Tesi sul tema "INSPOC"

Inositol phosphates (IPs) are important signalling molecules with various biological roles in a cell. One such role it is often associated with is DNA repair. The DNA repair process following DNA insult is considered crucial for the genomic integrity and stability. Failure to perform this task will result in mutations and possibly disease. Thus, it is important that we expand our knowledge on how these repair processes occur and identify the key factors involved in its regulation. The aim of this project was to investigate whether DNA repair was mediated by inositol diphosphates (IDPs). Using a family of yeast knockout mutants with modulated levels of IPs, it was found that IDPs are crucial in repair of DNA following insult with bleomycin and 5-fluorouracil. The observed sensitivity of the mutants was thought to be due to lack of functional repair protein, UDG-like or APE-like, in the absence of essential cofactor such as IDPs. Experiments conducted revealed that the hypersensitive kcs1Δ contain both the repair proteins required to process the DNA lesions. However, extreme extraction methods were required to access these proteins, suggesting that the proteins are mislocalised and unavailable to access the damage site and perform DNA repair. GFP-tagging the proteins Ung1, Apn1 and Rad52 in kcs1Δ proved to be of little use as it failed to show exact localisation, movement and functionality status of these proteins following bleomycin insult. The enzymes accountable for the dephosphorylation of the IDPs in vivo are the diphosphoinositol polyphosphate phosphohydrolases (DIPPs). Little is known regarding the Michaelis-Menten kinetics parameters for Ddp1p/DIPPs. In this study, using improved methods for the enzymatic synthesis and electrophoretic purification of 1-InsP7, 5-InsP7 and InsP8, the DIPP family has been kinetically characterised. Each DIPP was found to ii display similar Km values for every substrate tested (range: 35-148 nM). The rank order of Kcat values (1-InsP7 > 5-InsP7 = InsP8) was identical for each enzyme, although DIPP-1 activity was observed to be 10- to 60-fold more than DIPP-2α/β and DIPP-3α/β, irrespective of the substrate. This study reveals that Ddp1, the yeast DIPP, is capable of hydrolysing not only 5-InsP7 but also 1-InsP7 and InsP8 to a single product, InsP6. The HPLC data found InsP7 accumulation to be relatively little during InsP8 breakdown by DIPPs. Such low build-up was found to be due to rapid conversion of InsP7 to InsP6. Through this study it is also clear that InsP8 prefers to dephosphorylate through 1-InsP7. In contrary, metabolically and functionally significant steady-state route of InsP8 synthesis was observed to be via 5-InsP7. Oesophageal cancer is considered as one of the deadliest cancers worldwide because of its aggressive nature and low survival rate. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of oesophageal cancer. The data presented in this study show the effects of a number of in-house synthesized novel aspirin analogues on oesophageal cancer cell lines, squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues, fumaryldiaspirin (PN517) and benzoylsalicylates (PN524, PN528 and PN529), were observed to be more potent against the oesophageal cell lines than aspirin itself. Both, quantitative and qualitative apoptosis experiments conducted revealed that these compounds largely induced apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The SSC cells (oe21) displayed increased sensitivity to the aspirin analogues compared to the ADC cell lines (flo-1 and oe33). The anticancer properties of these novel aspirin compounds appear to not involve the COX-enzymes at the tested concentrations. These initial findings support further studies into the potential of these aspirin analogues as chemotherapeutic agents against oesophageal cancer.

L’étude des inositols hautement phosphorylés est un domaine en pleine expansion. Leurs essors ne datent que d’une dizaine d’années, mais de nombreuses fonctions y sont déjà associées bien qu’ils en restent sans doute encore à découvrir. Les inositols phosphates (incluant les inositols hautement phosphorylés) s’inscrivent dans un cycle dont le représentant le plus connu est inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). De ce fait, chaque inositol phosphate influence directement ou indirectement les autres membres de ce cycle.<p>Au cours de la thèse, nous avons pu éclaircir une controverse de la littérature sur la voie de synthèse des inositols hautement phosphorylés. Grâce à un modèle de cellules MEF (mouse embryonic fibroblast) n’exprimant aucune des trois isoformes de l’inositol 1,4,5-trisphosphate 3-kinase (ITPK) et à l’aide des cellules souches déficientes pour l’inositol polyphosphate multikinase (IPMK), nous avons pu révéler le rôle majeur de cette dernière dans la génération de l’InsP5 et l’InsP6.<p>Dans un second temps, nous avons comparé la neurogenèse de ces cellules souches IPMK+/+ et IPMK-/- mises dans un milieu de différenciation par défaut (DDM). Les cellules dépourvues de l’IPMK entrent en apoptose et se différencient très difficilement en progéniteurs neuronaux et en neurones. Afin de comprendre le mécanisme sous-jacent pouvant expliquer ce phénomène, nous avons réalisé des PCRs quantitatives qui ont montré une sous expression des gènes du neuroectoderme ainsi qu’une augmentation de l’expression de gènes du mésoderme dans les cellules IPMK-/- par rapport aux cellules IPMK+/+. De plus, nous avons découvert que le phénomène d’apoptose observé au cours de la différenciation en DDM était spécifique à ce milieu. En effet, nous n’avons pas pu mettre en évidence un tel phénomène au cours de la différenciation en corps embryoïdes.<p>Durant la thèse, nous avons également développé des anticorps dirigés contre l’isoforme B de l’inositol 1,4,5-trisphosphate 3-kinase et contre la forme native de l’IPMK. Ceci nous a permis de mener à bien nos expériences et d’ouvrir de futures perspectives de recherche.<p>En conclusion, nous avons démontré le rôle majeur de l’IPMK dans la voie de synthèse des inositols hautement phosphorylés. Nous avons également découvert que l’IPMK est très importante pour la survie de ces cellules souches en cours de différenciation et nous avons également introduit une nouvelle fonction pour l’IPMK dans la neurogenèse.<p><br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished

The ability for an organism to sense and respond appropriately to its environment is often critical for survival. One mechanism for this is the inositol phosphate (InsP) signaling pathway. This work focuses on the role of InsP signaling in maintaining energy homeostasis in the plant. InsP signaling is connected to energy sensing in plants via a protein complex containing both the inositol polyphosphate 5-phosphatases (5PTase13) and the Sucrose non-Fermenting Related Kinase 1 (SnRK1). SnRK1 is considered a fuel gauge for the plant cell that senses energy status and reprograms growth appropriately. While the SnRK1.1 gene has been well studied, the role other SnRK1 isoforms play in energy or stress signaling is less well understood. This work examined the role of 3 SnRK1 isoforms in energy signaling, finding that SnRK1.1 and SnRK1.2 are regulated and function differently in Arabidopsis. The second part of this work focuses on the inositol pyrophosphates, which are a novel group of InsP signaling molecules containing diphosphate or triphosphate chains (i.e. PPx) attached to the inositol ring. These PPx-InsPs are emerging as critical players in the integration of cellular metabolism and stress signaling in non-plant eukaryotes. Most eukaryotes synthesize the precursor molecule, myo-inositol (1,2,3,4,5,6)-hexakisphosphate (InsP6), which can serve as a signaling molecule or as storage compound of inositol, phosphorus, and minerals. Even though plants produce huge amounts of InsP6 in seeds, almost no attention has been paid to whether PPx-InsPs exist in plants, and if so, what roles these molecules play. This work details the presence of PPx-InsPs in plants and delineates two Arabidopsis gene products (AtVip1 and AtVip2) capable of PP-InsP5 synthesis. We further examined the subcellular location of enzymes connected to PPx-InsP synthesis as well as the developmental and tissue specific patterns of expression of the genes that encode these enzymes. We localized the enzymes involved in InsP6 and PPx-InsP production to the nucleus and endoplasmic reticulum (ER). The subcellular compartmentalization of PPx-InsP signaling may be unique to plants. An increased understanding in the pathways involved in energy sensing and metabolic response may reveal novel strategies to improve crops for yield and viability in the future.<br>Ph. D.

Today, we spend various types of spaces in a day. It would be private spaces or public spaces. Public spaces have more variety function than private one. One type is for acting with public on purpose which is represented parks, public transportations, and libraries. The other is kind of waiting area, that is taken to go any public space. My project is about the creation of a familiar experience and mood in public spaces in order to enable people to feel more comfortable in unfamiliar public environments. I focus my explorations on waiting areas, like in airports or train stations, where being exposed to unfamiliar space could cause aggravation or even distress while one has to spend time in these unfamiliar spaces.  I try to transfer home feeling, one of the most private spaces, to the public spaces, by using sense of sight, hear, and smell, determinant of atmospheres in certain spaces. Among the sense, I more investigate light and shadows which are related with sense of sight. Unlike common used method in interior design, changing construction, colours, and so on, I try to make combination of real and unreal with light and shadows in one space.

This thesis deals with a more work-efficient and time-efficient method of calibration of standard glass scales, with practical use in the Czech Metrology Institute Regional Inspectorate in Brno. The desired streamlining of calibration were achieved in the use of a 3D coordinate measuring machine Micro-Vu Excel 4520. In the service software InSpec, six measuring programs were designed in the use of a standard glass scale brand SIP. The measurement uncertainties of this calibration were presented and calculated. This thesis draws up a draft proposal of the calibration procedure and drafts a formalized document of the calibration.

Inom geodetisk mätning har den tekniska utvecklingen inom terrester laserskanning (TLS) gått fort framåt sedan millennieskiftet. Tack vare dess framgång har TLS etablerat sig väl på marknaden som skanningsmetod och användningsområdena har därefter utvidgats. Leica Geosystems AB är ett internationellt mätningsteniskt företag, vilka har lanserat sin nya multistation Leica Nova MS60 med fältmjukvaran Leica Captivate. Till mjukvaran hör också applikationen Inspect a Surface, som möjliggör mätningsingenjör att kunna utvärdera erhållna skanningsdata ute i fält. Applikationen är ämnad att användas vid kontroll av ett skannat objekt genom att testa punktmolnet mot en definierad referens. Företaget har intresse av att en studie av denna karaktär utförs på deras produkter då det inte gjorts tidigare. Undersökningens primära syfte är att utröna i vilken grad fältmjukvaran Leica Captivate med applikationen Inspect a Surface i en Leica Nova MS60 står sig i jämförelse med traditionell efterbearbetning i extern mjukvara. Skanningar utfördes både i utom- och inomhusmiljö mot objekt som vanligen går att finna på byggarbetsplatser, såsom fasad, vägg, golv och cylindriska objekt med varierande radie och materialsegment. De horisontella och vertikala ytorna testades mot inmätta referenspunkter respektive interpolerade referenspunkter. Skanningsdata för cylindrar erhölls av MS60 respektive Leica Scan Station C10 för att visuellt undersöka fenomenet ”mixed pixels”. En cylinderinpassning i Leica Cyclone gjordes mot respektive segment för att se dess radie-avvikelse från referens och jämföra resultaten för respektive instrument. Även signifikanstest utfördes. Resultatet av undersökningen visar att utvärdering av ytor ger likvärdiga resultat i samtliga mjukvaror. Felkällan mixed pixels influerade i varierande grad för punktmolnen erhållet från MS60 och C10. Felkällan var som mest förekommande på materialet aluminium och tapetsegmentet som var närmast golvet. Cylinderpassning mot punktmoln från respektive instrument avvek på millimeternivå från varandra och referensen. Enstaka större avvikelser förekom bland annat på aluminiumsegmentet. Den slutsats som drogs var att applikationen är tillfredsställande att användas för efterbearbetning direkt ute i fält. Skanning av cylindrarna ledde till slutsatsen att skanningsdata från MS60 drabbas av felkällan mixed pixel i större grad än C10 bara om en yta är nära bakom cylindern. Samtidigt drabbades punktmolnet från C10 av mixed pixels om det var fritt bakom cylindrarna. Att använda sig av MS60 för skanning av cylindriska objekt visade sig vara tillfredsställande.<br>The technical development of terrestrial laser scanning has quickly proceeded in geodetic measurement since the millennium shift. Its success has made TLS well established on the market as a method of scanning and its field of applications has expanded. Leica Geosystems is an international company in the field of surveying and measurement instruments. They have developed a new multistation, Leica Nova MS60 with the field software Leica Captivate. In addition to the software the application Inspect a Surface allows surveyors to evaluate obtained point clouds in the field. The application serves the purpose of controlling an object by comparing a pointcloud with a defined reference. The company is interested of such a study to be made on their products, as it has not been conducted before. The main purpose of the study is to determine to what extent the field software Leica Captivate with Inspect a Surface in a Leica Nova MS60 manages with traditional post processing in external software. Scanning in indoor and outdoor environment was performed on objects common on construction sites, such asfacade, wall, floor, and cylindrical objects with varying radius and material segments. The horizontal and vertical surfaces were tested against measured reference points and interpolated reference points. Scanning data for cylinders was obtained by MS60 and Leica Scan Station C10 for a visual control of the phenomenon “mixed pixels”. In Leica Cyclone, a cylinder was fitted on each segment in order to determine radius deviation from reference and compare the results from each instrument. A hypothesis test was also conducted. The study shows that surfaces had equivalent results in all softwares. The error source mixed pixels influenced pointclouds from MS60 and C10 in varying degree. The error source was occurred most frequenlty on the aluminum and wallpaper segment which were close to the floor. Cylinder fitting on point cloud from, MS60 and C10 deviates millimeters from each other and the reference, apart from a few bigger deviations, the aluminum-segment for instance. The conclusion is that the application is satisfactory for post processing in the field. Scanning of cylinders leads to the conclusion thad mixed pixels occurs for MS60 more than C10 only if a surface is behind the cylinder. On the contrary, mixed pixels occur on C10 if there is free space behind the cylinder. Using MS60 for scanning of cylindrical object turns out to be satisfactory.

Detailed observations of geosynchronous satellites from earth are very limited. To better inspect these high altitude satellites, the use of small, refuelable satellites is proposed. The small satellites are stationed on a carrier platform in an orbit near the population of geosynchronous satellites. A carrier platform equipped with deployable, refuelable SmallSats is a viable option to inspect geosynchronous satellites. The propellant requirement to transfer to a targeted geosynchronous satellite, perform a proximity inspection mission, and transfer back to the carrier platform in a nearby orbit is determined. Convex optimization and traditional optimization techniques are explored, determining minimum propellant trajectories. Propellant is measured by the total required change in velocity, delta-v. The trajectories were modeled in a relative reference frame using the Clohessy-Wiltshire equations. Mass estimations for the carrier platform and the SmallSat were determined by using the rocket equation. The mass estimates were compared to the mass of a single, non-refuelable satellite performing the same geosynchronous satellite inspection missions. From the minimum delta-v trajectories and the mass analysis, it is determined that using refuelable SmallSats and a carrier platform in a nearby orbit can be more effcient than using a single non-refuelable satellite to perform multiple geosynchronous satellite inspections.

The diploma thesis is structured into three chapters, while the first chapter informs about theoretical concept of B-2-B marketing, defines basic specifics of B-2-B market and concerns about actual trends and frequent mistakes, which are made while preparing B-2-B marketing strategy. Next chapter informs about actual situation on the server market in the Czech Republic and mainly focuses on the external and internal environment of the firm. The last chapter is based on the personal discussion with potential distribution and service partners that provided useful information about the concurrence, actual situation on the market and defined trade requirements towards Inspur.

The intracellular second messenger InsP₃ is a vital molecule in the regulation of Ca²⁺ signalling. Ca²⁺ mediates a wide range of cellular activities from fertilisation and cell differentiation through to apoptoisis. Using X-ray crystal structure data and molecular modelling, a series of novel InsP₃ analogues were designed as selective InsP₃R-antagonists. Two novel synthetic routes have been developed for the synthesis of these analogues. The first route uses a Ferrier-II rearrangement to provide enantiopure inositol intermediates, whereas, the second route employs a diastereomeric resolution to obtain the enantiopure inositols. The successful synthesis of InsP₃ and a series of 5-position modified analogues are reported herein.

Intrazelluläre Calcium Signale bilden einen der wichtigsten Bestandteile vieler Signalwege in der Zellbiologie. Der Fokus dieser Arbeit liegt auf der hierachischen Struktur der Calcium Muster, welche durch die Rückkopplung von Ip3 Rezeptor (Ip3R) mit Calcium verursacht wird. Auf der obersten Stufe stehen zellweite Wellen aus Calcium. Das zweite Level der Hierarchie bilden sogenante Puffs oder Sparks und entspricht der Freisetzung von Calcium von einzelnen Clustern. Das untere Ende wird durch Blibs gebildet: kleine Calcium Signale einzelner Kanäle. Die Entstehung der Calcium Wellen und der Zusammenhang mit den Ip3 Bindungszuständen individueller Ip3 Kanäle stehen dabei im Vordergund. Ein erstes Modell verwendet ein System von Reaktions-Diffusions-Gleichungen zur Beschreibung der Calciumentwicklung in der Umgebung einzelner Cluster. Es wird festgestellt, dass ein Cluster nicht-stereotype Puffs erzeugen kann, wobei Dauer und Amplitude durch die Ip3-Konzentration moduliert werden. Stärkere Ip3-Stimulation erhöht die Wahrscheinlichkeit, lang anhaltende Freisetzungsereignisse zu beobachten, welche als die Quelle der Wellenbildung identifiziert werden. Die simulierten Daten werden mit experimentellen Ergebnissen aus Xenopus-Oozyten verglichen, wo eine ähnliche Durchsetzung der Wellen- und Puff-Muster beobachtet werden kann. Ein zweites grobkörniges und phänomenologisches Modell auf Basis von ODEs ermöglicht das Sampling langer Trajektorien für ein größeres System aus gekoppelten Clustern mit vertretbarem Rechenaufwand. Auf einem Gitter von Clustern wird gezeigt, dass die wellenartigen Freisetzungsereignisse sich synchronisieren. Während die Wellenfrequenz mit Ip3 zunimmt, gibt es eine optimale Synchronisation für die mittlere Ip3-Anregung. Dieses Modell zeigt, dass die Terminierung der Wellen durch Dissosation von Ip3 erreicht werden kann, was dazu führt, dass sich Kanäle nicht mehr öffnen, und somit eine anhaltende Freisetzung von Ca2+ verhindert wird.<br>The dynamics of intracellular calcium represent one of the most important signal pathways in cell biology. Within this work, the focus lies on the hierarchical structure of calcium release events emerging from the feedback of Ip3 receptor Ca2+ ion channel with Ca2+ itself. The head of this hierarchy consists of calcium waves or global oscillations. Release events from individual clusters of channels, constitute the intermediate level. Single channel release events are called blibs. This work investigates the emergence and termination of waves by using a stochastic Ip3R model with non-equilibrium Ip3 binding and discrete individual channel states. First, a system of reaction diffusion equations of calcium and buffers around a single cluster is used as a description of the calcium evolution. It is found, that a cluster can produce non stereotype puffs, where duration and amplitude are modulated by the Ip3 concentration. For increasing Ip3 stimulation, the likelihood to observe long lasting release events increases, and these events are identified as the source of wave formation. The simulated data is compared to experimental results from Xenopus oocytes, where a similar interspersion of puffs between waves can be observed. Specifically, experiments and simulations support the hypothesis of wave-like events already on a single cluster scale. The insights of the first model are then used to develop a second coarse grained and phenomenological model based on ODEs. It allows sampling of long trajectories of a system of coupled clusters with reasonable computational effort. Within a grid of coupled clusters, it is showed that the wave-like release events synchronize. While the wave frequency increases with Ip3, there is an optimal synchronization for intermediate Ip3 excitation. This model indicates that wave termination is achieved by unbinding of Ip3 from the receptor, which renders the channel unable to open, and hence prohibits any further sustained release.

Made available in DSpace on 2015-03-05T14:01:20Z (GMT). No. of bitstreams: 0 Previous issue date: 19<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>Composição de serviços em dispositivos móveis está se tornando indispensável para as atuais e futuras necessidades dos usuários de TI. Estas necessidades são suportadas pela convergência de arquiteturas centralizadas para arquiteturas distribuídas que estimulam a composição de serviços web. Estes serviços web, motivados pela arquitetura Web Services, logo evoluíram para SOA. Esta arquitetura por sua vez, no contexto de orquestração de serviços, tem exigido linguagens de composição para sua efetiva implementação. Linguagens estas, que têm progredido para linguagens interpretadas e declarativas. Neste contexto de evolução, este trabalho apresenta, uma linguagem declarativa de composição de serviços chamada inSOA. Esta linguagem foi desenvolvida para ser executada em dispositivos móveis como parte de um projeto de uma arquitetura ubíqua colaborativa chamada de U-SOA. inSOA é uma solução focada em Web Services com vocação SOA e aderente aos patterns de composição de serviços, além de poder ser embutida em lin<br>Services composition on mobile devices is becoming essential for current and future needs of IT users. These needs are supported by the convergence from centralized to distributed architectures that encourage the web services composition. These web services, motivated by the Web Services architecture, soon evolved into an SOA. This architecture in turn, in the services orchestration, has required composition language for their effective implementation. These languages, has advanced to interpreted and declarative languages. In this evolution context, this work presents, a declarative language of services composition services called inSOA. This language was developed to execute on mobile devices as part of a project of a collaborative ubiquitous architecture called USOA. InSOA is a solution focused on Web Services and SOA adherent to the patterns of services composition, and can be embedded in a language of general purpose and light in the better DSL languages style. As a way to test and evaluate the langu

Made available in DSpace on 2015-03-03T14:03:54Z (GMT). No. of bitstreams: 1 Sarah_DVM_DISSERT_PARCIAL.pdf: 746876 bytes, checksum: f638a2adc04ebb6e7a39258725abbfde (MD5) Previous issue date: 2009-09-28<br>Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior<br>Uma glucana insol?vel foi isolada de fermento biol?gico (Saccharomyces cerevisiae), o qual foi submetido a um tratamento com base e o res?duo acidificado. An?lises qu?micas e resson?ncia magn?tica nuclear (NMR) em uma e duas dimens?es (1D e 2D) mostraram que uma ?-(1 3) glucana linear foi purificada, a qual n?o estava contaminada com outros carboidratos, prote?nas ou compostos fen?licos. Os efeitos desta glucana na cicatriza??o de feridas foi avaliado em ?lceras venosas humanas por an?lise histopatol?gica ap?s 30 dias de tratamento. A ?-(1 3) glucana favoreceu a cicatriza??o das ?lceras, promovendo o aumento da hiperplasia epitelial, das c?lulas inflamat?rias, angiog?nese e prolifera??o fibrobl?stica. Este foi o primeiro estudo que investigou o efeito da ?-(1 3) glucana na cicatriza??o de ?lceras venosas em humanos. Os achados sugerem que a glucana ? um potente modificador da resposta biol?gica na cicatriza??o de feridas

Made available in DSpace on 2014-12-17T14:13:35Z (GMT). No. of bitstreams: 1 BolivarPGLD_DISSERT.pdf: 1624811 bytes, checksum: 4e49d5598ae806bbd9ddd7c33b6e903c (MD5) Previous issue date: 2010-06-19<br>Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico<br>Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market<br>In?meros produtos farmac?uticos v?m sendo desenvolvidos nos ?ltimos anos com a finalidade de incrementar o tratamento de doen?as pelo aumento da efic?cia de f?rmacos. Grande parte destes novos produtos est? baseada nos novos sistemas transportadores de f?rmacos. Entre eles destacamse as microemuls?es, que foram primeiramente estudadas em 1943 por Hoar e Schulman. Microemuls?o pode ser definida como um sistema termodinamicamente est?vel, isotr?pico, transl?cido e transparente de dois l?quidos imisc?veis estabilizados por um filme de tensoativos localizados na interface ?leo/?gua. O objetivo deste trabalho foi incorporar anfotericina B e sinvastatina em um sistema microemulsionado e analisar suas propriedades f?sico-qu?micas e suas a??es terap?uticas ap?s a incorpora??o destes f?rmacos ao sistema. Alguns resultados muito promissores foram alcan?ados como a redu??o da toxicidade e a perman?ncia da efic?cia da anfotericina B incorporada em uma microemuls?o durante o estudo farmacotoxicol?gico in vitro. Quanto ? incorpora??o da sinvastatina na microemuls?o, foi constatada uma melhora significativa no potencial antiinflamat?rio e antiinfeccioso (efeitos pleiotr?picos da sinvastatina) em feridas tratadas com esse sistema. Portanto, podemos concluir que a incorpora??o desses f?rmacos em sistemas microemulsionados faz das microemuls?es uma nova e promissora apresenta??o farmac?utica, habilitando-a a futuros ensaios com a finalidade de torn?-los dispon?veis no mercado farmac?utico

L’inflammation neurogène cutanée (INC) est une inflammation de la peau induite par l’activation des fibres nerveuses intra-épidermiques qui secrètent des neuropeptides tels que la substance P (SP). L’INC est impliquée dans des dermatoses inflammatoires prurigineuses comme le psoriasis, la dermatite atopique (DA) et le syndrome de Netherton (SN). Un nouveau concept émerge, suggérant que les kératinocytes sont également des acteurs majeurs de l’INC. Le récepteur activé par des protéases de type 2 (PAR-2) est fortement incriminé dans l’INC associée à ces dermatoses, ce qui permet de comprendre les voies du prurit non-histaminergique. Les enjeux thérapeutiques sont de taille puisqu’il n’existe actuellement aucun traitement efficace permettant la prise en charge spécifique du prurit histamino-indépendant au cours des dermatoses prurigineuses associées à l’INC.Bien que le rôle de PAR-2 dans la sécrétion de neuropeptides à partir des neurones sensoriels soit clairement établi, son implication dans la modulation de gènes pouvant contribuer à l’entretien ou l’amplification de l’INC reste méconnue. Le rôle inflammatoire de PAR-2 a également été démontré sur des kératinocytes cultivés en monocouche via la sécrétion de cytokines par des mécanismes dépendants du Ca2+. La surexpression de PAR-2 et la perte d’expression de certains canaux calciques impliqués dans sa réponse calcique dans les kératinocytes différenciés suggèrent des mécanismes d’action de PAR-2 différents pour ceux-ci. Dans le but d’étudier le rôle pro-inflammatoire de PAR-2 au cours des dermatoses prurigineuses, nous avons analysé l’effet de son activation sur des monocultures de neurones sensoriels issus de ganglions rachidiens dorsaux (GRD) de rat et de kératinocytes humains différenciés (DhPK), en criblant l’expression de médiateurs de l’inflammation. Pour approfondir, les voies calciques de PAR-2 sous-jacente à la modulation d’expression dans les kératinocytes différenciés, des expériences d’imagerie calcique ont été réalisées et différents antagonistes ont été utilisés pour analyser les acteurs impliqués.Dans le cadre d’un partenariat avec les laboratoires dermatologiques d’Uriage, nous avons testé les effets de l’eau thermale d’Uriage sur la modulation de gènes induite par PAR-2 dans les DhPK. Nous avons également utilisé une lignée de PC12 différenciables en neurones par le NGF afin de les utiliser comme alternatives des neurones sensoriels issus des GRD de rat pour l’étude de l’INC.L’ensemble des résultats obtenus au cours du criblage des gènes modules par PAR-2 confirme le rôle pro-inflammatoire de PAR-2 dans les neurones sensoriels de rat et dans les DhPK. La découverte d’une nouvelle voie calcique de PAR-2 dans les DhPK offre de nouvelles pistes thérapeutiques pour les dermatoses prurigineuses telles que le psoriasis, la DA et le NS. Les résultats obtenus avec l’eau thermale d’Uriage peuvent présenter une perspective thérapeutique pour les patients souffrants de dermatoses prurigineuses réfractaires aux traitements conventionnels. L’utilisation d’une lignée neuronale comme lesPC12 pour l’étude de l’INC serait une alternative utile dans le développement des tests cosmétiques avec les industriels pour notre laboratoire<br>Cutaneous neurogenic inflammation (CNI) is an inflammation of the skin induced by the activation of intraepidermal nerve fibers that release neuropeptides such as substance P (SP). CNI is involved in pruritic inflammatory skin disorders such as psoriasis, atopic dermatitis (AD) and Netherton syndrome (NS). A new concept is growing, suggesting that keratinocytes could also trigger INC. The proteases activated receptor 2 (PAR-2) is strongly incriminated in CNI associated with these dermatoses, which allow to understand the histamine-independent itching pathways. The therapeutic stakes are high since there is currently no effective treatment allowing the specific management of histamine-independent pruritus during skin disorders associated with CNI.Although the role of PAR-2 in the secretion of neuropeptides from sensory neurons is clearly established, its involvement in the modulation of genes involved in the maintenance or amplification of CNI remains unknown. The inflammatory role of PAR-2 on keratinocytes has also been demonstrated through the production of cytokines in a Ca2+-dependent mechanisms. The overexpression of PAR-2 and the loss of ORAI1 expression, a calcium channel following keratinocytes differentiation suggest different signaling pathways downstream to PAR-2 activation between undifferentiated and differentiated keratinocytes.In order to study the pro-inflammatory role of PAR-2 during pruritic dermatoses, we analyzed the effect of its activation on rat primary sensory neurons from dorsal spinal ganglia (DRG) and on differentiated human primary keratinocytes (DhPK) by screening the expression of inflammatory mediators. To deepen the Ca2+ pathways underlying PAR-2-mediated inflammatory mediator modulation in DhPK, we performed Ca2+ imaging experiments and different antagonists were used to analyze the involvement of intracellular actors. In a partnership with the dermatological laboratories of Uriage, we tested the effects of Uriage thermal water on PAR-2-induced gene modulation in DhPK. We also used a PC12 cell line differentiable in neurons by the NGF in order to use them as alternatives of rat primary sensory neurons from DRG for the study of INC. We also used a PC12 cell line differentiable in neurons by the NGF use them as alternatives of rat primary sensory neurons from DRG for the study of INC.The results obtained during the screening of the PAR-2-modulated genes confirmed the proinflammatory role of PAR-2 in rat primary sensory neurons and in DhPK. The discovery of a new PAR-2-mediated Ca2+ pathway in DhPK offers new therapeutic pathways for pruritic dermatoses such as psoriasis, AD and NS. The results obtained with the thermal water of Uriage can present a therapeutic perspective for patients suffering from pruritic dermatoses refractory to conventional treatments. The use of a neuronal cell line as the PC12 for the study of INC would be an useful alternative in the development of cosmetic tests

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T13:37:47Z No. of bitstreams: 1 TES_NATALIA_BORGES_POLESSO_COMPLETO.pdf: 8181672 bytes, checksum: a0c1b2c84d812ddd15d4b4c56c6974b6 (MD5)<br>Made available in DSpace on 2017-06-30T13:37:48Z (GMT). No. of bitstreams: 1 TES_NATALIA_BORGES_POLESSO_COMPLETO.pdf: 8181672 bytes, checksum: a0c1b2c84d812ddd15d4b4c56c6974b6 (MD5) Previous issue date: 2017-01-16<br>Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES<br>This thesis analyzes thirteen novels, written between 1897 and 2013, which expressly mentioned Porto Alegre as a reference space, not episodic or replaceable, to map and list the most prominent elements of the landscape/townscape. The novels, representative of the formation of the imaginary of the city, contribute to the cultural repertoire in the southern capital. The geography of literature deepens the theme, focusing on three major topics: cartography, landscapes/townscapes and horizons. Some constituent aspects of these topics, geographies, referentialities, experiences, urbanities, narratives and virtualities are explored for conducting the research on space in literature. The experience of urbanity determines how the pens?e-paysage emerges as an aesthetic act. The exploration of horizons results in the transformation of the observation that elucidates the city. We understand the subject in his narrative experience as an essential element in the understanding of this gaze at the city.<br>Esta tese analisa treze romances, escritos entre 1897 e 2013, com men??o expressa a Porto Alegre como espa?o referencial, n?o epis?dico nem substitu?vel, para cartografar e elencar os mais proeminentes elementos da paisagem. Os romances, representativos da forma??o do imagin?rio da cidade, contribuem para o repert?rio cultural da capital sulina. A geografia da literatura aprofunda o tema, enfocando tr?s grandes t?picos: cartografias, paisagens e horizontes. Os aspectos constituintes desses t?picos, geografias, referencialidades, experi?ncias, urbanidades, narrativas e virtualidades s?o explorados para a condu??o da pesquisa acerca do espa?o na literatura. A experi?ncia de urbanidade determina como surge o pensamento-paisagem, enquanto ato est?tico. A explora??o dos horizontes resulta na transforma??o do olhar que elucida a cidade. Entendemos o sujeito em sua experi?ncia narrativa como essencial na compreens?o deste olhar para a cidade.

Made available in DSpace on 2014-12-17T14:57:53Z (GMT). No. of bitstreams: 1 JoaoMS.pdf: 1515806 bytes, checksum: fd1b665e0003e03823a56f9ce0f2eaaf (MD5) Previous issue date: 2009-09-11<br>Petr?leo Brasileiro SA - PETROBRAS<br>The modern technology of materials and structural integrity of pipelines requests the use of inspection tools named inspection pigs to detect, localize and measure the length, width and depth dimensions of the thickness losses of walls of buried and underwater pipelines in service. These tools run them internally, performing and recording measurements, with performance that varies according to the pig s technology. It has been developed recently an instrumented pig technology, called feller pig. This work aims to indicate factors that influence the feller pig technology performance in the detection and in the accuracy of measurement of the length, width and depth dimensions of the thickness losses on the internal surface of an oil pipeline wall under normal conditions of oil pipe inspection with pig. In this work, is made a collection of factors and an analyses of the technology based on the available literature, as well as an experiment to observe the technology and the factors operating. In the experiment, a feeler pig is used in a pipeline built in carbon steel and in operation that flows petroleum, in witch are observed areas with internal thickness losses occurred naturally. Some of these areas and their dimensions taken by automated ultra-sound scanner are compared with the ones indicated by the feller pig. Based on the data collection, on the analysis and on the experiment, the influence of factors object of this research is discussed. It is concluded that, among these, there are factors related to pipe fabrication tolerances, to wear of pig components, to internal adhesive wear of pipeline, to other pipeline damages and to technology characteristics. Finally, actions are suggested to know better, improve and define the applicability of this technology<br>A moderna tecnologia de materiais e de integridade estrutural de dutos pressup?e o uso de ferramentas de inspe??o denominadas pigs de inspe??o para detectar, localizar e medir comprimento, largura e profundidade das perdas de espessura de parede de dutos em servi?o enterrados ou submersos. Essas ferramentas os percorrem internamente, realizando e registrando medi??es, com desempenho que varia de acordo com a tecnologia do pig. Recentemente foi desenvolvida uma tecnologia de pig de inspe??o, chamada de pig de perfilagem. O objetivo desta pesquisa ? indicar fatores que influenciam o desempenho da tecnologia de pig de perfilagem na detec??o e na exatid?o de medi??o de comprimento, largura e profundidade de perdas de espessura na superf?cie interna da parede de um oleoduto, em condi??es normais de inspe??o de oleodutos com pig. Neste trabalho, faz-se um levantamento de tais fatores e uma an?lise desta tecnologia, baseados na literatura dispon?vel, bem como um experimento para observar a tecnologia e fatores operando. No experimento, utiliza-se um pig de perfilagem em um duto constru?do em a?o carbono e em opera??o escoando petr?leo, no qual se constata ?reas com perdas de espessura internas ocorridas naturalmente. Algumas destas ?reas e suas dimens?es, medidas por varredura de ultra-som automatizado, s?o comparadas com as indicadas pelo pig de perfilagem. Com base no levantamento, na an?lise e no experimento, discute-se a influ?ncia de fatores objetos desta pesquisa. Conclui-se que, entre estes, ocorrem fatores relacionados ? toler?ncia de fabrica??o dos tubos, ao desgaste de componentes do pig, ao desgaste adesivo interno ao duto, a outros danos no duto e a caracter?sticas da tecnologia. Por fim, s?o sugeridas a??es para conhecer melhor, aprimorar e delimitar a aplicabilidade desta tecnologia

Universiẗat, Diss., 2007 u.d.T.: Heiser, Beate: Die persönliche Besicherung von Gesellschaftsgläubigern durch einen persönlich haftenden Gesellschafter im Insolvenzverfahren unter besonderer Berücksichtigung der Unternehmenssanierung--Frankfurt (Main).

Made available in DSpace on 2014-12-17T15:42:07Z (GMT). No. of bitstreams: 1 GolberyHL_DISSERT.pdf: 2464917 bytes, checksum: 6b60a21d93303b984fd3d1615e88b055 (MD5) Previous issue date: 2013-04-29<br>Among the various layered silicates, vermiculite has been used as one of the adsorbent material by presenting the ion exchange capacity which facilitates the removal of organic compounds which are potential pollutants in relation to the water surface. The importance of the modification of clay minerals by hydrophobization with carnauba wax establishes the increase in oil removal capacity in aqueous medium, it contributes to a better environment for life in ecosystems. The vermiculite when expanded decreases its hydrophobicity requiring the use of a hydrophobizing leaving - the organoclay. In this work were used in the process of modifying the particle sizes of vermiculite -18+16, -16 +20 and -20 +35 #. Samples of vermiculite hydrophobized with carnauba wax and clay mineral without hydrophobizing were characterized with physicochemical analyzes and analytical. Techniques were used: thermal analysis (thermogravimetry and derivative thermogravimetry), infrared spectroscopy, scanning electron microscopy, fluorescence rays - x adsorption tests. The TG / DTG was used to evaluate the thermal behavior of expanded vermiculite and carnauba wax and samples hidrofobizadas with percentages of 5, 10 and 15 % by weight of hydrophobizing. The results of FTIR confirmed increase of the characteristic signs of carnauba wax in samples hidrofobizadas as the greatest amount of hydrophobizing the clay mineral used in hydrophobization. Thermogravimetry and FTIR show based on the results that coating the surface of the vermiculite occur homogeneously. The data obtained by the technique of x-ray fluorescence with loss on ignition confirmed the results of thermogravimetric analysis in relation to the percentage of wax incorporated. The fluorescence indicates through information provided by the analysis shows that the material covered - is homogeneous. The mev inspection was used to texture and morphology of the clay mineral with and without carnauba wax. The scanning electron microscopy confirms the deposition of wax evenly over the surface of the mineral as indicated by the other techniques. To verify the adsorption capacity of the clay without hydrophobizing hydrophobized and used a fixed volume of water to 1 ? liters in each experiment with 3 g to 50 g of oil sample. The results show that better extraction of oil for the material processed corresponds to 260 % relative to the weight of the sample coated and greater than 80 % of the oil drop in the system<br>Dentre os v?rios silicatos em camadas, a vermiculita tem sido uma das mais empregadas como material adsorvente por apresentar a capacidade de troca i?nica o que facilita na remo??o de compostos org?nicos que s?o poluentes em potencial no que se refere a superf?cies das ?guas. A import?ncia da modifica??o do argilomineral atrav?s da hidrofobiza??o com a cera de carna?ba estabelece o aumento na capacidade de remo??o de ?leo no meio aquoso, isso contribui para um ambiente mais prop?cio para a vida nos ecossistemas. A vermiculita quando expandida diminui a sua capacidade hidrof?bica sendo necess?ria a utiliza??o de um hidrofobizante deixando-a organof?lica. Neste trabalho foram utilizadas no processo de modifica??o da vermiculita as faixas granulom?tricas de -8+16, -16+20 e -20+35 #. As amostras de vermiculita hidrofobizada com cera de carna?ba e do argilomineral sem o hidrofobizante foram caracterizadas com an?lises qu?micas e f?sico-qu?micas. Foram utilizadas as t?cnicas: an?lise t?rmica (termogravimetria e termogravimetria derivada), espectroscopia no infravermelho, microscopia eletr?nica de varredura, fluoresc?ncia de raios-x e testes de adsor??o. A TG/DTG foi utilizada para avaliar o comportamento t?rmico da vermiculita expandida da cera de carna?ba e das amostras hidrofobizadas com porcentagens de 5, 10 e 15 % em massa do hidrofobizante. Os resultados de FTIR constataram o aumento dos sinais caracter?sticos da cera de carna?ba nas amostras hidrofobizadas conforme a maior quantidade de hidrofobizante. A termogravimetria e o FTIR mostraram com base nos resultados obtidos que o recobrimento da superf?cie da vermiculita ocorreu de forma homog?nea. Os dados obtidos pela t?cnica de fluoresc?ncia de raios-x com perda ao fogo comprovaram os resultados das an?lises termogravim?tricas em rela??o aos percentuais de cera incorporados. A fluoresc?ncia indicou atrav?s das informa??es fornecidas pelas an?lises que o material recoberto apresentou-se homog?neo. A MEV foi utilizada para inspe??o da textura e morfologia do argilomineral com e sem a cera de carna?ba. A microscopia eletr?nica de varredura reafirmou a deposi??o da cera de forma homog?nea sobre a superf?cie do mineral como indicavam as outras t?cnicas. Para verificar a capacidade de adsor??o da argila sem o hidrofobizante e hidrofobizada foi utilizado um volume de ?gua fixo de 1 ? litro em cada experimento com 3 g de ?leo para 50 g de amostra. Os resultados obtidos mostraram que a melhor extra??o de ?leo pelo material transformado corresponde a 260 % em rela??o ? massa da amostra recoberta e maior que 80% do ?leo suspenso no sistema

TRPV4 is a non-selective cation channel with a wide expression and multiple cellular and systemic functions. Described initially as an osmosensor, it can also be activated by temperature and cell swelling. Due to this variety of activating stimuli it may have a promiscuous gating behavior which is mostly unknown. This Thesis research aims to get in-depth in the understanding of the molecular determinants of TRPV4 regulation. I provide evidences that the inositol trisphosphate receptor and its modulatory function on TRPV4 relies on its binding to the C-terminal tail of TRPV4. I discuss the role of the channels’ N-terminal tail in osmotransduction and show how a mutation that results in a channel with an impaired response to osmotic environments is associated to a pathophysiological condition such as hyponatremia. I also highlight the importance of this N-terminal tail and the binding to the regulatory protein PACSIN3 for the global conformation of the channel.<br>El TRPV4 és un canal catiònic no selectiu d’expressió generalitzada i funcions diverses. Tot i que inicialment es va descriure com un osmosensor sistèmic, avui sabem que també es pot activar per temperatura o per augments del volum cel•lular. Degut a la diversitat d’estímuls, el canal presenta diferents vies d’activació la major part de les quals són desconegudes. Aquesta Tesi pretén estudiar en detall els mecanismes moleculars que regulen l’activitat del canal. Aportem evidències del lloc d’unió a la cua C-terminal del receptor d’inositol trifosfat així com la seva modulació sobre l’activitat del TRPV4. També discutim el rol de la cua N-terminal en la osmotransducció i presentem una mutació, generadora d’un canal amb una resposta anòmala a estímuls hipotònics, que està associada a una condició fisiopatològica com la hiponatremia. També destaquem la importància de la cua N-terminal i de la unió de la proteïna reguladora PACSIN3 en la conformació global del canal.

I detta arbete ville jag undersöka hur två gymnasielärare i svenska använde samtalsmetoden lösningsfokus i sina utvecklingssamtal. Jag observerade fem utvecklingssamtal vardera hos de båda lärarna, varpå jag intervjuade dem. Under observationerna såg jag att fokus överfördes till eleverna och de fick även huvudansvaret för sitt skolarbete. Intervjuerna kompletterade bilden och det blev tydligt vilka motiv lärarna hade för att använda lösningsfokus. Till exempel ansåg de att eleverna själva är experter på sitt eget skolarbete, samt på hur de kan arbeta för att nå sina mål. Efter mina undersökningar kunde jag dra slutsatsen att lärarna använder lösningsfokus i sina utvecklingssamtal, exempelvis genom att inte diskutera varför och hur problem har uppstått, utan istället fokusera på hur de kan lösas. Båda lärarna anser att det är ett bra verktyg som påverkar samtalen på ett positivt sätt, bland annat genom att eleven blir mer aktiv och formulerar sina egna lösningar. Lärarna känner också att det är skönt att ha en metod att utgå ifrån, då samtalsmetodik inte fått något nämnvärt utrymme i deras utbildning.<br>In this essay I wanted to look into how two teachers used solution focus in their development conversations. I observed five development conversations with each teacher, after which I interviewed the teachers. During the observations I saw that focus were transferred on to the students as well as the main responsibility for the students schoolwork. The interviews completed the picture and it became clear what motives the teachers had using solution focus. For example they believed that the students are experts in their own schoolwork and in how they can work to achieve their goals. After my surveys I came to the conclusion that the teachers use solution focus in their development conversations, by not discussing why, or how problems had occurred, but instead to focus on how they can be solved. Both teachers believe that solution focus is a commendable method that influences the conversations in a positive way. The students becomes more active and formulates their owns solutions for example. The teachers also feel that using a certain method provides a sense of security, as they didn’t study conversation methods during their teacher education.

Objetivo: Novas tendências na avaliação de risco trazem evidências de que modelos externos recalibrados ou remodelados funcionam melhor localmente. O objetivo deste estudo foi validar dois modelos externos e formular um modelo local, comparando-os na predição de mortalidade nos pacientes operados de coronária e/ou valva no InCor-HCFMUSP. Método: Entre 2007 e 2009, 3.000 pacientes foram sequencialmente operados de coronária e/ou valva no InCor-HCFMUSP. No banco de dados, foi realizada a validação dos modelos 2000 Bernstein-Parsonnet (2000BP) e EuroSCORE (ES), mediante testes de calibração e discriminação. O InsCor de 2.000 pacientes foi elaborado mediante a utilização de técnicas de bootstrap. Nos próximos 1.000 pacientes foi realizada a validação interna do modelo, e seu desempenho medido frente ao 2000BP e ES. Resultados: Houve uma diferença significativa na prevalência dos fatores de risco entre as populações do estudo, ES e 2000BP. Na validação externa dos modelos, o ES apresentou uma boa calibração (P=0,596); no entanto, o 2000BP revelou-se inadequado (P=0,047). Na discriminação, a área abaixo da curva ROC revelou-se boa para ambos os modelos, ES (0,79) e 2000BP (0,80). Utilizando a técnica de bootstrap, 10 variáveis: idade >70 anos, sexo feminino, cirurgia associada, infarto do miocárdio <90 dias, reoperação, cirurgia da valva aórtica, cirurgia da valva tricúspide, creatinina <2mg/dl, fração de ejeção <30% e estado pré-operátorio crítico (eventos), foram selecionadas para formulacão do InsCor. Na validação interna do InsCor, a calibração foi adequada, com P=0,184. Na discriminação, a área abaixo da curva ROC foi boa (0,79). Neste grupo, a área abaixo da curva ROC foi de 0,81 e 0,82 para o ES e 2000BP, respectivamente, mostrando-se apropriada para ambos os modelos. Conclusões: O InsCor e o ES tiveram melhor desempenho que o 2000BP em todas as fases da validação; pórem o novo modelo, além de se identificar com os fatores de risco locais, é mais simples e objetivo para a predição de mortalidade nos pacientes operados de coronária e/ou valva no InCor-HCFMUSP<br>Background: New trends in risk assessment bring evidence that recalibrated or remodeled external models work best locally. The aim of this study was to validate two external models and formulate a local model, comparing them to predict mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP. Method Between 2007 and 2009, 3.000 patients were sequentially operated to coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP. The database was assessment to validate the models 2000 Bernstein-Parsonnet (2000BP) and EuroSCORE (ES) through calibration and discrimination tests. The InsCor of 2,000 patients (2/3 of database) was elaborated using bootstrap techniques. Over the next 1000 patients (1/3 of database) the internal validation of the InsCor was performed and its performance compared against the 2000BP and ES. Results: Significant difference in the prevalence of risk factors was found among the external and study populations (P<0,001). In the external validation of these models, the ES showed good calibration (P = 0.596); however, 2000BP was inadequate (P = 0.047). In discrimination, the area under the ROC curve was good for both models, ES (0.79) and 2000BP (0.80). With the bootstrap technique, 10 variables: age> 70 years, female, CABG + valve surgery, myocardial infarction <90 days, reoperation, aortic valve surgery, tricuspid valve surgery, creatinine <2mg/dl, ejection fraction <30% and critical preoperative state (events) were chosen to formulate the InsCor. In the validation of InsCor, the calibration was appropriate with P = 0.184. In discrimination, the area under the ROC curve was good (0.79). In this group, the area under the ROC curve was 0.81 and 0.82 for ES and 2000BP, respectively, being suitable for both models. Conclusions: The InsCor and ES outperformed the 2000BP at all stages of validation, but the new model, besides identifying itself with the local risk factors, is more simple and objective for the prediction of mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP.

碩士<br>南臺科技大學<br>機械工程系<br>107<br>The bearing is a precision component. It consists of three parts: bearing ring, ball and retainer, which are often used in transmission systems. The bearing ring is usually machined by CNC, which often causes problems in the use of the product after assembly due to thermal deformation of the process. However, the bearing ring is a curved shape. If it is measured by a general measuring tool, it is not only time-consuming but also impossible to obtain the correct inner groove ring size. At present, the bearing inspection is mainly based on sampling. For bearings with incorrect dimensions or defects, there are often undetected problems. Therefore, this study will propose a high-precision automatic inspection system combining high-speed measurement, image processing and robot for bearing ring size and appearance defects. In the automatic bearing ring inspection system, the outer ring size and appearance defects are mainly detected by CCD, and the moving bearing ring coordinate value is captured by the image positioning system, and the coordinate value is transmitted to the robot in real time by communication. This allows the robot to precisely grasp the bearing ring to be measured at the fixed point. With the non-contact single-point laser displacement meter, the clamped bearing ring can be measured by 360 multi-point internal groove, and the size of the inner groove can be obtained quickly, accurately and stably. The overall measurement time is only 3 seconds, and the deviation is about 0.02mm. After comparison with the CMM, the results show that the trends are completely the same. After the modular measurement system is further combined with the human-machine interface, it is now possible to perform remote monitoring and detection functions, so that the measurement of the bearing can achieve accurate, rapid and intelligent automatic detection.

碩士<br>國立臺北大學<br>法學系<br>92<br>The article has eight chapters : Chapter one of this text is the introduction : explain my research motive , range and order , and the research approach. Chapter two : First introduce the clause of fraud which the domestic criminal law scholar points out , and then compare the clause of fraud and other property crime in order to discover the characteristics of the objective constitution in fraud . Chapter three : Discussion the questions of the criminal person’s swindle behavior . First explain the meaning of 「swindle」 under the criminal law explanation , then analysis the rule of the fraud clause─「by swindle」, after the basic concept showed finish , this article will explain the important questions of 「perform swindle」at last . Chapter four : Explain the objective constitution which about the victim of fraud . The main and important content about the victim in the clause of fraud is the related questions of 「sink into the mistake」 and 「payment belongings」 , then illustrate the victim theory of criminology how to utilizes into fraud in criminal law . Chapter five : The main discussion object in this chapter is the most disputable principle of the objective constitution in fraud─property casualty . First examine whether the property casualty belongs the objective constitution of fraud , then explain the difficult position in the criterion of the property casualty in many judgements .Finally propose this article’s standard of regarding the property casualty . Chapter six : The main explanation of this chapter is the related questions of subjective constitution in fraud . First explain the concept of 「fraud purpose」 and 「the illegal intentions of own」in order to find the special standard connotation in the subjective constitution of fraud . Chapter seven : After examine the related questions of fraud , this chapter will give explanations of the special questions in fraud in detail . Chapter eight : Discusses the summary for this article . After reorganize the clause of fraud this article clarify different opinion with the traditional criminal theory again , then point out the characteristic of fraud which this article discover .

碩士<br>國立臺灣海洋大學<br>河海工程學系<br>107<br>Auto Regression Integrated Moving Average (ARIMA) is often used as an instrument for stock price forecasting. This study aims to take Taiwan Semiconductor Manufacturing Co., Ltd. (TSMC) and Foxconn Technology Group (Foxconn) as examples to apply the ARIMA model for prediction. The models are identified by the goodness of fit and verified by validity indexes to determine the best mode. The results showed that the values of the Root Mean Square Error (RMSE), the Mean Average Error (MAE), and the Mean Absolute Percentage Error (MAPE) are in acceptable ranges. Therefore, the prediction effects of the ARIMA (1,1,1) of TSMC and the ARIMA (2,0,0) of Foxconn modes are acknowledged. When using these modes, in the future, we must notice its applicability and consider the factors of non-stationary state to improve the forecast accuracy of stock prices.

Intricate interactions among constituent components are defining hallmarks of biological systems and sculpt physiology across different scales spanning gene networks to behavioural repertoires. Whereas interactions among channels and receptors define neuronal physiology, interactions among different cells specify the characteristic features of network physiology. From a single-neuron perspective, it is now evident that the somato-dendritic plasma membrane of hippocampus pyramidal neurons is endowed with several voltage-gated ion channels (VGICs) with varying biophysical properties and sub cellular expression profiles. Structural and physiological interactions among these channels define generation and propagation of electrical signals, thereby transforming neuronal dendrites to actively excitable membrane endowed with complex computational capabilities. In parallel to this complex network of plasma membrane channels is an elegantly placed continuous intraneuronal membrane of the endoplasmic reticulum (ER) that runs throughout the neuronal morphology. Akin to the plasma membrane, the ER is also endowed with a variety of channels and receptors, prominent among them being the inositol trisphosphate (InsP3) receptors (InsP3Rs) and ryanodine receptors (RyR), both of which are calcium release channels. Physiological interactions among these receptors transform the ER into a calcium excitable membrane, capable of active propagation of calcium waves and of spatiotemporal integration of neuronal signals. Thus, a neuron is endowed with two continuously parallel excitable membranes that actively participate in the bidirectional flow of intraneuronal information, through interactions among different channels and receptors on either membrane. Although the interactions among sets of channels and receptors present individually on either membrane are very well characterized, our understanding of cross-membrane interactions among channels and receptors across these two membranes has been very limited. Recent literature has emphasized the critical nature of such cross-membrane interactions and the several physiological roles played by such interactions. Such cross-channel interactions include ER depletion-induced signaling involving store-operated calcium channels, generation and propagation of calcium waves through interactions between plasma membrane and ER membrane receptors, and the plasticity of plasma membrane VGICs and receptors induced by ER Ca2+. Such tight interactions between these two membranes have highlighted several roles of the ER in the integration of intraneuronal information, in regulating signalling microdomains and in regulating the downstream signaling pathways that are regulated by these Ca2+ signals. Yet, our understanding about the functional interactions between the ion channels and receptors present on either of these membranes is very limited from the perspective of the combinatorial possibilities that encompass the span of channels and receptors across these two membranes. In this context, the first part of this thesis deals with two specific instances of such cross-membrane functional interactions, presented as two subparts with each probing different direction of impact. Specifically, whereas the first of these subparts deals with the impact of plasma membrane VGICs on the physiology of ER receptors, the second subpart presents an instance of the effect of ER receptor activation on plasma membrane VGIC. In the first subpart of the thesis, we establish a novel role for the A-type potassium current in regulating the release of calcium through inositol triphosphate receptors (InsP3R) that reside on the endoplasmic reticulum (ER) of hippocampus pyramidal neurons. Specifically, the A-type potassium current has been implicated in the regulation of several physiological processes including the regulation of calcium influx through voltage-gated calcium channels (VGCCs). Given the dependence of InsP3R open probability on cytosolic calcium concentration ([Ca2+]c) we asked if this regulation of calcium influx by A-type potassium current could translate into the regulation of release of calcium through InsP3Rs by the A-type potassium current. To answer this, we constructed morphologically realistic, conductance-based neuronal models equipped with kinetic schemes that govern several calcium signalling modules and pathways, and constrained the distributions and properties of constitutive components by experimental measurements from these neurons. Employing these models, we establish a bell-shaped dependence of calcium release through InsP3Rs on the density of A-type potassium current, during the propagation of an intraneuronal calcium wave initiated through established protocols. Exploring the sensitivities of calcium wave initiation and propagation to several underlying parameters, we found that ER calcium release critically depends on dendrite diameter and wave initiation occurred at branch points as a consequence of high surface area to volume ratio of oblique dendrites. Further, analogous to the role of A-type potassium channels in regulating spike latency, we found that an increase in the density of A-type potassium channels led to increases in the latency and the temporal spread of a propagating calcium wave. Next, we incorporated kinetic models for the metabotropic glutamate receptor (miler) signalling components and a calcium-controlled plasticity rule into our model and demonstrate that the presence of mGluRs induced a leftward shift in a BCM-like synaptic plasticity profile. Finally, we show that the A-type potassium current could regulate the relative contribution of ER calcium to synaptic plasticity induced either through 900 pulses of various stimulus frequencies or through theta burst stimulation. These results establish a novel form of interaction between active dendrites and the ER membrane and suggest that A-type K+ channels are ideally placed for inhibiting the suppression of InsP3Rs in thin-caliber dendrites. Furthermore, they uncover a powerful mechanism that could regulate biophysical/biochemical signal integration and steer the spatiotemporal spread of signalling micro domains through changes in dendritic excitability. In the second subpart, we turned our focus to the role of calcium released through InsP3Rs in regulating the properties of VGICs present on the plasma membrane, thereby altering neuronal intrinsic properties that are dependent on these VGICs. Specifically, the synaptic plasticity literature has focused on establishing necessity and sufficiency as two essential and distinct features in causally relating a signalling molecule to plasticity induction, an approach that has been surprisingly lacking in the intrinsic plasticity literature. Here, we complemented the recently established necessity of inositol trisphosphate (InsP3) receptors (InsP3R) in a form of intrinsic plasticity by asking if ER InsP3R activation was sufficient to induce plasticity in intrinsic properties of hippocampus neurons. To do this, we employed whole-cell patch-clamp recordings to infuse D-myo-InsP3, the endogenous ligand for InsP3Rs, into hippocampus pyramidal neurons and assessed the impact of InsP3R activation on neuronal intrinsic properties. We found that such activation reduced input resistance, maximal impedance amplitude and temporal summation, but increased resonance frequency, resonance strength, sag ratio, and impedance phase lead of hippocampus pyramidal neurons. Strikingly, the magnitude of plasticity in all these measurements was dependent upon [InsP3], emphasizing the graded dependence of such plasticity on InsP3R activation. Mechanistically, we found that this InsP3-induced plasticity depended on hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. Moreover, this calcium-dependent form of plasticity was critically reliant on the release of calcium through InsP3Rs, the influx of calcium through N-methyl-D -aspartate receptors and voltage-gated calcium channels, and on the protein kinase A pathway. These results delineate a causal role for InsP3Rs in graded adaptation of neuronal response dynamics through changes in plasma membrane ion channels, thereby revealing novel regulatory roles for the endoplasmic reticulum in neural coding and homeostasis. Whereas the first part of the thesis dealt with bidirectional interactions between ER membrane and plasma membrane channels/receptors within a neuron, second part focuses on cross-cellular interactions, specifically between ER membrane on astrocytes and dendritic plasma membrane of neurons. Specifically, the universality of ER-dependent calcium signalling ensures that its critical influence extends to regulating the physiology of astrocytes, an abundant form of glial cells in the hippocampus. Due to the presence of calcium release channels on ER membrane, astrocytes are calcium excitable, whereby they respond to neuronal activity by increase in their cytosolic calcium levels. Specifically, astrocytes respond to the release of neurotransmitters from neuronal presynaptic terminals through activation of metabotropic receptors expressed on their plasma membrane. Such activation results in the mobilization of cytosolic InsP3 and subsequent release of calcium through InsP3 on the astrocytes ER membrane. These ER-dependent [Ca2+]c elevations in astrocytes then result in the release of gliotransmitters from astrocytes, which bind to corresponding receptors located on neuronal plasma membrane resulting in voltage-deflections and/or activation of signaling pathways in the neuron. Although it is well established that gliotransmission constitutes an important communication channel between astrocytes and neurons, the impact of gliotransmission on neurons have largely been centered at the cell body of the neurons. Consequently, the impact of the activation of astrocytic InsP3R on neuronal dendrites, and the role of dendritic active conductances in regulating this impact have been lacking. This lacuna in mapping the spatial spread of gliotransmission in neurons is especially striking because most afferent synapses impinge on neuronal dendrites, and a significant proportion of information processing in neurons is performed in their dendritic arborization. Additionally, given that active dendritic conductances play a pivotal role in regulating the impact of fast synaptic neurotransmission on neurons, we hypothesized that such active-dendritic regulation should extend to the impact of slower extrasynaptic gliotransmission on neurons. The second part of the thesis is devoted to testing this hypothesis using dendritic and paired astrocyte-neuron electrophysiological recordings, where we also investigate the specific roles of active dendritic conductances in regulating the impact of gliotransmission initiated through activation of astrocytic InsP3Rs. In testing this hypothesis, in the second part of the thesis, we first demonstrate a significantly large increase in the amplitude of astrocytically originating spontaneous slow excitatory potentials (SEP) in distal dendrites compared to their perisomatic counterparts. Employing specific neuronal infusion of pharmacological agents, we show that blocking HCN channels increased the frequency, rise-time and width of dendritically-recorded spontaneous SEPs, whereas blockade of A-type potassium channels enhanced their amplitude. Next, through paired neuron-astrocytes recordings, we show that our conclusions on the differential roles of HCN and A-type potassium channels in modulating spontaneous SEPs also extended to SEPs induced through infusion of InsP3 in a nearby astrocyte. Additionally, employing subtype-specific receptor blockers during paired neuron-astrocyte recordings, we provide evidence that GluN2B-and GluN2D-containing NMDARs predominantly mediate perisomatic and dendritic SEPs, respectively. Finally, using morphologically realistic conductance-based computational models, we quantitatively demonstrate that dendritic conductances play an active role in mediating compartmentalization of the neuronal impact of gliotransmission. These results unveil an important role for active dendrites in regulating the impact of gliotransmission on neurons, and suggest astrocytes as a source of dendritic plateau potentials that have been implicated in localized plasticity and place cell formation. This thesis is organized into six chapters as follows: Chapter 1 lays the motivations for the questions addressed in the thesis apart from providing the highlights of the results presented here. Chapter 2 provides the background literature for the thesis, introducing facts and concepts that forms the foundation on which the rest of the chapters are built upon. In chapter 3, we present quantitative analyses of the physiological interactions between A-type potassium conductances and InsP3Rs in CA1 pyramidal neurons. In chapter 4, using electrophysiological recordings, we investigate the role of calcium released through InsP3Rs in induction of plasticity of intrinsic response dynamics, and demonstrate that this form of plasticity is consequent to changes in neuronal HCN channels. In chapter 5, we systematically map the spatial dynamics of the impact of gliotransmission on neurons across the somato-apical trunk, also unveiling the role of neuronal HCN and A-type potassium channels in compartmentalizing such impact. Finally, chapter 6 concludes the thesis highlighting its major contributions and discussing directions of future research.