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Wolf, Edward. "Impact damage mechanisms in several laminated material systems." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/12823.
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Yau, Desmond. "Analysis of coupling, guiding and radiation mechanisms on several microwave structures /." [St. Lucia, Qld.], 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16164.pdf.
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Seehamart, Kompichit. "Investigation of the diffusion mechanisms of several hydrocarbons in the Metal-Organic-Framework Zn(tbip)." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-68125.
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Most of the computer simulations of molecules in Metal-Organic Frameworks (MOFs) to be found in the literature are done with rigid framework. But, Molecular Dynamics (MD) simulations of the self-diffusivity, Ds, of ethane within the one-dimensional 4.5 Å channels of the MOF type Zn(tbip)(H2 tbip = 5-tert-butyl isophthalic acid) presented in this work have shown not only quantitative, but also qualitative, differences in the Ds values for fixed and flexible lattices. Particularly, the dependence of Ds upon the concentration of molecules, c, is strongly influenced by the lattice flexibility. The reasons for this influence are investigated with the aid of probability density plots, free energy landscapes and barriers, along with a determination of the structural changes accompanying increasing c. It is found that for flexible lattices, the tighter, more constrained parts of the channels become wider at higher c; this allows more molecules to diffuse in the central region of the channels.
The investigations for Zn(tbip) have been extended to three equimolar mixtures of ethane/ethane, CO2/ethane and CO2/methanol. The simulations take into account the lattice flexibility. The diffusional characteristics are discussed in relation to molecule properties and lattice geometry. The results show that Zn(tbip) may be a useful material for separating methane/ethane and CO2/ethane mixtures at low concentrations, and CO2/methanol mixtures at high concentrations.
The temperature and concentration dependence of the self-diffusivity of propane diffusion in Zn(tbip) have been investigated as well by performing normal MD and hyper-MD with bias potential simulations. The obtained temperature dependence of the self-diffusivities is analyzed using an Arrhenius relationship, yielding the activation energy to be 9.53 kJ/mol and the pre-exponential factor to be 4.48×10-9 m2s-1. Using this hyper-MD method, interesting mechanisms of the propane molecules able to pass each other and exchange their sites in the channels can be observed. Because of mutual hindrance of propane molecules, the propane self-diffusivities decrease with increasing concentration.
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Gurevic, Ilya. "Studies on the hydride transfer and other aspects of several thymidylate synthase variants." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6586.
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The nucleotide 2'-deoxythymidine 5'-monophosphate (thymidylate, dTMP) is phosphorylated twice to become a substrate for DNA polymerases, which copy a cell’s genetic information in advance of cell division. The main route to dTMP is mediated by the enzyme thymidylate synthase (TSase) and goes through 2'-deoxyuridine 5'-monophosphate (dUMP); dUMP’s heterocyclic aromatic pyrimidine ring loses a proton from its C5 position and gains a methylene and a hydride from the other reactant, methylene tetrahydrofolate (MTHF). In general, intricate knowledge of an enzyme’s mechanism can yield insight that leads to the development of precision-targeted inhibitors tailored exactly to thymidylate synthase. In fact, even more careful targeting could be achievable: Although E. coli TSase has served as a model system, investigators have increasingly been directing their lines of inquiry toward human TSase.
A general enzymatic catalytic cascade is complex, comprising substrate binding, the chemical steps and product release; typically, the product release step is rate-limiting. TSase, however, is partially rate-limited by the chemistry portion of the process. The enzymatic mechanism has been considered for decades, yet recently has undergone a reassessment. After substrate binding – for which there is strong evidence for preference to dUMP as the first ligand in the wild-type E. coli enzyme – the important events are methylene transfer from MTHF to dUMP, proton abstraction and hydride transfer. The last of these – hydride transfer – is irreversible and rate-limiting (to a large degree without Mg2+, and to a small but noticeable degree with Mg2+). The studies described here are aimed at three therapeutically relevant questions: (a) determining the extent of negative charge accumulation at the O4 position of the hydride transfer acceptor; (b) expanding knowledge of the differential properties of E. coli and human TSase; and (c) gaining insight into the molecular origin of the drug resistance seen in a clinically relevant human TSase mutant.
The properties touched on in this work include steady-state kinetics; inhibition constants toward 5-fluoro dUMP, substrate binding sequence and the temperature dependency of intrinsic hydride transfer kinetic isotope effects (KIEs). Intrinsic KIEs are a specialized measurement that permits the investigator to examine a particular hydrogen transfer step in isolation; it is achieved by labeling the bond to hydrogen broken in the reaction with protium (1H, also written as H), deuterium (2H, also written as D) or tritium (3H, also written as T). The latter is radioactive. The reaction is conducted with a mixture of two hydrogen isotopes at a time, and the extent to which the heavier isotope is disfavored against reaction is assessed; this covers multiple steps. Heavier isotopes directly participating in a chemical step react slower both because of zero-point vibrational energies if a semi-classical view is taken and because of the mass-dependence of tunneling probabilities if a quantum-mechanical view is taken. Each of the two-way isotopic comparisons mentioned above furnishes an observed KIE for that competition between two isotopes. Mathematical combination of two isotopic comparisons cancels out the effect of isotopically insensitive steps and provides rich insight into the hydride transfer alone. The ultimate result is the ratio of rate constants for the isotopologues; this ratio’s magnitude and variation with temperature report on the compactness of the active site and its resistance to thermal fluctuation, respectively.
Our results reveal a possible role for E. coli asparagine 177 (N177) in the hydride transfer transition state (TS) stabilization, as revealed by its disruption in the aspartate mutant, N177D. This disruption was found to be alleviated to a high extent when the substrate was changed to dCMP, consistent with the N177 stabilizing partial negative charge at the TS for hydride transfer. This has drug design implications. Our work on human TSase underscores slightly weaker substrate binding preference, insensitivity to Mg2+ and mild alteration of hydride transfer TS when compared with E. coli TSase. Finally, analysis of the Y33H mutant of human TSase – the affected residue being remote from the active site – indicated the drug resistance was because of a higher inhibition constant for 5F-dUMP and that the hydride transfer step is disrupted, with a wider variation among donor-acceptor distances (between the two carbons involved in the hydride transfer at the TS for that step). Other researchers’ crystallographic evidence reveals greater positional uncertainty for a set of active-site side chains in the E. coli equivalent mutant. In totality, the data available implicate enzyme motions as relevant to drug binding and to catalysis for human TSase.
In summary, the research described herein enriches the understanding of several aspects of the behavior of multiple TSase variants – the overall performance as seen via steady-state kinetics; the pattern of substrate binding as seen with observed KIEs for the proton abstraction step; and the efficiency of active site preparation for hydride transfer as evidenced in the temperature dependency of intrinsic hydride transfer KIEs.
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Casalena, Lee. "Multimodal Nanoscale Characterization of Transformation and Deformation Mechanisms in Several Nickel Titanium Based Shape Memory Alloys." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1499568013015563.
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Seehamart, Kompichit [Verfasser], Jörg [Akademischer Betreuer] Kärger, and Berend [Akademischer Betreuer] Smit. "Investigation of the diffusion mechanisms of several hydrocarbons in the Metal-Organic-Framework Zn(tbip) / Kompichit Seehamart. Gutachter: Jörg Kärger ; Berend Smit. Betreuer: Jörg Kärger." Leipzig : Universitätsbibliothek Leipzig, 2011. http://d-nb.info/1020088958/34.
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Cawthorn, Christopher John. "Several applications of a model for dense granular flows." Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/245044.
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This dissertation describes efforts to evaluate a recently proposed continuum model for the dense flow of dry granular materials (Jop, Forterre & Pouliquen, 2006, Nature, 441, 167-192). The model, based upon a generalisation of Coulomb sliding friction, is known to perform well when modelling certain simple free surface flows. We extend the application of this model to a wide range of flow configurations, beginning with six simple flows studied in detailed experiments (GDR MiDi, 2004, Eur. Phys. J. E, 14, 341-366). Two-dimensional shearing flows and problems of linear stability are also addressed. These examples are used to underpin a thorough discussion of the strengths and weaknesses of the model. In order to calculate the behaviour of granular material in more complicated configurations, it is necessary to undertake a numerical solution. We discuss several computational techniques appropriate to the model, with careful attention paid to the evolution of any shear-free regions that may arise. In addition, we develop a numerical scheme, based upon a marker-and-cell method, that is capable of modelling two-dimensional granular flow with a moving free surface. A detailed discussion of our unsuccessful attempt to construct a scheme based upon Lagrangian finite elements is presented in an appendix. We apply the marker-and-cell code to the key problem of granular slumping (Balmforth & Kerswell, 2005, J. Fluid Mech., 538, 399-428), which has hitherto resisted explanation by modelling approaches based on various reduced (shallow water) models. With our numerical scheme, we are able to lift the assumptions required for other models, and make predictions in good qualitative agreement with the experimental data. An additional chapter describes the largely unrelated problem of contact between two objects separated by a viscous fluid. Although classical lubrication theory suggests that two locally smooth objects converging under gravity will make contact only after infinite time, we discuss several physical effects that may promote contact in finite time. Detailed calculations are presented to illustrate how the presence of a sharp asperity can modify the approach to contact.
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Jones, Christopher David Stanford. "On the cross-sectional form of the patella in several primates." Title page, table of contents and abstract only, 2003. http://web4.library.adelaide.edu.au/theses/09PH/09phj764.pdf.
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Kong, Dali. "Analytical and numerical studies of several fluid mechanical problems." Thesis, University of Exeter, 2012. http://hdl.handle.net/10036/3651.
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In this thesis, three parts, each with several chapters, are respectively devoted to hydrostatic, viscous and inertial fluids theories and applications. In the hydrostatics part, the classical Maclaurin spheroids theory is generalized, for the first time, to a more realistic multi-layer model, which enables the studies of some gravity problems and direct numerical simulations of flows in fast rotating spheroidal cavities. As an application of the figure theory, the zonal flow in the deep atmosphere of Jupiter is investigated for a better understanding of the Jovian gravity field. High viscosity flows, for example Stokes flows, occur in a lot of processes involving low-speed motions in fluids. Microorganism swimming is such typical a case. A fully three dimensional analytic solution of incompressible Stokes equation is derived in the exterior domain of an arbitrarily translating and rotating prolate spheroid, which models a large family of microorganisms such as cocci bacteria. The solution is then applied to the magnetotactic bacteria swimming problem and good consistency has been found between theoretical predictions and laboratory observations of the moving patterns of such bacteria under magnetic fields. In the analysis of dynamics of planetary fluid systems, which are featured by fast rotation and very small viscosity effects, three dimensional fully nonlinear numerical simulations of Navier-Stokes equations play important roles. A precession driven flow in a rotating channel is studied by the combination of asymptotic analyses and fully numerical simulations. Various results of laminar and turbulent flows are thereby presented. Computational fluid dynamics requires massive computing capability. To make full use of the power of modern high performance computing facilities, a C++ finite-element analysis code is under development based on PETSc platform. The code and data structures will be elaborated, along with the presentations of some preliminary results.
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Nunes, da Silva Ana Sofia. "Characterization of the molecular mechanisms involved in severe malaria pathogenesis." Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC065.
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L'importante virulence de P. Falciparum a été reliée à la capacité du parasite à adhérer aux cellules endothéliales de la microvasculature ou aux syncytiotrophoblastes placentaires. La séquestration de globules rouges infectés dans différents organes conduit à l'apparition des symptômes cliniques de la maladie. Les protéines variables PfEMP1, exprimées à la surface des hématies parasitées, sont les ligands parasitaires majeurs responsables de la cytoadhérence. PfEMP1-VAR2CSA est le candidat vaccinal le plus prometteur pour lutter contre le paludisme gestationnel. Afin de mieux caractériser les interactions entre la protéine VAR2CSA et son ligand naturel, la CSA, nous avons généré des VEIH contre VAR2CSA. Nous avons obtenu 19 VHHs, en grand partie dirigés contre le domaine DBLIX. Quatre VHHs contre DBL1X étaient capable d'inhiber les interactions entre les hématies parasitées et la CSA, montrant que le domaine DBL1X fait partie ou est localisé très proche du site de liaison au récepteur. Le paludisme sévère a été associé la séquestration des hématies parasitées, exprimant les cassettes de domaines DC8 ou DC13, au récepteur endothélial de la protéine C (EPCR) exprimé à l'endothélium vasculaire. Dans cette étude nous avons montré que la cassette DC8 de IT4VAR19 adhère avec une plus grande affinité à l'EPCR et HBEC5i que le domaine CIDRŒ I. 1 seul. Nous avons observé que, même si IT4VAR19 est le variant préférentiellement exprimé par la souche IT4 après sélection à l'EPCR, l'immunité humorale contre IT4VAR19-DC8 cassette et IT4VAR19-CIDR n'est pas stimulé pendant un épisode de paludisme pédiatrique sévère au Bénin. En conclusion, ce projet de thèse permet de mieux comprendre les interactions moléculaires impliquées dans l'adhérence des globules rouges parasités aux cellules endothéliales de l'hôte et contribuera à l'élaboration d'approches vaccinales ou thérapeutiques visant à protéger les patients des symptômes cliniques du paludisme sévèreSequestration of infected erythrocytes (IEs) is the prime mediator of disease and is mediated by members of the highly diverse PfEMP1. The aim of this thesis was to characterize the molecular mechanisms associated to pregnancy associated malaria (PAM) and severe malaria, in order to design new intervention strategies to protect patients against severe malaria clinical symptoms. PfEMP 1 -VAR2CSA stands today as the leading vaccine candidate aiming to protect future pregnant women against the severe clinical outcomes of PAM. In order to better characterize the interactions between PfEMPI-VAR2CSA and its receptor CSA, we generated VAR2CSA specific nanobodies. Following immunization of a Ilama with the full-length VAR2CSA recombinant protein, we obtained 19 nanobodies, mainly targeting the DBL1X. Four nanobodies targeting DBL1X reproducibly inhibited CSA adhesion of erythrocytes infected with the homologous NF54-CSA parasite strain, providing evidences that DBL1X domain is part or close to the CSA binding site. Severe malaria was recently associated with binding of IEs, expressing domain cassettes DC8 and DC13, to Endothelial Protein C Receptor (EPCR) pr'sent in the host endothelium. In this study we demonstrated that the IT4VAR19-DC8 binds to EPCR with a greater affinity than the CIDRa1. L domain alone and also the binding to EPCR-expressing endothélial cell line (HBEC5i) is more pronounced. We observed that although IT4VAR19 is the preferentially selected EPCR-binding variant from IT4 strain, the humoral immunity against the EPCR binding IT4VAR19-DC8 cassette or the CIDRa1. 1 domain is not boosted during a severe pediatric malaria episode in Benin. In conclusion, this thesis provide new insights on the molecular mechanisms underlying the binding of P. Falciparum infected erythrocytes to the host endothelium that will help in the development of anti-adhesive strategies to protect patients against severe malaria clinical outcomes
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Nieto-Silleras, Olmo. "Device-independent randomness generation from several Bell estimators." Doctoral thesis, Universite Libre de Bruxelles, 2018. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/271365.
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The device-independent (DI) framework is a novel approach to quantum information science which exploits the nonlocality of quantum physics to certify the correct functioning of a quantum information processing task without relying on any assumption on the inner workings of the devices performing the task. This thesis focuses on the device-independent certification and generation of true randomness for cryptographic applications. The existence of such true randomness relies on a fundamental relation between the random character of quantum theory and its nonlocality, which arises in the context of Bell tests. Device-independent randomness generation (DIRG) and quantum key distribution (DIQKD) protocols usually evaluate the produced randomness (as measured by the conditional min-entropy) as a function of the violation of a given Bell inequality. However, the probabilities characterising the measurement outcomes of a Bell test are richer than the degree of violation of a single Bell inequality. In this work we show that a more accurate assessment of the randomness present in nonlocal correlations can be obtained if the value of several Bell expressions is simultaneously taken into account, or if the full set of probabilities characterising the behaviour of the device is considered. As a side result, we show that to every behaviour there corresponds an optimal Bell expression allowing to certify the maximal amount of DI randomness present in the correlations. Based on these results, we introduce a family of protocols for DIRG secure against classical side information that relies on the estimation of an arbitrary number of Bell expressions, or even directly on the experimental frequencies of the measurement outcomes. The family of protocols we propose also allows for the evaluation of randomness from a subset of measurement settings, which can be advantageous when considering correlations for which some measurement settings result in more randomness than others. We provide numerical examples illustrating the advantage of this method for finite data, and show that asymptotically it results in an optimal generation of randomness from experimental data without having to assume beforehand that the devices violate a specific Bell inequality.L'approche indépendante des appareils ("device-independent" en anglais) est une nouvelle approche en informatique quantique. Cette nouvelle approche exploite la non-localité de la physique quantique afin de certifier le bon fonctionnement d'une tâche sans faire appel à des suppositions sur les appareils menant à bien cette tâche. Cette thèse traite de la certification et la génération d'aléa indépendante des appareils pour des applications cryptographiques. L'existence de cet aléa repose sur une relation fondamentale entre le caractère aléatoire de la théorie quantique et sa non-localité, mise en lumière dans le cadre des tests de Bell. Les protocoles de génération d'aléa et de distribution quantique de clés indépendants des appareils mesurent en général l'aléa produit en fonction de la violation d'une inégalité de Bell donnée. Cependant les probabilités qui caracterisent les résultats de mesures dans un test de Bell sont plus riches que le degré de violation d'une seule inégalité de Bell. Dans ce travail nous montrons qu'une évaluation plus exacte de l'aléa présent dans les corrélations nonlocales peut être faite si l'on tient compte de plusieurs expressions de Bell à la fois ou de l'ensemble des probabilités (ou comportement) caractérisant l'appareil testé. De plus nous montrons qu'à chaque comportement correspond une expression de Bell optimale permettant de certifier la quantité maximale d'aléa présente dans ces corrélations. À partir de ces resultats, nous introduisons une famille de protocoles de génération d'aléa indépendants des appareils, sécurisés contre des adversaires classiques, et reposant sur l'évaluation de l'aléa à partir d'un nombre arbitraire d'expressions de Bell, ou même à partir des fréquences expérimentales des résultats de mesure. Les protocoles proposés permettent aussi d'évaluer l'aléa à partir d'un sous-ensemble de choix de mesure, ce qui peut être avantageux lorsque l'on considère des corrélations pour lesquelles certains choix de mesure produisent plus d'aléa que d'autres. Nous fournissons des exemples numériques illustrant l'avantage de cette méthode pour des données finies et montrons qu'asymptotiquement cette méthode résulte en un taux de génération d'aléa optimal à partir des données expérimentales, sans devoir supposer à priori que l'expérience viole une inégalité de Bell spécifique.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Oliveira, Jena Hanay Araujo de. "Aspectos psicol?gicos de obesos grau III antes e depois de cirurgia bari?trica." Pontif?cia Universidade Cat?lica de Campinas, 2006. http://tede.bibliotecadigital.puc-campinas.edu.br:8080/jspui/handle/tede/376.
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Previous issue date: 2006-12-18Evaluates depression, anxiety, psychopathologic symptoms, alexithymia and defensive style of grade III obese patients, before and after bariatric surgery, as well as estimates the level of association among such variables. Methodological study design was correlational crosssectional type. 65 patients took part in the study (Group 1: surgical candidates vs. Group 2: postoperative patients), mainly females (92,3%), who answered the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Symptoms Assessment Scale (EAS- 40), and the version in Portuguese of The Toronto Alexithymia Scale (TAS-26) and of the Defensive Style Questionnaire (DSQ-40). Gr 1 showed mild anxiety and depression levels and Gr 2 minimum level (respectively, p< 0,001 e p< 0,01). The total average score for EAS- 40 and F2 and F3 (obesity-compulsion and somatization) were higher in Gr 1 when compared to Gr 2 (repetitively, p< 0,005, p< 0,005 e p< 0,001). On TAS, the total average score for F1 (ability to identify and describe feelings and distinguish them from bodily sensations) were higher in Gr 1 than in Gr 2 (respectively, p< 0,01 e p< 0,005). According to DSQ-40, there was a tendency for an immature defensive style in Gr 1 in comparison to Gr 2 (p< 0,02). In relation to the association between the variables and BMI, the correlations were negative for Gr 1 and F2 of TAS (daydreaming, p < 0,05) and for the mature factor of DSQ- 40 and Gr 2 (p < 0,05), which shows a trend towards a more mature and adaptive style in Gr 2. Correlations were positive and significant in relation to immature defenses - acting out (Gr 1: p<0,005 and Gr 2: p<0,05) and in the autistic fantasy in Gr 1 (p<0,05). The results show the psychological status of the participants, who are apt for bariatric surgery and point to a decrease in psychopathological symptoms proportional to weight loss after surgery.
Avalia depress?o, ansiedade, sintomas psicopatol?gicos, alexitimia e o estilo defensivo de pacientes obesos grau III, antes e depois de cirurgia bari?trica, e estima o grau de associa??o entre essas vari?veis. O delineamento metodol?gico foi correlacional de tipo cross-sectional. Participaram do estudo 65 pacientes (Gr 1: pr?-cir?rgico vs. Gr 2: p?scir?rgico), predominantemente do sexo feminino (92,3%), que responderam o Invent?rio de Depress?o de Beck (BDI), o Invent?rio de Ansiedade de Beck (BAI), a Escala de Avalia??o de Sintomas (EAS-40), a Vers?o em Portugu?s da Escala de Alexitimia de Toronto (TAS-26) e a Vers?o em Portugu?s da Defensive Style Questionnaire (DSQ-40). O Gr 1 apresentou n?vel de depress?o e ansiedade leve e o Gr 2 n?vel m?nimo (respectivamente, p< 0,001 e p< 0,01). O escore m?dio total da EAS-40 e de F2 e F3 (obsessividade-compulsividade e somatiza??o) foram mais elevados no Gr 1 quando comparados aos do Gr 2 (respectivamente, p< 0,005, p< 0,005 e p< 0,001). Na TAS, o escore m?dio total e de F1 (habilidade de identificar e descrever sentimentos e distingui-los de sensa??es corporais) foram maiores no Gr 1 do que no Gr 2 (respectivamente, p< 0,01 e p< 0,005). De acordo com o DSQ-40, houve tend?ncia a um estilo defensivo imaturo no Gr 1 quando comparado ao Gr 2 (p< 0,02). Em rela??o ? associa??o das vari?veis com o IMC, as correla??es foram negativas no Gr 1 e o F2 da TAS (sonhar acordado, p < 0,05) e no fator maduro do DSQ-40 e o Gr 2 (p < 0,05), apontando uma propens?o de estilo mais maduro e adaptativo no Gr 2. As correla??es foram positivas e significantes nas defesas imaturas acting out (Gr 1: p<0,005 e Gr 2: p<0,05) e na fantasia aut?stica no Gr 1 (p<0,05). Os resultados mostram o modo de funcionamento psicol?gico dos participantes aptos ? cirurgia bari?trica e assinalam uma diminui??o da sintomatologia psicopatol?gica na propor??o da perda de peso ap?s a cirurgia.
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Chell, Benjamin James. "Psychological mechanisms underpinning severe performance loss in sport : applying theory to practice." Thesis, Sheffield Hallam University, 2005. http://shura.shu.ac.uk/20641/.
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This thesis provided a detailed examination of severe performance loss in competitive sport. Baumeister's (1984) model of choking under pressure and Masters, Polman and Hammond's (1993) model of skill failure under pressure have largely predicted the direction of the current research associated with this phenomenon. Both models control for dispositional and situational factors. The research underpinning these theories has produced equivocal findings. Furthermore, mechanisms associated with these models have been derived from limited research, lacking empirical or qualitative grounding in sport. The primary aims of this thesis were to identify psychological mechanisms that underpin severe performance loss, examine how the dominant mechanisms within the problem interact and establish coping strategies to counteract this phenomenon. Three research designs were used across this thesis. The first study adopted an inductive qualitative design. Studies two, three and four adopted a group-based design. The final study adopted a single-subject reversal design. The final two studies also used qualitative interview techniques. Study one investigated from the athlete's perspective, psychological mechanisms that underpin severe performance loss in sport. Inductive techniques produced five main themes that described athletes' experiences: stress, anxiety, self-consciousness, conscious processing and automaticity disruption. Athletes followed a similar sequence of events outlined by Masters' (1992) conscious processing hypothesis and reported dispositional characteristics consistent with Masters et al.'s (1993) model of skill failure under pressure. The contentions of Baumeister (1984) were not supported. Masters et al. (1993) constructed the Reinvestment Scale which they claimed to be a predictor of performance loss under stress. Study two investigated the predictive power of the Reinvestment Scale in skilled soccer players executing a gross dynamic motor task under stress. Results indicated that high reinvesters were more susceptible to performance loss under stress than low reinvesters, which provided support for the predictive power of the Reinvestment Scale. Study three investigated the effect of holistic and process learning methods and reinvestment on the performance of an adapted basketball free-throw task under stress. Results indicated that minimising the acquisition of explicit task knowledge in high reinvesters using holistic style learning performance loss, precipitated by conscious processing could be prevented when under stress. These findings have practical implications for rule-based orthodox coaching strategies used in sport. Study four investigated whether or not the use of different attentional foci could prevent performance loss in skilled golfers, high in reinvestment when they performed a putting task under stress. Results indicated that loading heavily on working memory (e.g. random letter generation focus) desensitised high reinvesters to stress. Thus, conscious processing of explicit task knowledge was prevented and automaticity promoted, which enabled consistent performance under stress. The final study investigated the influence of a two-phase putting intervention strategy on skilled golfers high in reinvestment. The intervention strategy successfully counteracted conscious processing by loading on working memory to prevent access to explicit knowledge during putting execution, whilst still enabling critical environmental information to be processed prior to putting execution via the use of external imagery. Interview data indicated that all participants would feel confident in using the putting intervention during competition. It is the author's belief that, although unanswered questions remain, this research programme has enriched the conceptual and practical understanding of severe performance loss in competitive sport for researchers, practitioners and coaches. Future research should investigate the relationship between personality and environmental factors on learning styles and skilled performance to establish a richer understanding of this phenomenon. Research also needs to examine the efficacy of psychological intervention strategies used to counteract severe performance loss in a variety of sports and ecologically valid competitive environments.
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Iseri, Erkut Inan. "Exciton Simulations Of The Optical Properties Of Several Photosynthetic Light-harvesting Complexes." Phd thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/3/12605040/index.pdf.
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The work presented in this thesis was aimed to investigate the structure-function relationship of several photosynthetic Light-Harvesting Complexes (LHCs) including Chlorophyll Protein 29 (CP29) and Light-Harvesting Complex II (LHCII) of green plants, and Fenna-Matthews-Olson (FMO) complex of green sulfur bacterium Chlorobium tepidum. Based on the exciton calculations, a model was proposed to the electronic excited states (EES) of both CP29 and LHCII complexes by incorporating a considerable part of the current information offered by structure determination, mutagenesis analysis and spectroscopy in the modeling. The essential parameters for characterizing the excited states, Qy dipole orientations and site energies were assigned by suggesting a model that can explain both the key features of the linear (polarized) absorption spectra and the time scales of the energy transfer processes in CP29 and LHCII. The idea of offering structural information through setting connection between the spectroscopy and the spectral simulations were supported by the presented results on CP29 and LHCII. New spectroscopic measurements (absorption, linear dichroism (LD) and circular dichroism), carried out at 4 K on the FMO complex were presented, and also the LD spectrum was corrected for the degree of orientation of the sample, in order to provide comparison of not only the shape but also the size of the simulated and experimental spectra. The EES structure of the FMO complex was studied by simulating the measured optical spectra with more realistic model than the previously applied models. Simulations have been carried out with a computer program based on exciton model, which includes inhomogeneous, homogeneous and lifetime broadenings explicitly.
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Mills, Nathan (Nathan Matthew). "Design and testing of a pan-tilt mechanism for severe environments." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104300.
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Thesis: Nav. E., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2016.Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references (page 210).
U.S. Navy ships have non-rotating radar and electronic warfare devices installed, which are often supported and trained by two-axis gimbals. In current shipboard solutions the payloads are often placed on a platform above the gimbal drive train, which results in high moment loads on drive components during a wave impact. As the payloads grow in size, the moment grows as well, and the current gimbal design is insufficient to support some payload geometries. This thesis presents a novel design for a low-mass two-axis machine that supports large payloads without large impact moments by locating the center of action along the axis of rotation. A functional prototype intended for shipboard installation was manufactured, assembled, and characterized in laboratory tests. The prototype was also subjected to environmental testing to military standards for temperature, vibration, and shock. Future improvements in machine function, promising areas for optimization, and an initial direction for taking the machine from prototype to product are presented.
by Nathan Mills.
Nav. E.
S.M.
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Hall, Sara L. M. S. "Molecular Mechanisms of Synergy Between IL-13 and IL-17A in Severe Asthma." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505125099399164.
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Leung, Hiu-lan Nancy, and 梁曉灡. "Mechanism of antibody-dependent enhancement in severe acute respiratory syndrome coronavirus infection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47327066.
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Severe lymphopenia is a clinical feature of Severe Acute Respiratory Syndrome
(SARS) patients. However, lymphocytes do not express receptor for SARS-CoV,
neither the widely accepted viral receptor angiotensin converting enzyme 2 (ACE2)
nor the putative receptors Dendritic Cell- and Liver/lymph-Specific Intercellular
adhesion molecule-3-Grabbing Non-integrin (DC-SIGN and L-SIGN). Our group
previously showed in vitro that, SARS-CoV Spike pseudotyped particles (SARSCoVpp)
could infect human B cells only when inoculated in presence of anti-SARSCoV
Spike immune serum. Such observations raised concerns about the possible
occurrence of antibody-dependent enhancement (ADE) of infection, a phenomenon
during which a virus bounded by antibodies could gain entry into cells through
mechanisms involving complement receptors or Fc receptors. Recently, we have
demonstrated the participation of the human Fc gamma receptor II (hFcγRII)
molecules in granting SARS-CoV an opportunity to infect human immune cells.
The aim of this study was to decipher the molecular mechanism leading to antibodymediated,
FcγRII-dependent infection of immune cells by SARS-CoV. By using
transduction experiment, I highlighted that different members of the hFcγRII family
(namely hFcγRIIA, hFcγRIIB1 and hFcγRIIB2) could confer susceptibility to ADE of
SARS-CoVpp infection. I further demonstrated that purified anti-viral
immunoglobulin G, but not other soluble factor(s) from heat-inactivated immune
serum, was the determinant for occurrence of ADE infection. Additionally, with the
development of a cell-cell fusion assay, I illustrated that in contrast to the ACE2-
dependent pathway, ADE infection did not occur at the plasma membrane, but rather
require internalization of virus/antibodies immune complexes by the target cells. In
line with this hypothesis, my results using a panel of FcγRII-expressing mutants
demonstrated that binding of immune complexes to cell surface FcγRII was a
prerequisite but was not sufficient to trigger ADE infection. In these experiments,
only FcγRII signaling-competent constructions conferred susceptibility to ADE of
SARS-CoVpp infection.
Altogether my results point toward a role of the anti-SARS-CoV Spike IgG in vitro in
granting SARS-CoV an opportunity to infect cells bearing signaling-competent
FcγRII receptors. If further confirmed, such observations could have implications for
understanding SARS-CoV tropism and SARS pathogenesis, as well as warrant for
careful design of SARS vaccines and immunotherapy based on anti-viral antibodies.published_or_final_version
Microbiology
Master
Master of Philosophy
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Li, Siran. "Analysis of several non-linear PDEs in fluid mechanics and differential geometry." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:20866cbb-e5ab-4a6b-b9dc-88a247d15572.
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In the thesis we investigate two problems on Partial Differential Equations (PDEs) in differential geometry and fluid mechanics. First, we prove the weak L p continuity of the Gauss-Codazzi-Ricci (GCR) equations, which serve as a compatibility condition for the isometric immersions of Riemannian and semi-Riemannian manifolds. Our arguments, based on the generalised compensated compactness theorems established via functional and micro-local analytic methods, are intrinsic and global. Second, we prove the vanishing viscosity limit of an incompressible fluid in three-dimensional smooth, curved domains, with the kinematic and Navier boundary conditions. It is shown that the strong solution of the Navier-Stokes equation in H r+1 (r > 5/2) converges to the strong solution of the Euler equation with the kinematic boundary condition in H r, as the viscosity tends to zero. For the proof, we derive energy estimates using the special geometric structure of the Navier boundary conditions; in particular, the second fundamental form of the fluid boundary and the vorticity thereon play a crucial role. In these projects we emphasise the linkages between the techniques in differential geometry and mathematical hydrodynamics.
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Torrance, Hew D. T. "Immune dysfunction following severe polytrauma & major surgery : exploring mechanisms & identifying potential therapies." Thesis, Queen Mary, University of London, 2017. http://qmro.qmul.ac.uk/xmlui/handle/123456789/24865.
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Introduction Following polytrauma and major surgery patients experience a period of immunosuppression, which can predispose them to the development of nosocomial infections. This thesis examines how polytrauma and surgery influences T-helper (Th) cell differentiation and antigen presentation, whilst exploring how the detrimental immunomodulatory effects of these insults may be reversed. Methods Serial blood samples were drawn from two cohorts of patients at The Royal London Hospital; following severe polytrauma (n=112) or major abdominal surgery (n=119). mRNA levels of candidate cytokines and transcription factors were assayed, along with protein levels of key cytokines IL-10 and IL-6. Associations between these data, acquisition of nosocomial infection and outcome were described. As a validated surrogate of immune competence CD14+HLA-DR levels were quantified. In vitro models explored the reversibility of tissue damage induced immunosuppression and determined the role of individual circulating mediators in altering host immune function. Results A consistent up-regulation in gene expression of prototypical anti-inflammatory pathways in conjunction with features of depressed pro-inflammatory Th cell pathways was detected across both cohorts. This was accompanied by early down-regulation of CD14+HLA-DR. Gene expression changes were quantitatively associated with the subsequent acquisition of nosocomial infections. Allogeneic blood transfusion exacerbated these findingsand was independently associated with an increased risk of nosocomial infection. Culture experiments determined that postoperative decreases in antigen presentation were IL-10 dependent and reversible in the presence of Interferon-Gamma and Granulocyte Monocyte- Colony Stimulating Factor. Conclusions This thesis describes a significant host immune response immediately following significant tissue damage which is dominated by features of immune suppression. Blood transfusion appears to have a distinct, additive effect. These data identify a potential role for targeted treatment with currently licenced immune stimulants (IFN-γ and GM-CSF). In addition exploitation of the IL-10 signalling pathway may be of importance as a strategy to reduce the incidence of nosocomial infections.
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Beautyman, Michael John Jr. "Load bearing interface design for a pan-tilt mechanism for severe marine environments." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/111896.
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Thesis: Nav. E., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 123-125).
The Naval Research Laboratory (NRL) requested the design of a two-axis gimbal device for the shipboard support of a sensor payload. Previous design efforts presented a low-mass two-axis (pan and tilt) machine. Vibration and shock testing induced failure in the interface between the payload and the tilt shaft, through which the control cabling connected to the sensors, taking the system out of service and creating a hazard for Sailors. This thesis proposes a tapered, hollowed shaft and flange interface connected by an interference fit that is preloaded and retained by a single hollowed bolt for ease of maintenance at sea. This simplified design is a departure from existing rotary tapered interfaces, such as seen in machine tooling, and focuses on connecting massive payloads to their actuators when subjected to severe loading. This design is uniquely suited to withstand large bending moments and loading as demanded by military standards for shock. A custom rig was designed and constructed to subject reduced-scale designs to military standard environmental testing for shock in the laboratory. These test results were analyzed using moving average filtering to develop confidence intervals to validate the design mathematics. A full-scale prototype was manufactured and subjected to shock testing and analysis. The design exceeded all requirements and is ready for immediate integration into the gimbal. This research also revealed the potential for tapered interfaces to connect massive payloads to their actuators in industry.
by Michael John Beautyman, Jr.
Nav. E.
S.M.
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Golde, Sabrina Helena [Verfasser]. "Neurobiological mechanisms of emotion inhibition under stress in severe early life trauma / Sabrina Helena Golde." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2020. http://d-nb.info/1223929027/34.
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Clark, Jessica Ann. "NEUROPSYCHOLOGICAL CORRELATES AND UNDERLYING CORTICAL MECHANISMS OF WORKING MEMORY IN MODERATE TO SEVERE TRAUMATIC BRAIN INJURY." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/3.
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Functional magnetic resonance imaging (fMRI) is a relatively new tool that has been used to examine patterns of neural activation within those with traumatic brain injuries (TBI). A review of relevant literature is presented, including alterations in activity within the frontal and parietal regions that are thought to be compensatory in nature. In addition, possible explanations for discrepancies within this research are discussed. The current study expands upon previous work by incorporating a delayed-match-to-sample (DMS) task within an event-related paradigm and neuropsychological testing to compare 12 individuals with a history of TBI to 12 control participants with orthopedic injuries (OI). Participants in the TBI group were high functioning and in the chronic stage of recovery. Neuropsychological testing revealed statistically significant group differences in measures of working memory, processing speed, memory, and executive functioning. However, groups were comparable in accuracy on the DMS task. Percent signal changes in fMRI data revealed statistically significantly increased activation within the right dorsolateral prefrontal cortex (BA 46) for the TBI group compared to controls. Additional alterations in activation were found between groups within the inferior temporal (BA 37) and parietal (BA 7) regions. Regression analyses showed no relationship between neuropsychological testing and percent signal change within BA 46, but predictive relationships between testing and BA 37 and BA 7. Logistic regression analyses suggest that fMRI data did not add any incremental predictive value beyond neuropsychological testing alone when attempting to predict group (TBI vs. OI) membership.
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Fisher, Rebecca. "The underlying mechanisms : an investigation of attachment and mentalization within adolescent severe and enduring mental ill health." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/6000.
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Background Regarding adolescence developmental psychopathology and the psychological correlates associated with the onset of severe and enduring mental health in adolescence, this thesis proposes that early attachment related experiences underlie the successful ability to regulate emotions, negotiate interpersonal interactions, assess and utilise social support and develop the necessary mentalizing skills for organizing and understanding both the self and others. Insecure attachment and poor reflective function appear to be linked to clinical samples yet the underlying mechanisms for how these constructs affect adolescent psychopathology and subsequent psychological adaptation have still to be examined. Objectives A quantitative cross sectional design was utilised to investigate the following research questions; 1) Is attachment and reflective function directly and indirectly associated with psychological adaptation to mental health difficulties in adolescence? 2) Do emotion regulation, interpersonal difficulties and social support mediate the effect of attachment and reflective function? Methods 75 participants were recruited from three Tier IV Child and Adolescent Mental Health Services in Edinburgh. They were asked to complete questionnaires measuring the variables of mood, interpersonal difficulties, emotion regulation and social support. The Adult Attachment Interview was administered and coded to ascertain the individual‟s attachment classification and was scored to measure their levels of reflective function when considering their childhood experiences. Structural equation modelling (SEM) was used to analyse the data. Results The emergent clinical picture of this sample was one of adolescents with interpersonal difficulties, moderate distress and poor psychological adaptation. The dominant attachment classification was insecure/ dismissing. The observed level of reflective function indicated that participants could refer to mental states but that these references were not made explicit and their understanding of the intentions of others was likely to be general or superficial. SEM analysis demonstrated that reflective function significantly and directly predicted psychological adaptation but not low mood. In contrast attachment demonstrated a significant indirect path to adaptation, being fully mediated by internally dysfunctional emotion regulation strategies. These maladaptive emotion regulation strategies directly predicted low mood and indirectly predicted psychological adaptation. In terms of the social support construct, the discrepancy between the support desired and the support received directly predicted adaption and partially mediated the relationship between reflective function and and psychological adaptation. Discussion The theoretical implications of the results centred on the importance of investigating the underlying mechanisms of attachment and mentalization in the psychological adaptation of adolescents with severe and enduring mental health difficulties. Emotion regulation, interpersonal difficulties and social support were found to play a significant role in low mood and adaptation thus enhancing the current understanding of psychological distress and chronic difficulties for this population. Further clinical implications were discussed concerning the recommendation of promoting and utilizing a mentalization based approach when working with clinical adolescent populations.
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Grampa, Valentina. "Characterization of the pathophysiological mechanisms associated with NEK8/NPHP9 mutations identified in patients with severe renal ciliopathies." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB099.
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Les ciliopathies sont un groupe de maladies génétiques multi-systémiques liées à un dysfonctionnement du cil primaire, une structure sensorielle présente à la surface des cellules qui régule des voies de signalisation clés au cours du développement et de l'homéostasie tissulaire. Afin d'identifier de nouveaux gènes responsables de ciliopathies développementales sévères, ~ 500 patients / fétus ont été analysés par une approche de séquençage à haut débit de l'exome ciblant > 1 200 gènes ciliaires ("ciliome"). Nous avons identifié huit nouvelles mutations dans le gène NEK8/NPHP9 chez cinq familles dont les syndromes se chevauchent. NEK8/NPHP9 code une protéine kinase de la famille des NIMA qui se localise au niveau du compartiment Inversine du cil primaire et agit comme un régulateur de la signalisation Hippo, une voie essentielle contrôlant la taille des organes. Nous montrons pour la première fois que les mutations du gène NEK8 sont associées à une agénésie rénale et une hypodysplasie. De plus, notre travail met en évidence une corrélation génotype/phénotype: les mutations "perte de fonction" de NEK8 conduisant à reins élargies et kystiques, des kystes pancréatiques et hépatique, alors que les mutations faux-sens de NEK8 causent une hypodysplasie/agénésie rénale associée à une cardiopathie et une paucité des canaux biliaires. La première partie de mon projet de thèse porte sur l'étude de l'impact des mutations faux-sens de NEK8 sur divers processus cellulaires et des voies de signalisation dépendantes de NEK8. Nous avons démontré un effet "gain de fonction" des mutations faux-sens de NEK8 puisqu'elles affectent la ciliogenèse et la composition du compartiment Inversine (localisation ciliaire de ANKS6). De plus, ces mutations altèrent la localisation nucléaire de YAP, le principal acteur de la voie Hippo, ainsi que l'expression des gènes cibles de YAP dans les fibroblastes de patients et dans la lignée cellulaire rénale (mIMCD3) invalidée pour NEK8. De même, nous avons montré une accumulation anormale de YAP nucléaire dans les reins polykystiques de la souris Jck, porteuse d'une mutation faux-sens de Nek8. Un déséquilibre de la voie Hippo serait donc à l'origine des défauts de morphogenèses épithéliales. En effet, les cellules mIMCD3 invalidées pour NEK8 forment en culture 3D des structures anormales et/ou des sphères élargies qui s'accompagnent d'une persistance du marquage nucléaire de YAP et Ki-67 et forment de grandes sphères par rapport aux cellules contrôles. Des défauts plus sévères ont été observés pour les cellules ré-exprimant les différents mutants de NEK8, confirmant la pathogénicité de ces mutations et leur effet "gain de fonction". Enfin, le traitement par la Vertéporfine, un inhibiteur spécifique de l'activité transcriptionnelle de YAP, améliore non seulement le phénotype des fibroblastes de patients et des cellules rénales invalidées pour NEK8 en culture 3D, mais également in vivo les anomalies observées chez les embryons de poisson zèbre dues à la surexpression de la forme NEK8 humaine, confirmant ainsi l'implication d'une dérégulation de YAP dans les mécanismes physiopathologiques. Par ailleurs, nous avons observé que les mutants de NEK8 s'accumulent de manière anormale au niveau de l'appareil de Golgi dans les fibroblastes de patients, et que cet appareil de Golgi apparait dispersé. Nos résultats montrent que le recrutement de NEK8 au Golgi est sensible à la Brefeldine A et dépendrait donc de ARF1, une petite GTPase impliquée dans le trafic de protéines entre les compartiments du Golgi et du réticulum endoplasmique. Nous avons démontré que NEK8 interagit et co-localise préférentiellement avec la forme d'ARF1 liée au GDP, suggérant pour NEK8 une possible fonction de facteur d'échange d'ARF1 à des sites spécifiques (appareil de Golgi, membranes, cil) afin de promouvoir le trafic vésiculaire de protéines telles que les protéine ciliaires. (...)Ciliopathies are a group of genetic multi-systemic disorders related to dysfunction of the primary cilium, a sensory organelle present at the cell surface that regulates key signaling pathways during development and tissue homeostasis. In order to identify novel genes whose mutations would cause severe developmental ciliopathies, ~500 patients/fetuses were analyzed by a targeted high throughput sequencing approach allowing exome sequencing of > 1200 ciliary genes. We have identified eight novel mutations in NEK8/NPHP9 in five independent families with severe overlapping syndromic disorders. NEK8/NPHP9 encodes a NIMA-related kinase that localizes at the inversin compartment of the primary cilium and acts as a regulator of Hippo signaling, a pathway that is essential for control of organ size during development. We show for the first time that NEK8 mutations are associated with renal agenesis and hypodysplasia, and our work highlights a genotype/phenotype correlation with NEK8 loss-of-function mutations leading to enlarged cystic kidney, pancreas and liver, whereas NEK8 gain-of-function (missense) mutations cause renal hypodysplasia, cardiopathy and paucity of bile ducts. The first part of my thesis project focuses on the study of the impact of these NEK8 missense mutations on various cellular processes and NEK8-dependent signaling pathways. We demonstrate that NEK8 missense mutations impair the Inversin (INVS) compartment composition and ciliogenesis, and also alter the nuclear localization of the main Hippo signalling effector, YAP, as well as expression of its target genes in patient fibroblasts and renal cell lines. We also demonstrated that this Hippo pathway imbalance causes epithelial morphogenesis defects in 3D matrigel culture. Indeed, mIMCD3 cells depleted for NEK8 showed persistent YAP and Ki-67 staining and formed bigger spheres compared to control cells. Abnormal sphere volume was also observed in cells re-expressing NEK8-GFP mutations, suggesting their pathogenicity. We confirm these data in vivo in Jck mice, a model of polycystic kidney disease bearing a Nek8 missense mutation. Finally, treatment with Verteporfin, a specific inhibitor of YAP transcriptional activity, improves the mutant phenotype of both cellular models and zebrafish embryos overexpressing human NEK8, further supporting the involvement of YAP dysregulation in the pathogenic cellular mechanisms. Surprisingly, in patient fibroblasts, we showed that mutated NEK8 accumulates at the Golgi that appeared dispersed. NEK8 recruitment at the Golgi apparatus is dependent on ARF1 (Brefeldin A sensitive), a small GTPase involved in protein trafficking between Golgi compartments and ER. We notably demonstrated that NEK8 mostly interacts and localizes with the dominant negative form of ARF1 (T31N), suggesting that NEK8 could act as an activator (GEF) of ARF1 to promote vesicular trafficking of ciliary proteins. The second part of my project focuses on a new candidate gene for which a missense homozygous mutation has been identified in 3 individuals presenting a late onset NPH with hepatic fibrosis. This gene encodes ANKS3, an evolutionarily conserved protein whose function is still poorly characterized. Interestingly, ANKS3 has been reported to be a partner of NEK8, even though we showed it does not localize at the INVS compartment with NEK8 but is rather present at the base of cilia in fibroblasts. We showed that the missense mutation does not affect ANKS3 localization but leads to longer cilia and abnormal accumulation of NEK8 at the cilium base in patient fibroblasts and kidney tubules. Altogether, my work focused on NEK8 and its partners, ANKS6 and ANKS3, each of whose related gene is mutated in patients presenting a broad clinical spectrum of phenotypes. (...)
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Mohseni, Hamidreza Materials Science & Engineering Faculty of Science UNSW. "Microstructural development and thermal stability of aluminium-based composites processed by severe plastic deformation." Awarded by:University of New South Wales. School of Materials Science and Engineering, 2006. http://handle.unsw.edu.au/1959.4/26793.
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Equal channel angular pressing ECAP is a process whereby simple shear is applied to a billet during multiple passages through an angled channel of constant cross section. The process is capable of generating very large plastic strains that significantly refines the microstructure without altering the external dimensions of the billet. A number of properties are influenced by grain refinement with the generation of a submicron grain structure SMG by ECAP resulting in improved strength and hardness and enhanced superplasticity. In this thesis, both an AA7075 alloy and AA7075 Al-base metal matrix composite MMC reinforced with 5 wt. percent of 50 nm diameter SiC particles was produced by a powder metallurgy route followed by hot extrusion. The materials were subsequently deformed by ECAP at 350 C to a true effective strain of 4.6 in an attempt to refine the microstructure and further distribute the SiC reinforcement phase in the composite. The high temperature microstructural stability of both the as-deformed alloy and composite was investigated to elucidate the effect of the reinforcement phase on continuous and discontinuous grain coarsening. It was found that ECAP generated a fine equiaxed grain size of ~ 2.3 !m and ~1.8 !m in the alloy and composite, respectively. The composite was more refined after ECAP since the SiC particles allow the matrix to undergo more grain refinement during deformation. ECAP was found to be a reasonable method for further distributing SiC clusters in this composite which is important for optimizing the reinforcement phase in terms of ambient temperature strengthening and enhanced grain stability at elevated temperature. Both the alloy and composite were annealed at times up to 5h at 500 C to assess grain stability. During annealing, the grain structure of both materials evolved in a continuous manner unlike the discontinuous process of recrystallization. Such a process is similar to continuous recrystallization observed in a range of heavily deformed Al alloys. Substantial grain boundary interactions with MgZn2 precipitates and oxide particles were found in the alloy, with precipitate, oxide and SiC particles found in the composite. The strong pinning force exerted by these particles minimised grain growth in both materials with the composite exhibiting a finer less than 2.5 !m grain size than the alloy less than 3.5 !m after extended annealing. This enhanced grain stability was attributed to the high volume fraction SiC particles which resulted in a large value of the dispersion parameter f/d which results in significant boundary pinning during annealing. Grain stability was also analysed in terms of a recently-proposed mean field model of annealing where it was predicted that the composite should not undergo discontinuous coarsening, as observed experimentally.
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Ferron, Joëlle C. Strom-Gottfried Kim. "Psychological mechanisms to treatment adherence among people with severe mental illness validating treatment motivation and working alliance measures /." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1473.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Social Work." Discipline: Social Work; Department/School: Social Work.
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Lennard, A. T. "An investigation of drought in the Severn Trent Water region : re-evaluating drought severity, characteristics and generating mechanisms." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3004783/.
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Schneider, Nathan A. "Prediction of surface ship response to severe underwater explosions using a virtual underwater shock environment." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2003. http://library.nps.navy.mil/uhtbin/hyperion-image/03Jun%5FSchneider.pdf.
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Thesis (Mechanical Engineer and M.S. in Mechanical Engineering)--Naval Postgraduate School, June 2003.Thesis advisor(s): Young S. Shin. Includes bibliographical references (p. 161-162). Also available online.
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Takemi, Tetsuya. "Studies on the Structure, Evolution, and Maintenance Mechanism of a Severe Squall Line in an Arid Region." 京都大学 (Kyoto University), 1998. http://hdl.handle.net/2433/86315.
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Shi, Haijian. "Nonlinear finite element modeling and characterization of guyed towers under severe loading." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4703.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on February 29, 2008) Vita. Includes bibliographical references.
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Biserova, Tahchieva Alisiya. "Estudio del comportamiento del acero inoxidable dúplex y superdúplex después de deformación plástica severa." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/672573.
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Los diferentes grados de aceros inoxidables dúplex (DSS) se caracterizan por sus atractivas propiedades de resistencia mecánica y resistencia a la corrosión, debido a su microestructura equilibrada de ferrita (δ) y austenita (γ). Sin embargo, son susceptibles a la precipitación de fases secundarias cuando no se controlan los procesos de fabricación y/o de procesado durante su instalación. La formación de estas fases, particularmente fase sigma (σ) enriquecida en Cr y Mo y nitruros/carburos metálicos (Cr2N, M23C6), se produce en el rango de temperaturas de entre 600ºC y 900ºC a lo largo de un periodo de tiempo. Son particularmente investigadas ya que pueden perjudicar las propiedades mecánicas y la resistencia a la corrosión del material, dependiendo de su cantidad en la microestructura del material.
A diferencia de los procesos convencionales que se llevan acabo para la obtención de estos aceros, el proceso de deformación plástica severa (SPD) - torsión a alta presión (HPT) ofrece la posibilidad de aportar propiedades mecánicas extraordinarias al material a consecuencia de la nanoestructuración obtenida, manteniendo hasta cierto modo sus dimensiones iniciales. La obtención de una microestructura de grano ultrafino o nanoestructura conlleva cambios internos desde el punto de vista termodinámico, un aumento de la energía interna debido al incremento de límites de grano. Por consiguiente, la precipitación de las fases secundarias se vería afectado en cierto modo.
Por otro lado, la aportación de elementos intersticiales desde la superficie hacia el interior del material, por el proceso de difusión, mediante métodos termoquímicos como la nitruración o cementación, se aplican generalmente para mejorar las propiedades tribologías de los materiales bajo estudio. Sin embargo, desde el punto de vista termodinámico, la introducción de los elementos de C y/o N por difusión, puede tener influencia sobre la formación de las fases secundarias. Estos elementos son los principales para la formación de fases intermetálicas como carburos y/o nitruros metálicos. Por consiguiente, la precipitación en general en la microestructura resulta ser afectada y es oportuno determinar las consecuencias de estas modificaciones.
En la presente tesis se propone el estudio y análisis microestructural del acero inoxidable dúplex UNS S32205 y superdúplex UNS S32750 después de ser deformados por torsión a alta presión. Se realiza una comparativa entre el material recocido y el material deformado para ver la influencia del proceso mecánico sobre la evolución de la precipitación de fases. Además, se analiza la microestructura tratada termoquímicamente mediante el proceso de nitruración y el de carburación con el fin mismo objetivo.
La caracterización de las distintas fases se realiza mediante la utilización del microscopio electrónico de barrido (Scanning Electron Microscope – SEM), así como la disfracción de electrones retrodispersados (Electron Basckscatter Diffraction – EBSD) para determinar la distribución de las fases y su orientación cristalina. Además, mediante la microscopia electrónica de transmisión (Transmission Electron Microscope – TEM) y la técnica de difracción de electrones por precesión (Precession Electron Diffraction – PED) se realiza una mejor interpretación de las fases secundarias debido a la mayor resolución e información cristalográfica obtenida por los equipos. Se utiliza el sistema automático de medida de la orientación cristalina (Automatic Crystal Orientation Measurements – ACOM) tras observar la limitación de la técnica EBSD para la determinación de la distribución y orientación cristalina de fases en las muestras nanoestructuradas, siendo deformadas por HPT. La mejora de las propiedades mecánicas se determina mediante ensayos de microdureza y la influencia de la precipitación se analiza en el comportamiento general a la corrosión.
Los resultados muestran que la precipitación de las fases secundarias tanto en el acero inoxidable dúplex como en el superdúplex es básicamente de la fase sigma (σ) y de nitruros de cromo (Cr2N), observada tras un tratamiento isotérmico posterior a la deformación plástica severa. El aumento de la deformación por cizallamiento provoca una nanoestructura y tras el tratamiento isotérmico, las fases secundarias aumentan considerablemente su cantidad, sobretodo en el acero inoxidable superdúplex. Esto contribuye al aumento en la dureza del material debido al fenómeno de envejecimiento por deformación, en comparación al mismo material sin haber sido deformado por HPT. En ambos casos se considera que la precipitación es una transformación invariante, donde la fase sigma es un producto de una fase inicial en estado sólido con distinta estructura cristalina.
El comportamiento a la corrosión general del acero inoxidable dúplex y superdúplex no empeora excesivamente, y muestra una pasivación estable debido a la nanoestructuración de los materiales.
La nitruración y cementación como procesos termoquímicos influyen considerablemente en el aumento de la precipitación de fase sigma, sin alterar significativamente el comportamiento a la corrosión.Duplex stainless steels (DSS) are characterized by their attractive properties of mechanical strength and corrosion resistance, due to the balanced microstructure of ferrite (δ) and austenite (γ). However, they are susceptible to secondary phase precipitation during uncontrolled manufacturing processes or heat treatments. The formation of these phases, particularly sigma (σ) phase, enriched in Cr and Mo, and intermetallic nitrides/carbides (Cr2N, M23C6), occurs in the range of 600ºC and 900ºC during different time. They are particularly investigated since they can decrease the mechanical properties and corrosion resistance of the material, depending on their amount in the microstructure. Unlike the conventional processes that are carried out to obtain these steels, severe plastic deformation process (SPD) by high-pressure torsion (HPT) provides extraordinary mechanical properties to the material due the obtained nanostructure, maintaining to a certain point its initial dimensions. Obtaining an ultra-fine grain microstructure or nanostructure entails internal changes from the thermodynamic point of view, an increase in internal energy due to the increments of grain boundaries. Consequently, the precipitation of the secondary phases would be altered. On the other hand, the introduction of interstitial elements from the surface to the inner part of the material by diffusion, mainly by thermochemical methods, such as nitriding or carburizing, can influence the formation of the undesirable phases. Consequently, the precipitation in the microstructure is affected and it is opportune to determine the influences of these modifications. The current thesis proposes the study and microstructural analysis of duplex stainless steel UNS S32205 and superduplex stainless steel UNS S32750 after being deformed by high-pressure torsion. A comparison between the annealed materials and the deformed materials is carried out to see the influence of the mechanical process on the evolution of secondary phase precipitation. The characterization of the different phases has been realized by using Scanning Electron Microscope - SEM, as well as the Electron Basckscatter Diffraction – EBSD technique to determine the distribution of the phases and their crystalline orientation. In addition, Transmission Electron Microscope - TEM and the Precession Electron Diffraction - PED technique as a high-resolution techniques have been used for a better interpretation of the secondary phases. The use of the Automatic Crystal Orientation Measurements – ACOM method has been required after observing the limitation of EBSD for the distribution and crystalline orientation determination of the nanostructured samples, being deformed by HPT. The improvement in mechanical properties has been determined by microhardness tests and the influence of the secondary phases has been analysed on the general corrosion behaviour of the materials. The results showes that the precipitation in both duplex and superduplex stainless steel is basically of sigma phase (σ) and of chromium nitrides (Cr2N), observed after an isothermal treatment after the severe plastic deformation. The increase in shear deformation causes a nanostructure and after an isothermal treatment, the secondary phases increase considerably in quantity, especially in the superduplex stainless steel. This contributes to the increase in the hardness of the material due to the phenomenon of aging by deformation, compared to the same material without having been deformed by HPT. In both cases, precipitation is considered as an invariant transformation, where sigma phase is a product of a solid- state initial phase with different crystalline structure. The general corrosion behaviour of both stainless steels is not deteriorated and it shows stable passivation due to the nanostructuring of the materials. Nitriding and carburizing as thermochemical processes considerably influence the increase in sigma phase precipitation, without significantly altering the corrosion behaviour.
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Gilby, Krista Lynn. "An investigation into the mechanism responsible for Clomethiazole-induced neuroprotection in a rat model of severe global ischemia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/NQ57363.pdf.
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Albertsson, Pontus. "Occupant casualties in bus and coach traffic : injury and crash mechanisms." Doctoral thesis, Umeå : Deptartment of Surgical and Perioperative Sciences, Division of surgery, Umeå university, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-482.
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Hogan, Lynne. "An exploration of the coping mechanisms of caregivers of persons diagnosed with severe mental illness, in the Western Cape, South Africa." Master's thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20701.
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This exploratory study on the coping mechanisms of caregivers in the Western Cape was undertaken in order to gain a better understanding of what caregivers experience and utilise in order to cope with their role as caregivers. Informal caregivers are the primary carers for people with a severe mental illness living within communities. They often carry a significant burden in this role and have many stresses which they need to deal with. It is therefore essential that a better understanding of their experience is gained in order to provide relevant support services and interventions. Hopefully the insights gained in this study will contribute to the formation of policies and interventions for caregivers which are appropriate and lead to further research in this field. This study was a qualitative study, conducted with 18 caregivers who participated in in-depth interviews. The results show that there is a large variety of both positive and negative coping mechanisms which caregivers employ dealing with the challenges and stresses they face. Positive coping mechanisms ranged from: making use of services and facilities available, working or keeping busy, knowledge of mental illness, support from family and friends, faith, finding the right doctor for the mentally ill person, support from hospital or clinic staff, looking after self and using challenges to grow, having lots of patience, taking one day at a time and listening to others' stories. Some of the negative coping mechanisms were: ignoring the mentally ill person or cutting off emotions, taking on all responsibility for the mentally ill person or controlling them, using verbal threats or abuse, isolating themselves and using medication to cope. The carers interviewed were also able to identify and access a number of social support mechanisms and systems available to them. Some of these provided psychological and emotional support, others provided physical / practical help and many provided both. The predominant social support mechanisms and systems were: hospitals and clinics, family and friends, churches and faith, support groups, Cape Mental Health and various NGOs. Participants in the study spoke about challenges and barriers in their role as carers. The research indicates that there are two main divides: challenges tend to be concerned with the person they are caring for while barriers tend to be external factors which carers have to deal with. Common challenges which carers face are: drug or alcohol use by the mentally ill person, unpredictable and disturbed thinking and behaviour, issues with medication and non-compliance, lack of person's insight, isolation and withdrawal from family life, lack of understanding from family and friends, financial problems. Barriers which are more external to the family unit include: lack of adequate medical services and facilities for the mentally ill person, lack of support services for the carer, lack of suitable accommodation for mentally ill people, carers not included in the treatment team and plan, police not helpful when asked for assistance with a mentally ill person, negative perceptions of mental illness in society. Recommendations of the study are for further research in this field; that mental health care services provide more support and interventions for caregivers; and that clear policies are developed and implemented for caregivers.
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Suleman, Farhana. "Characterisation of the Phenotype and Disease Mechanisms in a Knock-In Mouse Model of Severe Pseudoachondroplasia Resulting from a D469 Comp Mutation." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518430.
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Mantovani, Rocco. "Modelling complex systems in the severely undersampled regime: a Bayesian model selection approach." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/18019/.
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L'inferenza di modelli di spin è uno strumento diffuso nell'approccio statistico ai sistemi complessi.
Tipicamente ci si limita a modelli con interazioni a uno e due corpi:
per il principio di massima entropia,
ciò equivale
ad assumere che magnetizzazioni e correlazioni a coppie costituiscano le variabili rilevanti (statistiche sufficienti)
del sistema.
L'assunzione non è giustificabile nel caso generale sulla base di argomenti puramente statistici;
il problema della selezione tra modelli con interazioni di ordine arbitrario
è però alto-dimensionale. Esso può essere affrontato tramite
una particolare euristica Bayesiana che permette di
ottenere le variabili rilevanti direttamente dal campione;
la selezione avviene nella classe delle misture, e
i risultati vengono proiettati sulla
rappresentazione di spin.
Il risultato è l'ottenimento delle statistiche sufficienti senza alcuna assunzione a priori.
Il numero di tali statistiche
è modulato da quello di differenti frequenze empiriche nel campione; in regime di sottocampionamento,
esso è molto minore della dimensione del modello completo. Ciò rende il problema di inferenza dei parametri
tipicamente basso-dimensionale.
Il principale scopo di questo lavoro è quello di investigare esplicitamente come l'informazione sia organizzata
nella mappa tra misture e modelli di spin.
La comprensione dettagliata di tale mappa suggerisce nuovi approcci per la regolarizzazione;
inoltre i risultati gettano luce sulla natura delle statistiche sufficienti,
che risultano essere funzioni degli stati solo tramite le frequenze empiriche di questi.
Mostriamo come da un approccio integralmente Bayesiano emerga sotto opportune condizioni
un termine regolarizzatore "L2"; verifichiamo numericamente se tali condizioni sono tipicamente soddisfatte.
Presentiamo infine alcune osservazioni qualitative circa l'emersione di loop stuctures
nella mappa da misture a spin; queste aprono scenari interessanti per la ricerca futura.
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Tan, Evren. "Severe Plastic Deformation Of Age Hardenable Aluminum Alloys." Phd thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614968/index.pdf.
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Industrial products of high-strength Al-alloys are currently manufactured by thermo-mechanical processes, which are only applicable in the integrated plants requiring high investment cost. Moreover, reduction of the average grain size not less than 10 &mum and re-adjustment of process parameters for each alloy type is evaluated as disadvantage. Therefore, recently there have been many research studies for development of alternative manufacturing techniques for aluminum alloys. Research activities have shown that it is possible to improve the strength of Al-alloys remarkably by severe plastic deformation which results in ultra-fine grain size. This study aims to design and manufacture the laboratory scale set-ups for severe plastic deformation of aluminum alloys, and to characterize the severely deformed samples. The stages of the study are summarized below: First, for optimization of die design and investigation of parameters affecting the deformation finite element modeling simulations were performed. The effects of process parameters (die geometry, friction coefficient) and material properties (strain hardening, strain-rate sensitivity) were investigated. Next, Equal Channel Angular Pressing (ECAP) system that can severely deform the rod shaped samples were designed and manufactured. The variations in the microstructure and mechanical properties of 2024 Al-alloy rods deformed by ECAP were investigated. Finally, based on the experience gained, a Dissimilar Channel Angular Pressing (DCAP) system for severe plastic deformation of flat products was designed and manufactured
then, 6061 Al-alloy strips were deformed. By performing hardness and tension tests on the strips that were deformed by various passes, the capability of the DCAP set-up for production of ultra-fine grain sized high-strength aluminum flat samples were investigated.
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Nakajima, Tamie, Yukio Yamori, Katsumi Ikeda, Satoru Tsuchikura, Xiaofang Jia, Hazuki Tamada, Nozomi Yamagishi, et al. "Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat." Thesis, Springer, 2012. http://hdl.handle.net/2237/16803.
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Mandala, Wilson Lewis. "Immunological mechanisms that determine why some African children develop severe malarial anaemia while others develop cerebral malaria in response to infection with Plasmodium falciparum." Thesis, University of Liverpool, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485895.
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Introduction and Objectives: In Sub-Sahara Africa, malaria is an infectious disease caused mainly by Plasmodium falciparum. Most cases occur in children under five years of age. About 98 percent of the children suffer only from uncomplicated malaria (UCM) but a minority develop life-threatening severe malaria. Severe malaria encompasses three clinical syndromes; cerebral malaria (CM), severe malarial. anaemia (SMA) and severe respiratorY distress (SRD). The underlying reasons for this disparity are ·still unknown. The objective of this study was to investigate the immunological mechanisms that determine why some children develop CM while others develop SMA when infected with P. falciparum. Materials and Methods: Leucocyte and lymphocyte subsets were determined in Malawian children aged between 6 months and 5 years presenting with UCM, SMA and CM and in healthy controls. Activation and memory status of different cells were also determined. Sera Th1 and Th2 cytokines and percentages of cytokine-producing cells were measured for all groups. Results: CM patients were characterised by transient pan-lymphopenia, neutrophilia and thrombocytopenia while SMA patients were characterised by lymphocytosis. Interestingly, the percentage of T regulatory cells was lower in acute SMA patients compared to acute CM patients. Lymphocytes from CM patients were more activated and had a higher proportion with a memory phenotype compared with those from SMA patients, but monocytes in both groups showed a lack of activation markers. The sera of CM patients contained higher concentrations of both Th1 and Th2 cytokines. Surprisingly, CM patients had lower percentages of TNF-u, IFN-y and IL-2producing CD4+, CD8+ and yo T cells and NK cells compared to controls, whereas SMA patients had higher percentages of cytokine-producing lymphocyte subsets compared to controls. Both CM and SMA patients had low percentages of TNF-u and IL-6 producing monocytes compared to controls, but recovery of function was quicker in CM patients. Conclusion: Children with CM and SMA have cytokine profiles and lymphocyte activation and memory phenotypes which are consistent with the hypothesis that CM is a result of immunopathological response while SMA is a result of a na'ive response to the malaria infection. However, the panlymphopenia and apparently low proportion of cytokine-producing lymphocytes and monocytes in the CM group do not fit this hypothesis and require further investigation.
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Lütticke, Ashley L. [Verfasser], and Thomas [Akademischer Betreuer] Schulze. "Understanding the involvement of environmental exposures, genetic risk, and epigenetic mechanisms in the course of severe mental illness / Ashley L. Lütticke ; Betreuer: Thomas Schulze." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1216417806/34.
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Al, Mashhadani Mahmood Yaseen Hachim [Verfasser]. "The use of integrative OMICs to decipher heterogeneous chronic complex disease mechanism : severe asthma as a model / Mahmood Yaseen Hachim Al Mashhadani." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1227545096/34.
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Tort, Morgan. "The effects of severe plastic deformation on an age hardenable Al-2.5Cu-1.5Mg alloy." Thesis, Clermont-Ferrand 2, 2015. http://www.theses.fr/2015CLF22578.
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Les effets du pressage à canaux égaux (ECAP), un procédé de déformation plastique sévère, ont été examinés dans un alliage Al-2.5Cu-1.5Mg (pourcentage en masse) prône à être durci par traitement thermique et précipitant dans la région α + S. Une multitude de techniques microscopiques, calorimétriques et analytiques ont été utilisés pour caractériser et quantifier les microstructures, incluant la diffraction Kikuchi, la microscopie électronique en transmission, la calorimétrie différentielle à balayage et la sonde atomique tomographique. Quatre différents traitements thermiques initiaux ont été réalisés pour créer quatre microstructures différentes, contenant soit aucun précipités, des clusters Cu-Mg ou/et des composés intermétalliques Al2CuMg. Chaque spécimen a été soumis au procédé ECAP à température ambiante et les effets correspondants sur la microstructure et les propriétés mécaniques ont été analysés. Des expériences en compression pour de petite déformation (inférieures à 7%) ont aussi été entreprises sur les échantillons trempés pour étudier les effets de la compression sur la formation des clusters. Après la trempe et la compression, des clusters Cu-Mg ont été trouvés dans la matrice et il a été élucidé que la formation des clusters était déclenchée par la compression. La fraction volumique des clusters est corrélée directement par la déformation appliquée : plus la déformation est importante, plus la fraction volumique des clusters est importante. Après ECAP, la microstructure est constituée de longues bandes nanocristallines séparée par de gros grains non-déformés pour les échantillons contenant seulement des clusters avant la déformation, tandis que la présence de phase S, avant ECAP, conduit à des microstructures constituées de zones à gros grains et de zones à grains raffinés, distribués d’une façon homogène à travers les échantillons. Bien que les spécimens présentaient clairement des microstructures différentes après ECAP, impliquant que différents mécanismes de renforcement entre en jeux, la limite élastique se situait au-delà de 500 MPa. La limite élastique des échantillons fabriqués par ECAP a été modélisée en superposant les différents mécanismes de renforcement et en saisissant les paramètres microstructurels venant de la caractérisation dans le modèle. Il a été démontré qu’une très bonne corrélation existait entre les limites élastiques provenant du modèle et celles expérimentalesThe effects of equal channel angular pressing (ECAP), a severe plastic deformation (SPD) technique, were investigated in an age hardenable Al-2.5Cu-1.5Mg (weight percent (wt.%)) alloy precipitating in the α + S phase field. A variety of microscopy, calorimetry and analytical techniques were employed to characterize and quantify the microstructure, including transmission kikuchi diffraction (TKD), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and atom probe tomography (APT). Four different initial heat-treatments were conducted to achieve four different microstructures, containing either no precipitates, Cu-Mg clusters or/and Al2CuMg intermetallics. Each specimen was subjected to ECAP at room temperature and the related effects on the microstructure and mechanical properties were analysed. Compression experiments for small strains (less than 7%) were also undertaken on the as-quenched samples to investigate the effects of compression on the formation of clusters.After quenching and compression, Cu-Mg clusters were found in the matrix and it was elucidated that the formation of clusters was triggered by pressing. The volume fraction of clusters was found to be correlated to the strain applied: the higher the strain, the higher the volume fraction.After ECAP, the microstructure was constituted of long nanocrystalline bands separated by large undeformed grains for the samples containing only clusters before deformation, while the presence of S phase, prior to ECAP, lead to microstructures constituted of both coarse and refined zones distributed homogeneously throughout the sample. Although the samples presented clearly different microstructures after ECAP, implying that different strengthening mechanisms were active, the yield strength was found to lie above 500 MPa. The yield strength of the ECAP processed samples was modelled by superposing the different strengthening mechanisms altogether and by inputting the microstructural parameters coming from characterisation in the model. It was demonstrated that a very good correlation existed between the modelled and experimental yield strength values
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Zemaryalai, Khatera. "Investigations into the roles of potassium channels in hair growth : studies confirming the presence of several ATP-sensitive potassium (K+ATP) channels in hair follicles and exploring their mechanism of action using molecular biological, cell culture, organ culture and proteomic approaches." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/4461.
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Hair disorders cause significant distress. The main, but limited, treatment for hair loss is minoxidil, an ATP-sensitive potassium (KATP) channel opener whose mechanism of stimulation is unclear. The regulatory component of KATP channels has three forms: SUR1, SUR2A and SUR2B which all respond to different molecules. Minoxidil only opens SUR2B channels, though SUR1 and SUR2B are present in human hair follicles. To expand our understanding, the red deer hair follicle model was used initially. Deer follicles expressed the same KATP channel genes as human follicles when growing (anagen), but no channels were detected in resting follicles. This reinforces the importance of KATP channels in active hair growth and the usefulness of the deer model. To assess whether SUR1 KATP channels are actually involved in human hair growth, the effects of a selective SUR1 channel opener, NNC55-9216, on scalp follicle growth in organ culture was examined. NNC55-9216 stimulated anagen; its effect was augmented by minoxidil. This creates the potential for more effective pharmaceuticals to treat hair loss via SUR1 channels, either alone or in combination with minoxidil. The dermal papilla plays a crucial regulatory role in hair follicle activity determining the type of hair produced. Minoxidil had no effect on dermal papilla cell proliferation, but altered the profile of proteins produced when assessed by proteomics. Further research into the roles of KATP channels and greater understanding of the significance of these protein changes should enhance our knowledge of hair biology and help the development of new, improved therapies for hair pathologies.
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Koç, Gamze [Verfasser], Annegret H. [Akademischer Betreuer] Thieken, Attila [Akademischer Betreuer] Çiner, Annegret H. [Gutachter] Thieken, Attila [Gutachter] Çiner, and Johann [Gutachter] Stötter. "A comprehensive analysis of severe flood events in Turkey : event documentation, triggering mechanisms and impact modelling / Gamze Koç ; Gutachter: Annegret H. Thieken, Attila Çiner, Johann Stötter ; Annegret H. Thieken, Attila Çiner." Potsdam : Universität Potsdam, 2021. http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-517853.
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Tavares, Lucas Alves. "O envolvimento da proteína adaptadora 1 (AP-1) no mecanismo de regulação negativa do receptor CD4 por Nef de HIV-1." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17136/tde-06012017-113215/.
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O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal.The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.
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Moreira, Ana Sofia Pereira. "Study of modifications induced by thermal and oxidative treatment in oligo and polysaccharides of coffee by mass spectrometry." Doctoral thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/17074.
Full textAbstract:
Doutoramento em BioquímicaOs polissacarídeos são os componentes maioritários dos grãos de café verde e torrado e da bebida de café. Os mais abundantes são as galactomananas, seguindo-se as arabinogalactanas. Durante o processo de torra, as galactomananas e arabinogalactanas sofrem modificações estruturais, as quais estão longe de estar completamente elucidadas devido à sua diversidade e à complexidade estrutural dos compostos formados. Durante o processo de torra, as galactomananas e arabinogalactanas reagem com proteínas, ácidos clorogénicos e sacarose, originando compostos castanhos de alto peso molecular contendo nitrogénio, designados de melanoidinas. As melanoidinas do café apresentam diversas atividades biológicas e efeitos benéficos para a saúde. No entanto, a sua estrutura exata e os mecanismos envolvidos na sua formação permanecem desconhecidos, bem como a relação estrutura-atividade biológica. A utilização de sistemas modelo e a análise por espectrometria de massa permitem obter uma visão global e, simultaneamente, detalhada das modificações estruturais nos polissacarídeos do café promovidas pela torra, contribuindo para a elucidação das estruturas e mecanismos de formação das melanoidinas. Com base nesta tese, oligossacarídeos estruturalmente relacionados com a cadeia principal das galactomananas, (β1→4)-Dmanotriose (Man3), e as cadeias laterais das arabinogalactanas, (α1→5)-Larabinotriose (Ara3), isoladamente ou em misturas com ácido 5-Ocafeoilquínico (5-CQA), o ácido clorogénico mais abundante nos grãos de café verde, e péptidos compostos por tirosina e leucina, usados como modelos das proteínas, foram sujeitos a tratamento térmico a seco, mimetizando o processo de torra. A oxidação induzida por radicais hidroxilo (HO•) foi também estudada, uma vez que estes radicais parecem estar envolvidos na modificação dos polissacarídeos durante a torra. A identificação das modificações estruturais induzidas por tratamento térmico e oxidativo dos compostos modelo foi feita por estratégias analíticas baseadas principalmente em espectrometria de massa, mas também em cromatografia líquida. A cromatografia de gás foi usada na análise de açúcares neutros e ligações glicosídicas. Para validar as conclusões obtidas com os compostos modelo, foram também analisadas amostras de polissacarídeos do café obtidas a partir de resíduo de café e café instantâneo. Os resultados obtidos a partir dos oligossacarídeos modelo quando submetidos a tratamento térmico (seco), assim como à oxidação induzida por HO• (em solução), indicam a ocorrência de despolimerização, o que está de acordo com estudos anteriores que reportam a despolimerização das galactomananas e arabinogalactanas do café durante a torra. Foram ainda identificados outros compostos resultantes da quebra do anel de açúcares formados durante o tratamento térmico e oxidativo da Ara3. Por outro lado, o tratamento térmico a seco dos oligossacarídeos modelo (individualmente ou quando misturados) promoveu a formação de oligossacarídeos com um maior grau de polimerização, e também polissacarídeos com novos tipos de ligações glicosídicas, evidenciando a ocorrência de polimerização através reações de transglicosilação não enzimática induzidas por tratamento térmico a seco. As reações de transglicosilação induzidas por tratamento térmico a seco podem ocorrer entre resíduos de açúcares provenientes da mesma origem, mas também de origens diferentes com formação de estruturas híbridas, contendo arabinose e manose como observado nos casos dos compostos modelo usados. Os resultados obtidos a partir de amostras do resíduo de café e de café instantâneo sugerem a presença de polissacarídeos híbridos nestas amostras de café processado, corroborando a ocorrência de transglicosilação durante o processo de torra. Além disso, o estudo de misturas contendo diferentes proporções de cada oligossacarídeo modelo, mimetizando regiões do grão de café com composição distinta em polissacarídeos, sujeitos a diferentes períodos de tratamento térmico, permitiu inferir que diferentes estruturas híbridas e não híbridas podem ser formadas a partir das arabinogalactanas e galactomananas, dependendo da sua distribuição nas paredes celulares do grão e das condições de torra. Estes resultados podem explicar a heterogeneidade de estruturas de melanoidinas formadas durante a torra do café. Os resultados obtidos a partir de misturas modelo contendo um oligossacarídeo (Ara3 ou Man3) e 5-CQA sujeitas a tratamento térmico a seco, assim como de amostras provenientes do resíduo de café, mostraram a formação de compostos híbridos compostos por moléculas de CQA ligadas covalentemente a um número variável de resíduos de açúcar. Além disso, os resultados obtidos a partir da mistura contendo Man3 e 5-CQA mostraram que o CQA atua como catalisador das reações de transglicosilação. Por outro lado, nas misturas modelo contendo um péptido, mesmo contendo também 5-CQA e sujeitas ao mesmo tratamento, observou-se uma diminuição na extensão das reações transglicosilação. Este resultado pode explicar a baixa extensão das reações de transglicosilação não enzimáticas durante a torra nas regiões do grão de café mais ricas em proteínas, apesar dos polissacarídeos serem os componentes maioritários dos grãos de café. A diminuição das reações de transglicosilação na presença de péptidos/proteínas pode dever-se ao facto de os resíduos de açúcares redutores reagirem preferencialmente com os grupos amina de péptidos/proteínas por reação de Maillard, diminuindo o número de resíduos de açúcares redutores disponíveis para as reações de transglicosilação. Além dos compostos já descritos, uma diversidade de outros compostos foram formados a partir dos sistemas modelo, nomeadamente derivados de desidratação formados durante o tratamento térmico a seco. Em conclusão, a tipificação das modificações estruturais promovidas pela torra nos polissacarídeos do café abre o caminho para a compreensão dos mecanismos de formação das melanoidinas e da relação estrutura-atividade destes compostos.
Polysaccharides are the major components of green and roasted coffee beans, and coffee brew. The most abundant ones are galactomannans, followed by arabinogalactans. During the roasting process, galactomannans and arabinogalactans undergo structural modifications that are far to be completely elucidated due to their diversity and complexity of the compounds formed. During the roasting process, galactomannans and arabinogalactans react with proteins, chlorogenic acids, and sucrose, originating high molecular weight brown compounds containing nitrogen, known as melanoidins. Several biological activities and beneficial health effects have been attributed to coffee melanoidins. However, their exact structures and the mechanisms involved in their formation remain unknown, as well as the structure-biological activity relationship. The use of model systems and mass spectrometry analysis allow to obtain an overall view and, simultaneously, detailed, of the structural modifications in coffee polysaccharides promoted by roasting, contributing to the elucidation of the structures and formation mechanisms of melanoidins. Based on this thesis, oligosaccharides structurally related to the backbone of galactomannans, (β1→4)-D-mannotriose, and the side chains of arabinogalactans, (α1→5)-Larabinotriose, alone or in mixtures with 5-O-caffeoylquinic acid, the most abundant chlorogenic acid in green coffee beans, and dipeptides composed by tyrosine and leucine, used as models of proteins, were submitted to dry thermal treatments, mimicking the coffee roasting process. The oxidation induced by hydroxyl radicals (HO•) was also studied, since these radicals seem to be involved in the modification of the polysaccharides during roasting. The identification of the structural modifications induced by thermal and oxidative treatment of the model compounds was performed mostly by mass spectrometry-based analytical strategies, but also using liquid chromatography. Gas chromatography was used in the analysis of neutral sugars and glycosidic linkages. To validate the conclusions achieved with the model compounds, coffee polysaccharide samples obtained from spent coffee grounds and instant coffee were also analysed. The results obtained from the model oligosaccharides when submitted to thermal treatment (dry) or oxidation induced by HO• (in solution) indicate the occurrence of depolymerization, which is in line with previous studies reporting the depolymerization of coffee galactomannans and arabinogalactans during roasting. Compounds resulting from sugar ring cleavage were also formed during thermal treatment and oxidative treatment of Ara3. On the other hand, the dry thermal treatment of the model oligosaccharides (alone or when mixed) promoted the formation of oligosaccharides with a higher degree of polymerization, and also polysaccharides with new type of glycosidic linkages, evidencing the occurrence of polymerization via non-enzymatic transglycosylation reactions induced by dry thermal treatment. The transglycosylation reactions induced by dry thermal treatment can occur between sugar residues from the same origin, but also of different origins, with formation of hybrid structures, containing arabinose and mannose in the case of the model compounds used. The results obtained from spent coffee grounds and instant coffee samples suggest the presence of hybrid polysaccharides in these processed coffee samples, corroborating the occurrence of transglycosylation during the roasting process. Furthermore, the study of mixtures containing different proportions of each model oligosaccharide, mimicking coffee bean regions with distinct polysaccharide composition, subjected to different periods of thermal treatment, allowed to infer that different hybrid and non-hybrid structures may be formed from arabinogalactans and galactomannans, depending on their distribution in the bean cell walls and on roasting conditions. These results may explain the heterogeneity of melanoidins structures formed during coffee roasting. The results obtained from model mixtures containing an oligosaccharide (Ara3 or Man3) and 5-CQA and subjected to dry thermal treatment, as well as samples derived from spent coffee grounds, showed the formation of hybrid compounds composed by CQA molecules covalently linked to a variable number of sugar residues. Moreover, the results obtained from the mixture containing Man3 and 5-CQA showed that CQA acts as catalyst of transglycosylation reactions. On the other hand, in the model mixtures containing a peptide, even if containing 5-CQA and subjected to the same treatment, it was observed a decrease in the extent of transglycosylation reactions. This outcome can explain the low extent of non-enzymatic transglycosylation reactions during roasting in coffee bean regions enriched in proteins, although polysaccharides are the major components of the coffee beans. The decrease of transglycosylation reactions in the presence of peptides/proteins can be related with the preferential reactivity of reducing residues with the amino groups of peptides/proteins by Maillard reaction, decreasing the number of reducing residues available to be directly involved in the transglycosylation reactions. In addition to the compounds already described, a diversity of other compounds were formed from model systems, namely dehydrated derivatives formed during dry thermal treatment. In conclusion, the identification of the structural modifications in coffee polysaccharides promoted by roasting pave the way to the understanding of the mechanisms of formation of melanoidins and structure-activity relationship of these compounds.
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Fenollosa, Artés Felip. "Contribució a l'estudi de la impressió 3D per a la fabricació de models per facilitar l'assaig d'operacions quirúrgiques de tumors." Doctoral thesis, Universitat Politècnica de Catalunya, 2019. http://hdl.handle.net/10803/667421.
Full textAbstract:
La present tesi doctoral s’ha centrat en el repte d’aconseguir, mitjançant Fabricació Additiva (FA), models per a assaig quirúrgic, sota la premissa que els equips per fer-los haurien de ser accessibles a l’àmbit hospitalari. L’objectiu és facilitar l’extensió de l’ús dels prototips com a eina de preparació d’operacions quirúrgiques, transformant la pràctica mèdica actual de la mateixa manera que en el seu moment ho van fer tecnologies com les que van facilitar l’ús de radiografies. El motiu d’utilitzar FA, en lloc de tecnologies més tradicionals, és la seva capacitat de materialitzar de forma directa les dades digitals obtingudes de l’anatomia del pacient mitjançant sistemes d’escanejat tridimensional, fent possible l’obtenció de models personalitzats. Els resultats es centren en la generació de nou coneixement sobre com aconseguir equipaments d’impressió 3D multimaterials accessibles que permetin l’obtenció de models mimètics respecte als teixits vius. Per facilitar aquesta buscada extensió de la tecnologia, s’ha focalitzat en les tecnologies de codi obert com la Fabricació per Filament Fos (FFF) i similars basades en líquids catalitzables. La recerca s’alinea dins l’activitat de desenvolupament de la FA al CIM UPC, i en aquest àmbit concret amb la col·laboració amb l’Hospital Sant Joan de Déu de Barcelona (HSJD). El primer bloc de la tesi inclou la descripció de l’estat de l’art, detallant les tecnologies existents i la seva aplicació a l’entorn mèdic. S’han establert per primer cop unes bases de caracterització dels teixits vius -sobretot tous- per donar suport a la selecció de materials que els puguin mimetitzar en un procés de FA, a efectes de millorar l’experiència d’assaig dels cirurgians. El caràcter rígid dels materials majoritàriament usats en impressió 3D els fa poc útils per simular tumors i altres referències anatòmiques. De forma successiva, es tracten paràmetres com la densitat, la viscoelasticitat, la caracterització dels materials tous a la indústria, l’estudi del mòdul elàstic de teixits tous i vasos, la duresa d’aquests, i requeriments com l’esterilització dels models. El segon bloc comença explorant la impressió 3D mitjançant FFF. Es classifiquen les variants del procés des del punt de vista de la multimaterialitat, essencial per fer models d’assaig quirúrgic, diferenciant entre solucions multibroquet i de barreja al capçal. S’ha inclòs l’estudi de materials (filaments i líquids) que serien més útils per mimetitzar teixits tous. Es constata com en els líquids, en comparació amb els filaments, la complexitat del treball en processos de FA és més elevada, i es determinen formes d’imprimir materials molt tous. Per acabar, s’exposen sis casos reals de col·laboració amb l’HJSD, una selecció d’aquells en els que el doctorand ha intervingut en els darrers anys. L’origen es troba en la dificultat de l’abordatge d’operacions de resecció de tumors infantils com el neuroblastoma, i a la iniciativa del Dr. Lucas Krauel. Finalment, el Bloc 3 té per objecte explorar nombrosos conceptes (fins a 8), activitat completada al llarg dels darrers cinc anys amb el suport dels mitjans del CIM UPC i de l’activitat associada a treballs finals d’estudis d’estudiants de la UPC, arribant-se a materialitzar equipaments experimentals per validar-los. La recerca ampla i sistemàtica al respecte fa que s’estigui més a prop de disposar d’una solució d’impressió 3D multimaterial de sobretaula. Es determina que la millor via de progrés és la de disposar d’una pluralitat de capçals independents a fi de capacitar la impressora 3D per integrar diversos conceptes estudiats, materialitzant-se una possible solució. Cloent la tesi, es planteja com seria un equipament d’impressió 3D per a models d’assaig quirúrgic, a fi de servir de base per a futurs desenvolupaments.La presente tesis doctoral se ha centrado en el reto de conseguir, mediante Fabricación Aditiva (FA), modelos para ensayo quirúrgico, bajo la premisa que los equipos para obtenerlos tendrían que ser accesibles al ámbito hospitalario. El objetivo es facilitar la extensión del uso de modelos como herramienta de preparación de operaciones quirúrgicas, transformando la práctica médica actual de la misma manera que, en su momento, lo hicieron tecnologías como las que facilitaron el uso de radiografías. El motivo de utilizar FA, en lugar de tecnologías más tradicionales, es su capacidad de materializar de forma directa los datos digitales obtenidos de la anatomía del paciente mediante sistemas de escaneado tridimensional, haciendo posible la obtención de modelos personalizados. Los resultados se centran en la generación de nuevo conocimiento para conseguir equipamientos de impresión 3D multimateriales accesibles que permitan la obtención de modelos miméticos respecto a los tejidos vivos. Para facilitar la buscada extensión de la tecnología, se ha focalizado en las tecnologías de código abierto como la Fabricación por Hilo Fundido (FFF) y similares basadas en líquidos catalizables. Esta investigación se alinea dentro de la actividad de desarrollo de la FA en el CIM UPC, y en este ámbito concreto con la colaboración con el Hospital Sant Joan de Déu de Barcelona (HSJD). El primer bloque de la tesis incluye la descripción del estado del arte, detallando las tecnologías existentes y su aplicación al entorno médico. Se han establecido por primera vez unas bases de caracterización de los tejidos vivos – principalmente blandos – para dar apoyo a la selección de materiales que los puedan mimetizar en un proceso de FA, a efectos de mejorar la experiencia de ensayo de los cirujanos. El carácter rígido de los materiales mayoritariamente usados en impresión 3D los hace poco útiles para simular tumores y otras referencias anatómicas. De forma sucesiva, se tratan parámetros como la densidad, la viscoelasticidad, la caracterización de materiales blandos en la industria, el estudio del módulo elástico de tejidos blandos y vasos, la dureza de los mismos, y requerimientos como la esterilización de los modelos. El segundo bloque empieza explorando la impresión 3D mediante FFF. Se clasifican las variantes del proceso desde el punto de vista de la multimaterialidad, esencial para hacer modelos de ensayo quirúrgico, diferenciando entre soluciones multiboquilla y de mezcla en el cabezal. Se ha incluido el estudio de materiales (filamentos y líquidos) que serían más útiles para mimetizar tejidos blandos. Se constata como en los líquidos, en comparación con los filamentos, la complejidad del trabajo en procesos de FA es más elevada, y se determinan formas de imprimir materiales muy blandos. Para acabar, se exponen seis casos reales de colaboración con el HJSD, una selección de aquellos en los que el doctorando ha intervenido en los últimos años. El origen se encuentra en la dificultad del abordaje de operaciones de resección de tumores infantiles como el neuroblastoma, y en la iniciativa del Dr. Lucas Krauel. Finalmente, el Bloque 3 desarrolla numerosos conceptos (hasta 8), actividad completada a lo largo de los últimos cinco años con el apoyo de los medios del CIM UPC y de la actividad asociada a trabajos finales de estudios de estudiantes de la UPC, llegándose a materializar equipamientos experimentales para validarlos. La investigación amplia y sistemática al respecto hace que se esté más cerca de disponer de una solución de impresión 3D multimaterial de sobremesa. Se determina que la mejor vía de progreso es la de disponer de una pluralidad de cabezales independientes, a fin de capacitar la impresora 3D para integrar diversos conceptos estudiados, materializándose una posible solución. Para cerrar la tesis, se plantea cómo sería un equipamiento de impresión 3D para modelos de ensayo quirúrgico, a fin de servir de base para futuros desarrollos.
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Mallangi, Siva Sai Reddy. "Low-Power Policies Based on DVFS for the MUSEIC v2 System-on-Chip." Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-229443.
Full textAbstract:
Multi functional health monitoring wearable devices are quite prominent these days. Usually these devices are battery-operated and consequently are limited by their battery life (from few hours to a few weeks depending on the application). Of late, it was realized that these devices, which are currently being operated at fixed voltage and frequency, are capable of operating at multiple voltages and frequencies. By switching these voltages and frequencies to lower values based upon power requirements, these devices can achieve tremendous benefits in the form of energy savings. Dynamic Voltage and Frequency Scaling (DVFS) techniques have proven to be handy in this situation for an efficient trade-off between energy and timely behavior. Within imec, wearable devices make use of the indigenously developed MUSEIC v2 (Multi Sensor Integrated circuit version 2.0). This system is optimized for efficient and accurate collection, processing, and transfer of data from multiple (health) sensors. MUSEIC v2 has limited means in controlling the voltage and frequency dynamically. In this thesis we explore how traditional DVFS techniques can be applied to the MUSEIC v2. Experiments were conducted to find out the optimum power modes to efficiently operate and also to scale up-down the supply voltage and frequency. Considering the overhead caused when switching voltage and frequency, transition analysis was also done. Real-time and non real-time benchmarks were implemented based on these techniques and their performance results were obtained and analyzed. In this process, several state of the art scheduling algorithms and scaling techniques were reviewed in identifying a suitable technique. Using our proposed scaling technique implementation, we have achieved 86.95% power reduction in average, in contrast to the conventional way of the MUSEIC v2 chip’s processor operating at a fixed voltage and frequency. Techniques that include light sleep and deep sleep mode were also studied and implemented, which tested the system’s capability in accommodating Dynamic Power Management (DPM) techniques that can achieve greater benefits. A novel approach for implementing the deep sleep mechanism was also proposed and found that it can obtain up to 71.54% power savings, when compared to a traditional way of executing deep sleep mode.Nuförtiden så har multifunktionella bärbara hälsoenheter fått en betydande roll. Dessa enheter drivs vanligtvis av batterier och är därför begränsade av batteritiden (från ett par timmar till ett par veckor beroende på tillämpningen). På senaste tiden har det framkommit att dessa enheter som används vid en fast spänning och frekvens kan användas vid flera spänningar och frekvenser. Genom att byta till lägre spänning och frekvens på grund av effektbehov så kan enheterna få enorma fördelar när det kommer till energibesparing. Dynamisk skalning av spänning och frekvens-tekniker (såkallad Dynamic Voltage and Frequency Scaling, DVFS) har visat sig vara användbara i detta sammanhang för en effektiv avvägning mellan energi och beteende. Hos Imec så använder sig bärbara enheter av den internt utvecklade MUSEIC v2 (Multi Sensor Integrated circuit version 2.0). Systemet är optimerat för effektiv och korrekt insamling, bearbetning och överföring av data från flera (hälso) sensorer. MUSEIC v2 har begränsad möjlighet att styra spänningen och frekvensen dynamiskt. I detta examensarbete undersöker vi hur traditionella DVFS-tekniker kan appliceras på MUSEIC v2. Experiment utfördes för att ta reda på de optimala effektlägena och för att effektivt kunna styra och även skala upp matningsspänningen och frekvensen. Eftersom att ”overhead” skapades vid växling av spänning och frekvens gjordes också en övergångsanalys. Realtidsoch icke-realtidskalkyler genomfördes baserat på dessa tekniker och resultaten sammanställdes och analyserades. I denna process granskades flera toppmoderna schemaläggningsalgoritmer och skalningstekniker för att hitta en lämplig teknik. Genom att använda vår föreslagna skalningsteknikimplementering har vi uppnått 86,95% effektreduktion i jämförelse med det konventionella sättet att MUSEIC v2-chipets processor arbetar med en fast spänning och frekvens. Tekniker som inkluderar lätt sömn och djupt sömnläge studerades och implementerades, vilket testade systemets förmåga att tillgodose DPM-tekniker (Dynamic Power Management) som kan uppnå ännu större fördelar. En ny metod för att genomföra den djupa sömnmekanismen föreslogs också och enligt erhållna resultat så kan den ge upp till 71,54% lägre energiförbrukning jämfört med det traditionella sättet att implementera djupt sömnläge.
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Seng, Shin Chen, and 施振聖. "Mechanisms of Gastric Mucosal Hemorrhagic Ulceration Induced by Arecoline-seizure : Protection by Several Drugs." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/15531626408773747925.
Full textAbstract:
碩士國立成功大學
藥理學研究所
87
Seizure is commonly and frequently found in many diseases and drug-intoxication. When seizure occurs, patients may suffer from tremor, tonic-clonic convulsion, oxidative stress and coma. These manifestations of seizure may nonspecifically damage various organs, including liver, heart, and lungs. Several chemicals, including pennicillin, kainic acid, pentylenetetrazole and cholinergic agonists also are able to induce seizures. Arecoline (ACL), one of the ingredients of betel quid chewing, possesses potent cholinergic effect. In the present study, we induced seizure by intracerebroventricular injection of graded doses of arecoline (0, 1, 3 and 10 mg/kg in 10 ml of ACSF solution) to SD rats. The present proposal is aimed to study: (1) whether seizure may influence the integrity of gastric mucosa ; and (2) the pharmacolo-gical effects of several mucosal protective drugs on gastric mucosa in seizure rats. Rats were deprived food but allowed free access to water for 24 h. Under ether anesthesia, gastric surgical procedures were performed and the stomachs were cleansed. After recoverd from anesthesia, arecoline was injected and the rats stomachs were irrigated for 2h with an acid solution containing 100mM HCl and 54 mM NaCl. The duration and scores of seizure induced by arecoline were recorded. Gastric mucosal glutathione (GSH) concentrations, histamine levels, lipid peroxide (LPO) generations as well as luminal hemoglogin contents and stomach ulcers also were determined. The results showed that (1) gastric hemorragic ulcer can be produced by central ACL- seizure in rat stomachs irrigated with an acid solution; (2) the ulcerogenesis of ACL-seizure is associated with lower mucosal GSH levels and augmentation of mucosal histamine release and LPO production; (3) seizure induced by ACL can be abolished or prevented by pre-treatment with muscarinic receptor antagonists; (4) central ACL seizure-induced gastric hemorrhagic lesions in acid perfused stomachs may at least via vagal mediation; (5) several drugs, including histamine receptor antagonists and antioxidants, are able to ameliorate gastric hemorrhagic damages during seizure in rats.
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Chen, Chun-Yu, and 陳俊宇. "Mechanisms of Gastric Mucosal Hemorrhagic Ulceration in Salmonella typhimurium-infected Rats：Protection by Several Drugs." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/abtx9z.
Full textAbstract:
碩士國立成功大學
藥理學研究所
90
Salmonella species are a common pathogenic bacteria. When they enter into body, they will cause damages of many organs including liver、kidney、intestine and other important organs. Salmonella typhimurim are a kind of Salmonella species, they can infect many kinds of animals including human, poultry, livestock, experimental animals, etc. Effects of Salmonella species are often studied for many organs in human, but studies for stomach are less. Because studies for stomach are not enough, we interest in gastric effects during infection of Salmonella species. 1ml 1x109 CFU/ml Salmonella typhi- murim were injected into male Wistar rats by intravenous from femoral vein. After 21 hours, the animal were deprived of food for 24 hr to empty food from stomach. Gastric vagotomy was performed, followed by irrigation the stomachs for 3hr with a physiological acid containing 100mM HCl plus 54mM NaCl and 600mg/L pepsin. The ulcerogenic parameters including gastric acid back-diffusion, ulcer area, mucosal lipid peroxide (LPO)、glutathione (GSH) and histamine concentrations, and luminal hemoglobin (Hb) contents were determined. Our results show that a marked increase in acid back- diffusion and in hemorrhagic ulceration was found in infected rats. A significant enhancement in mucosal lipid peroxide and histamine concen- tration, and marked decrease in mucosal glutathione levels in infected rats. Because of oxygen radical and histamine played an important role, we hypothesis that several drugs including free radical scavenger, mast cell stabilizer, histamine receptor antagonist may be used during infection. Our results suggest the gastric damages will be improved after treatment of these drugs.