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1
Brousseau-Nault, Mathieu. "Chronic periodontitis is associated with platelet factor 4 (PF4) secretion". Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59016.
Testo completoAbstract (sommario):
Aim: Platelets contribute to chronic inflammation but their role in periodontitis is not well understood. The aim of this study was to compare platelet recruitment and activation in healthy and inflamed periodontium.
Materials and Methods: Gingival crevicular fluid (GCF) samples were obtained from sites of healthy periodontium, gingivitis and periodontitis. Platelets were quantified in the GCF by staining and microscopy. GCF concentrations of platelet factor 4 (PF4) [PF4]GCF and glycoprotein IIbIIIa ([GPIIbIIIa]GCF) were determined by ELISA. Blood samples were obtained from the 3 patient groups. Platelets were isolated from whole blood and stimulated with lipopolysaccharide (LPS) from P. gingivalis to evaluate and compare the LPS-induced PF4 release.
Results: Compared to controls, platelet recruitment was increased at gingivitis and periodontitis sites, based on platelet counts and [GPIIbIIIa]GCF. [PF4]GCF was elevated in periodontal pockets but not at gingivitis or healthy sites. Circulating plasma levels of PF4 were higher in patients with generalized severe periodontitis (SP), compared to patients with gingivitis or healthy periodontium. Platelets isolated from SP patients contained and released more PF4 in response to P. gingivalis LPS than platelets from gingivitis or periodontally healthy patients.
Conclusions: Periodontitis is associated with increased platelet activation and PF4 release, both locally and systemically.Dentistry, Faculty of
Graduate
2
XI, XIAODONG. "Role du pf4 et de l'il-13 dans la regulation de l'hematopoiese". Paris 7, 1995. http://www.theses.fr/1995PA077261.
Testo completoAbstract (sommario):
De nombreux regulateurs (positifs ou negatifs) sont impliques dans la regulation de l'hematopoiese. Deux de ces regulateurs, le pf4 et l'il-13, font l'objet de cette these. Le chapitre i presente les techniques utiles developpees pour la realisation du travail et les resultats obtenus a partir de ces techniques. Le chapitre ii porte sur les effets differenciateurs de l'il-13 sur la croissance des progeniteurs hematopoietiques: stimulation de la lignee megacaryocytaire et inhibition de la lignee granulomacrophagique. C'est un rapport original concernant l'effet de l'il-13 sur les megacaryocytes. Dans le chapitre iii, le mecanisme d'action du pf4 sur les progeniteurs megacaryocytaires a ete analyse en comparaison de l'action du tgf-beta 1. Une inhibition directe et reversible du pf4 sur la croissance des progeniteurs megacaryocytaires a ete montree. En outre, l'auteur a suggere qu'une conservation des cellules plus immatures, reactives au scf, resultant de l'inhibition reversible, peut etre responsable de la protection des progeniteurs vis-a-vis de la cytotoxicite du 5-fu
3
Purcell, Jenny. "The effects of PF4 on Ascaris suum somatic muscle cells : an electrophysiological study". Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/29954.
Testo completoAbstract (sommario):
PF4 is a FaRP which was isolated from the free-living nematode Panagrellus redivivus and which has been shown to have activity in other nematodes, including Ascaris suum. A. suum, the large parasitic nematode found in domestic pigs, is often used as an experimental model in studying nematodes due to its large size and easy availability. The nematodes used in this study were obtained from three different sources. The action of PF4 on the somatic muscle cells of A.suum was investigated using the two electrode current clamp technique. PF4 caused these cells to hyperpolarise by 2 to 12 mV. The FaRP also caused an increased in membrane conductance of up to 3mS. The response to PF4 was shown to be due to the opening of chloride ion channels in the somatic muscle cell membrane. In experiments to examine the delay between application of PF4 and the response, PF4 was found to act as the directly gating ligand g-amino butyric acid. This observation is consistent with the argument that PF4 directly gates ion channels. PF4 was investigated further with patch clamp experiments that were carried out on membrane vesicles produced by treating the muscle cells with collagenase. Using vesicle-attached and isolated inside-out patches, PF4 was shown to open small amplitude channels (1.5 to 6.2 pS) with a relatively high probability of opening (Popen) of 0.05 to 0.65 at [PF4] 0.003 mM. The channel conductance and the Popen recorded in each experiment varied with the origin of the worms, suggesting genetic diversity within A. suum. The mean open time of the channel was found to be voltage sensitive; it varied from 522±+120 mV. The behaviour of the channels did not alter after patch isolation, which is further evidence for them being directly gated by PF4. When the cytoplasmic side of the patches was exposed to a G-protein inhibitor (guanosine 5'-O-(2-thiodiphosphate), the conductance of the channels reduced and the Popen increased. This finding suggests that these ion channels can be modulated by one or more G-proteins. The results of this project suggest that that FaRP, PF4, directly activates low conductance chloride channels by combining with a receptor on the outside of the muscle membrane. The channels are different from those described previously in nematodes or vertebrates and therefore present a potential anthelmintic target site.
4
Dubrac, Alexandre. "Analyse fonctionnelle et structurale du facteur antiangiogénique pf4v1". Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13751/document.
Testo completoAbstract (sommario):
De nombreuses équipes se sont intéressées aux fonctions antiangiogéniquesde PF4 (Platelet Factor 4 ou Facteur Plaquettaire 4). Ses capacités inhibitrices vis-àvisde la prolifération et de la migration des cellules endothéliales in vitro et son effetinhibiteur sur lʼangiogenèse in vivo ne sont plus à démontrer. En revanche, il existeencore de nombreuses interrogations sur les mécanismes dʼaction responsables deson activité antiangiogénique. La chimiokine PF4v1 (Platelet Factor 4 variant 1)mature ne diverge de PF4 que par trois acides aminés mais son potentielangiostatique est beaucoup plus élevé que celui de PF4. Lʼétude comparative de PF4et PF4v1 est donc susceptible de fournir des éclairages intéressants sur lesmécanismes dʼaction de lʼactivité antiangiogénique de PF4. La question se pose desavoir si la différence dʼactivité antiangiogénique entre ces deux chimiokines pourraitsʼexpliquer par des différences dʼaffinité aux GAGs (Glycoaminoglycans), à unrécepteur ou bien aux voies de transduction utilisées pour médier leurs effets ?Comme les mécanismes dʼaction de PF4v1 demeurent très largement incompris(bien que son utilisation comme agent thérapeutique antiangiogénique soit trèsprometteuse), nous avons adopté plusieurs axes de travail pour élucider lescaractéristiques spécifiques de cette chimiokine.Dans un premier temps, nous avons étudié les caractéristiques de diffusibilité etde biodisponibilité des facteurs PF4 et PF4v1. Nous avons déterminé que cesparamètres étaient liés aux affinités de PF4 et PF4v1 pour lʼhéparine et les GAGs, etnous avons identifié lʼacide aminé principalement responsable des différencesobservées.Sur le plan de lʼactivité antiangiogénique de ces deux chimiokines, nousmontrons une absence de corrélation avec lʼaffinité respective aux GAGs. Par contre,nous identifions que la liaison avec un récepteur spécifique pourrait être à lʼorigine dela différence dʼactivité antiangiogénique. Nous avons mené une étude permettant decomprendre le rôle de chaque acide aminé variant entre ces deux chimiokines dansla liaison spécifique au récepteur.Enfin, nous avons développé le premier anticorps monoclonal spécifique de laprotéine PF4v1 qui, de plus, neutralise son activité antiangiogénique. Ce nouvel outilapporte des informations sur la structure et sur lʼactivité biologique de PF4v1. Il nousa aussi permis de démontrer que la protéine PF4v1 est un nouveau biomarqueur ducancer du pancréas. Grâce à ce nouvel outil, nous avons aussi développé un dosageELISA anti-PF4v1. Dans le cadre de la recherche de nouveaux biomarqueurs pour ladétection précoce des cancers, nous pouvons envisager une utilisation de cet ELISAen collaboration avec des services cliniquesAbstract :
5
El, Golli Nargès. "Etude du trafic intracellulaire de la protéine alpha-granulaire plaquettaire : le facteur plaquettaire (PF4)". Paris 7, 2005. http://www.theses.fr/2005PA077136.
Testo completo
6
Lazar, Noureddine. "Structure secondaire et activité biologique : relations structure-fonction dans le PF4 Humain et la Prosomatostatine". Paris 6, 2003. http://www.theses.fr/2003PA066181.
Testo completo
7
Pertuy, Fabien. "Etude des mécanismes de formation des plaquettes sanguines : rôle de l'environnement médullaire". Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ092/document.
Testo completoAbstract (sommario):
Les mécanismes de formation des plaquettes sanguines à partir des mégacaryocytes ne sont pas totalement compris, mais l’environnement médullaire semble y avoir une influence cruciale. Dans ce travail nous montrons que i) les intégrines β3, récepteurs de protéines de matrice extracellulaire, semblent impliquées dans la mégacaryopoïèse et la formation des plaquettes, ii) la différenciation des cellules hématopoïétiques dans un environnement 3D de rigidité comparable à la moelle osseuse améliore la maturation des mégacaryocytes différenciés in vitro et iii) la myosine IIA est impliquée dans la distribution des organelles dans les mégacaryocytes. Parallèlement, Nous avons caractérisé la spécificité d’expression du transgène Pf4-cre pour valider son utilisation dans nos approches expérimentales. Ce travail apporte un éclairage nouveau sur le rôle de la myosine IIA et des intégrines dans les mégacaryocytes et souligne l’influence de la rigidité de l’environnement dans la mégacaryopoïèseMegakaryocytes differentiation (megakaryopoiesis) and platelet formation mechanisms are not entirely understood, but the bone marrow environment seems to be crucial in these processes. In this thesis, we show i) that integrin β3, the extracellular matrix protein receptors, are involved in megakaryopoiesis and platelet formation, ii) that recreating a 3D environment of stiffness in the range of that of bone marrow improves the maturation of in vitro differentiated megakaryocytes and iii) a new role for myosin IIA in the cytoplasmic distribution of organelles within the megakaryocyte. As a side-project, we characterized the specificity of expression of the Pf4-cre transgene to validate its use in our experimental approaches. This work enlightens new roles for myosin IIA and integrins in megakaryocytes and indicates that stiffness of the environment influences megakaryopoiesis
8
Schulze, Annika [Verfasser]. "Charakterisierung der anti-PF4/Heparin-Antikörper-sezernierenden B-Zellen im Mausmodell nach systemischer Immunisierung / Annika Schulze". Greifswald : Universitätsbibliothek Greifswald, 2015. http://d-nb.info/1068082143/34.
Testo completo
9
AIDOUDI, SALLOUHA. "Effet protecteur du facteur plaquettaire 4 (pf4) en comparaison avec un myeloprotecteur, le tetrapeptide acsdkp, sur l'hematopoiese de souris traitees par la chimiotherapie". Paris 7, 1997. http://www.theses.fr/1997PA077354.
Testo completoAbstract (sommario):
Le pf4 est une proteine synthetisee par la lignee megacaryocytes/plaquettes dont l'activite inhibitrice a ete recemment montree sur la lignee megacaryocytaire humaine et murine. Il a ete montre que l'effet du pf4 est predominant sur la lignee megacaryocytaire, mais a plus forte doses, il inhibe aussi la proliferation des autres lignees hematopoietiques. Le but de ce travail a consiste a etudier l'effet du pf4, en comparaison avec un inhibiteur et myeloprotecteur connu de l'hematopoiese l'acsdkp, sur l'hematopoiese des souris traitees avec deux chimiotherapies : le 5-fu ou ara-c. Les resultats obtenus dans cette etude ont montre que le pretraitement des souris avec le pf4 ou l'acsdkp chez les souris traitees par la chimiotherapie entraine une augmentation significative du nombre des cellules souches hpp-cfc des progeniteurs medullaires (cfu-gm, cfu-mk) et des mk matures. Ces resultats indiquent que le pf4 et l'acsdkp agissent aussi bien sur les cellules souches hpp-cfc que sur les progeniteurs hematopoietiques augmentant leur nombre, ce qui traduit une meilleure recuperation et donc une protection. La suite de ce travail a consiste a essayer de caracteriser le domaine responsable de l'activite inhibitrice/protectrice du pf4. Les resultats obtenus in vitro et in vivo chez la souris normale ont montre que les peptides correspondant aux regions 1-24 et 13-24 c-terminale du pf4 native (c1-24, c13-24, c13-24de) mais pas c1-13 ont une activite inhibitrice similaire au pf4 natif sur la formation des colonies cfu-mk et le nombre des mk isoles. De facon interessante, le pretraitement des souris avec le c13-24 de chez les souris traitees avec le 5-fu provoque, comme le pf4 natif, une augmentation significative des cellules souches hpp-cfc, des progeniteurs (cfu-gm et cfu-mk) ainsi que des mk matures. Ces resultats suggerent fortement que la region 13-24 c-terminale du pf4 est impliquee dans son activite inhibitrice/protectrice.
10
Libraire, Julie. "Le facteur 4 plaquettaire (PF4/CXCL4) prévient la formation du complexe initial de l’inhibiteur de l’activateur du plasminogène (PAI-1) avec sa cible d’origine tissulaire (t-PA)". Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05P654.
Testo completoAbstract (sommario):
Le facteur 4 plaquettaire (PF4/CXCL4) est un tétramère constitué de quatre sous-unités identiques de 7,8 kDa qui est libéré en grande quantité par les plaquettes lors de l’hémostase primaire (ensemble des phénomènes permettant un colmatage initial d’une lésion vasculaire). L’étude de la formation d’un caillot de fibrine en présence de PF4 montre une augmentation de la turbidité finale du caillot : le PF4 modifie le réseau formé. Etant donné que la plupart des acteurs de la fibrinolyse se lie au caillot de fibrine et que le PF4 modifie sa structure, nous avons pensé qu’il serait intéressant de rechercher si le PF4 influençait aussi la fibrinolyse. La lyse d'un caillot est effectuée par la plasmine issue de l'activation du plasminogène par son activateur d’origine tissulaire (t-PA) en présence d’un cofacteur qui n'est autre que la fibrine. Nous avons étudié la lyse de caillots de plasma, obtenus par activation de la cascade de la coagulation, en condition statique et à l'aide d'un modèle de thrombose artérielle (système Chandler loop). Dans les deux cas, une diminution du temps de demi-lyse a été observée en présence de PF4. Cependant, la lyse de caillots préparés par simple ajout de thrombine sur du fibrinogène ne permet pas de retrouver cet effet du PF4. Ceci suggère que l’influence du PF4 sur la structure du caillot n’est pas à l’origine de l’effet sur sa lyse et que le PF4 n’influence pas (ou très peu) l'activation du plasminogène, ainsi que l'activité de la plasmine résultante. Cette hypothèse a été confirmée par l’étude de l’activité amydolytique du t-PA et de la plasmine (quelle soit ajoutée ou générée). En système purifié, les inhibiteurs plasmatiques de la fibrinolyse sont absents. Les deux principaux sont l'inhibiteur de l'activateur du plasminogène de type 1 (PAI-1) et l’α2-antiplasmine (α2-AP). La lyse de caillots préparés à partir de plasma déficient en α2-AP montre une diminution du temps de demi-lyse en présence de PF4 (comme pour le plasma normal), alors qu’avec le plasma dépourvu de PAI-1 le temps de demi-lyse n'est plus influencé. De plus, l’ajout de PAI-1 dans le système purifié entraine une diminution du temps de demi-lyse en présence de PF4. Ceci suggère que le PF4 prévient directement ou indirectement l'inhibition du t-PA par PAI-1. L’étude de la cinétique d'inhibition de l’activité amidolytique du t-PA par le PAI-1, la détermination de la stœchiométrie de cette inhibition, et l’analyse de ces cinétiques par immuno-empreinte montrent que le PF4 est un modulateur de la fibrinolyse qui agit en retardant la formation d'un complexe initial entre le t-PA et le PAI-1. Cette nouvelle fonction du PF4 est cohérente, et vient en complément de celle décrite récemment d’inhibiteur de l'activation du TAFIPlatelet factor 4 (PF4/CXCL4) is a tetramer constituted of four identical 7,8 kDa subunits released in large quantities by platelets during primary heamostasis (allowing initial clogging of a vascular injury). Study of fibrin clot formation in the presence of PF4 shows an increase of the final clot turbidity: PF4 modifies the formed network. Given that most fibrinolysis actors are bound to the fibrin clot and that PF4 modifies its structure we thought it would be interesting to investigate if PF4 also influences fibrinolysis. Clot lysis is performed by plasmin originating from activation of its precursor by tissue plasminogen activator (t-PA) with fibrin itself as cofactor of the reaction. We have studied lysis of plasma clots formed by activation of the coagulation cascade in static condition and in a Chandler loop model mimicking arterial thrombosis. Half-times of lysis decreased in the presence of PF4 in both systems. However, PF4 had no longer detectable influence on the half-time of lysis with clots formed by direct addition of thrombin on purified fibrinogen. Observation suggested that the observed decrease of the half-time of lysis induced by PF4 did not originate from its influence on fibrin clot formation and that PF4 had little effect if any on plasminogen activation or plasmin activity. We confirmed this hypothesis by comparing amydolytic activities of t-PA and plasmin (added or generated through plasminogen activation). In purified system, fibrinolysis inhibitors are absent. The two main inhibitors are plasminogen activator inhibitor-1 (PAI-1) and α2-antiplasmin (α2-AP). Lysis of clots obtained from α2-AP deficient plasma showed a decrease of the half-time of lysis in the presence of PF4 (as in normal plasma), whereas in PAI-1 deficient plasma half-time of lysis was unchanged. Moreover if PAI-1 was added to the purified system, half-time of lysis decreased in the presence of PF4. Observations therefore suggested that PF4 prevented directly or indirectly t-PA inhibition by PAI-1. Kinetics of the amidolytic activity of t-PA inhibition by PAI-1 in the presence or not of PF4, determination of its stoichiometry and Western blot analysis of these inhibition kinetics revealed that PF4 is a fibrinolysis modulator which delays formation of the initial (Michaelis) complex between t-PA and PAI-1. This new feature of PF4 is consistent and complementary with its recently described role as a modulator of TAFI activation
11
Tortuel, Damien. "Vers la compréhension du rôle de SigX dans la réponse au stress de l'enveloppe chez Pseudomonas aeruginosa Pf4 phage infection induces SOS and cell envelope stress responses in Pseudomonas aeruginosa Pf4 phage infection reduced virulence-associated phenotypes in Pseudomonas aeruginosa The temperature-regulation of Pseudomonas aeruginosa cmaX-cfrX-cmpX operon reveals an intriguing molecular network involving the sigma factors AlgU and SigX". Thesis, Normandie, 2020. http://www.theses.fr/2020NORMR002.
Testo completoAbstract (sommario):
Pseudomonas aeruginosa est un pathogène opportuniste très résistant, pour lequel il est critique de trouver de nouvelles thérapies. Cette bactérie s’adapte facilement à son environnement grâce à son grand génome et à sa grande proportion de régulateurs permettant une régulation très fine de ses gènes. L’enveloppe est la première barrière au contact direct de l’environnement, et est un lieu d’échanges très important entre ce dernier et la bactérie. L’enveloppe représente donc une cible thérapeutique potentielle intéressante. SigX est un facteur sigma à fonction extracytoplasmique, permettant de répondre à des situations de stress d’enveloppe détectées par la bactérie, mais dont le stimulus exact reste à déterminer. Ce facteur sigma pourrait faire partie d’un nouveau système de transduction atypique du signal, qui pourrait coupler SigX à un canal mécanosensible. Ces travaux ont mené à la découverte de trois nouvelles conditions activatrices de SigX, l’infection par des phages Pf4, la perte du canal mécanosensible CmpX, et le choc froid. Ces dernières semblent provoquer de fortes perturbations et une augmentation de la rigidité membranaire qui pourrait être le stimulus activateur de SigX. Ces travaux ont permis d’étoffer les connaissances et de se rapprocher de la condition activatrice de SigX, et de préciser les fonctions cellulaires et régulatrices des membres du système SigX-CfrX-CmpX, mettant en exergue l’implication d’un canal mécanosensible dans la physiologie de Pseudomonas aeruginosaPseudomonas aeruginosa is a very resistant opportunistic pathogen, for which it is critical to find new therapies. This bacterium easily adapts to its environment, through its large genome and proportion of regulators allowing a very fine regulation of its genes. The cell wall is the first barrier in contact with environment, and therefore represents a very important place ofexchange. The cell wall thus represents an interesting potential therapeutic target. SigX is an extracytoplasmic function sigma factor, responding to cell wall stresses detected by the bacterium, but the precise stimulus remains to discover. This sigma factor could be part of a new atypical signal transduction system that could couple SigX with a mechanosensitive channel. This work has led to the discovery of three new sigX activating conditions, which are Pf4 phage infection, loss of the CmpX mechanosensitive channel, and cold shock. These conditions seem to cause strong perturbations and an increase in membrane stiffness that could be the activating stimulus of SigX. This work has led to a better understanding of the activating condition of SigX, and to the clarification of the cellular and regulatory functions of the SigXCfrX-CmpX system members, highlighting the involvement of a mechanosensitive channel in the physiology of Pseudomonas aeruginosa
12
LEBEURIER, ISABELLE. "Implication de la region c-terminale du pf4 dans la regulation negative de la megacaryocytopoiese et dans l'acceleration du recouvrement hematopoietique chez la souris traitee par 5-fluorouracile". Paris 7, 1996. http://www.theses.fr/1996PA077085.
Testo completoAbstract (sommario):
Le facteur plaquettaire 4 (pf4), une heparin-binding protein specifique de la lignee megacaryocyte (mk) plaquette impliquee dans la regulation negative de la megacaryocytopoiese. Nous avons precedemment montre que le pf4 et une molecule apparentee, la -thromboglobulin (-tg) inhibaient la croissance de la lignee erythroleucemique humaine (hel). Le but de ce travail a ete d'etudier l'effet du pf4, de la -tg et de peptides apparentes sur la croissance de differentes lignees leucemiques humaines et sur la megacaryocytopoiese murine pour determiner une specificite d'action et les relations pouvant exister entre l'activite inhibitrice et la structure du pf4 et de ses molecules apparentees. Les resultats ont montre que le pf4 et la -tg conservaient leur activite inhibitrice sur la croissance de la lignee meg-01. De plus, les peptides dimeriques correspondant a la region 1-24 (c1-24) et 13-24 (c13-24) c-terminale du pf4, mais pas ceux correspondant a la region 16-24 (c16-24), 21-29 (p-tg) et 20-28 (pil-8) c-terminale du pf4, de la -tg et de l'il-8, inhibaient les lignees megacaryoblastiques. Le peptide c13-24 de forme monomerique (c13-24m) et/ou mutee (c13-24a) pour laquelle la cysteine a ete remplacee par une arginine, n'a pas retenu l'activite inhibitrice du pf4. De meme, les peptides c1-24 et c13-24 ont revele une activite inhibitrice in vitro et in vivo sur la megacaryocytopoiese murine contrairement au peptide c1-13. Cette activite inhibitrice peut etre neutralisee par addition d'heparine. Ces resultats suggerent que le domaine responsable de l'activite inhibitrice du pf4 serait localise dans sa region 13-24 c-terminale incluant en partie le domaine de liaison a l'heparine. Une structure dimerique semblerait necessaire a l'activite des peptides. D'autre part, le pretraitement par le pf4 et/ou le peptide c13-24de permettrait d'augmenter le recouvrement des cellules souches et des progeniteurs hematopoietiques chez des souris traitees par 5-fluorouracile
13
Amanuma, Kazushi. "Dielectric properties of PFN-PFT solid solution synthesized by the molten salt method". Master's thesis, This resource online, 1991. http://scholar.lib.vt.edu/theses/available/etd-01202010-020152/.
Testo completo
14
Scarparo, Pamela. "Studio dei fattori di rischio genetico nella Trombocitopenia da Eparina". Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3427560.
Testo completoAbstract (sommario):
Heparin induced thrombocytopenia (HIT) is a rare and life threatening complication of heparin therapy, characterized by great reduction of platelet’s count, that may be complicated in 30-50% of cases by a paradoxical thrombotic syndrome (HITT), either arterial or venous. As reported by major clinical series in the literature, about 1% of patients receiving unfractionated heparin (UFH) or low molecular weight heparin (LMWH) develop IgG-mediated heparin-induced thrombocytopenia. HIT pathogenesis can be due to antibodies (Abs) formation, which are direct against a complex formed by Heparin (H) and PF4. H/PF4 antibodies bind the platelets receptor FcγRIIA, inducing platelet activation and aggregation, by modulating the affinity of GpIIb-IIIa for fibrinogen and induce release of platelet granules. PECAM-1 has been shown to negatively regulate platelet activation downstream FcγRIIA, but the mechanism of this process is still unclear. Moreover the receptor FcγRIIIA, expressed on macrophages, seems to play an important role on the clearance of IgG-coated platelets.
However HIT and HITT does not develop in all patients, different factors may play a role in the onset of clinical syndrome, like: heparin type, antibodies functionality, individual genetic variations (genetic polymorphisms), and in vivo cofactors, such as local trauma. In particular we have studied four different polymorphisms, located in the four receptor previously described: FcγRIIA-H131R, GpIIb/IIIa-HPA1, PECAM1-L125V (in linkage disequilibrium with S563N and R670G) and FcγRIIIA-F158V.
The aim of the present study is to understand if polymorphisms of platelets receptors may influence the clinical features of patients who develop H/PF4/Abs, combining immunological, functional and genetic studies. In particular our aim is to discover why some patients with Abs develop HIT syndrome, with or without thrombotic complications, while other not.
First we used ELISA commercial test to determine the presence of H/PF4 antibodies in the plasma samples, than we used HIPA as functional test to understand whether the antibodies found were or not able to activate donor’s platelets. Using the 4T score for HIT and the result of immunological and functional test, we define three groups of patients:
51 H/PF4/Ab patients, with antibodies not able to activate platelets and without thrombocytopenia.
50 HIT patients with antibodies able to activate platelets and thrombocytopenia
53 HITT patients with antibodies able to activate platelets, thrombocytopenia and thrombosis.
We used molecular biology techniques to determine the genotype for the four polymorphisms previously described, in particular: for FcγRIIA-H131R, PECAM1-L125V and FcγRIIIA-F158V we perform an allele-specific PCR, and for HPA1 polymorphism we set an allelic discrimination real time PCR using taqman probes.
Hardy–Weinberg equilibrium was tested for each polymorphism. Allele or genotype frequencies between patients and controls were compared by the χ2 test. Than we use Multiple Regression analysis for multiple confront between different polymorphisms.
Comparing the polymorphisms frequencies between the three patients groups (H/PF4/Ab;HIT;HITT) we found some significative differences, in particular between HIT and HITT group. The frequency of the R/R131 genotype (FcγRIIA) is increased in HITT group (p<0,05), the same for the a/b genotype frequency (GpIIIa-HPA1) (p<0,05). The frequency of the polymorphic setting VNG (V/V125-N/N563-G/G670) for the PECAM receptor is also increased in the HITT group compare with the other two groups, but the p value is not statistically significative. We found that R/R131 associated with a/b-HPA1 have a relation with HITT but with a p-value (0,07) near significance.
There were no great differences between the genotypes of the four polymorphisms comparing HIT group with H/PF4/Ab group.
We suppose that platelets R/R for the receptor FcγRIIA, cleared less efficiently than H/H ones, can circulate longer enhancing the risk for HIT thrombosis. We can suggest that the setting VNG for PECAM1 can have less inhibitory activity on FcγRIIA receptor. Furthermore the b allele for the HPA1 polymorphism is a known risk factor for thrombosis.
Together these polymorphisms could create a genetic setting that could enhance thrombotic complications in HIT pathology. We found a p value = 0,07, near significance, for the association of R/R and a/b with HITT (Multiple regression analysis), we think that increasing our cases we could obtain a significant association (p value < 0,05).La piastrinopenia indotta da eparina (HIT) è una rara e grave complicanza della terapia eparinica, caratterizzata da una marcata riduzione del numero delle piastrine (trombocitopenia) che può esere complicata nel 30-50% dei casi da episodi trombotici sia venosi che arteriosi (HITT). La letteratura al riguardo riporta che circa l’1% dei pazienti che ricevono Eparina standard o a basso peso molecolare sviluppano una trombocitopenia da eparina IgG-mediata. L’eziologia della HIT dipende dalla formazione di anticorpi (Abs) rivolti contro un complesso formato da eparina (H), a dosi terapeutiche, e fattore piastrinico 4 (PF4). Gli immunocomplessi H/PF4/Abs che si legano al recettore piastrinico FcγRIIA, inducono attivazione piastrinica e aggregazione, modulando l’affinità della GpIIb/IIIa per il fibrinogeno. PECAM1 regola negativamente l’attivazione piastrinica mediata da FcγRIIA, anche se i meccanismi di tale inibizione non sono ancora stati del tutto chiariti. Le piastrine ricoperte da IgG sono poi riconosciute e rimosse dai macrofagi splenici per mezzo del recettore FcγRIIIA. La HIT e la HITT non si sviluppano in tutti i pazienti che ricevano eparina, numerosi fattori potrebbero giocare un ruolo nella patogenesi: il tipo di eparina utilizzata, l’eterogeneità degli anticorpi, variazioni genetiche interindividuali (polimorfismi) e altri cofattori come stati infiammatori del paziente. In questo studio si sono presi in considerazione in particolare quattro differenti polimorfismi genetici che si trovano sui recettori precedentemente citati: FcγRIIA-H131R, GpIIb/IIIa-HPA1, PECAM1-L125V (in linkage disequilibrium con S563N e R670G) e FcγRIIIA-F158V. L’obiettivo del presente lavoro, combinando studi immunologici, funzionali e genetici, è determinare se i polimorfismi genetici di alcuni recettori piastrinici e monocitari siano implicati nell’insorgenza della HIT o nelle complicanze trombotiche di questa patologia, a parità di presenza di anticorpi E’ stato utilizzato un test ELISA per determinare la presenza degli anticorpi H/PF4 nel plasma dei pazienti e successivamente un test HIPA per determinare se tali anticorpi fossero funzionalmente in grado di attivare le piastrine di donatori in vitro. Utilizzando lo score clinico delle 4T e i risultati dei test immunologico e funzionale, sono stati definiti tre gruppi di pazienti: 51 pazienti H/PF4/Ab, con anticorpi non in grado di attivare le piastrine, senza trombocitopenia. 50 pazienti HIT, con anticorpi funzionalmente in grado di attivare le piastrine e trombocitopenia. 53 pazienti HITT, con anticorpi funzionalmente in grado di attivare le piastrine, trombocitopenia e trombosi. Per determinare il genotipo di tutti i pazienti per i quattro polimorfismi in analisi, sono state utilizzate diverse tecniche di biologia molecolare: per FcγRIIA-H131R, PECAM1-L125V e FcγRIIIA-F158V è stata messa a punto una PCR allele-specifica, per il polimorfismo HPA1, invece, una discriminazione allelica in real time PCR, utilizzando sonde Taqman. Le differenze tra le frequenze alleliche e genotipiche dei tre gruppi di pazienti sono state analizzate con il test statistico del χ2 . Successivamente è stata utilizzata una Multiple Regression Analysis per il confronto tra polimorfismi multipli. Prima di procedere all’analisi statistica è stato testato l’equilibrio di Hardy-Weinberg per ogni polimorfismo. Sono emerse alcune differenze significative confrontando le frequenze dei polimorfismi tra i tre gruppi di pazienti (H/PF4/Ab;HIT;HITT), in particolare tra il gruppo HIT e HITT. La frequenza del genotipo R/R (FcγRIIA) è aumentata nel gruppo HITT (p<0,05), così come la frequenza del genotipo a/b (GpIIIa-HPA1) (p<0,05). Anche la frequenza del setting polimorfico VNG (V/V125-N/N563-G/G670) per il recettore PECAM1 è aumentata nel gruppo HITT rispetto agli altri gruppi, anche se non in modo statisticamente significativo. L’analisi multivariata ha mostrato che l’associazione tra R/R131 e a/b-HPA1 è in relazione con il gruppo HITT, con una p vicina alla significatività statistica (0,07). Non sono state invece rilevate differenze significative per i quattro polimorfismi analizzati tra il gruppo HIT e il gruppo H/PF4/Ab. Possiamo quindi supporre che le piastrine R/R (per il recettore FcγRIIA), eliminate in modo meno efficace delle H/H, rimangano in circolo più a lungo, portando ad un rischio trombotico maggiore nella HIT; tale rischio è aumentato anche dall’allele b di HPA1 (polimorfismo protrombotico per diverse patologie). Si può inoltre ipotizzare che il setting VNG per PECAM 1 possa avere un minor effetto inibitorio sul recettore FcγRIIA. Insieme questi polimorfismi potrebbero creare un setting genetico che porti una maggior frequenza trombotica nella Trombocitopenia da eparina. Per l’associazione dei genotipi R/R e a/b con la HITT, abbiamo ottenuto un valore p=0,07 vicino alla significatività (Multivariate regression analysis); possiamo quindi supporre che aumentando la nostra casistica potremo riuscire ad ottenere un’associazione statisticamente significativa (p<0,05).
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Newman, Peter Michael Pathology UNSW. "Antibody and Antigen in Heparin-Induced Thrombocytopenia". Awarded by:University of New South Wales. Pathology, 2000. http://handle.unsw.edu.au/1959.4/17485.
Testo completoAbstract (sommario):
Immune heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy and is associated with antibodies directed against a complex of platelet factor 4 (PF4) and heparin. Early diagnosis of HIT is important to reduce morbidity and mortality. I developed an enzyme immunoassay that detects the binding of HIT IgG to PF4-heparin in the fluid phase. This required techniques to purify and biotinylate PF4. The fluid phase assay produces consistently low background and can detect low levels of anti-PF4-heparin. It is suited to testing alternative anticoagulants because, unlike in an ELISA, a clearly defined amount of antigen is available for antibody binding. I was able to detect anti-PF4-heparin IgG in 93% of HIT patients. I also investigated cross-reactivity of anti-PF4-heparin antibodies with PF4 complexed to alternative heparin-like anticoagulants. Low molecular weight heparins cross-reacted with 88% of the sera from HIT patients while half of the HIT sera weakly cross-reacted with PF4-danaparoid (Orgaran). The thrombocytopenia and thrombosis of most of these patients resolved during danaparoid therapy, indicating that detection of low affinity antibodies to PF4-danaparoid by immunoassay may not be an absolute contraindication for danaparoid administration. While HIT patients possess antibodies to PF4-heparin, I observed that HIT antibodies will also bind to PF4 alone adsorbed on polystyrene ELISA wells but not to soluble PF4 in the absence of heparin. Having developed a technique to affinity-purify anti-PF4-heparin HIT IgG, I provide the first estimates of the avidity of HIT IgG. HIT IgG displayed relatively high functional affinity for both PF4-heparin (Kd=7-30nM) and polystyrene adsorbed PF4 alone (Kd=20-70nM). Furthermore, agarose beads coated with PF4 alone were almost as effective as beads coated with PF4 plus heparin in depleting HIT plasmas of anti-PF4-heparin antibodies. I conclude that the HIT antibodies which bind to polystyrene adsorbed PF4 without heparin are largely the same IgG molecules that bind PF4-heparin and thus most HIT antibodies bind epitope(s) on PF4 and not epitope(s) formed by part of a PF4 molecule and part of a heparin molecule. Binding of PF4 to heparin (optimal) or polystyrene/agarose (sub-optimal) promotes recognition of this epitope. Under conditions that are more physiological and sensitive than previous studies, I observed that affinity-purified HIT IgG will cause platelet aggregation upon the addition of heparin. Platelets activated with HIT IgG increased their release and surface expression of PF4. I quantitated the binding of affinity-purified HIT 125I-IgG to platelets as they activate in a plasma milieu. Binding of the HIT IgG was dependent upon heparin and some degree of platelet activation. Blocking the platelet Fc??? receptor-II with the monoclonal antibody IV.3 did not prevent HIT IgG binding to activated platelets. I conclude that anti-PF4-heparin IgG is the only component specific to HIT plasma that is required to induce platelet aggregation. The Fab region of HIT IgG binds to PF4-heparin that is on the surface of activated platelets. I propose that only then does the Fc portion of the bound IgG activate other platelets via the Fc receptor. My data support a dynamic model of platelet activation where released PF4 enhances further antibody binding and more release.
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Weathers, Krystin. "Expression of Foreign Genes in the Pseudomonas Bacteriophage Pf3". VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/357.
Testo completoAbstract (sommario):
Filamentous bacteriophages were engineered to express foreign genes with the ultimate purpose of displaying transmission control anti-malarial peptides as in phage display. It was hypothesized that expression of foreign genes would be possible using the phage’s promoters. This hypothesis was tested by assuming that promoters for the phage major coat protein (MCP) gene would also promote the expression of any foreign gene inserted downstream of the MCP gene. As proof of principle, the bacteriophages Pf3, Pf1, and M13 were engineered in this way to successfully synthesize Enhanced Green Fluorescent Protein (EGFP). Type 88 phage display on the EGFP recombinant Pf3 was attempted by fusing a second copy of its MCP gene to the existing EGFP gene. This resulted in a phage display Pf3 replacement vector which was then used to construct a phage for displaying an anti-malarial peptide.
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LECOMTE, RACLET LAURENCE. "Mecanisme d'action du facteur plaquettaire 4 dans la regulation negative de l'hematopoiese : role des regions c-terminale et centrale du pf4. etude realisee grace a la mise au point d'un systeme d'analyse d'image permettant le comptage automatique des colonies de megacaryocytes". Paris 7, 1998. http://www.theses.fr/1998PA077086.
Testo completoAbstract (sommario):
L'hematopoiese est controle par une balance de regulateurs positifs et negatifs. Nous nous sommes plus particulierement interesse a un regulateur negatif, le facteur plaquettaire 4. Cette proteine de 7,8 kda est un membre de la famille des chemokines cxc dont le mecanisme d'action reste encore a elucider. Le but de cette etude est d'identifier les domaines fonctionnels du pf4 et de determiner leur implication dans la regulation negative de cette chemokine. Afin d'evaluer l'action inhibitrice du pf4 et de ses peptides sur la lignee megacaryocytaire, nous avons mis au point un systeme automatique d'analyse d'images, base sur la coloration a l'acethylcholinesterase. Cet appareil nous permet d'etudier la phase de proliferation en mesurant le nombre le nombre de megacaryocytes (mk) et de leur colonies (cfu-mk), ainsi que la phase de maturation en calculant la surface de chaque mk. Afin de mieux comprendre le mode d'action du pf4, nous avons synthetise differents peptides apparentes au pf4 et mesure leur effet sur la proliferation des progeniteurs hematopoietiques. Nous avons etudier le role de la region c-terminale du pf4 sur une lignee megacaryoblastique meg-01, puis le domaine centrale du pf4 sur des cellules de moelle osseuse de souris. La molecule native et les peptides p47-58 et p47-70 de la region c-terminale sont actifs a partir de 650 nm alors que les peptides p47-55 et p58-70 n'ont aucune action inhibitrice. En revanche, les peptides p17-58 et p34-58 inhibent la formation des cfu-mk, cfu-gm et bfu-e, a partir de 22 nm, contrairement au pf4 qui possede une specificite vis a vis de la lignee megacaryocytaire. Tandis que l'activite des peptides de la region c-terminale est neutralisee par l'heparine, celle des peptides de la region centrale n'est pas modulee par cette molecule. En effet, la sequence responsable de la haute affinite pour l'heparine est omise dans le peptide p34-58, empechant ce peptide de s'associer a l'heparine. Le motif dlq, specifique du pf4 et present dans le peptide p34-58 est indispensable a l'activite inhibitrice. Jusqu'a present, les propriete inhibitrice du pf4 etaient liees a son domaine liant l'heparine qui lui permettait d'interagir avec la surface cellulaire. L'ensemble de nos resultats mettent en evidence un nouveau domaine fonctionnel dans la partie centrale du pf4 (34-58) dependant du motif dlq.
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GROSSE, ANNE. "Modulation de l'hematopoiese in vitro : activite stimulante des oligodesoxynucleotides antisens transforming growth factor-1 (tgf-1) sur les cellules souches hematopoietiques (csh), et activite inhibitrice/protectrice du facteur plaquettaire 4 (pf4) sur ces csh traitees par les agents cytotoxiques aracytine, bleomycine et etoposide". Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13011.
Testo completoAbstract (sommario):
Apres un traitement aplasiant, les csp representent une alternative aux cellules medullaires chez des patients atteints de tumeurs solides ou de pathologies hematologiques. Si l'expansion in vitro a permis d'elargir les criteres d'inclusions des greffes de csp, elle pose neanmoins deux incertitudes essentielles : ses effets sur les precurseurs les plus immatures, et sur le contaminant tumoral. L'etat de quiescence des precurseurs les plus primitifs est majoritairement du a tgf-1, un des plus puissants inhibiteurs de l'hematopoiese precoce. Des cellules cd34 + circulantes de patients et de donneurs sains cultivees pendant 3 jours en milieu liquide et en presence d'odn-as tgf-1, montrent une augmentation significative du nombre et de la proportion des progeniteurs precoces cd34 +cd38 , ainsi que du nombre et de la taille de differentes colonies issues de tout le compartiment des progeniteurs. Ainsi couple aux cytokines, l'antisens tgf-1 amplifierait-il la proliferation de cellules quiescentes primitives que les cytokines seules ne permettraient pas ou beaucoup plus lentement de recruter. Si l'expansion confere un avantage proliferatif aux cellules saines, une contamination tumorale residuelle serait parfois responsable de rechutes apres autogreffes. Dans le cadre d'une purge active in vitro, nous avons etudie l'effet du pf4 sur les cellules cd34 + de csp et de sang de cordon traitees par plusieurs agents phase-specifiques. Les resultats montrent l'absence d'effet inhibiteur et chimioprotecteur du pf4 sur plusieurs lignees hematopoietiques. Sur les cellules saines, l'effet du pf4 depend de l'agent chimiotherapeutique : il protege significativement les cellules traitees par l'etoposide ou la bleomycine, mais potentialise l'action cytotoxique de l'aracytine. L'application de ces resultats permettrait successivement la purge active, puis l'amplification rapide et optimale d'un greffon de csp, laissant presager une perpective de transplantation dans les meilleures conditions.
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Guidotti, Alex. "Progetto ottimizzato di reti FTTH PON multioperatore". Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016.
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Schmitt, Dominik [Verfasser], Caroline [Gutachter] Kisker, Thomas [Gutachter] Müller, Robert [Gutachter] Hock e Hanspeter [Gutachter] Naegeli. "Structural Characterization of the TFIIH Subunits p34 and p44 from C. thermophilum / Dominik Schmitt ; Gutachter: Caroline Kisker, Thomas Müller, Robert Hock, Hanspeter Naegeli". Würzburg : Universität Würzburg, 2017. http://d-nb.info/1142114236/34.
Testo completo
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Henry, Jeff. "Expression characterization of PFK-liver, PFK-muscle, and PFK-brain RNA isoforms in murine preimplantation embryos using RT-PCR". Virtual Press, 2006. http://liblink.bsu.edu/uhtbin/catkey/1355601.
Testo completoAbstract (sommario):
The regulatory enzyme 6-phosphofructo-l-kinase (PFK) controls the key, rate-limiting step in glycolysis. There are 3 known mammalian isoforms termed PFK-muscle (PFK-A), PFK-liver (PFK-B), and PFK-brain (PFK-C) that randomly aggregate to form active homo- and heterotetrameric isozymes with their respective frequencies and kinetic properties contingent upon the presence and concentration of individual subunits. This study utilized RT-PCR and densitometry analyses to characterize the expression patterns of the mRNA for each isoform during mouse preimplantation development. PFK-B is increasingly expressed across these stages with a significant increase in PFK-B transcript between 8-cell (0.425 ± 0.158) and morula (0.579 ± 0.197) stages (p < 0.0005). Neither PFK-A nor PFK-C mRNA was detected at any of the preimplantation stages tested. The statistically significant increase in PFK-B corresponded with the known juncture of the switch from the oxidation of maternally supplied pyruvate to a predominant glycolyticmetabolism. Such timing suggested the direct involvement of elevated PFK-B transcription with an increase in glycolysis.Department of Biology
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Emms, S. "Crystallisation of PFA glasses". Master's thesis, University of Cape Town, 1994. http://hdl.handle.net/11427/8485.
Testo completoAbstract (sommario):
Bibliography: leaves 79-81.Glasses with various compositions, falling in the CaO-AI20rSi02 and MgO-CaOAI20rSi02 systems were made, using pulverised fuel ash and silica, hydrated lime, kaolin and magnesium carbonate. Titania or ferric oxide and chromia were used as nucleants. Various crystallisation heat treatments were carried out and the nucleation and crystallisation behaviour was studied. A minimum MgO:CaO was found to be necessary for bulk nucleation to occur. The activation energy for viscous flow decreased with increased MgO:CaO ratios. This was accompanied by an increase in the surface crystal growth rates and a decrease in the activation energy for surface crystal growth. Titania also lowered the activation energies for viscous flow and surface crystal growth and caused an increase in the surface crystal growth rates.
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Lacková, Martina. "Finanční analýza PFT, s.r.o". Master's thesis, Vysoká škola ekonomická v Praze, 2013. http://www.nusl.cz/ntk/nusl-193621.
Testo completoAbstract (sommario):
The financial situation of limited company PFT is evaluated in the period 2008 to 2013 through techniques of financial analysis. Then the resulting values are compared with the recommended values, sector averages and values of selected competing companies with limited liability. Multivariate methods of intercompany comparison are applied for a more comprehensive assessment of financial management. The conclusion is focused on summarizing the results, identifying strengths and weaknesses and proposing appropriate measures.
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Nascimento, William Junior do. "Sinterização de cerâmicas multiferróicas nanoestruturadas de Pb(Fe1/2Nb1/2)O3 e Pb(Fe2/3W1/3)O3 via Spark Plasma Sintering SPS". Universidade Federal de São Carlos, 2013. https://repositorio.ufscar.br/handle/ufscar/4960.
Testo completoAbstract (sommario):
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Considering the search for miniaturization of electronic devices, the development of new methods and techniques for the production and characterization of nanostructured materials is fundamental, beyond understanding of the effect of grain size on the properties of materials in nanoscale. Therefore, it was proposed in this work the obtaining of nanostructured multiferroic materials, in bulk, with high density and microstructural control, with grains ranging from micrometer to nanometer scale. To achieve this goal, was developed a methodology for obtaining the powder of lead iron niobate, Pb(Fe1/2Nb1/2)O3 (PFN) and lead iron tungstate, Pb(Fe2/3W1/3)O3 (PFW), with average particle size around 150 nm, contamination-free, minimal agglomeration and with highly reproductive results using the micro-milling technique. Regarding consolidation materials, conventional sintering requires higher temperatures and long holding times for a satisfactory densification, resulting in a grain growth higher than the desired. Through the fast sintering technique, only high heating rates are not sufficient to ensure a satisfactory densification and also inhibit the growth of grains. The obtain nanostructured dense samples with average grain size of approximately 200 nm was only possible using spark plasma sintering technique (SPS), which allows sintering at temperatures corresponding to the intermediate sintering stage, inhibiting the grain growth. PFN and PFW samples obtained through the SPS technique showed high conductivity at room temperature due the extreme reduction suffers in the system plus the use of high current densities during sintering, being necessary the samples oxidation. Through the dielectric characterization, the decrease in grain size of micrometer to nanometer scale results in lower permittivity values in phase transition temperature, besides a peak broadening. Moreover, the SPS technique added to the oxidation process makes it possible to obtain PFW samples with high dielectric values (in order of 104) at room temperature, a motivation results with regard to the application.
Considerando a busca pela miniaturização dos dispositivos eletrônicos é fundamental o desenvolvimento de novos métodos e técnicas para a produção e caracterização de materiais nanoestruturados, além do entendimento do efeito do tamanho de grão sobre as propriedades dos materiais em escala nanométrica. Dessa forma, propôs-se neste trabalho a obtenção de materiais multiferróicos nanoestruturados, na forma de bulk com alta densidade e controle microestrutural, com grãos variando de escala micrométrica a nanométrica. Para alcançar este objetivo, foi desenvolvida uma metodologia para a obtenção de pós de niobato de ferro e chumbo, Pb(Fe1/2Nb1/2)O3 (PFN) e tungstanato de ferro e chumbo, Pb(Fe2/3W1/3)O3 (PFW), com tamanhos médios de partículas em torno de 150 nm, livre de contaminação, mínima aglomeração e com resultados altamente reprodutivos por meio da técnica de micromoagem. Em relação à consolidação dos materiais, o procedimento convencional requer altas temperaturas e longos tempos de patamar para uma densificação satisfatória, resultando em um crescimento de grão superior ao desejado. Por meio da técnica de sinterização rápida fast sintering , somente altas taxas de aquecimento não são suficientes para garantir uma densificação satisfatória bem como inibir o crescimento de grãos. A obtenção de amostras densas nanoestruturadas com tamanhos médio de grão de aproximadamente 200 nm só foi possível utilizando a técnica spark plasma sintering (SPS), que permite a sinterização a temperaturas correspondentes ao estágio intermediário de sinterização, inibindo o crescimento de grãos. As amostras de PFN e PFW obtidas por meio da técnica de SPS apresentaram alta condutividade à temperatura ambiente devido às condições extremas de redução que a amostra sofre somada ao uso de altas densidades de corrente durante a sinterização, sendo necessária a oxidação das mesmas. Através da caracterização dielétrica, verifica-se que a diminuição nos tamanhos de grãos de escala micrométrica para nanométrica resulta em menores valores de permissividade na temperatura de transição de fase, além de um alargamento dos picos. Contudo, a técnica de sinterização SPS somada ao processo de oxidação torna possível a obtenção de amostras de PFW com altos valores de constate dielétrica (na ordem de 104), a temperatura ambiente, resultado extremamente motivador no que diz respeito à aplicação.
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Bignold, Simon M. "Optimisation of the PFC functional". Thesis, University of Warwick, 2016. http://wrap.warwick.ac.uk/80984/.
Testo completoAbstract (sommario):
In this thesis we develop and analyse gradient-fl ow type algorithms for minimising the Phase Field Crystal (PFC) functional. The PFC model was introduced by Elder et al [EKHG02] as a simple method for crystal simulation over long time-scales. The PFC model has been used to simulate many physical phenomena including liquid-solid transitions, grain boundaries, dislocations and stacking faults and is an area of active physics and numerical analysis research. We consider three continuous gradient fl ows for the PFC functional, the L2-, H-1- and H2-gradient fl ows. The H-1-gradient flow, known as the PFC equation, is the typical flow used for the PFC model. The L2-gradient flow is known as the Swift-Hohenberg equation. The H2-gradient ow appears to be a novel feature of this thesis and will motivate our development of a line search algorithm. We analyse two methods of time discretisation for our gradient fl ows. Firstly, we develop a steepest descent algorithm based on the H2-gradient fl ow. We further develop a convex-concave splitting of the PFC functional, recently proposed by Elsey and Wirth [EW13], to discretise the L2- and H-1-gradient flows. We are able to prove energy stability of both our steepest descent algorithm and the convex-concave splitting scheme of [EW13]. We then use the Lojasiewicz gradient inequality (first developed in [ Loj62]) to prove that all three schemes converge to equilibrium. For numerical simulations we undertake spatial discretisation of our schemes using Fourier spectral methods. We consider a number of implementation issues for our fully discrete algorithms including a striking issue that occurs when the number of spatial grid points is low. We then perform several numerical tests which indicate that our new steepest descent algorithm performs well compared with the schemes of [EW13] and even compared with a Newton type scheme (the trust region method).
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Kantzon, David. "PFC-design for frequency converter". Thesis, Linköpings universitet, Fysik och elektroteknik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-124547.
Testo completoAbstract (sommario):
This thesis deals with power factor correction for three-phase systems. A boost-buck topology was described, modeled and then simulated in MATLAB/Simulink. The simulation results show that the system provides a power factor over 99% over the tested power output range. Moreover, the harmonic injection concept was introduced which reduces the total harmonic distortion to 8.72% at full output power. A prototype system was also built using an FPGA for the control system. The prototype did not provide the performance seen in simulation but showed that the method is valid and does provide a higher power factor when used.
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Ribeiro, Ricardo Luiz Mendes. "PFL: do PDS ao PSD". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/8/8131/tde-09092016-130237/.
Testo completoAbstract (sommario):
Este trabalho aborda a trajetória do PFL (Partido da Frente Liberal), desde a sua fundação em 1985 até 2010, quando já sob nova denominação DEM deixou de contar com seus três principais líderes: Jorge Bornhausen, Marco Maciel e Antônio Carlos Magalhães. A tese busca explicar as razões do sucesso do partido, até 2002, e de sua decadência a partir de então. Como principal hipótese, argumenta-se que a conexão com o governo federal foi a causa principal tanto do sucesso quanto da decadência da legenda, desencadeada pela passagem do PFL para a oposição após a vitória do Partido dos Trabalhadores na eleição presidencial de 2002. A análise da inserção do PFL no presidencialismo de coalizão e a narrativa da atuação dos três principais líderes do partido junto às altas esferas do governo federal foram os principais subsídios para a construção indutiva da comprovação da hipótese acima formulada.This work addresses the path of the PFL (Partido da Frente Liberal), since its foundation in 1985 until 2010, when already under the new name - DEM - no longer count on its three main leaders: Jorge Bornhausen, Marco Maciel and Antonio Carlos Magalhães. The thesis seeks to explain the reasons for the party\'s success, until 2002, and its decline from then on. As the main hypothesis it is claimed that the connection to the federal government was the main cause of both, the success and the decline, triggered by the passage of the PFL to the opposition after the Workers Party (PT) victory in the presidential election of 2002. The analysis of PFL in the Brazilian coalitional presidentialism and the narrative of the three main important party leaders connections with high ranks of federal government provide the inductive proof of the above hypothesis.
28
Lin, Quan. "Mechanisms of the P44-multigene family expression and characterization of the P44 homologous gene MSP2 expression in anaplasma phagocytophilum". The Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1078603660.
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29
Duchovnay, Alan. "Comparative Electrochemistry, Electronic Absorption Spectroscopy and Spectroelectrochemistry of the Monometallic Ruthenium Polypyridyl Complexes, [Ru(Bpy)(Dpb)2](Pf6)2, [Ru(Bpy)2(Dpb)](Pf6)2, [Ru(Bpy)2(Dpq)](Pf6)2, [Ru(Bpy)(Dpq)2](Pf6)2". Thesis, Virginia Tech, 2011. http://hdl.handle.net/10919/31917.
Testo completoAbstract (sommario):
The novel compound [Ru(bpy)(dpb)â (PFâ )â was synthesized, in a manner similar to the literature synthesis of [Ru(bpy)(dpq)â (PFâ )â . For the sake of completeness, the related analogs, [Ru(bpy)â (dpb)](PFâ )â , [Ru(bpy)â (dpq)](PFâ )â and [Ru(bpy)(dpq)â ](PFâ )â were also synthesized. Alumina adsorption chromatography was used for purification purposes. Liquid secondary ion mass spectroscopy was used to confirm identity of compounds. The new compound contained 1% electroactive impurity as determined by OSWV. Spectroelectrochemical studies were conducted with both a bulk H-cell and a ~0.2 mm pathlength, optically transparent thin layer electrode (OTTLE) cell. High reversibility (a 99%) is possible with dilute solutions (ca 10⠻⠴ M) and the OTTLE cell as compared to ca 50% with the H-cell. Spectroelectrochemical data supported the following electronic transitions for the new compound [Ru(bpy)(dpb)â ](PFâ )â : (1) the Ru (dÏ ) â dpb MLCT at 552 nm, (2) a d â d at 242 nm, a bpy Ï â Ï * at 285 nm. (3) The location of the Ru (dÏ ) â bpy MLCT peak is obscured by shoulders from 390-420 nm. (4) The strong peak at 316 nm may be dpb Ï â Ï â *, the location of the lower energy intraligand dpb Ï â Ï â * is uncertain. Upon oxidation of the metal center, no LMCT was observed within the UV-VIS range. This is in direct contrast to the results of Gordon et al. This author hypothesizes that their LMCT found in the visible region was actually the result of incomplete electrochemical conversion and that a LMCT should be seen in the NIR. The spectroelectrochemical properties of [Ru(bpy)(dpq)â ](PFâ )â were also presented for the first time. These results indicated that the 256 nm transition was d â d and not bpy Ï â Ï â * as suggested by Rillema et al.Master of Science
30
Seoh, Seungwon 1975. "Innovative application of PFI to Korea". Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/47920.
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31
Al-Ani, Mahier Nawf Abbod. "The use of PFA in concrete". Thesis, University of Birmingham, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496907.
Testo completoAbstract (sommario):
The study of previous classifications of pulverised fuel ash (pfa) has led the author to believe that a new approach is required to look Into the physical properties of pfa. In this study a large number of tests have been carried out In an attempt to establish a criterion which is related to the performance of, fresh and hardened pfa concrete. A classification for pfa Is proposed, based on Its particle size distribution, followed by , determination of the grading modulus (Gf). The results of the research show a close correlation between workability as measured by the VB time and. grading modulus with a marginally lower correlation between compressive strength and grading modulus. - The correlation values with Gf being higher than with the percentage mass retained on 45 m sieve. Taking Gf as the physical criterion which influences the behaviour of pfa concrete, the author proceeded to develop a mix design based upon Gf, whereby the required strength and workability can be achieved accurately by replacing a portion of the opc with pfa. Furthermore, the new design method is capable of achieving a wide range of workability and strength with different cement contents, and covers a variety of pfa finenesses (Gf). The cement and pfa content being adjusted in accordance with the properties and content of the aggregates. A newly developed technique, using the Scanning Electron Microscope, which investigated the hydration and porosity of hardened cementitious paste was implemented. The results showed that fog curing Is essential for the development of hydration products. The Interlock between the pfa particles and the matrix showed an influence on the strength of opc/pfa paste which was more pronounced than the porosity of the hydration products. Porosity was also measured, using an alcohol exchange method, which was found to give a higher porosity than the method using the Scanning Electron Microscope. The former measuring total porosity whilst the latter only measures pores in the matrix and does not take Into consideration cracks, capillaries or air voids.
32
Guerois, Rozenn. "A grammar of Cuwabo (Bantu P34, Mozambique)". Thesis, Lyon 2, 2015. http://www.theses.fr/2015LYO20032.
Testo completoAbstract (sommario):
Le cuwabo est une langue bantoue parlée par plus de 800.000 locuteurs au Nord-Est du Mozambique. Elle est répertoriée sous le code P34 selon la classification de Guthrie et appartient donc au groupe makhuwa (P30). Le cuwabo se divise en cinq variétés: le cuwabo central, le karungu, le mayindo, le nyaringa, et le manyawa. Ce travail se base sur le cuwabo central parlé dans le district de Quelimane. Des données de première main ont pu être collectées auprès d’une dizaine de locuteurs, lors de trois terrains réalisés entre 2011 et 2013, totalisant 10 mois. Cette thèse fournit une description grammaticale de la langue couvrant en détail les domaines de la phonologie et de la morphosyntaxe. La phonologie comprend deux chapitres : le premier est dédié à la phonologie segmentale tandis que le deuxième analyse le fonctionnement du système tonal de la langue. Notons que le cuwabo est l’unique langue P30 ayant retenu un ton lexical contrastif sur les thèmes lexicaux et verbaux. Morphologiquement, le syntagme nominal est dominé par un riche système d’accords des classes nominales, typique dans les langues bantoues. Le verbe cuwabo a une morphologie de type agglutinant, qui renferme un riche système de Temps-Aspect-Mode combinant préfixes et suffixes finaux. Il convient de noter l’existence de plusieurs enclitiques selon les constructions (enclitiques locatifs, enclitiques pronoms personnels dans les relatives, enclitiques comitatif ou instrumental). Enfin, la syntaxe s’étend sur trois chapitres : le premier s’intéresse aux constructions prédicatives verbales et non-verbales ; le deuxième s’intéresse aux constructions relatives et à la formation des questions ; le dernier aborde la question de l’ordre des constituants en lien avec la structure informationnelle. Les domaines préverbaux et postverbaux sont examinés, ainsi que leur interaction avec le marquage morphologique sur le verbe qui distingue les formes conjointes et les formes disjointes. L’annexe de cette thèse compile sept textes, glosés et traduits, qui permettent d’illustrer en contexte un grand nombre d’items grammaticaux présentés dans les chapitres descriptifsCuwabo is a Bantu language, spoken by more than 800,000 people (INE 2007) in the north-eastern part of Mozambique. It is numbered P34 in Guthrie’s classification, and thus belongs to the P30 Makhuwa group. Cuwabo can be subdivided into five main varieties: central Cuwabo, Karungu, Mayindo, Nyaringa, and Manyawa. This work is based on central Cuwabo spoken in the district of Quelimane. First-hand data were recorded from 10 speakers in the course of three fieldtrips realised between 2011 and 2013, achieving a total duration of 10 months. This thesis provides a grammatical description of the language, covering in detail its phonology and its morphosyntax. Phonology is divided into two chapters: the first is devoted to segmental phonology whereas the second describes the tonal system of the language. Note that Cuwabo is the only P30 language whose nominal and verbal stems have retained a lexical tone contrast. Morphologically, the noun phrase is marked by a rich agreement system ruled by the noun classes, as typical in Bantu. Cuwabo has a highly agglutinative verbal morphology, which conveys a rich Tense-Aspect-Mood system combining both prefixes and final suffixes. Note the existence of several enclitics depending on the constructions (locative enclitics, personal pronoun enclitics in relative clauses, comitative or instrumental enclitics). The last three chapters address syntactic issues: the first presents a description of the basic clause structure, involving verbal and non-verbal predication; the second looks into the relative constructions in close interaction with question formation; the last one investigates word order and information structure in Cuwabo. Preverbal and postverbal constituents are examined, as well as their interaction with the morphological marking on the verb, distinguishing conjoint and disjoint tenses. The appendix contains seven Cuwabo texts glossed and translated into English, which allow to illustrate in context many of the grammatical items presented in the descriptive chapters
33
Cederberg, Jessica. "Changing financial behaviors using mobile PFM tools". Thesis, Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-19735.
Testo completoAbstract (sommario):
This paper investigates the needs of a PFM (Personal Financial Management) tool in a projected banking app, where information is presented as statistics of the users’ personal economy. By studying how youths would like to monitor their finances in a banking app the paper aims to investigate what a PFM tool could include to attract consumers to use it in order to get a better control of their finances. The question of the paper is therefore: How can a banking app containing a PFM contribute to greater awareness of the users’ finances and savings, and how should such an app be designed? User tests were made to investigate what kind of statistics the users want in a PFM tool in a mobile app. The Delphi method was used to get a ranked list of ten suggestions, and a focus group interview was conducted to analyze the results further and to contribute to a qualitative view of the paper. The test results together with previous research show that a PFM tool included in a banking app could attract the target group to monitor their money, and also encourage them to save more. The respondents would like to have general statistics over their economy in a PFM tool, but also the possibility to monthly set personal budgets and monitor how well they are respected.
34
Lam, Kin-san, e 林建新. "Plant establishment in compost/PFA amended soil". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1994. http://hub.hku.hk/bib/B31212396.
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35
Mason, Sarah Louise. "Regulation of E2F activity by p14'A'R'F". Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368592.
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36
Miller, Daniel [Verfasser]. "Optimierung einer eingangsgleichrichterlosen Leistungsfaktorkorrekturschaltung (PFC) / Daniel Miller". München : Verlag Dr. Hut, 2018. http://d-nb.info/1156510481/34.
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37
Byars, Ewan Alexander. "PFA concrete : strength development and permeation properties". Thesis, University of Dundee, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343527.
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38
Schiff, Albrecht Johannes. "Optimised PFC circuits for efficient power conversion". Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611141.
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39
Zhuang, Jianqin, e Ruediger Voelkel. "Emulsion droplet size distribution by PFG NMR". Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-195027.
Testo completo
40
Shariati, Hossein. "Micromechanical study of PFZ in aluminum alloys". Thesis, KTH, Hållfasthetslära (Inst.), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-190115.
Testo completoAbstract (sommario):
There are a number of experiments showing that the ductility of aluminum alloys decreases during age-hardening heat treatment. Observing the grains of age-hardened aluminum alloys at the micron scale, one can notice that there are precipitate-free zones (PFZs) along the grain boundaries. PFZ has yield stress three times lower than the grain interior (bulk) due to absence of alloying elements. As a result, PFZ is suspected to be the reason for ductility reduction of alloys. On the other hand, a number of experiments performed on specimens with micron-scale dimensions have shown that the plastic deformation of crystalline materials is size-dependent. These micron-scale dimensions which can influence the mechanical behavior, such as yield stress or hardening, are not taken into account in the conventional plasticity theory, therefore another theory has been developed. That theory is Strain Gradient Plasticity (SGP). The specific SGP theory used here is a so called ‘higherorder theory’ in the sense that higher order stresses as well as additional boundary conditions are included in the theory. SGP theory also includes length scale parameters in order to be dimensionally consistent. On a recent study conducted by Fourmeau et al. (Fourmeau, 2015), transmission electron microscopy (TEM) is used to display the geometrical properties and the chemical composition of PFZ in the AA7075-T651 aluminum alloy. It is observed that the width of PFZ is about 20 to 40 nm. In the present thesis, the properties for PFZ and bulk material provided by that study are used for a micromechanical finite element model of a microstructure including the bulk, PFZ and the grain boundary (GB). A uniaxial loading condition is applied to the representative volume element (RVE) and SGP theory is hired in order to capture the plastic strain fields as well as the stress triaxiality in PFZ and bulk region. Moreover a damage criterion is employed and studied for models with PFZ and without PFZ to understand the role of PFZ in reduction of the ductility of aluminum alloys. It is found that the damage parameter is much higher in the presence of PFZ. Finally, the void growth is studied by adding voids at critical locations to the model.
41
Lam, Kin-san. "Plant establishment in compost/PFA amended soil /". Hong Kong : University of Hong Kong, 1994. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17095268.
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42
Chroustovský, David. "Skladovací hala PFM Flexi - stavebně technologický projekt". Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2018. http://www.nusl.cz/ntk/nusl-371958.
Testo completoAbstract (sommario):
The aim of this diploma thesis is the design of an effective construction-technological project for the construction of reinforced concrete prefabricated storage halls by PFM-Flexi, s.r.o. The solution of the chosen problem is the design of the building site equipment, the verification of the transport routes of the key materials, the assembly schemes, the technological regulation and the control and test plan for the precast reinforced concrete frame, the BOZP plan, the comparison of the two versions of the installation in financial terms, the budget item and the schedule of the main building, timetable, calculation timetable and environmental aspects of the construction.
43
Matejov, Michal. "Pasivní PFC filtry pro spínané napájecí zdroje". Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2008. http://www.nusl.cz/ntk/nusl-217598.
Testo completoAbstract (sommario):
This work deals with theory of switched power sources. There is description of the ways for connection and their practice purposes. In the next parts there are defined requirements on input supply circuit for these sources, especially for the form of output current. There are mentioned the basic connecting methods of PFC circuits and these methods modify the output current to meet the requirements of specification ČSN EN 61000- 3- 2. In the next parts there are shown simulations of PFC circuits made by Pspice application. Further is the basic description of sources construction for the sources which were used for testing and measuring. The final part deals with evaluation of the measuring on the chosen computer’s source. It compares between the manufacturer’s solutions and PFC circuit made by ourselves.
44
Henderson, Wendy M. "User satisfaction in PFI and non-PFI hospitals in the UK : in particular the outpatients' department reception/waiting areas". Thesis, University of Bedfordshire, 2008. http://hdl.handle.net/10547/300624.
Testo completoAbstract (sommario):
Few studies have been undertaken which examine the correlation between design of the receptionl/waiting areas of the outpatients' departments and the implications for Private Finance Initiative (PFI) and non-PFI hospitals, in particular the interior environment with reference to user satisfaction. This study investigates to what degree user satisfaction has been achieved in the design of the receptionlwaiting areas in PFI and non-PFI hospitals. The aim of the investigation is to determine whether user satisfaction can be achieved in PFI or non-PFI hospital environments, particular in the outpatients' department. To ascertain whether hospital environments facilitate user friendly and therapeutic characteristics/attributes conducive to user satisfaction, two strands of investigation were undertaken; a) investigation and analysis of PFI and non-PFI hospital design; b) the study of users (PFI and non-PFI) via questionnaire surveys and analysis of their perceptions. The research methods utilised combinations of qualitative information from interviews, discussions with hospital end users, architects/designers and Consortium executives. The surveys undertaken with patients, hospital staff and NHS Trust Managers provided quantitative data to measure the degree to which user satisfaction had been achieved. The main findings of the design analysis identify the strengths and weaknesses in the design of the 'main' and 'sub' reception/waiting areas respectively. The results of the patient surveys, discussions and interviews revealed more positive perceptions of the hospital facilities for PFI hospitals and a general acceptance of the hospital facilities in the non-PFI hospitals. However, the other comments section of the questionnaires reveals some psychological needs of the user were not being met. The hospital staff surveys, discussions and interviews revealed the spatial planning was not ideal for their functional needs. The survey of NHS Trust Managers, Architects/Designers and Building Contractors revealed the difficulties associated with the collaborative process and the implications for the design development process, when reflecting upon 'cost effectiveness' and 'value for money' issues. The conclusions drawn from the study suggest that there is a case for the standardisation of therapeutic environments in the development of 'new build' hospital projects via the design development and collaborative process. The recommendation (see p. 313) provides a design protoeo/that enhance and aids the design development process via selective expertise, which addresses the functional and psychological needs of the hospital end user.
45
Vaucher, Rodrigo de Almeida. "Influência do peptídeo P34 na expressão gênica em Listeria spp. e estudo da citotoxicidade dos peptídeos P34 e P40". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/23977.
Testo completoAbstract (sommario):
Neste estudo foram realizados inicialmente, experimentos para avaliar a ação sinérgica do peptídeo antimicrobiano P34 com sobrenadantes de culturas de algumas bactérias lácticas selecionadas e isoladas de queijo Minas Frescal. Foi investigada a influência deste peptídeo na expressão de genes em L. monocytogenes e L. seeligeri, sua citotoxicidade em diferentes células eucarióticas e toxicidade “in vivo”. Também foram realizados alguns testes para avaliar a citotoxicidade do peptídeo antimicrobiano P40. A adição do peptídeo P34 no queijo provocou uma diminuição de até 3 ciclos logarítmicos na contagem de células viáveis de L. monocytogenes inoculada artificialmente. Um aumento significativo na expressão dos genes dltA, Imo 1695 e mptA de L. monocytogenes foi observado após 96 h com a presença do peptídeo P34 no queijo. A influência do peptídeo P34 na expressão de genes associados aos componentes do envelope celular de L. monocytogenes e L. seeligeri, promoveu um aumento não significativo nos níveis de transcrição de genes dltA, Imo1695 e mptA observados em L. monocytogenes após inoculação em placas e incubação por 24 h a 37°C ou 240 h a 4°C. Em L. seeligeri uma diminuição significativa na expressão do gene dltA foi observada. Os genes Imo1695 e mptA demonstraram uma diminuição significativa de sua expressão (2000 e 31872 vezes, respectivamente) na presença do peptídeo P34 e incubação por 24 h a 37°C. A inoculação da placa com o peptídeo P34 e incubação por 240 h a 4ºC não promoveu diminuição significativa da expressão do gene mptA. A citotoxicidade dos peptídeos P34 e P40 foi avaliada em células VERO, tratadas com diferentes concentrações (0,02 - 2,5 μg ml-1). Nos ensaios de MTT, NRU e LDH as EC50 para o peptídeo P34 foram 0.60, 1.25, 0.65 μg ml-1 e do peptídeo P40 foram 0,30, 0,51 e 0,57 μg ml-1, respectivamente. A atividade hemolítica em eritrócitos humanos foi de (5,8%) e (19%), respectivamente. Os efeitos sobre a viabilidade, motilidade e exocitose acrossomal de espermatozóides humanos também foram avaliadas para o peptídeo P34. Não houve reações de hipersensibilidade ou aumento significativo de títulos de anticorpos durante os experimentos imunogenicidade ou morte dos animais durante experimentos de toxicidade aguda ou subcrônica. A DL50 foi superior a 332,3 ± 0,76 mg/kg. Não foram observadas alterações significativas nos parâmetros bioquímicos séricos nos animais tratados com o peptídeo P34. Não foram detectados sinais de possível toxicidade nos animais do grupo tratado com 0,825 mg/ kg/dia do peptídeo P34. Neste grupo apenas alterações histológicas no baço com a presença de megacariócitos foram observadas. A partir destes resultados evidencia-se o potencial do peptídeo P34 para ser utilizado como bioconservante em alimentos.In this study initial experiments were performed to evaluate synergistic action of the antimicrobial peptide P34 and culture supernatants of some selected lactic acid bacteria isolated from Minas Frescal cheese. The influence of this peptide in the expression of genes in L. monocytogenes and L. seeligeri, their cytotoxicity in differents eukaryotic cells and “in vivo” toxicity was investigated. Also, some tests were carried out o evaluate the cytotoxicity of the antimicrobial peptide P40. The peptide P34 caused a decrease of up to 3 log cycles in viable counts of L. monocytogenes artificially inoculated in cheese. A significant increase in expression of genes dltA, Imo1695 mptA of L. monocytogenes was observed after 96 h incubation of the peptide P34 in cheese. The influence of peptide P34 on the expression of genes associated to components of cell envelope of L. monocytogenes and L. seeligeri, promoted a non significant increase in the levels of transcription of genes dltA, Imo1695 and mptA were observed after incubation of L. monocytogenes for 24 hs at 37°C and 240 hs at 4°C in plates. In L. seeligeri a significant decrease was observed in gene expression dltA. The gene Imo1695 showed a significant decrease in its expression (2000-fold) after inoculation with the peptide P34. A significant decrease of expression was also observed for the gene mptA (31872 - times) after inoculation with the peptide P34 and incubation for 24 hours at 37°C. The inoculation of the plate with the P34 peptide and incubated for 240 hrs at 4°C, showed a non-significant decrease of gene expression. The cytotoxicity of the peptide P34 and P40 was assessed in VERO cells treated with different concentrations (0.02 - 2.5 μg ml- 1). In MTT, NRU and LDH assays the EC50 to the peptide P34 were 0.60, 1.25, 0.65 μg ml-1 and the peptide P40 were 0.30, 0.51 and 0.57 μg ml-1, respectively. The hemolytical activity on human erythrocytes was of (5.8%) and (19%), respectively. The effects on viability, motility and acrosomal exocytosis of humam sperm were also evaluated for peptideP34. There were no hypersensitivity reactions or significant increase in antibody titer during the immunogenicity experiment or death of animals during the acute or subchronic toxicity tests. The LD50 was more the 332.3 ± 0.76 mg/kg. No significant changes in the serum biochemical parameters were observed in the animals treated with the peptide P34. Signs of possible toxicity were no detected in animals in the group treated with 0.825 mg/kg day of peptide P34. In this group only histological changes in the spleen with the presence of megakaryocytes were observed. From these results show the potential o peptide P34 to be used in future as biopreservative in foods.
46
Wang, Xueqi. "Expression analysis and antibody neutralization of P44 major surface proteins of anaplasma phagocytophilum during mammalian infection". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1149083249.
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47
Li, Na. "Critical role of transcription cofactor PC4 in mammals". Diss., kostenfrei, 2010. http://d-nb.info/1001408519/34.
Testo completo
48
Wang, Meng. "A Tesla-Blumlein PFL-Bipolar pulsed power generator". Thesis, Loughborough University, 2016. https://dspace.lboro.ac.uk/2134/22802.
Testo completoAbstract (sommario):
A Tesla-Blumlein PFL-Bipolar pulsed power generator, has been successfully designed, manufactured and demonstrated. The compact Tesla transformer that it employs has successfully charged capacitive loads to peak voltages up to 0.6 MV with an overall energy efficiency in excess of 90%. The Tesla driven Blumlein PFL generator is capable of producing a voltage impulse approaching 0.6 MV with a rise time close to 2 ns, generating a peak electrical power of up to 10 GW for 5 ns when connected to a 30 Ω resistive load. Potentially for medical application, a bipolar former has been designed and successfully implemented as an extension to the system and to enable the generation of a sinusoid-like voltage impulse with a peak-to-peak value reaching 650 kV and having a frequency bandwidth beyond 1 GHz. This thesis describes the application of various numerical techniques used to design a successful generator, such as filamentary modelling, electrostatic and transient (PSpice) circuit analysis, and Computer Simulation Technology (CST) simulation. All the major parameters of both the Tesla transformer, the Blumlein pulse forming line and the bipolar former were determined, enabling accurate modelling of the overall unit to be performed. The wide bandwidth and ultrafast embedded sensors used to monitor the dynamic characteristics of the overall system are also presented. Experimental results obtained during this major experimental programme are compared with theoretical predictions and the way ahead towards connecting to an antenna for medical application is considered.
49
Short, Nicholas J. "The DNA sequence of the filamentous bacteriophage Pf1". Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305822.
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50
Livingstone, Phil. "Nicotinic modulation of dopaminergic signalling in the PFC". Thesis, University of Bath, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528111.
Testo completo