis
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Diaz, Thierry. "Macro-amphiphiles cationiques à architecture contrôlée : synthèse par PRCN et étude de leur organisation en milieu aqueux." Nancy 1, 2004. http://www.theses.fr/2004NAN10010.
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Le développement récent de nouveaux nitroxydes, conçus pour contrôler notamment la polymérisation de monomères polaires, a conduit notre équipe à utiliser le N-t-butyl-N-(1-diéthylphosphono-2,2-diméthyl)propyl-nitroxyde (DEPN) pour préparer des copolymères amphiphiles cationiques riches en motifs hydrophiles ayant une structure bien définie et évolutive. Nos travaux ont montré que la 4-vinylpyridine (4VP) et le N,N-diméthylacrylamide (DMAA) peuvent polymériser de façon contrôlée en présence de DEPN et qu'il est possible de synthétiser des diblocs présentant de faibles indices de polymolécularité en polymérisant le DMAA avec une alcoxyamine macromoléculaire poly(4VP)-DEPN. Après quaternisation, ces diblocs ont conduit à une série de macro-amphiphiles de composition variable. Des études par viscosimétrie et par spectroscopie de fluorescence ont révélé que, dans des milieux riches en eau, ces composés forment des micro-domaines hydrophobes par le biais d'associations intramoléculairesThe ability of b-hydrogenated nitroxides to polymerize polar monomers according to a controlled process led our team to use the N-t-butyl-N-(1-diethylphosphono-2,2-dimethyl)propyl nitroxide (DEPN) to prepare new amphiphilic cationic diblock copolymers with a well-defined and variable structure. In this work, we have shown that the polymerization of 4-vinylpyridine (4VP) and N,N-dimethylacrylamide (DMAA) are controlled in the presence of DEPN, and that well-defined diblock copolymers of these two monomers can easily be achieved by polymerizing DMAA with a macromolecular alcoxyamine poly(4VP)-DEPN. The quaternization of these diblocks with different alkyl bromides led to a series of comb-like copolymers, and the behaviour of these products in aqueous medium was investigated by viscosimetry and fluorescence spectroscopy. Long alkyl chains were proved to form hydrophobic microdomains by intramolecular agregations
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Guzmán, Gilardi Magnan Alejandro José. "Pren/S.A. : la tensión entre el periodismo y la empresa por razones de condicionamiento comercial : caso El Comercio." Bachelor's thesis, Pontificia Universidad Católica del Perú, 2016. http://tesis.pucp.edu.pe/repositorio/handle/123456789/6827.
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Este trabajo plantea un acercamiento a ellas desde un punto de vista más definido: la
hipótesis principal de estas páginas es que la incompatibilidad conceptual entre el
periodismo y la empresa deriva en una tensión permanente en el ejercicio periodístico del
diario El Comercio, que cuando se consuma se manifiesta a través del condicionamiento
comercial en el contenido periodístico. La tensión es grande y polémica porque es el diario
más antiguo, uno de los que controla mayor cantidad de empleados, tiene una credibilidad
mayor a la competencia, es una de las empresas más poderosas del país y porque no por
coincidencia se llama “El Comercio”.Tesis
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Santos, Roberta Silva. "Forma??o de professores de l?ngua inglesa: par?metros que norteiam o ensino aprendizagem da pron?ncia." UFVJM, 2017. http://acervo.ufvjm.edu.br/jspui/handle/1/1616.
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O presente estudo consiste em identificar em que condi??es s?o trabalhados os aspectos fon?ticos-fonol?gicos da l?ngua inglesa durante o processo de forma??o docente do curso de Letras Portugu?s Ingl?s da Universidade Federal dos Vales do Jequitinhonha e Mucuri. Dentre esses aspectos, lan?a-se um olhar para os preceitos discutidos no N?cleo de L?ngua Franca, bem como ? orienta??o para o uso dos s?mbolos fon?ticos e da articula??o dos sons. Almeida Filho (2004) afirma que, para o docente de l?ngua estrangeira, h? cinco compet?ncias necess?rias, a serem adquiridas durante a forma??o; dentre elas, o autor destaca as compet?ncias lingu?sticocomunicativa e a impl?cita. Esta pesquisa entende que, al?m dessas, a compet?ncia te?rica tamb?m merece destaque, uma vez que ela ? respons?vel por unir e articular a teoria com a pr?tica. Nesse sentido, considerando a atual posi??o do ingl?s como l?ngua internacional e a necessidade de se obter uma pron?ncia intelig?vel, o estudo te?rico dos aspectos fon?ticos e fonol?gicos do ingl?s, segundo Mussalim (2001), s?o essenciais para reconhecer a estrutura da l?ngua e entender o funcionamento do sistema fonol?gico no processo de ensino-aprendizagem da linguagem. Em fun??o dessa vertente comunicativista, rompe-se com o par?metro de buscar uma pron?ncia igual ? de um nativo e desenvolve-se a perspectiva da comunica??o intelig?vel. Assim, o referencial te?rico desta disserta??o apresenta autores como Kenworthy (1987), Jenkins (2000), Rajagopalan (2004), Seidlhofer (2005), bem como Leffa (2001), Almeida Filho (2004), Gimenez (2004), dentre outros, que valorizam as premissas da inteligibilidade e o reflexo de seus princ?pios na forma??o docente. Para responder ? pergunta desta pesquisa, a constru??o da abordagem metodol?gica envolveu o uso da observa??o, an?lise do projeto pol?tico pedag?gico do curso de Letras da universidade investigada e a aplica??o de question?rio misto. Ap?s levantamento dos dados, realizaram-se an?lises qualitativa e quantitativa. Com o resultado, foi poss?vel inferir que as abordagens em rela??o ao sistema fonol?gico do ingl?s encontram-se superficialmente presentes no curso de Letras Portugu?s Ingl?s da Universidade Federal dos Vales do Jequitinhonha e Mucuri. Por isso, espera-se que os resultados deste estudo possam colaborar para intensificar o direcionamento em rela??o ? inteligibilidade na pron?ncia do ingl?s, tendo, como alternativa, por exemplo, o N?cleo de L?ngua Franca, proposto por Jenkins (2000).
Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Educa??o, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017.
The present study consists in identifying the existence of phonetic-phonological features in relation to the pronunciation of the English language in the education course of Letras Portugu?s/Ingl?s of the Universidade Federal dos Vales do Jequitinhonha e Mucuri. One of these features is related to the principles discussed in the Language Franca Core, as well as some orientation about the use of phonetic symbols and the articulation of sounds. Almeida Filho (2004) states that for the foreign-language teachers need to develop five competences during the education process, among these competences; the author emphasizes the linguisticcommunicative and the implicit one. This research understands that besides these, the theoretical competence also deserves to be highlighted, since it is responsible for connecting and articulating theory with practice. In this context, considering the current position of English as an international language and the conception of the intelligible pronunciation, it is necessary to study the theory of phonetic and phonological aspects of English language. According Mussalim (2001) it is essential to recognize the structure of the language and understanding the functioning of the phonological system in the process of teaching language learning. Because of this communicative aspect, it is interesting to break the pragmatic of a pronunciation similar to a native and develop a perspective of intelligible communication. For this reason, the theoretical reference of this dissertation presents authors such as Kenworthy (1987), Jenkins (2000), Rajagopalan (2004), Seidlhofer (2005), as well as Leffa (2001), Almeida Filho (2004), Gimenez (2004), among others. These authors emphasize the principles of intelligibility and the reflection of its ideologies in teacher education. To answer the question of this research, the methodological approach involved the use of observation, analysis of the pedagogical political project of the English education course, and a questionnaire. After data collection, qualitative and quantitative analyzes were implemented. According to the result, it was possible to infer that the approaches regarding the phonological system of English are superficially present in the Letras Portugu?s/Ingl?s course of the Universidade Federal dos Vales do Jequitinhonha e Mucuri. Therefore, it is expected that the results of this study can contribute to intensify the direction of intelligibility in the pronunciation of English, taking as an alternative, Language Franca Core proposed by Jenkins (2000).
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Leckey, Donna. "Therapeutic Non-pharmacological Interventions and PRN Psychotropic Medication Administration Practices of Mental Health RNs." Thesis, Carlow University, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3681319.
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PRN psychotropic medication administration is a common practice used by psychiatric RNs in acute inpatient mental health settings to manage anxiety and agitation in patients, and as a result, there are high incidences of PRN psychotropic medication administration (Mugoya & Kampfe, 2010). There is limited documentation indicating that therapeutic non-pharmacological interventions are utilized prior to PRN psychotropic medication administration (Curtis et al., 2007). The purpose of this scholarly project was to determine what non-pharmacological interventions are used by mental health RNs prior to or in lieu of administering PRN psychotropic medication to manage anxiety and agitation in adult psychiatric hospitalized patients. Another aim of this project was to determine what factors influence mental health RNs' decisions to administer PRN psychotropic medications. A descriptive study was conducted. Two survey-type self-reporting tools were used. Twenty RNs completed Nursing Surveys. Thirteen RNs completed both Nursing Surveys and Nursing Intervention Tracking Forms. Findings from this study revealed that non-pharmacological interventions successfully resolved problems over 1/3 of the time and may prevent the use of PRN psychotropic medications. In cases where PRN psychotropic medication was not administered, distraction was the non-pharmacological intervention most often used. The most common factor influencing RNs' decisions to administer PRN psychotropic medications was a high level of anxiety persistent after non-pharmacological interventions were used. This study reinforces the importance of RNs using non-pharmacological interventions to manage patients exhibiting signs or symptoms of anxiety or agitation.
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Gonzalez, Wania R. Coutinho. "Partidos políticos e educação: os projetos neoliberal e socialista: PFL, PRN, PDT e PT." reponame:Repositório Institucional do FGV, 1993. http://hdl.handle.net/10438/9249.
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L'objet d'étude du travail est l’analyse de la conception de la Politique éducationnelle de Partis Politiques qui opèrent dans le quadre politique Brésilien: PFL, PRN, PDT ET PT Le travail a été divisé en quatre parts. D'abord c'est détaillé le quadre théorique que ira traverser l'analyse des partis cités a partir de deux points. Le premier s'agit des rapports théoriques utilisé dans études autour des politiques sociaux et spécifiquement éducationnelles. En suite aborde la relation éducation et travail dans le mode de production capitaliste. La deuxième part du travail est relatif aux présuppositions théoriques que fond les Partis Politique: Néolibéralisme et socialisme. C'est delinée les points principaux du concept d'éducation de chaque versant. La troisième part sont fait considérations sur les Partis partisans aux libéralisme: PFL et PRN et au socialisme: PT et PDT. Sont sintentizer les points principaux des Programmes de ces Partis la. Enfin c'est procedée l'analyze du concretizacion de deux politiques éducationnelles: Du gouvernement Collor et les proposition du Parti des Ouvriers dans les municipes sur son gouvernement.
O objeto de estudo desse trabalho é a análise da concepção de política educacional de partidos políticos atuantes no cenário político brasileiro: PFL, PRN, PDT e PT. O trabalho foi subdividido em quatro partes. Na parte inicial é detalhado o quadro teórico que permeará a análise dos referidos partidos a partir de dois enfoques. O primeiro trata dos referenciais teóricos utilizados nos estudos acerca das políticas sociais e especificamente das educacionais. O segundo aborda a relação entre educação e trabalho no modo de produção capitalista. A segunda parte do trabalho é relativa aos pressupostos teóricos que embassam os partidos políticos: Neoliberalismo e Socialismo. Nela são delineados os pontos principais do conceito de educação de cada vertente. Na terceira parte são efetuadas considerações sobre os partidos adeptos do neoliberalismo (PFL e PRN) e do Socialismo (PT e PDT). São sintetizados os pontos principais dos programas desses partidos. Na última parte é procedida a análise da concretização de duas políticas educacionais: a do Governo Collor e a do Partido dos Trabalhadores nos municípios sob sua administração.
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Gomez-Zamorano, Dennis. "Etude de la régulation transcriptionnelle des gènes prn, catabolisme de la proline, chez "Aspergillus nidulans"." Paris 11, 1999. http://www.theses.fr/1999PA112408.
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Les résultats de ce travail permettent d'établir un modèle global de la régulation transcriptionnelle des gènes "prn". Ces gènes sont soumis à trois niveaux de régulation: la répression catabolique par le carbone, la répression métabolique par l'azote et une induction spécifique. Ces trois niveaux de régulation font intervenir, respectivement, le répresseur CreA, la protéine activatrice AreA et l'activateur spécifique de la voie la protéine PrnA. Les interactions qui s'établissent entre régulateurs à large spectre d'action, CreA et AreA, avec l'activateur spécifique, vont conduire, selon les conditions, à l'expression ou non-expression des différents gènes qui constituent cette voie. En présence de la protéine CreA active, deux fonctions activatrices, celle de la protéine PrnA et de la protéine AreA sont nécessaires pour rétablir l'expression de prnB, qui code pour la perméase de la proline. Cette double action positive s'effectue grâce à deux fonctions activatrices différentes qui peut jouer la protéine PrnA. Toujours en présence d'une protéine CreA active (répression par le glucose), l'inhibition de la protéine AreA (par l'ammonium ou la glutamine) ou l'élimination du site fixé par la protéine PrnA, qui lui permet de jouer un rôle activateur différent de celui qu'elle utilise pour induire la transcription, induit un blocage de l'expression de prnB, entraînant une exclusion de la molécule co-inducteur, nécessaire à l'activation transcriptionnelle des autres gênes. Le mécanisme par lequel les protéines PrnA et Area vont pouvoir contrecarrer l'effet de CreA serait une action synergique des deux activateurs, qui pourrait conduire à l'arrimage de l'appareil transcriptionnel sur le promoteur du gène prnB.
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Meyer, Lucas Joachim [Verfasser], and Albrecht [Akademischer Betreuer] Piiper. "Role of the Z-/turn motif and of the N-Terminus of PRK2 in the regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and 3-phosphoinositide dependent protein kinase 1 (PDK1) / Lucas Joachim Meyer. Betreuer: Albrecht Piiper." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2011. http://d-nb.info/1051405491/34.
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Müller, Bert. "Einfluß der Laserstrahlformung auf Hornhautprofil und Oberflächenrauheit bei der ohotorefraktiven Keratektomie mit dem 193 nm Excimer Laser." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2002. http://dx.doi.org/10.18452/14686.
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Hintergrund: Die Excimer Laser PRK zur Korrektur der geringen bis moderaten Myopie wird als präzises Verfahren der refraktiven Chirurgie angesehen und weltweit angewandt. Die Genauigkeit der PRK nimmt jedoch mit steigender Korrektur ab. Das Ziel dieser Untersuchung bestand darin, den Einfluß unterschiedlicher Laserstrahlapplikations- und -formungssysteme auf die korneale Oberflächenstruktur, das Hornhautprofil und die Zielrefraktion zu untersuchen. Materialien und Methoden: Es wurden mit dem Meditec Mel 60 und dem Schwind Keratom, zwei Excimer Laser der Wellenlänge 193 nm, an jeweils 10 enukleierten Schweinehornhäuten eine PRK mit einer Zielkorrektur von -3, -6, -9 D mit einem Ablationsdurchmesser von 6 mm (5 mm - 9D) durchgeführt, ein Silikonabdruck von der Hornhautoberfläche angefertigt und mit einem dynamisch fokussierenden Topometrie System UBM Microfocus vermessen. Hornhautradius, Brechkraft der stromalen Oberfläche, Profilabweichungen von der idealen sphärischen Form sowie Rauheitsparameter der verschiedenen Zonen wurden ermittelt. Ergebnisse: Epithelfreie Hornhäute besitzen ein sphärisches Profil. Der Meditec Mel60 Laser erzielte nach PRK von -3, -6 und -9 D sphärische Profile mit einer durchschnittlichen Refraktionsänderung von -3.4, -6.7 und -8.7 D. Das Schwind Keratom erzeugte eine mittlere Refraktionsänderung von -3.5, -5.8 und 8.4 D, wobei das korneale Ablationsprofil in allen Korrekturgruppen erhebliche Profilabweichungen in Form von zentralen Profilkuppen aufwies. Die durchschnittliche Höhe der zentralen Profilkuppen betrug nach der -3 D PRK 7.39 (±0.34) µm und stieg auf 16.31 (±1.06) µm bzw. 15.06 (±0.96) µm in der -6 und in der -9 D Serie. Die Relation zwischen der Profilkuppenhöhe und der Abtragtiefe lag zwischen 21 - 25% und konnte durch eine Anti-Central-Island Programm (ACI 100%) nur um 4% auf 18-20 % der Abtragtiefe reduziert werden. Die stromale Oberfläche der unbehandelten, epithelfreien Kontrollgruppe hat eine glatte, homogene Struktur. Die Rauheit der stromalen Oberfläche nach Ablation mit dem Meditec Laser war um 50 % stärker ausgeprägt als beim Schwind Keratom. Diskussion: Die Beschaffenheit der stromalen Oberfläche nach der Excimer Laser PRK zur Korrektur der Myopie, wird durch die Rauheitsparameter quantitativ beschrieben und ermöglicht den direkten Vergleich zwischen den Lasersystemen. Die Rauheit ist positiv mit der Ablationstiefe und dem Ablationsdurchmesser korreliert. Je höher eine myope Korrektur angestrebt wird, desto rauher ist die stromale Oberfläche und damit das Risiko, dass sich eine epitheliale Hyperplasie und subepitheliale Trübungen entwickeln, die ursächlich mit den klinisch beobachteten Phänomenen der myopen Regression, der Abnahme der Kontrastsehschärfe, dem Verlust der bestkorrigierten Sehschärfe und monokularer Doppelbilder in Zusammenhang stehen. Ob der Unterschied der Rauheit von durchschnittlich 50% sich in der Inzidenz der klinischen Komplikationen widerspiegelt, können nur vergleichende Studien belegen. Sicher ist, das die Vorhersagbarkeit des refraktiven Ergebnisses durch die Ablation mit dem Aesculap Meditec MEL 60 Laser besser einzuschätzen ist, als das mit zentralen Profilkuppen komplizierte Ablationsprofil des Schwind Keratoms.Purpose: To evaluate the predictability of refractive outcome, sphericitiy of corneal profiles and surface roughness parameters after myopic PRK with different, commercially available excimer laser beam delivery and beam shaping systems. Materials and Methods: Myopic Excimer Laser PRK of -3, -6 and -9 D in 6mm ablation zone (5 mm in -9 D) on performed on porcine eyes was performed with the Aesculap Meditec Mel 60, a slit scanning Laser and the Schwind Keratom I, a broad area laser with band mask beam shaping. A silicone replica was obtained to conserve the corneal profile and measured with a dynamic focusing topometry system (UBM Microfocus) to obtain radius, corrected corneal refraction and corneal surface roughness parameters. Results: Untreated corneas of the control group displayed spherical profiles. PRK of intended -3, -6 and -9 D correction with the slit scanning Aesculap Meditec Mel60 excimer laser achieved a refractive change of an average -3.4, -6.7 and -8.7 D respectively without major profile deviations. PRK with the Schwind Keratom, a broad area beam excimer laser resulted a refractive change of -3.5, -5.8 and -8.4 D respectively. The Ablation created considerable central profile deviations representing central islands of 7.39 (±0.34) µm after -3 D, 16.31 (±1.06) µm and 15.06 (±0.96) µm height after - 6 and -9 D PRK, respectively. Mean central island height was 21 - 25% of ablation depth and was reduced by anti-central-island-program to 18-20 % of ablation depth. Stromal surface roughness increased with ablation depth and was significantly rougher after scanning beam ablation compared to broad area ablation. Conclusions: Profile deviations increase with higher corrections and lessen the predictability of the refractive results. The Aesculap Meditec MEL60 Slit scanning system creates predictable spherical corneal profiles. The Schwind Keratom broad area laser create with band mask beam shaping central islands increasing with higher corrections. The application of an Anti-Central-Island Program does not eliminate the central profile elevations sufficiently. Stromal surface was rougher after scanning beam compared to broad area beam ablation.
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Modha, Rakhee. "NMR structural characterisation of the interaction of the small GTPase Rac1 with the HR1b domain of the kinase PRK1." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613752.
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Madec, Edwige. "Analyse moléculaire d'une protéine-kinase, PrkC, et d'une phosphatase, PrpC, impliquées dans deux processus de développement chez Bacillus subtilis." Paris 11, 2002. http://www.theses.fr/2002PA112283.
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La phosphorylation des protéines sur les résidus Ser/Thr/Tyr est d'une importance vitale dans de nombreux processus cellulaires. Mes travaux de thèse concernent la caractérisation, pour la première fois de PrkC, une Ser/Thr protéine-kinase de type eucaryote chez Bacillus subtilis. PrkC est une protéine membranaire dont l'organisation topologique est similaire à celle des récepteurs à activité kinase chez l'homme, avec un domaine extracellulaire, présumé senseur, un domaine transmembranaire unique (TMD) et un domaine kinase conservé. Grâce à l'utilisation d'un système génétique, j'ai montré que PrkC forme des dimères, le TMD et le domaine extracellulaire étant capables de promouvoir la dimérisation. En présence d'ATP, la protéine PrkC purifiée, est capable de s'autophosphoryler et de phosphoryler la protéine exogène MBP. Dans les deux cas, la phosphorylation concerne un ou plusieurs résidus thréonine. En collaboration avec Ole Jensen (Danemark), nous avons pu identifier après analyse par spectrométrie de masse en mode tandem MS/MS, huit résidus phosphorylés chez PrkC. Ainsi, quatre Thr sont localisées dans la boucle d'activation, trois Thr dans la région jouxtant la membrane et une Ser dans une région non conservée. La mutagénèse dirigée de ces résidus a montré que l'autophosphorylation de la Ser et des thréonines dans la boucle d'activation est essentielle pour l'activité kinase de PrkC. Parallèlement à ce travail, PrpC, une protéine homologue de la phosphatase humaine PP2C, a été caractérisée. La forme autophosphorylée de PrkC est déphosphorylée par PrpC. Le fait que PrkC et PrpC soient codées par deux gènes adjacents sur le chromosome et cotranscrits, suggère que ces enzymes pourraient fonctionner in vivo comme un couple kinase/phosphatase. La délétion des gènes prkC ou prpC réduit l'efficacité de la sporulation et la formation de biofilms. Une meilleure compréhension du rôle de PrkC et PrpC dans la cellule exige l'identification de leurs cibles/partenairesProtein phosphorylation on Ser/Thr/Tyr residues plays a vital role in many cellular processes. My studies in this Thesis concerned the characterization, for the first time of PrkC, a membrane linked protein kinase in Bacillus subtilis, belonging to the super-family of Hanks kinases, predominantly found in eukaryotes. PrkC was shown to be an integral membrane protein with the topology of some receptor kinases found in humans, with an external domain presumed sensor, a single transmembrane domain (TMD) and a highly conserved kinase domain. I have shown that PrkC forms dimers with both the extracellular domain and the TMD capable of promoting dimerization. In the presence of ATP, PrkC or its catalytic domain, PrkCc, autophosphorylates in vitro and phosphorylates MBP. In both cases, phosphorylation involves one or more Thr residues. In collaboration with Ole Jensen (Danemark), we were able to identify precisely eight phosphorylated residues in PrkC by mass spectrometry. These residues were localised to specific regions of a 3D structure of PrkCc modelled on known kinase structures. Four Thr were localised to the activation loop whereas three Thr are in the juxtamembrane region, and one Ser in a non conserved region. Site directed mutagenesis of these residues confirmed that autophosphorylation of Ser214 and the threonine residues in the activation loop is essential for kinase activity. In a complementary approach, PrpC, a protein phosphatase homologue of the human PP2C family was also characterized. The autophosphorylated form of PrkC was dephosphorylated by PrpC. PrkC and PrpC are encoded by adjacent genes which are co-transcribed. These results indicate that these enzymes form a functional protein kinase/phosphatase couple. Moreover, other studies showed that mutants deleted for prkC or prpC displayed reduced biofilm formation and sporulation frequencies. A better understanding of the role of PrkC and PrpC in the cell requires identification of targets/partners
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Absalon, Cédric. "Identification des cibles du couple Prkc/Prpc et analyse du rôle de la GTPase associée CPGA chez Bacillus subtilis." Paris 11, 2007. http://www.theses.fr/2007PA112171.
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Mes études ont concerné un système de signalisation de fonction inconnue, composé d’une kinase senseur de type eucaryote, d’une phosphatase et d’une GTPase, codées par un groupe de gènes, conservé chez un grand nombre de bactéries à Gram +. Nous avons fait l’hypothèse que PrkC, PrpC et CpgA constitue une voie unique de signalisation liée à la biogénèse de la paroi cellulaire – présence d’un domaine externe PASTA dans PrkC. Ceci s’appuie sur l’implication de CpgA dans la production de peptidoglycane (PG). Ainsi, les cellules déplétées pour CpgA présentent des formes anormales, un dépôt non uniforme de la paroi et l’accumulation de précurseurs tardifs du PG. Une part majeure de mes travaux a porté sur l’identification des cibles de PrkC et PrpC. Tout d’abord, j’ai démontré que CpgA est un substrat de PrkC et de PrpC in vitro, apportant ainsi un argument solide à la relation fonctionnelle des trois protéines. La structure cristalline de CpgA suggérait fortement son rôle comme facteur de traduction. Nous avons donc proposé que CpgA contrôle la synthèse de protéines, capable de coordoner l’expansion de la couche de PG à la synthèse des protéines. Cette hypothèse s’appuie sur ma démonstration que EF-Tu est aussi une cible de PrkC et PrpC. Enfin, j’ai pu identifier une troisième cible de PrkC/PrpC, in vitro et in vivo, YezB, une protéine de fonction inconnue. YezB est un composant du stressosome, connu pour transduire les signaux qui émanent de stress environnementaux, impliqué dans la réponse au stress général, en activant le régulon dépendant de sigma B. La fonction de YezB pourrait être de transduire l’expansion inappropriée du peptidoglycane ou son endommagement, via la phosphorylation par PrkCMy studies have concerned a signalling system of unknown function composed of a eukaryote-like sensor kinase, a phosphatase and a GTPase, encoded by a gene cluster, conserved in many Gram positive bacteria. We hypothesised that PrkC PrpC and CpgA constitute a single signalling pathway concerned cell wall biogenesis – the external PASTA domain of PrkC binds penicillin or peptidoglycan (PG). This was supported by my demonstration that CpgA is implicated in the biogenesis of PG. Thus, cells depleted for CpgA displayed bizarre shapes, non-uniform deposition of the cell wall and accumulation of late PG precursors. A major part of my work also involved identification of targets of PrkC and PrpC. First, the co-ordinated function of the 3 proteins was supported by demonstrating that CpgA is a substrate for PrkC and PrpC in vitro. The crystal structure of CpgA previously indicated a role as a translation factor. Thus we proposed that CpgA controls the synthesis of proteins, including morphogenic factors, or factors coupling the expansion of the PG layer with protein synthesis. This hypothesis is supported by my demonstration that EF-Tu is also a target for PrkC and PrpC. The third target of PrkC/PrpC identified was YezB, a protein of unknown function. YezB is apparently a component of the stressosome that is known to transduce signals, emanating from environmental stress or energy limitation, to activate the sigma B dependent general stress regulon. YezB could conceivably function as a transducer of inappropriate expansion of or damage to the peptidoglycan, via phosphorylation by PrkC
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STANKO, FREDERIC. "Elaboration d'un indicateur simplifie de mesure de la charge en soins infirmiers des secteurs d'hospitalisation de courte duree des services d'urgences : validation au centre germon et gauthier de bethune beuvry sur 120 patients." Lille 2, 1993. http://www.theses.fr/1993LIL2M049.
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Sandberg, Robert. "Assessment and Usability Test of Company Specific Hardware Configuration Tool." Thesis, Linköping University, Department of Computer and Information Science, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-16711.
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This master´s thesis consists of two parts. The first part is a study where the possibility to use existing tools from the market is assessed. The second part describes the design, development and usability test of a web based hardware configuration tool. The usability test made in the design process, was made in order to remove common usability problems and to assess whether or not the design decisions made during the thesis were good. The usability test that was performed followed the think aloud method and gave me very useful information that helped me improve the tool.
The study that was made in the beginning of the thesis was done in order to see if there were any programs on the market which already did the required tasks or could be adjusted to do them. I could not find a satisfying alternative amongst the five alternatives investigated. This lead to the decision to design a new tool. The main functions are the ability to save the current state the hardware is in, and at a later stage load this configuration back.
The tool was designed for the PRAN unit at Ericsson AB, in Linköping, Sweden.
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Rialp, Cervera Gemma. "Efectes fisiològics del decúbit pron i de la inhalació d'òxid nítric en malalts amb la síndrome del destret respiratori agut." Doctoral thesis, Universitat Autònoma de Barcelona, 2001. http://hdl.handle.net/10803/4374.
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Objectiu: Estudiar els efectes gasomètrics i hemodinàmics del tractament combinat amb decúbit pron (DP) i òxid nítric inhalat (iNO) en pacients amb la síndrome del destret respiratori agut (SDRA) precoç, així com determinar la influència de l'etiologia de la SDRA en la resposta als dos tractaments i conèixer els efectes del DP sobre la mecànica respiratòria.Pacients i mètode: Estudi amb 15 pacients ingressats a UCI amb SDRA precoç (8 amb SDRA d'origen pulmonar (Pu) i 7 amb SDRA d'origen extrapulmonar (EPu)), intubats i connectats a ventilació mecànica controlada per volum amb FiO2 1. S'ha ajustat del valor de PEEP amb la determinació del punt d'inflexió inferior de la corba pressió-volum en decúbit supí (DS) i PEEP 0 cm H2O, mantenint-se constant al llarg de l'estudi. S'analitza dades gasomètriques i hemodinàmiques recollides en les quatre situacions estudiades: DS (o situació basal), DS+iNO, DP, DP+iNO (la iNO es realitza de forma randomitzada en cada posició). A 12 pacients es realitza a més el càlcul del reclutament alveolar induït per la PEEP en DS i en DP. L'estudi estadístic utilitzat ha estat una anàlisi de la variància per a dades aparellades, el test Xi-quadrat per la comparació de les variables qualitatives. Per l'estudi de mecànica respiratòria s'ha utilitzat el test U de Mann-Whitney i el test de Wilcoxon. Valors de p<0,05 s'han considerat significatius.
Resultats: Tant la iNO com el DP produeixen un increment significatiu de la PaO2/FiO2 en relació a la situació basal (de 106 ± 58 mm Hg en DS a 131 ± 69 mm Hg en DS+iNO, p=0,01, i a 184 ± 67 mm Hg en DP, p < 0.001). Els efectes d'ambdós tractaments sobre l'oxigenació són de tipus additiu. Els pacients amb SDRA Pu i els pacients amb SDRA EPu mostren un augment similar de la PaO2/FiO2 amb el DP. Només els pacients amb SDRA Pu han mostrat un augment significatiu (p<0.001) de l'oxigenació induït per la iNO de 81 ± 45 mm Hg a 100 ± 50 mm Hg en DS, i de 146 ± 53 a 197 ± 98 mm Hg en DP. El DP s'associa a un augment significatiu del volum reclutat en relació al DS ( 227 ± 106 en DP i 186 ± 96 ml en DS, p=0,04). L'increment de la PaO2/FiO2 induït pel DP mostra una correlació positiva amb l'increment del volum reclutat induït pel DP (r=0,72; p=0,008).
Conclusió: El DP i la iNO presenten efectes de tipus additiu sobre l'oxigenació. El DP s'associa a una millora marcada de la PaO2/FiO2, independentment de la causa de la SDRA, mentre que la iNO millora l'oxigenació predominantment en els pacients amb SDRA Pu. L'augment de volum reclutat observat en DP en relació al DS es correlaciona directament amb l'increment en la PaO2/FiO2 induït pel DP.
Objective: To study the gas exchange and hemodynamic effects induced by the combination of prone position (PP) and inhaled nitric oxide (iNO) in patients with early ARDS, and to analyse whether or not pulmonary (Pu) or extrapulmonary (EPu) ARDS patients behave differently. We also studied the effects of PP on respiratory system mechanics.
Patients and methods: We studied 15 intubated patients admitted in our ICU with early ARDS (8 Pu ARDS and 7 EPu ARDS) under volume controlled mechanical ventilation and FiO2 1. PEEP levels were adjusted according to the lower inflection point of the pressure-volume curve of the respiratory system in supine position (SP) and PEEP 0 cm H2O, and were kept constant through the study. Gasometric and hemodynamic data were collected in four situations: SP (or baseline situation), SP+iNO, PP, PP+iNO (iNO was randomized in each position). Measurement of alveolar recruitment induced by PEEP in SP and PP was calculated in twelve patients. An analysis of variance for repeated measures with two factors was performed to compare both treatments. Mann-Whithey U test and Wilcoxon test were used to compare the effects on respiratory mechanics. Chi-square test was applied to compare qualitative variables. A p<0.05 was considered significant.
Results: In comparison with SP, iNO and PP induced significant increase in PaO2/FiO2 (from 106 ± 58 in SP to 131 ± 69 mm Hg in SP+iNO, p=0.01, and 184 ± 58 mm Hg in PP, p<0.001). Pu and EPu ARDS showed a similar improvement in PaO2/FiO2 with PP. Only Pu ARDS patients showed a significant increase (p<0.001) in oxygenation induced by iNO from 81 ± 45 to 100 ± 50 mm Hg in SP, and from 146 ± 53 to 197 ± 98 mm Hg in PP. PP is associated with a significant increase on the recruited volume in comparison with SP (227 ± 106 in PP and 186 ± 96 ml in SP, p=0.04). The improvement in PaO2/FiO2 observed with PP is directly correlated with the increase of the alveolar recruitment induced by PP (r=0.72; p=0.008).
Conclusion: PP and iNO show additive effects on oxygenation. PP is associated with a marked improvement in oxygenation, irrespective of the cause of ARDS, whereas oxygenation effects of iNO are mainly seen in patients with Pu ARDS. The increase of the recruited volume observed in PP in comparison with SP is directly correlated with the increase of PaO2/FiO2 induced by PP.
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GAVRIAS, VICTORIA. "Etudes moleculaires sur la regulation et la structure du groupe des genes prn chez aspergillus nidulans." Paris 11, 1992. http://www.theses.fr/1992PA112220.
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Les genes codant pour les activites impliquees dans le catabolisme de la proline, chez le champignon a. Nidulans, sont regroupes sur chromosome vii, formant le cluster prn. Le gene prnd code pour la proline oxydase, l'enzyme responsable de l'oxydation de la proline en 1-pyrroline-5-carboxylate. C'est une proteine de 469 acides amines qui est similaire a la proline oxydase de s. Cerevisiae. Prnc code pour la 1-pyrroline-5-carboxylate deshydrogenase, qui est une proteine de 561 acides amines qui presente des similitudes fortes avec l'enzyme equivalent chez s. Cerevisiae, ainsi qu'avec des aldehydes deshydrogenases. Un nouveau gene dans le cluster prn a ete aussi sequence et caracterise au niveau moleculaire et transcriptionnel. Malgre la recherche d'hypotheses variees sur le role de prnx, sa fonction reste encore inconnue. La construction et l'etude d'une souche portant une deletion de la plupart de la region intergenique entre prnb et prnd, suggere l'existence d'un element necessaire pour la regulation de l'utilisation de la proline, ainsi que des informations supplementaires sur l'interaction entre les proteines area et crea responsable de cette regulation
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Ahmedova, Renin. "Förhållandena inom refraktiv kirurgi i Sverige, vilka metoder används och vilka komplikationer finns?" Thesis, Linnéuniversitetet, Institutionen för medicin och optometri (MEO), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-54189.
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Syfte: Studiens syfte var att undersöka hur refraktiv kirurgi ser ut i Sverige idag, vilka komplikationer som finns och vilka metoder som används genom att göra en kort redovisning av de vanligaste teknikerna FS-lasik, LASEK, TransPRK och RLE som finns inom refraktiv kirurgi och med hjälp av en enkät ta reda på de olika komplikationerna mellan olika åldersgrupper. Metod: En enkätstudie inom refraktiv kirurgi i Sverige genomfördes. Enkäten var webbaserad och skapad i Google Docs (http://docs.google.com). Enkäten innehöll totalt 11 frågor som handlade om patientens tidiga refraktion, operationsmetod och ögonhälsa efter operationen. Enkäten spreds via sociala medier som Facebook, Instagram, Twitter, olika forumsiter, samt mail. En del av enkäten var även fördelad på två olika ögonkliniker i Lund. Resultat: Resultaten av enkäten visar att det finns inte någon skillnad i komplikationsgraden mellan de olika åldersgrupperna och komplikationerna efter kirurgin beror på typen av metod och patientens synfel och brytningsfel. Slutsats: Vid de olika metoderna förekommer olika komplikationer och ju mer närsynt patienten är desto större är risken för komplikationer i samband med operationen.Refractive surgery is an effective method for correcting visual refractive errors. The method has evolved quickly over the past decade. The aim of this study was to examine what refractive surgery is in Sweden today. What complications exist and which methods are used, are described by making a presentation of the refractive surgery techniques FS-LASIK, LASEK, TransPRK and RLE. This was done by a survey to find out the various complications between different age groups. A web-based survey was disseminated trough social media like Facebook, different forum sites and e-mail. The survey was also submitted to various eye clinics. The respondents were asked questions about their age, gender, the surgical method used and the complications after surgery. The results of the survey showed that there is no difference in the complication rate between the different age groups. Complications only depend on the type of method used and the patient’s refractive errors.
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Ghanem, Vinicius Coral. "Estudo comparativo entre a ceratectomia fotorrefrativa (PRK) e a ceratectomia subepitelial borboleta assistida a laser (LASEK borboleta)." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-24102007-153937/.
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OBJETIVO: Avaliar comparativamente os resultados de duas técnicas de cirurgia refrativa de superfície com excimer laser, ceratectomia fotorrefrativa (PRK) e ceratectomia subepitelial borboleta assistida à laser (LASEKb). LOCAL: Hospital de Olhos Sadalla Amin Ghanem, Joinville, Santa Catarina, Brasil. MÉTODOS: Realizou-se um estudo prospectivo, randomizado e duplo-cego envolvendo 102 olhos de 51 pacientes. Cada paciente teve aleatoriamente um dos olhos operado com a técnica do PRK e o outro com LASEKb. Os pacientes foram acompanhados por 1 ano. RESULTADOS: Não houveram diferenças significativas entre os dois grupos na acuidade visual (AV) para longe, sem correção, (P = 0,5593). No 12o mês pós-operatório (PO), 98,04% dos olhos no grupo do PRK e 96,08% no grupo do LASEKb atingiram AV sem correção de 20/20. A previsibilidade, eficácia, segurança e estabilidade não apresentaram diferença estatisticamente significativa entre os grupos. O índice de segurança foi de 1 no PRK e 0,996 no LASEKb. Um olho do grupo do LASEKb perdeu uma linha de visão. A porcentagem de olhos que apresentou EE aos 12 meses na faixa de ±0,50 D foi de 94,1% no grupo do PRK e de 86,3% no grupo do LASEKb (P = 0,1883). Enquanto que na faixa de ±1,0 D foi de 100% no grupo do PRK e 98% no grupo do LASEKb (P = 0,3125). Não houve necessidade de reoperações. O tempo médio de cirurgia na técnica PRK foi de 304,86 + 58,77 segundos (aproximadamente 5 minutos) e na técnica LASEKb de 608,35 + 76,88 segundos (aproximadamente 10 minutos) (P < 0,001). O tempo médio de reepitelização no grupo do PRK foi de 4,35 ± 0,48 dias (variação, 4 a 5 dias) e no grupo do BLASEK foi de 4,75 ± 0,72 dias (variação, 4 a 6 dias) (P < 0,002). Os níveis de dor e o desconforto ocular PO não foram estatisticamente diferentes entre os grupos, entretanto houve uma tendência para menor dor no PRK (3,31 ± 4,09 vs 4,43 ± 4,27; P = 0,18). Houve uma redução estatisticamente significativa nos valores do teste de Schirmer em todas as avaliação PO, tanto no PRK (23,6 ± 8,1 vs 19,4 ± 10,1; P < 0,002) quanto no LASEKb (22,4 ± 8,7 vs 18,9 ± 9,7; P = 0,01), entretanto não houve diferença entre os grupos. A opacificação corneana (OC) PO foi pequena nos dois grupos. Somente no 1o mês foi observado diferença estatística entre os grupos, com maior intensidade da OC no grupo do LASEKb (0,18 ± 0,3881) quando comparado ao PRK (0,08 ± 0,2109) (P = 0,039936). A maior intensidade foi observada no 3o mês, com redução gradativa até o 12o mês. CONCLUSÃO: Dentro das condições deste estudo, conclui-se que o PRK e o LASEKb mostraram resultados semelhantes, exceto que o PRK apresentou menor tempo cirúrgico, reepitelização corneana mais rápida e menor OC no 30o PO.PURPOSE: Comparatively evaluate the results of two techniques of surface excimer laser refractive surgery, photorefractive keratectomy (PRK) and butterfly laser-assisted subepithelial keratectomy (BLASEK). SETTING: Sadalla Amin Ghanem Eye Hospital, Joinville, Santa Catarina, Brazil. METHODS: This is a prospective, randomized and double-masked study including 102 eyes from 51 patients. Each patient was randomized to have one eye operated on with PRK and the other with BLASEK. Patients were followed for 1 year. RESULTS: There were no significant differences between the groups regarding uncorrected distant visual acuity (VA) (p= 0.5593). On the 12th post-operative (PO) month, 98.04% of the eyes in the PRK group and 96.08% in the BLASEK group reached uncorrected VA of 20/20. The predictability, efficacy, safety and stability did not present statically significant difference between groups. The safety index was of 1 for PRK and 0.996 for BLASEK. One eye of the BLASEK group lost one line on the 12th PO month. The percentage of the eyes that presented spherical equivalent at 12 months in the range of ±0.50 D was 94.1% in the PRK group and 86.3% in the BLASEK group (p = 0.1883). While in the range of ±1.0 D it was 100% in the PRK group and 98% in the BLASEK group (p = 0.3125). There were no retreatments. The mean surgical time was 304.86 + 58.77 seconds (approximately 5 minutes) in PRK and 608.35 + 76.88 seconds in BLASEK (approximately 10 minutes) (P < 0,001). The mean reepithelization time in the PRK group was 4.35 ± 0.48 days (range, 4 to 5 days), and in the BLASEK group was 4.75 ± 0.72 days (range, 4 to 6 days) (P < 0.002). Pain scores and ocular discomfort were not statistically different between groups, although there was a trend towards a lower pain level with PRK (3.31 ± 4.09 vs. 4.43 ± 4.27; P = 0.18). Schirmer test values were significantly reduced from preoperative levels through 12 months with both PRK (23.6 ± 8.1 vs. 19.4 ± 10.1; P < 0.002) and BLASEK (22.4 ± 8.7 vs. 18.9 ± 9.7; P = 0.01), however there was no difference between groups in any time point. Haze incidence was slight in both groups. Only in the 1st PO month statistical difference between the groups was observed, with higher intensity in the BLASEK group (0.18 ± 0.3881) when compared to the PRK (0.08 ± 0.2109) (p = 0.039936). The highest intensity was observed on the 3rd month, with gradual reduction until the 12th month. CONCLUSION: In the conditions of this study, it can be concluded that PRK and BLASEK showed similar results, except that PRK presented shorter surgical time, faster corneal reepithelization and less haze at 30th PO days.
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Sophianopoulou, Vicky. "Le groupe des gènes prn impliqués dans la dégradation de la L-proline chez Aspergillus nidulans : séquence du gène prnB codant pour la perméase de la L-proline, régulation des gènes prn et caractérisation de mutations régulatrices cis-actives." Paris 11, 1989. http://www.theses.fr/1989PA112140.
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Sauvageot, Beneria Paola. "Efecto de la cirugía refractiva corneal sobre la osmolaridad lagrimal y otros parámetros del flujo lagrimal." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/322816.
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OBJETIVO: Comparar el efecto de la fotoqueratomileusis in situ asistida con láser de femtosegundos (LASIK) y la queratectomía fororrefractiva (PRK) sobre la osmolaridad y otros parámetros de ojo seco.
MÉTODOS: Estudio prospectivo comparativo que incluye 56 ojos de 56 pacientes intervenidos de LASIK o PRK. Para cada paciente de cada grupo ( LASIK o PRK) se valoró el cuestionario OSDI (Ocular Surface Disease Index), el tiempo de rotura lagrimal (BUT), la tinción corneal, el test de Schirmer con y sin anestesia, la estesiometría corneal y la osmolaridad antes de la cirugía y a los 3, 6 y 12 meses de la intervención.
RESULTADOS: No se observaron diferencias en los parámetros de ojo seco entre los 2 grupos excepto para la estesiometría corneal que presentó una disminución significativa a los 3 meses de la intervención en el grupo LASIK comparado con el grupo PRK (U=270; P=0,043). La sensibilidad corneal presentó una disminución significativa a los 3 meses en ambos grupos comparado con los valores preoperatorios pero volvió a sus valores preoperatorios a los 6 meses de la cirugía en el grupo PRK y a los 12 meses en el grupo LASIK. La osmolaridad lagrimal no presentó cambios significativos a los 3 meses de la intervención comparado con los valores preoperatorios pero se observó un incremento significativo de sus valores a los 6 meses (LASIK group, P=0,04; PRK group, P=0,006) y a los 12 meses tras la intervención (LASIK group, P=0,005; PRK group, P=0,004).
CONCLUSIONES: A los 12 meses de la intervención, todas las variables vuelven a sus valores basales preoperatorios excepto la osmolaridad lagrimal. En ambos grupos, la osmolaridad lagrimal presenta alteraciones de inicio tardío y permanece significativamente aumentada un año después de la cirugía. Un mayor seguimiento será necesario para completar el estudio del efecto de la cirugía refractiva corneal sobre la osmolaridad lagrimal.PURPOSE: To compare the impact of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) on tear osmolarity and other dry eye tests. METHODS: A prospective and comparative study was done where 56 eyes of 56 myopic patients who underwent LASIK or PRK surgery and fulfilled the inclusion criteria were included in 2 matched groups. Dry eye tests were evaluated before the surgery and at 3, 6, and 12 months postoperatively, and included tear osmolarity, ocular surface disease index (OSDI) questionnaire, Schirmer I test with and without anesthesia, corneal esthesiometry, tear break up time (TBUT) and corneal staining. RESULTS: No significant difference in dry eye tests between the 2 groups was observed at any point. Only corneal sensibility was significantly decreased in LASIK group compared to PRK group after 3 months (U=270; P=0,043). Corneal sensibility was significantly reduced after 3 months compared to preoperative values in both groups but recovered to statistically similar to preoperative values after 6 (PRK group) and 12 months (LASIK group). Tear osmolarity values were comparable to preoperative values after 3 months but significantly increased in both groups after 6 (LASIK group, P=0,04; PRK group, P=0,006) and 12 months (LASIK group, P=0,005; PRK group, P=0,004). CONCLUSIONS: There was no significant difference in tear osmolarity and other dry eye tests between LASIK and PRK at any point of the follow-up except for corneal sensitivity which was significantly lower in the LASIK group than in the PRK group at 3 months postoperatively. Tear osmolarity significantly increased in both groups at 6 months after surgery compared to preoperative values, and remained statistically higher one year postoperatively. A longer follow-up will be necessary to assess whether tear osmolarity recovers its preoperative values after corneal refractive surgery.
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Dias, Paulo Thiago Fernandes. "A ado??o do ad?gio do in dubio pro societate na decis?o de pron?ncia : (in)constitucionalidade e (in)convencionalidade." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2016. http://tede2.pucrs.br/tede2/handle/tede/7261.
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This dissertation, linked to the Contemporary Legal and Criminal Systems line of research of the Graduate Program in Criminal Sciences stricto sensu of the Faculty of Law, is an expansive interdisciplinary, historical and in-depth study, concerning the unconstitutionality and unconventionality of how the adage in dubio pro societate incides into the judicial order, as a form of solving legal doubts as to the sufficiency of evidence as to criminal authorship and proof of materiality. Based on hermeneutical discussions, we seek to examine the decision-making act, notably in judicial analysis of the evidence produced by the parties. In this sense, the study found that such judicial protagonism, rather than providing fundamental rights protection, functions in fact, as a reminder of the inquisitorial culture to which the of Criminal Process Code of 1941 and much of the legal institutions that followed are linked. The adoption of the referred to adage as a decision-making standard for the solution of legal questions, violates the rule in dubio pro reo, or the presumption of innocence and human dignity, to the extent that it submits a person to trial, despite no certainty as to the minimum requirements for the delivery of the verdict. Finally, under the new Constitutional order established in 1988, and opening rules provided by paragraph 2 and paragraph 3 of Article 5, of the Federal Constitution, it is necessary to exercise conventional jurisdictional control of normative or judicial acts especially in the course of criminal proceedings. All of this occurs, within the continuing process of human rights internationalization of which Brazil is part of. Through a brief review, the study shows that despite all of the internal and external regulatory efforts to secure human rights, the Brazilian Judiciary, through its Superior Courts, has both systematically and massively been removing the presumption of innocence, in order to consecrate an incompatible adage to the founding values of the Republic.
A presente disserta??o, vinculada ? linha de pesquisa Sistema Jur?dico-Penais Contempor?neos do Programa de P?s-gradua??o stricto sensu em Ci?ncias Criminais da Faculdade de Direito, representa uma pesquisa expansiva e aprofundada, interdisciplinar, hist?rica sobre a (in)constitucionalidade e a (in)convencionalidade da incid?ncia do ad?gio do in dubio pro societate na decis?o de pron?ncia, como forma de solu??o da d?vida judicial quanto aos ind?cios suficientes de autoria e prova da materialidade delitivas. Com base em discuss?es de ordem hermen?utica, buscou-se analisar o ato decis?rio, notadamente no que pertine ? an?lise judicial das provas produzidas pelas partes. Nesse sentido, a investiga??o apurou que o protagonismo judicial, ao inv?s de proporcionar a prote??o dos direitos fundamentais, funciona, em verdade, como resqu?cio de uma cultura inquisit?ria da qual o C?digo de Processo Penal de 1941 e boa parte das Institui??es jur?dicas seguem vinculados. Al?m mais, a ado??o do ad?gio referido como standard probat?rio, para solu??o da d?vida judicial, viola, ao mesmo tempo, a regra do in dubio pro reo, enquanto decorr?ncia da presun??o de inoc?ncia, e a dignidade humana, na medida em que submete uma pessoa a julgamento, a despeito da n?o seguran?a quanto aos requisitos m?nimos para o proferimento da pron?ncia. Por fim, nos termos da nova ordem constitucional instaurada em 1988, e da abertura normativa proporcionada pelos ?2? e ?3?, do artigo 5?, da Constitui??o da Rep?blica, faz-se necess?rio o exerc?cio do controle jurisdicional de convencionalidade dos atos normativos e judici?rios, principalmente no bojo do processo penal. Trata-se, de um processo de internacionaliza??o dos direitos humanos do qual o Brasil se faz integrante. Em breve levantamento, a pesquisa demonstrou que, a despeito de todo o esfor?o normativo interno e externo para a valoriza??o dos direitos humanos, o Judici?rio brasileiro, por meio de seus Tribunais Superiores, vem, sistem?tica e maci?amente, afastando a presun??o de inoc?ncia para consagrar um brocardo incompat?vel com os valores fundantes da Rep?blica.
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Carr, David A. "The Role of Farnesyltransferase β-subunit in Neuronal Polarity in Caenorhabditis Elegans." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23784.
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Little is known about the molecular components and interactions of the planar cell polarity pathway that regulate neuronal polarity. This study uses a prkl-1 induced backwards locomotion defect as an array to perform a prkl-1 suppressor screen in C. elegans looking for new components of the planar cell polarity pathway involved in the neuronal polarization of VC4 and VC5. The screen discovered twelve new alleles of vang-1, one new allele of fntb-1 and five new mutations in unknown polarity genes. fntb-1 encodes for the worm ortholog of Farnesyltransferase β-subunit and is important for neuronal polarization. Acting cell and non-cell autonomously, fntb-1 regulates the function and localization of prkl-1 through the recognition of a CAAX motif. Therefore, fntb-1 modifies prkl-1 to regulate the neuronal polarity of VC4 and VC5.
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Palmer, Ruth Helen. "Cloning and characterisation of the PRK family : a novel family of protein kinases related to the PKC superfamily." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321771.
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LAIRE, TACHE EMMANUELLE. "Echanges plasmatiques et syndrome de guillain-barre : experience remoise dans le cadre de l'etude multicentrique francaise prn 85." Reims, 1992. http://www.theses.fr/1992REIMM056.
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Ghedini, Massimiliano. "Le relazioni sociali in Facebook. Sviluppo di un’applicazione per la raccolta ed analisi dei dati." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amslaurea.unibo.it/5064/.
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“Dì che ti piace questa pagina”.
Questo è uno dei tanti inviti rivolti a chi, ogni giorno, naviga in Internet. Che si stia leggendo un articolo sul sito de La Repubblica, o visitando il blog di un personaggio famoso o di un politico, i riferimenti ai social network sono ormai una presenza costante nelle pagine web. La facilità di restare in contatto con i propri amici, e la possibilità di collegarsi in qualsiasi momento, hanno portato gli utenti del Web 2.0 ad intensificare le discussioni, ed a commentare gli argomenti ed i contenuti prodotti dagli altri in un continuo e complesso “botta e risposta”.
È possibile che quest'ambiente abbia favorito lo sviluppo di una nuova prospettiva della Rete, inteso come un nuovo modo di vedersi e di rapportarsi con gli altri, di esprimersi e di condividere le proprie storie e la propria storia.
Per approfondire queste tematiche si è deciso di osservare alcuni dei social networks più diffusi, tra i quali Twitter e Facebook e, per raccogliere i dati più significativi di quest'ultimo, di sviluppare un'apposita applicazione software.
Questa tesi tratterà gli aspetti teorici che hanno portato questa ricerca su scala nazionale e l'analisi dei requisiti del progetto; approfondirà le dinamiche progettuali e lo sviluppo dell'applicazione entro i vincoli imposti da Facebook, integrando un questionario per l'utente alla lettura dei dati.
Dopo la descrizione delle fasi di testing e deployment, l'elaborato includerà un'analisi preliminare dei dati ottenuti per mezzo di una pre-elaborazione all'interno dell'applicazione stessa.
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Pereira, Vinícius Borges Porfírio. "Dor no pós-operatório da ceratectomia fotorrefrativa (PRK) com fosfato de codeína 30 mg/ paracetamol 500 mg: ensaio clínico aleatório." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-08052018-112512/.
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Introdução: A ceratectornia fotorrefrativa (PRK) é uma das técnicas de cirurgia refrativa mais empregadas no mundo. A despeito de sua efetividade e segurança no tratamento de miopia, hipermetropia e astigmatismo, a dor permanece ainda como um dos grandes desafios no período pós-operatório da PRK. Embora a associação dos fármacos codeína (opióide oral) e paracetamol (analgésico) seja amplamente empregada no período pós-cirúrgico de várias especialidades médicas. a eficácia e segurança dessa associação não foi avaliada no manejo da dor no pós-PRK. Objetivo: O objetivo da presente tese foi testar a combinação codeína + paracetamol no manejo da dor pós-PRK. Métodos: Trata-se de um ensaio clínico controlado por placebo, randomizado, paralelo e duplo-cego. O subdelineamento é do tipo \"add-on \", isto é. o grupo da intervenção recebeu a terapia padrão + a intervenção. enquanto o grupo controle recebeu a terapia padrão + placebo. A amostra foi composta por 41 participantes (82 olhos) - por meio do delineamento \"olhos pareados\" (paired-eye design), ou seja, o olho foi a unidade de análise. As cirurgias foram realizadas com duas semanas de intervalo. Um olho recebeu codeína (30 mg) + paracetamol (500 mg) 4x1dia por quatro dias (período A), enquanto o outro olho recebeu placebo 4x/dia por quatro dias (período B). Tanto a alocação (intervenção ou placebo) quanto a ordem (A-B ou B-A) foram aleatorizadas. A dor foi avaliada por meio de três escalas: questionário de dor McGill (MPQ). Inventário Resumido da Dor (I3PI) e escala visual análoga (EVA) nos períodos I, 24, 48 e 72 horas após a cirurgia. O período de seguimento total foi de quatro meses. Resultados: A idade média dos pacientes foi de 30 anos (rnin-máx: 22-52), dos quais 67% foram mulheres. Dos 82 olhos inicialmente arrolados no estudo, 80 completaram os quatro meses de seguimento (40 na intervenção e 40 no placebo). Os escores medianos de dor mensurados pela EVA foram significativamente mais baixos no grupo da intervenção comparado com o grupo placebo - durante todo o período do pós- cirúrgico imediato (1-48 horas). Os eventos adversos foram brandos e de fácil manejo clínico; os mais comuns foram sonolência, náusea e constipação. Após um seguimento de quatro meses, não foi observado nenhum retardo na resposta de cicatrização da córnea ou haze. Conclusões: A combinação de codeína (30mg) e paracetamol (500mg) via oral (4x/dia) é segura e significativamente superior ao placebo para o controle da dor após a PRKIntroduction: Photorefractive keratectomy (PRK) is one of most widely performed types of refractive surgery in the world. In spite of its effectiveness and safety for the treatment of myopia, hypermetropia and astigmatism, pain remains one of the biggest clinical challenges during the early postoperative period after PRK. Although the combination of codeine (an oral opioid) plus acetaminophcn (an analgesic) has been widely used during the postoperative period in many medical specialties, both its efficacy and safety have not been formally investigated for pain control after PRK. Objective: To carry out a randomized, controlled c1inical trial, specifically dcsigned to test whether the combination of codeine + acetaminophen is efficacious and safe for pain control after PRK. Methods: Double-blind (patients and outcome assessors), randomized, parallel, placebo-controlled trial. An add-on design was adopted. tl.at is, the intervention group received the standard of care therapy + codeine/acetaminophen, whereas the control group received the standard o[ care therapy + placebo. The sample encompassed 41 participants (82 eyes) through the \"paired-eye design\". In other words, the eye was the unity of analysis. Surgeries were performed two weeks ap311. One eye received codeine (30mg) + acetaminophen (500mg) 4x/day for four days (period A), whereas the fellow (control) eye received placebo 4x/day for four days (period B). Both treatrnents (intervention or placebo) and treatment order (A-B or B-A) were randomly chosen. Pain was asscsscd at 1, 24, 48 and 72h postopcrativcly by three scales: visual analogue scale (VAS), McGill Pain Questionnaire (MQP) and Brief Pain Inventory (BPI). The total follow-up period was 4 months. Results: The mean age of patients was 30 years (rnin-max: 22-52) and 67% (27/40) were female. Ofthe initial 82 eyes, 80 completed the trial (40 in the intervention 31m, 40 in the placebo arm). Median pain scores as measured by the VAS were significantly lower during treatment with codeine/acetaminophen compared to the placebo throughout the early postoperative period (1-48h). Virtually identical results were obtained by the MQP and BPI scales, suggesting that the intervention can have a positive impact not only on the pain intensity, but also on the multidimensional aspects of pain, such as interference on activities of daily living as well as emotional status. Adverse events (AEs) were usually mild and easily managed. The most common AEs were drowsiness, nausea and constipation. After a follow- up period of four months, no case of delayed epithelial healing or haze was observed in both treatment arms. Conclusions: When added to the standard of care therapy, the oral combination of codeine (30mg) and acetaminophen (500mg) given 4x/day was safe and significantly superior to placebo for pain control after PRK
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GELOEN, JACQUES. "Proposition d'un outil simple d'evaluation de la charge en soins en reanimation, systeme omega : validation a l'aide du systeme prn." Lille 2, 1990. http://www.theses.fr/1990LIL2M058.
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Carvalho, Luiz Fernando Meneses. "Tratamentos de fibras de carna?ba [copernicia prun?fera (miller) h. e. moore] para o desenvolvimento de comp?sito biodegrad?vel com matriz de polihidroxibutirato." Universidade Federal do Rio Grande do Norte, 2011. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12780.
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Previous issue date: 2011-06-20Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
The use of raw materials from renewable sources for production of materials has been the subject of several studies and researches, because of its potential to substitute petrochemical-based materials. The addition of natural fibers to polymers represents an alternative in the partial or total replacement of glass fibers in composites. In this work, carnauba leaf fibers were used in the production of biodegradable composites with polyhydroxybutyrate (PHB) matrix. To improve the interfacial properties fiber / matrix were studied four chemical treatments to the fibers..The effect of the different chemical treatments on the morphological, physical, chemical and mechanical properties of the fibers and composites were investigated by scanning electron microscopy (SEM), infrared spectroscopy, X-ray diffraction, tensile and flexural tests, dynamic mechanical analysis (DMA), thermogravimetry (TGA) and diferential scanning calorimetry (DSC). The results of tensile tests indicated an increase in tensile strength of the composites after the chemical treatment of the fibers, with best results for the hydrogen peroxide treated fibers, even though the tensile strength of fibers was slightly reduced. This suggests a better interaction fiber/matrix which was also observed by SEM fractographs. The glass transition temperature (Tg) was reduced for all composites compared to the pure polymer which can be attributed to the absorption of solvents, moisture and other low molecular weight molecules by the fibers
O uso de mat?rias-primas de fontes renov?veis para a produ??o de materiais vem sendo objeto de diversos estudos e pesquisas, devido ao seu potencial na substitui??o de derivados petroqu?micos. A adi??o de fibras vegetais a pol?meros representa uma alternativa na substitui??o parcial ou total de fibras de vidro em comp?sitos. Neste trabalho, fibras da folha de carna?ba (Copernicia prun?fera) foram utilizadas na produ??o de comp?sitos biodegrad?veis com matriz de polihidroxibutirato (PHB). Para melhorar as propriedades interfaciais fibra/matriz foram estudados quatro tratamentos qu?micos, para as fibras. O efeito dos diferentes tratamentos qu?micos nas propriedades morfol?gicas, f?sicas, qu?micas e mec?nicas das fibras e dos comp?sitos foram investigados por microscopia eletr?nica de varredura (MEV), espectroscopia no infravermelho, difra??o de raios-X, ensaios mec?nicos de tra??o e flex?o, an?lise din?mico-mec?nica (DMA) e an?lises t?rmicas por termogravimetria (TG) e calorimetria explorat?ria diferencial (DSC). Os resultados dos ensaios de tra??o dos comp?sitos indicaram um acr?scimo de resist?ncia ? tra??o ap?s modifica??o qu?mica das fibras, sendo o melhor resultado obtido com o tratamento de per?xido de hidrog?nio, mesmo havendo uma pequena redu??o na resist?ncia ? tra??o das fibras tratadas. Isto indica uma melhor intera??o entre as fibras e a matriz polim?rica que foi tamb?m observada nas imagens de microscopia eletr?nica de varredura. A temperatura de transi??o v?trea (Tg) foi reduzida para todos os comp?sitos em rela??o ao pol?mero puro o que foi atribu?do a absor??o de solventes, umidade e outras mol?culas de baixo peso molecular pelas fibras
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Slynko, Inna [Verfasser], Wolfgang [Akademischer Betreuer] Sippl, Mike [Akademischer Betreuer] Schutkowski, and Gerhard [Akademischer Betreuer] Wolber. "Structural analysis and computer-based design of novel inhibitors for human protein-kinase-C-related enzyme PRK1 / Inna Slynko. Betreuer: Wolfgang Sippl ; MIke Schutkowski ; Gerhard Wolber." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2015. http://d-nb.info/1076503179/34.
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Taylor, Colleen Y. "Predictors of nurses intentions to administer PRN opioid analgesics for pain relief to postoperative orthopedic patients in the acute care setting." University of Toledo / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1430507903.
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Wright, Jacqueline Lee. "Pediatric Delirium in Mechanically Ventilated Patients and Use of Benzodiazepines." Mount St. Joseph University Dept. of Nursing / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=msjdn1618957346676197.
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Tanner, Raymond. "A Role for the Planar Cell Polarity Pathway in Neuronal Positioning Along the AP Axis of C. elegans." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31521.
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We sought to investigate the role of the Planar Cell Polarity (PCP) pathway in neuronal positioning along the Anterior-Posterior (AP) axis of C. elegans, and chose the worm’s DD-type motor neurons as a model. The six DD neurons (DD1-DD6) are evenly spaced in the ventral nerve cord of wild type animals. Here we showed that mutations in core PCP genes caused DD neuron spacing and positioning defects. prkl-1 double mutant combinations with vang-1 and fmi-1 showed a suppression of the more severe prkl-1 single mutant defects, which was evidence of genetic interactions between these PCP components. We also conducted a candidate screen of Frizzled, Dishevelled, Wnt, and ROCK genes, and found that dsh-1/Dishevelled, mom-2/Wnt and let-502/ROCK also played roles in DD neuronal positioning. Both vang-1 and prkl-1 were found to function within the nervous system to guide DD neuronal positioning, and prkl-1 was further identified as playing a cell autonomous role. The origins of observed DD neuron anterior positioning defects were investigated during embryogenesis, in which 1.5 fold stage prkl-1(ok3182) embryos displayed delayed intercalation of the DD neurons. This represents a novel role for the PCP pathway in mediating DD neuronal intercalation.
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Prkno, Anna [Verfasser], Matthias [Akademischer Betreuer] Pletz, Peter [Akademischer Betreuer] Schlattmann, and Didier [Akademischer Betreuer] Keh. "Systematischer Review und Meta-Analyse zur Überlegenheit einer Procalcitonin-gesteuerten Therapie bei Patienten mit schwerer Sepsis und septischem Schock / Anna Prkno. Gutachter: Matthias Pletz ; Peter Schlattmann ; Didier Keh." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2015. http://d-nb.info/1078504784/34.
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