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Cato, Denys, and mikewood@deakin edu au. "An examination of the 'all hazards' approach to disaster management as applied to field disaster management and pre-hospital care in Australia." Deakin University. School of Health Sciences, 2002. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20051017.140738.
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Disasters, emergencies, incidents, and major incidents - they all come back to the same thing regardless of what they are called. The common denominator is that there is loss of life, injury to people and animals and damage and destruction of property.
The management of such events relies on four phases:
1. Prevention
2. Preparation
3. Response
4. Recovery
Each of these phases is managed in a different way and often by different teams. Here, concentration has been given to phases 2 and 3, with particular emphasis on phase 3, Response.
The words used to describe such events are often related to legislation. The terminology is detailed later. However, whatever the description, whenever prevention is not possible, or fails, then the need is to respond. Response is always better when the responders are prepared. Training is a major part of response preparation and this book is designed to assist those in the health industry who need to be ready when something happens. One of the training packages for responders is the Major Incident Medical Management and Support (MIMMS) Course and this work was designed to supplement the manual prepared by Hodgetts and Macway-Jones(87) in the UK.
Included is what the health services responder, who may be sent to an event in which the main concern is trauma, should know. Concentration is on the initial response and does not deal in any detail with hospital reaction, the public health aspects, or the mental health support that provides psychological help to victims and responders, and which are also essential parts of disaster management.
People, in times of disaster, have always been quick to offer assistance. It is now well recognised however, that the 'enthusiastic amateur', whilst being a well meaning volunteer, isn't always what is needed. All too often such people have made things worse and have sometimes ended up as victims themselves. There is a place now for volunteers and there probably always will be. The big difference is that these people must be well informed, well trained and well practiced if they are to be effective.
Fortunately such people and organisations do exist. Without the work of the St John Ambulance, the State Emergency Service, the Rural Fire Service the Red Cross and the Volunteer Rescue Association, to mention only a few, our response to disasters would be far less effective.
There is a strong history of individuals being available to help the community in times of crisis. Mostly these people were volunteers but there has also always been the need for a core of professional support. In the recent past,
professional support mechanisms have been developed from lessons learned, particularly to situations that need a rapid and well organised response.
As lessons are learned from an analysis of events, philosophy and methods have changed. Our present system is not perfect and perhaps never will be. The need for an 'all-hazards approach' makes detailed planning very difficult and so there will probably always be criticisms about the way an event was handled. Hindsight is a wonderful thing, provided we learn from it. That means that this text is certainly not the 'last word' and revisions as we learn from experience will be inevitable.
Because the author works primarily in New South Wales, many of the explanations and examples are specific to that state. In Australia disaster response is a State, rather than a Commonwealth, responsibility and consequently, and inevitably, there are differences in management between the states and territories within Australia. With the influence of Emergency Management Australia, these differences are being reduced. This means that across state and territory boundaries, assistance is common and interstate teams can be deployed and assimilated into the response rapidly, safely, effectively and with minimum explanation. This text sets out to increase the understanding of what is required, what is in place and how the processes of response are managed.
By way of introduction and background, examples are given of those situations that have occurred, or could happen.
Man Made Disasters has been divided into two distinct sections. Those which are related to structures or transport and those related directly to people. The first section, Chapter 3, includes:
Transport accidents involving land, rail, sea or air vehicles.
Collapse of buildings for reasons other than earthquakes or storms.
Industrial accidents, including the release of hazardous substances and nuclear events.
A second section dealing with the consequences of the direct actions of people is separated as Chapter 4, entitled 'People Disasters'. Included are:
Crowd incidents involving sports and entertainment venues.
Terrorism
From Chapter 4 on, the emphasis is on the Response phase and deals with organisation and response techniques in detail.
Finally there is a section on terminology and abbreviations. An appendix details a typical disaster pack content.
War, the greatest of all man made disasters is not considered in this text.
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El-Hajjar, Mohammed H. "Near-capacity MIMOs using iterative detection." Thesis, University of Southampton, 2008. https://eprints.soton.ac.uk/64487/.
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In this thesis, Multiple-Input Multiple-Output (MIMO) techniques designed for transmission over narrowband Rayleigh fading channels are investigated. Specifically, in order to provide a diversity gain while eliminating the complexity of MIMO channel estimation, a Differential Space-Time Spreading (DSTS) scheme is designed that employs non-coherent detection. Additionally, in order to maximise the coding advantage of DSTS, it is combined with Sphere Packing (SP) modulation. The related capacity analysis shows that the DSTS-SP scheme exhibits a higher capacity than its counterpart dispensing with SP. Furthermore, in order to attain additional performance gains, the DSTS system invokes iterative detection, where the outer code is constituted by a Recursive Systematic Convolutional (RSC) code, while the inner code is a SP demapper in one of the prototype systems investigated, while the other scheme employs a Unity Rate Code (URC) as its inner code in order to eliminate the error floor exhibited by the system dispensing with URC. EXIT charts are used to analyse the convergence behaviour of the iteratively detected schemes and a novel technique is proposed for computing the maximum achievable rate of the system based on EXIT charts. Explicitly, the four-antenna-aided DSTSSP system employing no URC precoding attains a coding gain of 12 dB at a BER of 10−5 and performs within 1.82 dB from the maximum achievable rate limit. By contrast, the URC aided precoded system operates within 0.92 dB from the same limit. On the other hand, in order to maximise the DSTS system’s throughput, an adaptive DSTSSP scheme is proposed that exploits the advantages of differential encoding, iterative decoding as well as SP modulation. The achievable integrity and bit rate enhancements of the system are determined by the following factors: the specific MIMO configuration used for transmitting data from the four antennas, the spreading factor used and the RSC encoder’s code rate. Additionally, multi-functional MIMO techniques are designed to provide diversity gains, multiplexing gains and beamforming gains by combining the benefits of space-time codes, VBLAST and beamforming. First, a system employing Nt=4 transmit Antenna Arrays (AA) with LAA number of elements per AA and Nr=4 receive antennas is proposed, which is referred to as a Layered Steered Space-Time Code (LSSTC). Three iteratively detected near-capacity LSSTC-SP receiver structures are proposed, which differ in the number of inner iterations employed between the inner decoder and the SP demapper as well as in the choice of the outer code, which is either an RSC code or an Irregular Convolutional Code (IrCC). The three systems are capable of operating within 0.9, 0.4 and 0.6 dB from the maximum achievable rate limit of the system. A comparison between the three iteratively-detected schemes reveals that a carefully designed two-stage iterative detection scheme is capable of operating sufficiently close to capacity at a lower complexity, when compared to a three-stage system employing a RSC or a two-stage system using an IrCC as an outer code. On the other hand, in order to allow the LSSTC scheme to employ less receive antennas than transmit antennas, while still accommodating multiple users, a Layered Steered Space-Time Spreading (LSSTS) scheme is proposed that combines the benefits of space-time spreading, V-BLAST, beamforming and generalised MC DS-CDMA. Furthermore, iteratively detected LSSTS schemes are presented and an LLR post-processing technique is proposed in order to improve the attainable performance of the iteratively detected LSSTS system. Finally, a distributed turbo coding scheme is proposed that combines the benefits of turbo coding and cooperative communication, where iterative detection is employed by exchanging extrinsic information between the decoders of different single-antenna-aided users. Specifically, the effect of the errors induced in the first phase of cooperation, where the two users exchange their data, on the performance of the uplink in studied, while considering different fading channel characteristics.
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Belghiti, Touria. "Synthèse de glycophanes mimes de cyclodextrines." Nancy 1, 2002. http://www.theses.fr/2002NAN10011.
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De nouveaux glycophanes ont été construits par le biais de la réaction de Ferrier, la réaction de Williamson et la réaction de couplage oxydant. La préparation originale de différents disaccharides 1,1' a été réalisée avec de bons rendements par double condensation de diols symétriques commerciaux sur le D-glucal. La réaction de Glaser s'est imposée pour la construction des cycles une fois un éther de propargyl installé sélectivement sur C-4 par transfert de phase après que la fonction alcool primaire ait été protégée par réaction avec le chlorure de trityle plus sélectif que les réactifs silylés (TBDMSCl et TBDPSCl). Deux stratégies de cyclisation ont été développées : la méthode directe, qui conduit aussi à une dimérisation par intracyclisation, et une méthode indirecte, dénommée " pas à pas ", qui permet d'orienter la cyclisation vers l'obtention de tétrasaccharides (et d'oligomères de plus grande taille) en se dispensant de protections orthogonales. La réduction ménagée de la double liaison sur le sucre a permis la synthèse de 2 glycophanes en quantités égales : un tétrasaccharide cyclique et un très remarquable octasaccharide cyclique, dimère du premier. Après isolement, le glycophane incorporant 4 résidus sucre a été partiellement réduit par hydrogénation catalytique ménagée. La plupart de ces macrocycles ont pu être pleinement caractérisés sans ambigui͏̈té à l'aide de la spectrométrie de masse MALDI-TOF.
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Probin, Jamie. "How ideal is the Mimas-Tethys resonance?" Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367166.
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Halie, Delphine. "Synthèse diastéréosélective de mimes du peptide RGD." Paris 5, 2006. http://www.theses.fr/2006PA05P639.
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Moris, Marc-Antoine Schlewer Gilbert. "Synthèse d'analogues de phosphates d'inositol mimes de l'adénophostine." Strasbourg : Université Louis Pasteur, 2006. http://eprints-scd-ulp.u-strasbg.fr:8080/505/01/MORIS2006.pdf.
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Moris, Marc-Antoine. "Synthèse d'analogues de phosphates d'inositol mimes de l'adénophostine." Strasbourg 1, 2006. https://publication-theses.unistra.fr/public/theses_doctorat/2006/MORIS_Marc-Antoine_2006.pdf.
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L'objet de ce travail est la synthèse et l'étude des propriétés pharmacologiques d'analogues de l'Ins(1,4,5)P3 mimes de l'adénophostine. Le rôle et les interactions biologiques de l'Ins(1,4,5)P3 et de l'adénophostine, de même que leurs relations structure/activité sont rappelés. Le potentiel thérapeutique lié au cycle des phosphates d'inositol est mentionné. L'orthoester du myo-inositol, inversant la conformation chaise de l'inositol, permet d'activer la position 2 ainsi équatoriale et d'introduire les espaceurs. Ce travail décrit une voie de synthèse innovante d'analogues de l'Ins(1,4,5)P3 chimères de l'adénophostine possèdant un bras butylique purinylé. Les propriétés pharmacologiques de nos analogues atteignent celles de l'Ins(1,4,5)P3. Ceci est plus perceptible si nous considérons le fait que nos composés sont racémiques. Ces résultats confirment le pharmacophore indiquant que la position 2 tolère la substitution, tel que l'indique le modèle de pharmacophore communément admisThe aim of this work was the synthesis and the study of the pharmacological properties of adenophostin mimes Ins(1,4,5)P3 analogues. The biological function and targets of Ins(1,4,5)P3 and adenophostin as well as their structure/activity relationships are reported. The therapeutic potential linked to the inositol phosphates cycle is mentioned. The use of a myo-inositol orthoester, inverting the inositol chair conformation, permitted the activation of the position 2 and the introduction of the lateral chains. This work describes an innovative synthetic pathway of adenophostin mimes Ins(1,4,5)P3 analogues possessing a purinylated butylic arm. The pharmacological properties of our analogues are matching those of the Ins(1,4,5)P3. This is more noticeable if we consider the fact that our compounds are racemic. These results support those of previous studies indicating that the position 2 tolerates some substitution, as indicated by the commonly admitted pharmacophore model
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Zagiel, Benjamin. "Chimie combinatoire dynamique pour l’identification de mimes de protéines." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS520.
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Les interactions protéines protéines (PPI) constituent des cibles thérapeutiques de premier intérêt mais la complexité des interfaces impliquées dans ces interactions rend le développement d’inhibiteurs de PPI difficile. Les peptides présentent un grand potentiel pour cibler les PPI mais sans structure 3D définie, ils ne présentent généralement pas d’affinité. Les peptides contraints dans une conformation contrôlée ou scaffolds constituent une solution efficace mais leur conception requiert une compréhension significative du complexe protéique à l’échelle de l’épitope. Ce travail a pour but de développer une approche de chimie combinatoire dynamique (DCC) pour la fonctionnalisation de scaffolds peptidiques. Cette approche permettrait de générer des librairies dynamiques par des réactions réversibles équilibrées entre des blocs moléculaires. Ces systèmes dynamiques étant sensibles aux stimuli, il est alors possible d’introduire une cible d’intérêt pour les cribler, le tout en une seule étape. Ce manuscrit présente la conception et la synthèse de blocs moléculaires et de scaffolds pour cette stratégie de DCC. La mise au point de cette méthodologie de DCC est ensuite présentée dans une approche pas à pas jusqu’à une tentative d’application à une cible d’intérêt : l’héparine. La développement d’une méthode d'analyse par spectrométrie de masse des composés générés par DCC est ensuite abordée. Enfin, l'analyse structurale des plateformes et l'influence de leur fonctionnalisation sur leur structuration est abordéeProtein protein interactions (PPI) are therapeutic targets of prime interest but the complexity of their interaction interfaces makes difficult the development of PPIs inhibitors. Peptides display great potential for targeting PPIs but without a defined 3D structure, they usually show no affinity. Constrained peptides with a controlled conformation or scaffolds constitute an effective solution but their design requires a significant comprehension of the protein complex at the epitope scale.This work aims at developing a dynamic combinatorial chemistry (DCC) approach to functionalize peptide scaffolds. This approach allows to generate dynamic libraries thanks to equilibrated reversible reactions between molecular building blocks. These dynamic systems being stimuli-responsive, it is therefore possible to introduce a relevant target to screen them in one step. This thesis presents the design and the synthesis of the building blocks and scaffolds for this DCC strategy. The development of the DCC methodology is then presented in a step by step approach up to an application attempt with heparin as the target. Next, the mass spectrometry method for the analysis of the DCC generated compounds and its setting up is addressed. Finally, the analysis of the peptide scaffolds structure and the influence of their functionalization on it is broached
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Manzoor, Suryyia 1984. "Materiais impressos molecularmente (MIMs) : síntese, caracterização e avaliação." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/250225.
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Orientadores: Adriana Vitorino Rossi, Regina BuffonTese (doutorado) - Universidade Estadual de Campinas, Instituto de Química
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Resumo: Este trabalho envolveu um estudo elaborado da técnica de impressão molecular para síntese, caracterização e avaliação de materiais impressos molecularmente (MIMs) para fluconazol (FLU), cafeína (CAF) e antocianinas (ACYs). O polímero de impressão molecular para FLU (FLUMIP) foi sintetizado utilizando-se ácido metacrílico (monômero funcional), etilenoglicoldimetacrilato (EGDMA) (agente reticulador) e acetonitrila em polimerização térmica. O FLUMIP foi caracterizado e aplicado como sorvente em cartuchos de extração em fase sólida (SPE). Sua capacidade de interação seletiva com o analito foi avaliada, obtendo-se alta afinidade para FLU, em comparação com análogos estruturais, com limite de detecção menor que 1,63X10 mmol/L com cromatografia de ultra alta eficiência acoplada com espectrometria de massas. Este MIP foi usado em cartuchos de SPE para extrair o analito de medicamento em cápsula, com recuperação de 91±10 % (n=9). Outro MIM obtido foi uma sílica organicamente modificada (ORMOSIL) para extração de CAF, a partir da reação de metacrilato de 3- (trimetoxisilil) propila e acetato de vinila, seguindo-se condensação e hidrólise com tetraetilortosilicato usando CAF como molécula modelo. Este ORMOLSIL foi caracterizado e testado quanto à sua eficácia de extrair CAF de amostras de café, com recuperação de 88±5 % (n=9); ele atuou como grupo seletivo com alta porcentagem de recuperação para teofilina (77 %) e teobromina (82 %). Limites de detecção e quantificação 5,14x10 e 1,71x10 mmol/L respectivamente foram obtidos com cromatografia líquida de alta eficiência. Também foi sintetizado um MIP usando rutina molécula modelo (RUTMIP), acrilamida (monômero funcional), EGDMA (agente reticulador) e tetraidrofurano por polimerização em bulk. Embora tenha sido alcançada impressão bem sucedida de rutina, confirmada pela comparação de afinidade de RUTMIP em aplicação de SPE (12 vezes maior que afinidade do polímero não impresso), não se alcançou a seletividade esperada para ACYs utilizando o RUTMIP
Abstract: This work involves an elaborative study of molecularly imprinting technique. Keeping in view its robustness and selectivity, this technique was applied for the synthesis of molecularly imprinted materials for the extraction of fluconazole (FLU), caffeine (CAF) and anthocyanins (ACYs). Molecularly imprinted polymer (MIP) for FLU (FLUMIP) was synthesized using methacrylic acid (functional monomer), ethyleneglycoldimethacrylate (crosslinker) and acetonitrile through thermal polymerization. The FLUMIP was characterized and applied as sorbent in solid phase extraction (SPE) cartridges. It was then evaluated for its ability to selectively interact with the analyte and presented an apparent affinity for FLU, which was confirmed by comparing it with structural analogues. The application of ultra high performance liquid chromatography with spectrometer mass detection, allowed a limit of detection 1.63x10 mmol/L. Furthermore, the SPE procedure was applied to extract FLU from medicine samples with recovery of 91±10 % (n=9). An organically modified silica (ORMOSIL) for CAF was also synthesized by reacting vinyl acetate and 3- (trimethoxysilyl) propyl methacrylate, followed by the condensation and hydrolysis with tetraethyl orthosilicate, using CAF as template molecule. The ORMOSIL was characterized and tested for its efficiency to extract the analyte from coffee samples and the percentage recovery of 88±5 % (n=9) was obtained. The cross reactivity studies for theophylline and theobromine showed high recovery (77 % and 82% respectively). The limit of detection and quantification, 5.14x10 and 1.71x10 mmol/L respectively, were achieved using high performance liquid chromatography. Also, a MIP for ACYs (RUTMIP) was synthesized using rutin (template molecule), EGDMA (cross linker) and tetrahydrofuran by the bulk polymerization method. A successful imprinting of rutin was attained. This can be confirmed by the high affinity of rutin for MIP (12 times greater than non imprinted polymer) during SPE procedure; however, the RUTMIP was not efficient enough to selectively extract ACYs from vegetal extracts
Doutorado
Doutora em Ciências
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Hernout, Olivier. "Mimes saccharides d'Inositol Phosphate Glycanne : synthèse et propriétés insulo-mimétiques." Nancy 1, 2005. http://www.theses.fr/2005NAN10014.
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Dans le but d'améliorer la compréhension du rôle que joue les IPG (Inositol Phosphate Glycanne) dans la signalisation de l'insuline, la synthèses de différents analogues de type O-et C-disaccharidique a été réalisée. Dans un premier temps, la synthèse de huit O-disaccharides dont les aglycones lyxose, arabinose et ribose portent un phosphate cyclique, est décrite. La deuxième partie est consacrée à la synthèses totale en treize étapes d'un C-disaccharide, portant également un phosphate cyclique. L'activité de ces composés sur la prolifération cellulaire a été mesurée sur des cellules d'adénocarcinomes de colon humain et des fibroblastes dermiques. Les effets insulino-mimétiques de ces molécules on été évalués sur la captation du glucose sur une lignée d'adipocytesThat work deals with the synthesis of O- and C-disaccharide analogues of PIG (Phosphate Inositol Glycan) in order to have a better understanding of its role in the signalisation of insulin. Firstly, th synthesis of eight O-disaccharides, in which the aglycon part (lyxose, arabinose and ribose) includes a cyclic phosphate. Secondly, we present th total synthesis in thirteen steps of C-disaccharide which also includes a cyclic phosphate. The biological activity of those compounds on the cellular growth was measured on human colon adenocarcinomae cells and on dermic fibroblasts. The insulino-mimetic effects of those compounds were evaluated on the glucose uptake in adipocytes
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Mendes, Maria Anita. "Tecnicas avançadas em espectrometria de massas - MIMS e suas derivadas CT-MIMS : aplicação na analise de compostos organicos volateis em matrizes ambientais." [s.n.], 1999. http://repositorio.unicamp.br/jspui/handle/REPOSIP/248669.
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Orientador: Marcos N. EberlinTese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica
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Doutorado
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Bonnet, Romaric. "Synthèse et utilisation de mimes de quadruplexes pour l'évaluation de ligands." Phd thesis, Université de Grenoble, 2012. http://tel.archives-ouvertes.fr/tel-00824972.
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Synthèse et utilisation de mimes de quadruplexes contraints pour l'évaluation de ligands II est maintenant bien connu que l'ADN simple brin peut s'associer sous différentes conformations telles que la double hélice, les triplexes, les i-motifs ou bien encore les G-quadruplexes. Ces dernières années les structures de type quadruplexes (G-quadruplexes et i-motif) ont suscité un certain intérêt notamment pour leur implications au niveau cellulaire (maintenance des télomères, activation de gènes...). C'est pourquoi de nombreuses équipes travaillent sur le développement de ligands affins pour ces structures qui pourraient agir en tant qu'anticancéreux. Cependant, le fait que les quadruplexes présentent un polymorphisme important(variabilité du nombre de brins dans la structure, des différents types de boucles et de l'orientation des brins) rend la compréhension des interactions entre un ligand et le quadruplexe plus difficile. Dans ce contexte, l'équipe développe un nouveau concept, " Template Assisted Synthesis of Quadruplexes " (TASQ) dont le but est d'obtenir un quadruplexe ne présentant qu'une topologie de façon contrôlée afin de permettre des études plus précises sur la façon dont un ligand pourrait interagir avec les quadruplexes. La première partie de ce manuscrit reporte l'évaluation par résonnance plasmonique de surface de complexes métalliques en tant que ligands de G-quadruplexe. Ces études reposent sur l'utilisation d'un premier mime de G-quadruplexe parallèle sur lequel deux séries de complexes sont testées : des métalloporphyrines et des ligands de type salphen. La seconde partie du manuscrit décrit la synthèse de mimes de G-quadruplexes antiparallèle. Elle repose sur l'utilisation du gabarit peptidique qui relié aux séquences spécifiques d'oligonucléotides de façon adéquat contraint la structure. Pour se faire, deux réactions chimiosélectives ont été utilisées : la cycloaddition 1,3 dipolaire de Huisgen et la ligation oxime. Les travaux reportés concernent trois types de structure mimant un i-motifs, des G-quadruplexes tétramoléculaires ou bimoléculaires.
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Wade, G. A., C. Neiner, E. Alecian, H. H. Grunhunt, V. Petit, B. Batz, D. A. Bohlender, et al. "The MiMeS Survey of Magnetism in Massive Stars: Introduction and Overview." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/2723.
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The MiMeS (Magnetism in Massive Stars) project is a large-scale, high-resolution, sensitive spectropolarimetric investigation of the magnetic properties of O- and early B-type stars. Initiated in 2008 and completed in 2013, the project was supported by three Large Program allocations, as well as various programmes initiated by independent principal investigators, and archival resources. Ultimately, over 4800 circularly polarized spectra of 560 O and B stars were collected with the instruments ESPaDOnS (Echelle SpectroPolarimetric Device for the Observation of Stars) at the Canada–France–Hawaii Telescope, Narval at the Télescope Bernard Lyot and HARPSpol at the European Southern Observatory La Silla 3.6 m telescope, making MiMeS by far the largest systematic investigation of massive star magnetism ever undertaken. In this paper, the first in a series reporting the general results of the survey, we introduce the scientific motivation and goals, describe the sample of targets, review the instrumentation and observational techniques used, explain the exposure time calculation designed to provide sensitivity to surface dipole fields above approximately 100 G, discuss the polarimetric performance, stability and uncertainty of the instrumentation, and summarize the previous and forthcoming publications.
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Rodrigues, Sheila Silva. "Biologia e sucesso reprodutivo de Mimus saturninus (aves: mimidae) no cerrado." reponame:Repositório Institucional da UnB, 2009. http://repositorio.unb.br/handle/10482/4585.
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Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2009.Submitted by Elna Araújo (elna@bce.unb.br) on 2010-04-14T21:06:24Z No. of bitstreams: 1 2009_SheilaSilvaRodrigues.pdf: 1800180 bytes, checksum: 8c111e6a38a51732822a8990fda9ea7e (MD5)
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O Sabiá-do-campo, Mimus saturninus (Mimidae) é bastante comum em cerrados, campos, pastos com árvores e arbustos esparsos, além de ser freqüentemente observado em ambientes urbanos. O presente trabalho teve o objetivo de estudar aspectos da sua biologia e sucesso reprodutivo em uma área natural de cerrado. A coleta de dados ocorreu na Estação Ecológica de Águas Emendadas (ESECAE) entre os anos de 2003 e 2008. Localizamos 64 ninhos da espécie para os quais, foi possível determinar o destino de 55 deles. Foram utilizados 45 ninhos para análise do sucesso reprodutivo e sobrevivência dos ninhos. A maioria dos ninhos foi encontrada em Cerrado ralo (50%). A incubação é assincrônica e a reprodução ocorre de agosto a dezembro. O ninho é em formato de tigela, constituído de gravetos, confeccionado principalmente em arbustos de Davilla elliptica (Dilleniaceae). A altura média do ninho em relação ao solo foi de 1,3 0,6 m. O tamanho da ninhada variou de um a seis ovos, com predominância de ninhadas de três ovos. Tanto o período médio de incubação como o de permanência dos ninhegos no ninho foram estimados em 14 0,27 dias. Encontramos apenas um ninho parasitado por Chopim, Molothrus bonariensis. O sucesso reprodutivo aparente, o sucesso de eclosão dos ovos e o sucesso estimado pelo método de Mayfield foram de 54,5; 40,5 e 54,6 %, respectivamente. A predação foi atribuída como a principal causa do fracasso reprodutivo (88%). Dentre os ninhos predados, 86,4% foram perdidos na fase de ninhego e 13,6% na de incubação. A infestação dos ninhegos por larvas de dípteras foi freqüente, porém nenhuma perda foi atribuída a esse fator. A probabilidade de sobrevivência dos ninhos, modelada pelo método de exposição logística, mostra que a sobrevivência pode variar de acordo com a idade do ninho e o tamanho da ninhada. Ninhadas maiores apresentam sobrevivência diária relativamente maior do que ninhadas pequenas. Ninhos no fim da fase de incubação sofrem um decréscimo na sobrevivência diária e as menores probabilidades de sobrevivência foram encontradas nos primeiros dias da fase de ninhego seguidas por um aumento no fim do mesmo período. A sobrevivência diária dos ninhos não foi afetada pelas fitofisionomias escolhidas para a nidificação e ao longo da estação reprodutiva. _________________________________________________________________________________ ABSTRACT
The Chalk-browed Mockingbird, Mimus saturninus (Mimidae) is a very common bird in cerrados, grasslands, and pasturelands with scattered trees or shrubs, also occurring in urban environments. Here I studied aspects of its breeding biology and success in a natural cerrado. Data was collected at Estação Ecológica de Águas Emendadas (ESECAE) from 2003 to 2008. I monitored 64 nests of which 55 had a known fate. I used 45 nests for the reproductive success and nest survival analyses. Most nests (50%) were found at open cerrado. Incubation was asynchronic and nesting lasted from August to December. Nests were an open-cup built with twigs usually on a Davilla elliptica (Dilleniaceae) shrub. Mean nest height above the ground was 1.3 0.6 m. Clutch size was invariably of three, but ranging from one to six eggs. Both the incubation and the nestling period lasted 14 0.3 days. Only one nest was parasited by the Shiny Cowbird, Molothrus bonariensis. The apparent success, the success of eggs and the Mayfield success were 54.5, 40.5 and 54.6 %, respectively. Predation was the main cause of nest failure, accounting for 88% of loses. Among the predated nests, 86.4% were lost during the nestling phase and only 13.6% were lost during the incubation phase. Nestling infestation by botflies was common but did not cause the death of nestlings. Nest survival rates, modeled by the logistic exposure method, showed that they could vary according to nest age and clutch size. Larger clutch sizes had higher survival rates than smaller clutch sizes. Nests at the end of incubation phase had a decrease in survival, had the lowest success in the first days of the nestling phase and increased again at the end of the nestling phase. Nests daily survival rates were not affected by vegetation type or by time of the season.
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Morisset, Vanessa. "Peinture et cinéma dans l'oeuvre de Mimmo Rotella autour de 1960." Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAH037/document.
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Depuis son invention, le cinéma a bouleversé la culture, au point que, de manière récurrente, des études s'interrogent sur l'influence qu'il a eue dans la pensée d'éminents intellectuels, par exemple Michel Foucault ou Erwin Panofsky. Mais qu'en est-il de l'influence du cinéma dans le travail des artistes ? Mimmo Rotella (1918-2006), peintre d'origine calalabraise installé après-guerre à Rome, spectateur assidu et passionné de cinéma, évoque un grand nombre de films dans un corpus d'œuvres réalisées autour de 1960 : des tableaux à base d'affiches de cinéma, de genres essentiellement populaires, décollées dans les rues. Ainsi, dans le contexte de l'apogée des studios de Cincecittà et d'un pic de fréquentation des salles obscures jamais égalé en Europe, l'articulation de la peinture et du cinéma prend à ce moment précis de sa pratique une tournure singulière qui exprime l'élargissement de l'art à des références inattendues. Mais, ce faisant, ses œuvres ne risqueraient-elles pas de n'être que le symptôme d'une pratique culturelle naissante, jonglant avec des références tantôt cultivées tantôt populaires, que plus tard Hal Foster nomme l'indistinction ou Richard Peterson l'omnivorité, ou incarnent-t-elles une réelle démocratisation de l'art ?Articulées autour du moment fort que constitue l'exposition monographique intitulée Cinecittà en 1962, les différentes parties de la thèse éclairent les aspects du travail de l'artiste qui introduisent le cinéma dans le champ de l'art. Deux bornes chronologiques, un voyage aux États-Unis qui le détourne de la peinture en 1952-53 et un séjour en prison en 1964 qui lui fait fuir l'Italie, l'éloigne du milieu romain et le coupe de la suite du déroulement de l'art italien, sont déterminantes pour la nature et le contenu du corpus d'œuvres étudiées.C'est tout d'abord l'arrière plan social et culturel comme contexte d'émergence du geste artistique Rotella qui est brossé. Ensuite, est opérée une caractérisation précise des films choisis à travers les affiches afin de développer la réflexion sur l'intrusion du cinéma populaire dans l'art. Puis, dans la partie centrale, l'exposition Cinecittà est étudiée depuis sa conception jusqu'à sa réception. La suite de la thèse analyse les conséquences de cette exposition dans l'œuvre de l'artiste qui se tourne vers des films plus reconnus qu'aux débuts, notamment en s'attachant de plus en plus aux figures de stars : un autre aspect de la culture populaire émanant du cinéma s'invite alors dans le milieu de l'art, le phénomène sociologique du fan. Mais étrangement, peu de référence sont faites au cinéma italien qui vit son âge d'or au même moment, ce dernier constat ouvrant une réflexion sur la cinéphilie confrontée à la conception de « l'homme ordinaire du cinéma » selon l'expression de Jean-Louis Schefer.Ponctué par des images qui apparaissent en tête de partie et de chapitre, le texte du volume 1 évoque les œuvres et les décrit, avec des renvois à un ensemble de planches en annexe dans le volume 2. Ces incursions iconographiques rappellent combien les oeuvres sont à la source de l'ensemble de la thèse.Ainsi, le corpus étudié est le point de départ d'une réflexion sur la manière dont le cinéma et la culture médiatique se sont introduit dans l'art italien des années 1950-1960, tout en débordant ce cadre : il permet de penser comment, depuis cette époque jusqu'à aujourd'hui, certaines références médiatiques constituent le socle d'une culture commune entre le public et les artistesSince its invention, cinema has transformed culture, to the point that studies have recurrently questioned the influence it has had on the thinking of prominent intellectuals, for example on Michel Foucault or Erwin Panofsky. But what of the influence of cinema in the work of artists? Mimmo Rotella (1918-2006), a painter from Calalabria who settled in post-war Rome, and an avid filmgoer with a passion for cinema, evokes a large number of films in a corpus of works produced around 1960: canvases based on movie posters, mostly of popular genres, torn off the city walls. Thus, at this precise time, in the context of the glory years of the Cincecittà studios and a peak of cinema attendance unequalled in Europe, the relationship between painting and cinema took a particular turn, reflecting a broadening of the art to unexpected references. But in embracing cinema, were Rotella's works not in danger of merely being a symptom of an emerging cultural practice, juggling sometimes cultivated and sometimes popular references, something which Hal Foster would later dub nobrow or Richard Peterson omnivorousness, or do they represent a genuine democratisation of art?Articulated around the high point of the 1962 monographic exhibition entitled Cinecittà, the various sections of the thesis illuminate aspects of the work of the artist who introduced cinema into the field of art. Two moments in time – a trip to the United States that diverted Rotella from painting in 1952-53 and a prison stay in 1964 that caused him to flee Italy, distancing him from the Roman scene and subsequently cutting him off from what was happening in Italian art – are critical to the nature and the content of the corpus of works studied.We begin by considering the social and cultural context in which Rotella's artistic act emerged. We then undertake a precise characterisation of the films he chose through the posters to analyse popular cinema's intrusion into art. Then, in the central part, the Cinecittà exhibition is studied from its conception to its reception. The thesis subsequently examines the consequences of this exhibition in the work of the artist, who begins to turn to more recognized films, for example by focusing increasingly on stars. Another aspect of popular culture stemming from cinema then enters the art world, the sociological phenomenon of the fan, although, strangely, no reference is made to Italian cinema, which in that very period was enjoying its golden age. This leads to a reflection on the love of cinema confronted with the conception of “the common man of cinema” as Jean-Louis Schefer puts it.Interspersed with images that appear at the head of the parts and chapters of the thesis, the text of volume 1 discusses the works and describes them with reference to a set of plates in the appendix in volume 2. These incursions into the iconography recall that the works are the source of the entire thesis.Thus the corpus studied is the starting point for a reflection on the way film and media culture were introduced into the Italian art of the 1950s-1960s, while extending beyond this context: it points to how, from that time to the present day, certain media references have constituted the foundation of a common culture shared by the public and artists
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Francois-Heude, Marc. "Mimes de Haut-Mannoses : synthèse, caractérisation et reconnaissance par les lectines." Amiens, 2014. http://www.theses.fr/2014AMIE0100.
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Les oligomannoses naturels de type N-glycane, notamment les Haut-Mannoses, sont liés de manière covalente à certaines protéines et sont impliqués dans de nombreux mécanismes biologiques. Leur synthèse, au laboratoire, reste difficile et coûteuse et les quantités obtenues ne permettent pas d'envisager une utilisation à grande échelle pour des applications thérapeutiques. La production de mime, moins coûteuse et plus rapide, se présente alors comme une alternative. Notre stratégie, avec pour objectif de conserver au mieux la structure tridimensionnelle native des Haut-Mannoses, consiste à substituer les trois mannoses internes par des unités 1,2,3 triazoles permettant l'ajout de six résidus mannoses / pseudo-mannoses en une seule étape de cycloaddition 1,3 dipolaire. Une bibliothèque de mimes a été synthétisée comprenant des analogues de petite taille dont le PMan3 (Pseudo Mannoside initialement constitué de 3 mannoses), le PMan4 et le PMan5. De manière similaire, le PMan8 et le PMan9, de tailles plus importantes, ont été synthétisés avec une quantité finale de l'ordre de la centaine de milligrammes. Les tests biochimiques (ELLA), réalisés sur deux lectines (La Concanavaline A (Con A) et une lectine de macrophage humain (rhMMR)) ont révélé des IC50 similaires pour le Man9 naturel et le PMan9 (respectivement de 3 et 7,1 M sur la Con A et de 4 et 5,5 M pour la rhMMR). Les constantes d'affinité (KD) des Haut-Mannoses naturels avec la Con A ont été déterminées par spectrométrie de masse. La détermination des KD des mimes est en cours. La résolution de la structure du complexe PMan9 / Con A par cristallographie montre que les mannoses terminaux sont reconnus de la même manière que les oligomannoses naturels. En résumé, nos résultats confirment que notre stratégie de synthèse conduit à la synthèse aisée de mimes de Haut-Mannoses dont les caractéristiques biochimiques et structurales sont proches de leurs homologues naturelsHigh-mannoses are natural N-glycan type oligomannoses which are covalently linked to definite proteins and are involved in diverse biological mechanisms. Their synthesis remains difficult and expensive, and the quantities obtained do not allow considering a large scale-up for therapeutic applications. The cheaper and faster mimic production can thus be seen as an alternative. The goal of our mimic (pseudo oligomannose) synthesis strategy is to conserve as much as possible the tridimensional features of natural High-mannoses. It is based on the substitution of the three internal mannose residues by 1,2,3 triazole units allowing the addition of six mannoses/pseudo-mannoses terminal residues in a single 1,3 dipolar cycloaddition step. A mimic library has been generated including the low molecular weight PMan3 (pseudo tri-mannose), PMan4 and PMan5 analogues. In a similar manner the PMan8 and PMan9 have been synthetized at the 100 mg scale. Biochemical ELLA assays using either the Concanavalin A (Con A) or the human macrophage lectin (rhMMR) have shown very similar IC50 values between the natural Man9 and its PMan9 mimic (3 and 7,1 M by using Con A, and 4 et 5,5 M by using rhMMR respectively). The dissociation constants of natural High-mannoses toward Con A have been determined by mass spectrometry and the same analyses are on-going for their mimic counterparts. Moreover, the crystal structure of the PMan9/Con A complex has been resolved and has shown that the terminal mannoses are recognized in a similar manner as the natural oligomannoses. Altogether, our results confirmed that our synthesis strategy leads easily to the production of high-mannose mimics whose biochemical and structural features are closed to their natural counterparts
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Perato, Serge. "Synthèse et études structurales de nouvelles oligophénylpyridines comme mimes d'hélice α." Caen, 2012. http://www.theses.fr/2012CAEN4079.
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Les foldamères sont des molécules ayant la capacité d’adopter une conformation spatiale similaire aux structures protéiques secondaires. On peut distinguer deux types de foldamères, les foldamères biotiques dont la structure est inspirée de biomolécules, et les foldamères abiotiques qui présentent quand à eux une grande variété structurale. Nous nous sommes plus particulièrement intéressés aux foldamères abiotiques de structure oligophénylpyridine accessibles par la mise en œuvre de la réaction de couplage de Suzuki-Miyaura. L’influence des différents acteurs et paramètres du couplage a été minutieusement étudiée dans le cas de la synthèse de bi(hétéro)aryles. Fort de l’expérience du laboratoire dans ce domaine, ce travail nous a permis de développer des voies de synthèse originales afin de constituer une chimiothèque de plus de 70 oligophénylpyridines diversement substituées. Des études de modélisation moléculaire, de cristallographie par diffraction des rayons X ainsi que de RMN ont alors été entreprises afin d’évaluer la capacité des oligophénylpyridines à mimer la distribution d’une hélice α. Par ailleurs, l’évaluation biologique de nos composés a été réalisée et les premiers résultats encourageants montrent que les oligophénylpyridines sont capables de perturber les interactions protéine-protéine intervenant dans les voies de signalisation de l’apoptose et en particulier des membres de la famille de protéines Bcl-2. Une partie expérimentale décrit les modes opératoires et les caractéristiques physico-chimiques de tous les dérivés nouveaux synthétisés. Enfin, près de 150 références bibliographiques replacent cette étude dans son contexte chimique et biologiqueFoldamers are oligomers that fold into a conformationally ordered spatial state similar to the protein secondary structures. Two kind of foldamères can be identified, biotic foldamers whose structure is inspired by biomolecules and abiotic foldamers characterized by various structures. We are particularly interested in abiotic foldamères with an oligophenylpyridyl structure which can be obtained by the implementation of Suzuki-Miyaura cross-coupling reaction. The study of the influence of different partners and coupling conditions in the case of synthesis of bi(het)aryl has been accurately carried out. Taking into account the laboratory’s experience in this field, this work has allowed us to develop original synthetic routes to create a chemical library of over 70 variously substituted oligophenylpyridines. Molecular modeling, crystallography X-ray diffraction and NMR studies were undertaken to assess the ability of oligophenylpyridines to mimic the α–helix. Moreover, biological evaluation of our compounds was carried out and the first encouraging results show that oligophenylpyridines are able to disrupt protein-protein interactions involved in signaling pathways of apoptosis and in particular of Bcl-2 family proteins. The experimental section describes procedures and physico-chemical properties of all new synthesized derivatives. Finally, nearly 150 references situate this study in its chemical and biological context
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Terrien, Anaïs. "Synthèse et étude structurale multi-échelle de peptides mimes de collagène." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066647/document.
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L'omniprésence du collagène dans le corps humain et les nombreuses pathologies qui sont associées à ses anomalies de structure en font un objet d'étude de premier plan. Le collagène possède dans sa séquence primaire de nombreux cycles pyrrolidines stabilisant une structure secondaire de type polyproline II (PPII) et une structure tertiaire en triple hélice correspondant à un superenroulement de trois chaines peptidiques. Lors de ce travail, nous nous sommes intéressés à la synthèse et la caractérisation structurale de peptides mimes de collagène (CMP), seuls ou en présence de collagène de type I. Pour appréhender les différents niveaux de structuration des CMP: conformation locale, structures secondaires, assemblages trimériques et supramoléculaires, nous avons privilégié une approche muti-échelle. Les études que nous avons menées par dichroïsme circulaire et RMN ont visé à analyser en détail les relations entre triples hélices et les différentes espèces monomériques présentes en solution. Grâce à l'utilisation de peptides modèles marqués, nous avons pu mesurer par RMN des paramètres structuraux locaux et les comparer à des simulations de dynamique moléculaire. La présence d'assemblages supramoléculaires a été mise en évidence et analysé d'un point de vue qualitatif, quantitatif et cinétique par des études de DLS, RMN et par différentes approches de microscopies. Enfin, l'ensemble de nos observations nous ont conduit à proposer de nouvelles molécules CMP. Nous avons ainsi entrepris la synthèse de peptidomimétiques fluorés en vue d'améliorer la cinétique de formation et la stabilité de la triple hélice et pour également favoriser des assemblages supramoléculaires ordonnésThe collagen is omnipresent in the human body and many diseases are associated with its structural anomalies, these are the main reasons to study its stability. Collagen has in its primary sequence many pyrrolidine cycles, which stabilize a secondary structure such polyproline II (PPII), and a triple helix structure where three left-handed helical polypeptide chains are supercoiled. In this work, we focused on the synthesis and structural characterization of collagen model peptides (CMP), alone or in the presence of type I collagen. To understand the different levels of CMP structuration: local conformation, secondary structures, trimeric and supramolecular assemblies, we favoured a multi-scale approach. The studies we conducted by circular dichroism and NMR aimed to analyze the relationship between triple helices and the different monomeric species present in solution. Through the use of labeled peptides models, we were able to measure NMR local structural parameters and compare them to molecular dynamics simulations. The presence of supramolecular assemblies was demonstrated and analyzed from a qualitative, quantitative and kinectics point of view by DLS, NMR and different microscopies approaches. Finally, all of our observations have led us to propose new CMP molecules. We undertook the synthesis of fluorinated peptidomimetics to improve the kinetics formation and stability of the triple helix, and also promote ordered supramolecular assemblies
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Cendret, Virginie. "Mimes de haut-mannose et glycoclusters pour l’étude des interactions sucres-lectines." Amiens, 2010. http://www.theses.fr/2010AMIE0116.
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Les oligosaccharides présents à la surface des cellules sont à l’origine de nombreux processus de reconnaissance. Ils sont en effet des points d’ancrages sur lesquels peuvent se fixer de manière spécifique d’autres cellules ou des agents pathogènes. Dans la famille des N-glycanes, lesoligosaccharides de type haut-mannose sont par exemple les premières espèces impliquées lors del’infection d’une cellule hôte par un virus ou un parasite. Pour la recherche, les hauts-mannoses constituent donc des cibles intéressantes. Toutefois, la synthèse de ces oligosaccharides reste difficile et fastidieuse. Dans ce contexte, nous avons entrepris deux projets en parallèle. L’objectif du premier projet était dans un premier temps de développer une méthodologie donnant accès plus rapidement à des structures similaires à celles des hauts-mannoses. Pour simplifier les synthèses, nous avons donc choisi de remplacer des unités mannoses par des groupements triazoles. Nous avons pour cela associé la réaction de glycosylation classique à une réaction de click chemistry et après avoir exploré plusieurs voies, nous sommes parvenus à synthétiser un pseudo-octamannoside. La seconde phase de ce projet, à savoir l’évaluation de ce composé en tant que mime de N-glycanes est sur le point de débuter. Le second projet qui a été mis en oeuvre est issu d’une collaboration entre le Laboratoire des Glucides et l’équipe du Dr. Sébastien Vidal et fut dédié à la synthèse de glycoclusters multivalents. Au cours de ce projet, un trimannoside a été couplé par réaction de click chemistry à des plateformes multivalentes de type porphyrine et calixarène. Quatre nouveaux glycoclusters protégés ont été obtenus. Toutefois, l’étape de déprotection de ces derniers pose quelques difficultés. Pour résoudre ce problème, le couplage sur la porphyrine de l’oligosaccharide libre a été réalisé. Les premiers résultats sont encourageants et suggèrent que cette approche est la plus appropriée pour l’obtention des glycoclusters souhaités. A l’issue des évaluations biologiques de ces composés, nous pourrons conclure quant à l’importance de la densité de ligand dans le processus de reconnaissance sucres-lectinesCells surface oligosaccharides are at the heart of many recognition processes: they are anchors to which other cells or pathogenic agents can specifically bind. In the N-glycan family, high-mannose type oligosaccharides are for instance the first species involved whenever a virus or a parasite infects a host cell. For research studies, high-mannoses therefore constitute interesting targets. However, the synthesis of these oligosaccharides remains difficult and tedious. In this context, we undertook two projects in parallel. The first one was firstly aimed at the development of a methodology providing faster access to high-mannose analogues. In order to simplify the synthesis, we chose to replace mannosidic units by triazole groups. Thus, we combined the classical glycosylation with a click chemistry reaction and after exploring several routes, we achieved the synthesis of a pseudo-octamannoside. The second stage of this project, that is to say the evaluation of this compound as N-glycans mime, is about to start. The second project stemmed from collaboration between the Laboratoire des Glucides and Dr. Sébastien Vidal team and was devoted to the synthesis of multivalent glycoclusters. In this work, a trimannoside was coupled to multivalent scaffolds such as porphyrins and calixarenes by a click chemistry reaction. Four new glycoclusters were obtained. However, their final deprotection at the end proved non trivial. To solve this problem, the coupling was realized with the free oligosaccharide. The first results are encouraging and suggest that this approach is the most appropriate for the synthesis of the desired glycoclusters. At the end of the biological assays of these compounds, we will be able to conclude about the importance of the ligand density in the carbohydrates-lectins recognition process
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Bar, Laure. "Etude et caractérisation du rituximab sur surface antigénique : conception de mimes d'anticorps." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAV061.
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Parce qu’ils reconnaissent les antigènes tumoraux de manière très spécifique, les anticorps monoclonaux (mAb) sont devenus un outil majeur pour le traitement de nombreux cancers. Malgré l’amélioration des taux de rémission, les mAbs présentent des inconvénients dont un poids moléculaire important freinant leur pénétration tumorale, un polymorphisme génétique rendant le traitement parfois inopérant, et une production par voie biologique coûteuse. La conception de mimes synthétiques de mAbs de petite taille est donc un moyen attractif de contourner ces problèmes. Afin de développer des mimes de grande efficacité et de haute spécificité, nous avons réalisé une étude approfondie de l’interaction anticorps/antigène appliquée à l’interaction rituximab/CD20 impliquée dans le traitement de certains lymphomes. La conception de ces mimes d’anticorps est basée sur des constructions macromoléculaires associant de courtes séquences peptidiques composant le paratope du rituximab. La sélection des peptides les plus affins dans le processus de reconnaissance a été effectuée par une technique d’analyse de surface, la résonance plasmonique de surface (SPR – Biacore). Ces études ont nécessité le développement de surfaces antigéniques dont la densité surfacique en CD20 a été optimisée pour réaliser du criblage peptidique. La caractérisation de ces surfaces fonctionnelles par microbalance à quartz (QCM-D), ellipsométrie spectroscopique (SE), et SPR a permis d’acquérir de nombreuses informations dont l’influence de la distance inter-CD20 sur la reconnaissance du mAb. Suite au criblage, les séquences peptidiques des zones d’interaction du paratope avec lesquelles le CD20 vient interagir ont pu être déterminées avec une grande précision. Elles ont par la suite été assemblées sur un châssis moléculaire pour la confection des mimes de mAb synthétiquesAs they recognize tumor antigens in a very specific manner, monoclonal antibodies (mAbs) became a major tool for the treatment of many cancers. Despite the improvement in remission rates, mAbs suffer from limitations that relate mainly to their high molecular weight, their high cost, and the polymorphism of their Fc region. The design of small synthetic mAb mimics is therefore an attractive way to bypass these problems. To design efficient and specific mimics, we studied in detail an antibody / antigen interaction, especially rituximab / CD20 interaction occurring in the treatment of some lymphoma. MAb mimics are macromolecular constructs composed of short peptide sequences included in the Rituximab paratope. The selection of the peptides deeply involved in the recognition of the tumor cell was carried out by using a surface sensitive technique called surface plasmon resonance (SPR - Biacore). To perform this selection, it was first necessary to develop an antigenic surface for peptide screening. The characterization of this surface by quartz crystal microbalance (QCM-D), spectroscopic ellipsometry (SE), and SPR made it possible to acquire a lot of information such as the dependence of the inter-CD20 spacing on the mAb recognition process. Following the screening, the peptide sequences of the paratope areas involved in CD20 recognition could be determined with high precision, and then be used to prepare synthetic mAb mimics
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Duckert, Jean-Frédéric. "Synthèses de mimes non peptidiques du glutathion, précurseurs d'analogues du leucotriène C4." Montpellier 2, 2002. http://www.theses.fr/2002MON20037.
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Tresse, Cédric. "Synthèse de mimes de mycolactones pour l’étude mécanistique de l’ulcère de Buruli." Thesis, Mulhouse, 2014. http://www.theses.fr/2014MULH9274.
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Ce projet de recherche se focalise sur les infections par mycobacterium ulcerans (maladie de l’ulcère de Buruli), une maladie de la peau dévastatrice caractérisée par la formation de lésions nécrotiques progressives et l’absence d’une réponse inflammatoire. Bien que négligée, cette infection est la troisième maladie mycobactérienne la plus répandue après la tuberculose et la lèpre et des cas sont rapportés dans plus de 30 pays à travers le monde. Mycobacterium ulcerans sécrète une toxine polycétidique complexe, appelée mycolactone A/B, qui est directement responsable des effets pathogènes de la maladie. Depuis sa découverte, les propriétés biologiques inhabituelles de la mycolactone A/B ont suscité de nombreux efforts de recherche dans différents domaines. Dans ce contexte, ce projet s’intéresse à l’élucidation du mécanisme d’action des mycolactones en utilisant la synthèse totale comme outil principal. Dans cette optique, notre équipe a mis en place une voie de synthèse permettant un accès facile et robuste à différents mimes de mycolactone. L’utilisation de cette méthode a conduit à la préparation de 13 mimes de la toxine au cours de cette thèse. D’autre part notre équipe s’intéresse également à la préparation de mimes possédant un ou plusieurs atomes de fluor. Ces derniers présentent un intérêt particulier pour améliorer la compréhension des interactions ayant lieu entre la toxine et sa cible cellulaire. Les travaux réalisés autours de la synthèse de mycolactones fluorés ont conduit à la mise au point d’une méthode générale et simple pour introduire un groupe trifluorométhyle sur un alcyne terminal, permettant ainsi des modulations inédites de la structure de la toxineThis research project focuses on mycobacterium ulcerans infection (Buruli ulcer disease), a severe skin disease characterized by the formation of progressive necrotic lesions and the lack of an acute inflammatory response. Although neglected, this infection is the third most common mycobacteriosis after Mycobacterium tuberculosis and Mycobacterium leprae, and cases are reported in more than 30 countries worldwide. Mycobacterium ulcerans secretes a complex polyketidic macrolide, called mycolactone A/B, which is directly involved in the biological effects of the disease. Since its discovery, the unusual biology triggered by this toxin has spurred research efforts. In this context, this research project aims at a better understanding of mycolactone A/B molecular interactions by using total synthesis as main tool. To this end, our research team has developed an efficient synthetic pathway allowing the preparation of different mimetics of the toxin. This synthesis has been used to prepare thirteen new mycolactone mimetics during this thesis. Moreover our team has also been interested in the synthesis of fluorinated mycolactone analogs. Such fluorinated mycolactones are of great interest to improve the interactions that occur between the toxin and its biological binding site. Work in this field led to the development of a simple and general method to introduce a trifluoromethyl group onto a terminal alkyne, allowing novel modulation of the structure of the toxin
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Murray, Robert Ian. "Towards the performer-creator in contemporary mime, with specific reference to the physical theatre of Andrew Buckland, 1988-2000." Thesis, Rhodes University, 2002. http://hdl.handle.net/10962/d1007720.
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Part one of this thesis investigates the conceptualisation of the performer-creator and its relevance in late twentieth century physical performance by examining some of the theoretical, but mainly artistic, traditions that suggest a movement towards this. Chapter one tackles the question of definition, linking mime within a wider physical theatre phenomenon. Chapter two looks at the importance of mime training for contemporary performance. This requires a focus on selected theatre practitioners who have significantly advanced the development of mime training and performance during the twentieth century. Chapter three examines the issue of silence in mime and questions a potential liberation of the word and language in contemporary performance and consequently how this affects the role of the performer, particularly in South Africa. Chapter four investigates the figure of the theatrical clown and how this late twentieth century development is playing an increasingly important role in contemporary performance. Chapter five then wraps up part one by pulling the preceding chapters together and thereby providing a working conceptualisation of the performer-creator, locating it within an overall appreciation of contemporary mime. Part two then tests the notion of the performer-creator by focussing on a case study through the investigation of Andrew Buckland to develop this idea. Andrew Buckland, and his work under the ethos of Mouthpeace from 1988-2000, provides a clear and unique example of this movement in contemporary South African performance. Trained as an actor and in classical illusion-based mime technique, as well as many dance forms such as ballet, contemporary and jazz, he has virtually single-handedly created and shaped a particular performance trend that is in line with contemporary international trends but retains a distinctive South African flavour. There is no space to attempt a definitive or exhaustive examination of his works, and nor is the intent to do so; rather, the aim is to draw from his work their essences that reveal his development as an artist: as both a creator and a performer.
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Philippe, Christine. "Conception et synthèse de mimes fluorés de peptidomimétiques et de ligands de récepteurs." Paris 11, 2009. http://www.theses.fr/2009PA114816.
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L’introduction d’un ou plusieurs atomes de fluor dans une molécule à visée thérapeutique peut améliorer sa biodisponibilité et son affinité pour la cible. Dans cette optique, nous avons conçu et synthétisé des peptidomimétiques fluorés pouvant être incorporés dans des inhibiteurs de protéases, et des analogues fluorés de ligands de transporteurs de monoaminesThe introduction of fluorine atoms into a bioactive molecule can improve it bioavailability and it affinity for the target. This was applied to the design and the synthesis of fluorinated peptidomimetics to be incorporated in protease inhibitors, and to fluorinated ligands of monoamines transporters
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Tang, Lu. "Nanoparticules mimes des propriétés biologiques des GAGs : vers un inhibiteur sélectif de CXCL12." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS072.
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L'Héparane Sulfate (HS), un polysaccharide linéaire, module les activités biologiques de nombreuses protéines. Afin d'élucider les interactions entre l'HS et les protéines, la synthèse chimique d'HS est un outil précieux, mais elle peut être difficile. Notre équipe a montré que des mélanges combinatoires obtenus par auto-assemblage de différentes combinaisons de dérivés disaccharidiques (lactose et lactose persulfaté) sur surfaces planes d'or peuvent reconnaître spécifiquement certaines protéines se liant à l'HS, telles que les isoformes de la chimiokine CXCL12 ou IFNγ. Avec ces dérivés, nous avons réalisé un auto-assemblage sur des nanoparticules d'or. Mais à cause de la toxicité des nanoparticules d'or, nous avons aussi adapté cette méthode à des nanoparticules lipidiques. En utilisant les conditions qui ont déjà été améliorées pendant la synthèse des dérivés lactose et lactose persulfaté, nous avons préparé deux autres dérivés disaccharidiques plus proches de la structure réelle d'HS. Ces nouveaux dérivés sont utilisés pour réaliser des nanoparticules d'or et nanoparticules lipidiques afin de comparer les propriétés avec les lactose et lactose persulfaté. Les tests d'affinité avec différentes protéines sont en cours de réalisationHéparan Sulfate (HS) is a linear polysaccharide that modulates the biological activities of numerous proteins. In order to elucidate the interaction between HS and proteins, the synthesis of HS is an invaluable tool, but the synthesis is sometimes difficult. Our group has demonstrated that the combinatorial mixtures obtained by self-assembly of different combinations of disaccharide derivatives (lactose and persulfated lactose) on gold plan surfaces could recognize specifically some HS binding proteins, such as the isoforms of the chemokine CXCL12 or IFNγ. Because of the toxicity of gold nanoparticles, we have also adapted this method to lipid nanoparticles. Using the conditions that have already improved during the synthesis of lactose and persulfated lactose derivatives, we have synthesized two other disaccharide derivatives, which were closer to the real structure of HS. These new derivatives were used to prepare the gold and lipid nanoparticles at the aim of comparing the properties with lactose and persulfated lactose. The tests of affinities with different proteins are in progress
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Martin, Charlotte. "De la silaproline à la synthèse d'homopolypeptides mimes d'hélice polyproline de type II." Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20246/document.
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Les acides α-aminés non naturels forment une famille de composés incontournables pour la conception de peptidomimétiques. Plus précisément, l'utilisation du silicium comme isostère du carbone sur la chaîne latérale des acides α-aminés a été largement reportée dans la littérature, montrant alors l'importance d'une telle modification. En particulier, compte tenu du rôle fondamental que joue la proline dans la structuration des peptides, et des avantages que peut apporter le silicium, il nous a paru intéressant de nous centrer sur la silaproline. Après avoir mis au point une synthèse permettant la production de la silaproline à grande échelle, nous avons mis au point la préparation d'homopolypeptides de ce résidu particulier. Dans un premier temps des oligomères monodisperses de silaproline ont été synthétisés. L'étude structurale par RMN, CD et modélisation moléculaire a permis de confirmer la conformation préférentielle en hélice polyproline de type II (PPII). Ensuite la synthèse de polymères plus longs, obtenus par polymérisation de N-carboxyanhydrides a été développée. Ces nouveaux biopolymères ainsi préparés ont conduit à des mimes de PPII lipophiles. Enfin, une nouvelle voie de polymérisation, dans des conditions douces, par réaction d'esters, a été optimisée, permettant d'accéder facilement à des polypeptidesUnnatural α-amino acids form a family of essential compounds for the design of peptidomimetics. More specifically, the use of silicon as an isostere of carbon on the side chain of α-amino acids has been widely reported in the literature, while demonstrating the importance of this modification. In particular, the fundamental role of proline in peptide structures, and the advantage of the silicon, promoted us to focus on the silaproline.After the development of a gram scale synthesis of silaproline, we prepared homopolypeptides of this particular residue. Firstly, monodisperse silaproline oligomers were synthesized. The structural study by NMR, CD and molecular modeling confirmed the conformational preference for polyproline type II helix (PPII). Then longer polymers were obtained by polymerization of N-carboxyanhydrides. These new biopolymers were prepared, leading to more lipophilic PPII mimics.Finally, a new way of polymerization by reacting esters under mild conditions has been optimized for easy access to polypeptides
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Lamotte, Yann. "Design, synthèse et évaluation biologique de mimes du paclitaxel dérivés de la proline." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066608/document.
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Parmi les nombreux agents thérapeutiques utilisés en oncologie, le paclitaxel (Taxol®) est sans doute celui qui a suscité le plus d'intérêt. Il est utilisé en clinique pour le traitement des cancers de l'ovaire, du sein et des poumons. Il agit comme poison du fuseau mitotique en favorisant l'assemblage de la tubuline en microtubules et en stabilisant le polymère formé. Initialement extrait de l'if du Pacifique (Taxus Brevifolia) puis obtenu par hémisynthèse à partir de la 10-déacétylbaccatine III, il est aujourd'hui produit par un procédé biotechnologique de fermentation de cellules végétales. Le paclitaxel possède une structure chimique complexe basée sur un squelette tétracyclique taxane. Une approche visant à remplacer ce squelette taxane par une structure chimique plus simple a été entreprise afin d'identifier des mimes du paclitaxel. L'identification d'un fragment chimique (fragment based drug design) dérivé de la proline par une étude de modélisation moléculaire a permis de développer de nouvelles séries de mimes du paclitaxel. Parallèlement, le remplacement du squelette taxane par une matrice peptidique cyclique utilisant des dérivés de la proline a été réalisé. Les études de modélisation moléculaire, la synthèse des mimes du paclitaxel et leur évaluation biologique seront présentéesAmong the many therapeutic agents used in oncology, paclitaxel (Taxol®) is probably the one that generated the most interest. It is used clinically for the treatment of ovarian, breast and lung cancers and acts as a mitotic spindle poison by promoting the assembly of tubulin into microtubules and stabilizing the polymer formed. Initially extracted from the Pacific yew (Taxus Brevifolia) and obtained by semi-synthesis from 10-deacetylbaccatin III, it is now produced by a biotechnological process of cell plant fermentation. Paclitaxel has a complex chemical structure based on a tetracyclic taxane skeleton. A process to replace the taxane skeleton with a simpler chemical structure was undertaken to identify paclitaxel mimics. The identification of a chemical fragment (fragment based drug design) derived from proline by a molecular modeling study has led to the design of a new series of paclitaxel mimics. Meanwhile, replacing the taxane skeleton by a cyclic peptide scaffold using proline derivatives was performed. Molecular modeling studies, synthesis of paclitaxel mimics and biological evaluation will be presented
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Tsamba, Lucie. "Modélisation prédictive de la formation de sous-produits de chloration dans les ambiances confinées. Applications aux piscines couvertes." Thesis, Rennes, Ecole nationale supérieure de chimie, 2018. http://www.theses.fr/2018ENCR0053/document.
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La formation des sous-produits de chloration dans les piscines couvertes dépend de nombreux paramètres cinétiques et hydrauliques. Cette étude propose le développement d’un modèle de prédiction de la formation de certains sous-produits de chloration et de leur transfert dans l’air. La construction du modèle est basée sur le couplage de constantes cinétiques déterminées à l’échelle laboratoire avec des modèles hydrauliques caractérisant les écoulements dans le bassin. Afin de calibrer et de valider les modèles, un bassin expérimental à l’échelle 1/10ème a été mis en place. Par ailleurs, une méthode de mesure des concentrations des sous-produits de chloration dans l’eau et dans l’air par Membrane Inlet Mass Spectrometry a été évaluée. La représentativité et la reproductivité des expériences réalisées sur le bassin ont été étudiées. À l’échelle laboratoire, les constantes cinétiques de consommation du chlore, de formation du chloroforme et de formation du dichloroacétonitrile par chloration du Body Fluid Analogue utilisé pour mimer les apports organiques des baigneurs ont été déterminées. Le comportement hydraulique du bassin a été modélisé par une série de réacteurs idéaux. Cette modélisation a été validée par la réalisation d’expériences de traçage sur le bassin expérimental. Enfin, les constantes de transfert eau-air des sous-produits de chloration volatils ont été déterminées et comparées avec plusieurs modèles de la littérature. Les résultats obtenus montrent que les modèles permettent de prévoir de façon satisfaisante l’évolution des paramètres modélisés. Le bassin expérimental constitue également un outil prometteur pour la calibration de modèles et l’évaluation de solutions de traitementThe formation of chlorination by-products in swimming pools depends on many kinetic and hydraulic parameters. This study presents the development of a predictive model for the formation of chlorination by-products as well as their water-to-air transfer. The model is based on the coupling of kinetic rates determined in batch with hydraulic models which describe the flows in the basin. A pilot pool unit has been built in order to collect experimental data for the calibration and validation of the models. Moreover an analytical method by Membrane Inlet Mass Spectrometry has been assessed. The representativeness and the reproducibility of experiments performed on the pilot pool unit have been described. Kinetic rates for chlorine consumption, chloroform formation and dichloroacetonitrile formation have been studied at lab scale, based on chlorination experiments of a Body Fluid Analogue, a mix of chemicals which reproduces human intakes in swimming pools. The hydraulic behavior of the basin has been modeled by a series of ideal reactors. The model has been validated by comparison with tracer-based experiments. Finally, water-to-air transfer rates have been determined and compared with models from the literature. The modeled parameters were satisfactorily modeled. Moreover the pilot pool unit has been demonstrated to be useful in calibrating models or in assessing treatment solutions
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Martin, Vincent. "Synthèse d’oligomères de mimes contraints de dipeptides pour la vectorisation intracellulaire de molécules bioactives." Thesis, Montpellier 2, 2014. http://www.theses.fr/2014MON20168/document.
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La synthèse d'une nouvelle famille d'oligomères de motifs contraints de dipeptides est décrite dans ce manuscrit. Les monomères utilisés sont des motifs 3(S)-amino-5-carbonylméthyl-2,3-dihydro-1,5-benzothiazépine-4(5H)-one (DBT), acide 2-aminométhyl-phényl-acétique (AMPA) et α-amino γ-lactames. La structure secondaire de ces édifices a été étudiée par spectroscopies RMN, IR, CD et RX. Nous avons montré tout d'abord que les oligomères de DBT sont capables d'adopter des structures stables et définies en ruban. En se basant sur ces structures, nous avons conçu de nouveaux systèmes beaucoup plus versatiles qui permettent de répartir diverses fonctions (basiques, acides, aromatiques) de part et d'autre de l'axe du ruban. Une stratégie de synthèse originale a été développée à cet effet. Elle consiste en la conversion directe de séquences peptidiques, incorporant des méthionines, en oligomères d'α-amino γ-lactames. Ils sont capables, au même titre que ceux de DBT, d'adopter des structures en ruban et de pénétrer dans les cellules. Enfin une étude in vivo chez la souris a montré le fort potentiel anti-tumoral d'un bioconjugué associant des oligomères d'AMPA à un inhibiteur de la Cathepsine D, enzyme lysosomale surexprimée et sécrétée par de nombreuses tumeurs solidesThe synthesis of a new type of constrained dipeptide motif oligomers is described. Monomers used are the (3S)-amino-5-(carboxylmethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (DBT), the 2-aminomethyl-phenyl-acetic acid (AMPA) and α-amino γ-lactams. The secondary structure of those architectures has been studied by NMR, IR, CD and X-ray spectroscopies. Firstly, we demonstrated that DBT oligomers are able to adopt stable and well defined ribbon like structures. Based on these structures, we designed new systems, far more versatile which are able to distribute various functions (basic, acidic, aromatic) on each side of the ribbon axis. An original strategy has been developed for this purpose. It consists in the direct conversion of peptidic sequences, incorporating methionine, in α-amino γ-lactams oligomers. They are able, as the DBT, to adopt ribbon like structures and to be internalized into cells. Finally, an in vivo study in mice showed the high anti-tumoral potency of a bioconjugate linking AMPA oligomers to an inhibitor of the cathepsin D, a lysosomal enzyme overexpressed and secreted by numerous solid tumors
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Burzicki, Grégory. "Synthèse de nouvelles oligopyridines potentielles mimes d’hélice alpha et perturbatrices des interactions protéine-protéine." Caen, 2010. http://www.theses.fr/2010CAEN4068.
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Dans le cadre de l’obtention de nouvelles molécules entrant dans la catégorie des mimes de forme d’hélice alpha, nous avons mis au point une méthode générale de synthèse de nouvelles oligopyridines en utilisant des réactions de couplage itératives de type Suzuki-Miyaura via une stratégie régiosélective basée sur le concept du Garlanding. La première partie traite des notions de chimiothèque et de criblage. Nous abordons ainsi la notion d’espace chimique et l’exploration de nouveaux espaces en vue de la découverte de nouveaux médicaments. Notre programme de recherche se place dans ce contexte, et en particulier celui des interactions protéine-protéine et des molécules « BH3 » mimétiques capables d’interagir avec les protéines de la famille Bcl-2. La seconde partie décrit les travaux personnels concernant la synthèse de bi-, ter-, quater-, quinque- et sexipyridines diversement substituées, en particulier par des groupements méthyles et styryles. Les études théoriques de modélisation moléculaire de certains composés sont présentées dans cette partie ainsi que les premiers résultats biologiques obtenus. Une partie expérimentale décrit les modes opératoires et les caractéristiques physico-chimiques de tous les dérivés nouveaux synthétisés. Enfin, 265 références bibliographiques replacent cette étude dans son contexte chimique et biologiqueIn order to obtain new non-peptidic scaffolds as potential alpha helix mimetics, we developed a convergent and highly flexible synthesis of new oligopyridines variously substituted by using iterative Suzuki-Miyaura cross-coupling reactions in a regioselective strategy named Garlanding. The first part presents chemical library and screening concepts. We focus on the chemical space concept and the exploration of new chemical spaces in order to discover new drugs. This is in this approach that our research program takes place, and particularly concerning protein-protein interactions and the “BH3” mimetics able to interact with the proteins of the Bcl-2 family. The second one describes the personal work of the author on the synthesis of bi-, ter-, quater-, quinque- and sexipyridines variously substituted, particularly by methyl or styryl groups. The molecular modelling studies and the first biological results of the compounds are presented in this part. Then experimental procedure and physico-chemical characteristics of all synthezised compounds are described. Finally, 265 bibliographical references replace this study in both its chemical and biological context
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Champenois, Sylvain. "Dynamique de la résonance entre Mimas et Tethys, premier et troisième satellites de Saturne." Observatoire de Paris (1667-....), 1998. https://hal.science/tel-02094982.
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Ce travail présente, d'une part, des méthodes visant à améliorer la représentation analytique des mouvements orbitaux des satellites naturels des planètes, ainsi que la détermination de leurs fréquences propres, et d'autre part, une étude détaillée de la dynamique du système Mimas-Tethys, en prenant en compte des termes ignores jusqu'à présent dans les équations de ce système. On a ainsi mis au point une méthode qui détecte les fréquences propres orbitales jusqu'a la précision machine si elles sont bien séparées, et qui donne encore de bons résultats si les fréquences sont proches (écart inferieur a deux fois la fréquence fondamentale). En outre, l'on a élaboré une méthode permettant de représenter des termes proches en fréquence par des séries de poisson, qui donne de très bons résultats si l'écart est inferieur a une demie fois la fréquence fondamentale. L’étude particulière du système Mimas-Tethys a montré, quant à elle, que le fait de considérer pour Tethys une orbite excentrique change radicalement la vision que l'on avait jusqu'à maintenant de la dynamique de cette résonance. En effet, le système a pu dans le passe traverser une zone chaotique importante, et aussi être capture dans l'une des résonances secondaires induites par les nouveaux termes pris en considération. En conséquence, les valeurs des éléments orbitaux avant la capture en résonance et de la probabilité de celle-ci peuvent avoir été bien différentes des valeurs admises jusqu'à présent. Finalement, nos résultats montrent que la dynamique d'un système résonant à priori bien connu peut réserver des surprises. De plus, nous pensons que l'application de nos méthodes peut permettre une très bonne détermination des fréquences d'un système dynamique.
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Galeotti, Nathalie. "Conception et synthèse de mimes peptidiques analogues de substrats de la protéase du VIH." Montpellier 2, 1993. http://www.theses.fr/1993MON20002.
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L'aspartyl protease du vih a un role fondamental dans la maturation des virus et donc dans la formation de nouveaux virus infectieux. La recherche d'inhibiteurs de cette enzyme est d'un grand interet pour une lutte antivirale. Dans cette optique, ce travail est consacre a la conception et la synthese de mimes peptidiques analogues de substrats de la protease du vih. Il a ete elabore des pseudopeptides analogues de substrats de la protease dans lesquels le site d'hydrolyse a ete modifie par differents motifs. Il a ete introduit, en premier lieu, des heterocycles de types oxazolines, thiazolines et thiazoles. Cette etude s'est conclue par une mise au point d'une methode de synthese d'oxazoline et de thiazoline utilisant la reaction de mitsunobu. L'introduction du fragment amino hydroxy acide derive de la proline dans des pseudopeptides a ete aussi effectuee. L'elaboration d'un tel motif a abouti a une etude stereochimique de la reduction d'acides tetramiques. L'activite antivirale des composes synthetises est exposee dans ce travail
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Perdriau, Camille. "Stabilisation et mimes de structures secondaires peptidiques : applications aux hélices alpha et feuillets beta." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0308.
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Des avancées en biologie moléculaire ont permis de voir émerger des molécules biologiques (anticorps, hormones) comme agents thérapeutiques. Les peptides qui peuvent adopter les structures secondaires (hélices α et feuillets β) rencontrées dans les protéines et qui possèdent des caractéristiques intermédiaires entre les petites molécules et les protéines, représentent donc un enjeu thérapeutique intéressant. Leurs principaux inconvénients résident dans leur faible stabilité plasmatique, leur faible pénétration cellulaire et leur flexibilité conformationnelle qui limitent leur développement thérapeutique. Stabiliser la structure secondaire de peptides dans leur conformation bioactive ou développer des squelettes non naturels comme peptidomimes sont devenus des moyens de contourner ces difficultés. A ce jour, diverses approches chimiques ont été proposées pour stabiliser le repliement en hélice α comme la macrocyclisation entre deux chaînes latérales d’un peptide. Une première partie de cette thèse a consisté à développer une stratégie de macrocyclisation menant à des agrafes peptidiques originales, comportant une fonction guanidine polaire. Différentes séquences peptidiques ont ainsi pu être macrocyclisées en (i, i+4) ou (i, i+7), et des études structurales ont été amorcées. L’introduction d’une guanidine pourrait apporter de nouvelles propriétés aux peptides macrocyclisés dont l’amélioration de leur perméabilité cellulaire. Le feuillet β multi-brins, l’autre structure secondaire d'intérêt, s'avère être moins étudié par les chimistes malgré son importance biologique, en raison probablement d'une tendance excessive à l’agrégation et la précipitation. Pour réussir à obtenir des peptidomimes stables de ces feuillets β, il est possible d’avoir recours à des squelettes non naturels comme les foldamères. Dans ce contexte, nous nous sommes intéressés à la conception d'une nouvelle classe de molécules programmées pour se replier en feuillets β, par formation de liaisons hydrogène intramoléculaires. Des foldamères alternant des motifs coudes et brins artificiels comportant des dérivés de diamine et diacide ont alors été synthétisés. Des études en solution et à l’état solide sur ces molécules ont attesté leur repliement en feuillet β multi-brinsRecent advances in molecular biology gave rise to the emergence of biologics (antibodies, hormones) as therapeutic agents. Peptides which are able to adopt secondary structures encountered in proteins and presenting intermediates features between small molecules and biologics are seen as potent therapeutics. The disadvantages of peptides lie in poor plasma stability and their poor cell membrane permeability as well as conformational flexibility, thus limiting their therapeutic potential. Stabilizing peptide secondary structures in their bioactive conformations and the development of non natural peptidomimetics became important tools to counteract those difficulties. Nowadays, several chemical approaches have been considered to stabilize α-helix folding such as the macrocyclization between two side chains of a peptide. The first project of this PhD thesis has focused on the design and the synthesis of new stapled peptides containing a guanidine motif. Several macrocyclized peptides with a guanidine bridge in (i, i+4) or in (i, i+7) positions have thus been obtained and some structural studies performed. Introduction the guanidine moiety could provide new properties to peptides such as improvement of their cell permeability. Notwithstanding their importance in biology, multi-stranded β-sheets, another protein secondary structure of interest, have comparatively been less studied by chemists probably because of their tendencies towards agregation and precipitation. To obtain stable peptidomimetics folded into βsheets it is possible to use non natural moieties such as foldamers. In this context, we have been interested in the design of a novel class of molecules programmed to fold into β-sheet structures through the formation of intramolecular hydrogen bonds. Foldamers alternating artificial strands and turns composed of diamine and diacid have been synthesized. Studies were performed in solution and in the solid state to confirm their folding into multi-stranded β-sheets architectures
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Duru, Christiane. "Synthèse et études structurales d'oligomères de mimes contraints de dipeptide : recherche de nouveaux foldamères." Montpellier 2, 2005. http://www.theses.fr/2005MON20120.
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Theillet, François-Xavier. "Comportements conformationnels et antigénicités de l'Ag-O de Shigella flexneri et de ses mimes." Paris 6, 2009. http://www.theses.fr/2009PA066562.
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Dans le contexte de la conception de nouvelles stratégies vaccinales contre les shigelloses, nous nous sommes appliqués à décrire les comportements conformationnels des polysaccharides antigéniques (Ag-O) de Shigella flexneri ainsi que de leurs mimes synthétiques. Nous avons étudié par des méthodes biophysiques complémentaires (cristallographie, RMN, modélisation moléculaire par informatique, ITC, SPR, etc. . ) les caractéristiques structurales des molécules mimes et de leur reconnaissance par des anticorps spécifiques de l'antigène naturel. Nous avons déterminé les comportements conformationnels adoptés par l'Ag-O de la plupart des sérotypes de S. Flexneri. Pour l'un de ces sérotypes, nous avons identifié les interactions intramoléculaires qui influencent le comportement conformationnel de l'Ag-O et de ses oligosaccharides mimes, ainsi que les conformations reconnues par le système immunitaire. Ces travaux permettront de mieux appréhender la conception de vaccins saccharidiques.
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Frémaux, Juliette. "Foldamères peptidomimétiques à base d’urées : vers le développement de structures complexes mimes d’architectures biologiques." Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR14857/document.
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La fonction d’une protéine dépend dans une large mesure de sa structure tridimensionnelle, c’est pourquoi de nombreux chercheurs se sont passionnés pour la synthèse des foldamères, molécules de synthèse, bioinspirées, capables d’adopter des structures repliées bien définies. Parmi les différentes classes de foldamères, les oligourées aliphatiques étudiées dans notre laboratoire s’organisent pour former des structures hélicoïdales voisines de l’hélice α des polypeptides naturels. Pour développer des hélices fonctionnelles mimes de structures biologiques, il est intéressant de mieux comprendre les règles de leur repliement, par exemple en modifiant la nature des unités monomériques. Au cours de cette thèse, nous avons donc testé la compatibilité de la géométrie de l’hélice d’oligourée avec des résidus comportant de fortes contraintes stériques comme des groupements gem-diméthyles et des cycles pyrrolidines. En utilisant les résidus pyrrolidine, nous avons ensuite développé une nouvelle stratégie de synthèse par condensation de segments permettant de concevoir des hélices de grande taille (jusqu’à 4 nm). Grâce à cette nouvelle stratégie de synthèse et aux informations obtenues sur la stabilité des hélices nous avons pu concevoir des architectures plus complexes (structures quaternaires) résultant de l’assemblage programmé d’hélices hydrosolublesThe biological functions of proteins are mainly correlated to their tridimensional structure. For this reason a large number of chemists are interested in the synthesis of foldamers, which are bioinspired artificial molecules possessing well-defined folded conformations. In particular, in our laboratories we focused on the study of oligourea foldamers, which form well-defined and remarkably stable helical structures, analogous to the natural polypeptides α-helix. In order to develop artificial functional helices able to mimic biological structures, it is interesting to understand the rules governing their folding, for example by comparing different residues substitution patterns. During this thesis we have investigated the compatibility of the helix geometry with residues containing steric constraints, such as gem-dimethylated units or pyrrolidine cycle. We have developed a new segment condensation strategy based on these residues, which enabled the facile synthesis of long helical segments (up to 4 nm). The use of this novel approach, combined with the information acquired on helical stability allowed us to produce more complex architectures (quaternary structures) resulting from the controlled assembly of water soluble helices
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Beniazza, Redouane. "Synthèse et désymétrisation de cycloheptatriènes silylés : application à la synthèse de mimes de sucres." Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13898/document.
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Cette thèse a porté sur la synthèse de cycloheptatriènes (CHT) silylés et leur désymétrisation pour l’obtention de mimes de sucres. Nous avons ainsi développé une approche synthétique d’analogues de calystégines et mis en évidence un réarrangement inattendu conduisant à un squelette nortropane original. Dans un second temps, nous avons étudié l’équilibre cycloheptatriène-norcaradiène (CHT-NCD) et mis au point une méthodologie de cycloaddition de CHT silylés avec des dérivés nitroso, efficace et hautement stéréosélective, pour la synthèse d’aminocarbasucres via une cascade : électrocyclisation (CHT-NCD)-cycloaddition-ouverture cationique-cycloaddition. En 3 étapes, à partir du CHT méthylsilylé, 7 centres stéréogènes, 5 liaisons C-O et 2 C-N sont formés de façon diastéréo- et régiocontrôlée. Une réaction Hétéro- Diels-Alder énantiosélective sur les CHT silylés, qui conduit en une étape à la formation de 3 centres asymétriques, a aussi été développéeThis work dealt with the synthesis of silylated cycloheptatrienes and their desymmetrisation toward the synthesis of sugar mimics. Calystegines analogues were synthesized and an unexpected rearrangement leading to an original nortropane skeleton was emphasized. In a second part, cycloheptatriene-norcaradiene (CHT-NCD) equilibrium was studied. Silylated cycloheptatriene were also shown to react through cycloaddition reaction with acylnitroso compounds, through cascade processes: electrocyclisation (CHT-NCD)-cycloaddition- cationique cyclopropane opening-cycloaddition, leading highly selectively to aminocarbasugars. Starting from methylsilylated CHT, 7 stereogenic centers, 5 C-O bonds and 2 C-N bonds were formed in only 3 steps. An enantioselective Hetero-Diels-Alder reaction was also developed
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Meunier, Antoine. "Les foldamères comme mimes de la seconde sphère de coordination des hydrogénases [Fe-Fe]." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0826/document.
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La possibilité de reproduire une activité enzymatique de manière artificielle est l’un des objectifs de la chimie moderne mais reste un grand défi, même dans le cas de l’activation de petites molécules. Dans le cas du dihydrogène, certaines bactéries s’en servent comme vecteur d’énergie par l’intermédiaire d’enzymes appelées hydrogénases qui peuvent former ou consommer le dihydrogène grâce à des complexes à base de métaux non nobles. Le dihydrogène pouvant être également utilisé comme vecteur d’énergie dans nos sociétés, les hydrogénases font l’objet de nombreuses recherches. Jusqu’à présent, la plupart des complexes modèles d’hydrogénases se sont employés à modifier la première sphère de coordination pour reproduire au mieux ses propriétés électroniques. Néanmoins, l’étude de mutations ciblées des hydrogénases indique que plusieurs résidus d’acides aminés présents dans le site actif sont indispensables à la stabilité du complexe et à son efficacité catalytique, montrant ainsi comment le mime d’une deuxième sphère de coordination pourrait améliorer les propriétés des catalyseurs artificiels. Notre approche a consisté en l’utilisation de foldamères de type oligoamide aromatique, formant un cône autour d’un complexe modèle d’hydrogénase. La synthèse convergente du composé final, son étude structurale à l’état solide (diffraction des rayons X), en solution (RMN, IR) ainsi que sa dynamique ont été étudiées. La modification de la première sphère de coordination du complexe modèle en présence du foldamère est également décrite et montrant notamment leur interactionThe ability to replicate enzymatic activity with a synthetic molecule is a highly sought after goal in modern chemistry. However, it remains a big challenge even in case of activation of small molecules. In the case of hydrogen, some bacteria can use it as energy carrier by means of enzymes called hydrogenases that can reversely make or break the bond of hydrogen molecules and are made of earth abundant metals. As hydrogen could be used for the same purpose of energy storage in our society, hydrogenases caught interest of scientific community. To date, most biomimetic hydrogenase models mainly focus on first coordination sphere modifications to fine-tune structure and physical properties. However, point mutation studies indicate that several of the amino acid residues surrounding the enzyme active site are required for structural stability or high turnover frequencies. It shows how mimicking second coordination sphere could improve the capabilities of synthetic catalysts. Our approach used aromatic oligoamide foldamers as helical scaffolds around an inspired 2Fe2S4cluster. Convergent synthesis of the final molecule and structural studies in the solid state (x-ray) and in solution (NMR, IR) as well as the dynamic behaviour are reported. Modifications of the first coordination sphere of the model complex in presence of the foldamer are also described, showing interactions between them
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Wilhelmsen, Hanne. "Resilience in emergency management teams." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for industriell økonomi og teknologiledelse, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-15049.
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This thesis is an explorative study of resilience in emergency management, including different actors’ experiences with, and expectations to, interaction by use of collaboration technology in situations of emergency. The study is comprised of interviews with important actors within the Norwegian petroleum industry, i.e. operators, contractors, authorities, and other relevant informants. Further, a literature review is presented upon the theme trust among distributed actors. The findings in this study show that there is a small degree of IO (Integrated Operations) concepts between the different external actors within emergency management. However, there is a somewhat higher utilization of these concepts between the company’s internal actors. This study recommends that the operator companies should turn to the organizations which offer to handle the 2nd line emergency management, and analyze what kind of collaboration technologies they utilize with respect to information sharing during an emergency. It is not possible to anticipate every possible scenario, meaning that the actors should focus on being prepared to be unprepared and thereby rely on their improvisation skills. Further, in order to make the emergency management more resilient, it is necessary to implement more of the IO concepts which are available today while, at the same time, trusting the technology to a greater extent. Another important factor is that the contractor companies wants to be more involved at the operator’s emergency management planning and training events. As mentioned in this thesis, my opinion is that the inclusion of contractor companies is something which the industry should take into consideration. Such a contribution may, along with implementation of IO concepts, make the emergency management more resilient and render possible to react on early warnings such that emergencies could be avoided.
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Johansen, Arve. "Eksponering for ultrafine partikler (UFP), totalpartikler, polysykliske aromatiske hydrokarboner (PAH) og høyere aldehyder ved steking av flesk (bacon) på elektrisk komfyr og gassbluss." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for industriell økonomi og teknologiledelse, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-15056.
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Det har tidligere vært funnet en sammenheng mellom eksponering for stekeos og helseeffekter, spesielt luftveisplager. Det har også blitt identifisert en rekke mutagene og karsinogene komponenter i sekeos, og insidensen av kreft i luftveissystemet har blitt funnet å være høyere enn blant resten av befolkningen (Lund, 1986), (Coggon et al., 1986), (Berg et al., 1988), (Ng et al., 1993), (Notani et al., 1993). IARC (2010) har utalt at PAH og aldehyder er viktige når det gjelder kreft og stekeos. Konsentrasjon av forurensinger i luften som følge av steking kan variere veldig. Hvilke typer forurensing som stekeosen inneholder kan variere ut i fra hva slags type/mengde mat som blir tilberedt og hvilken type/mengde stekeolje/fett som brukes, samt temperatur og tilberedningsmetode. Spesielt viktig er det å unngå brenning av oljen/fettet, da det øker generering av partikler i stor grad (Evans et al., 2008).Alle forsøk ble foretatt i et laboratoriekjøkken i kjelleren på Gamle Fysikk, NTNU, i uke 5, 8 og 10, 2011. I uke 5 ble det stekt lettsaltet sideflesk på elektrisk komfyr, i uke 8 lettsaltet sideflesk på gassbluss og i uke 10 røkt bacon på gassbluss. Forsøkene gikk over tre dager hver uke. Det ble gjennomført 5 stekerunder á 15 min som ble etterfulgt av 25 min pause, totalt 3 timer og 20 minutt. Det ble målt konsentrasjon av PAH, aldehyder og totalpartikler, samt konsentrasjon og størrelsesfordeling til partiklene. Alle målingene ble foretatt i pustesonen til testpersonene. Alt måleutstyr var personbåret, bortsett fra TSI-3936 Scanning Mobility Particle Sizer (SMPS) som ble brukt for å fastslå partikkelkonsentrasjon og størrelsesfordeling. Dette systemet er stasjonært, men målingene ble foretatt via en silikonslange som ble plassert i pustesonen til testpersonen som sto for stekingen. For å utføre stekingen ble det rekruttert tre kvinnelige studenter ved NTNU. Alle testpersonene hadde en dag som ”steker” hver uke. De andre dagene sto de rundt komfyren og var behjelpelig med å legge i og ta av ferdigstekt lettsaltet sideflesk/røkt bacon. Resultatene fra våre forsøk viser generelt at steking av lettsaltet sideflesk/røkt bacon genererer høyere peak-konsentrasjon av partikler enn det som har blitt funnet i andre forsøk med steking av mat (Yeung & To, 2008), (Buonanno et al. , 2009). Imidlertid har steking av oksebiff i soyaolje og margarin blitt vist å kunne generere høyere peak-konsentrasjon av partikler (Sjaastad et al., 2010). I våre forsøk har steking av lettsaltet sideflesk og røkt bacon på gassbluss blitt funnet å generere høyere konsentrasjon av partikler enn steking av lettsaltet sideflesk på elektrisk komfyr. Årsaken til dette er sannsynligvis brenning av gass og brenning av fett/matrester på gassblusset. Partikler generert ved brenning av gass på gassblusset har blitt vist å være kilden til de aller minste partiklene (<14,6 nm). Forskjellen i partikkelkonsentrasjon mellom steking av lettsaltet sideflesk og røkt bacon ved hjelp av gassbluss og steking av lettsaltet sideflesk på elektrisk komfyr er størst for partikler med mobilitetsdiameter på henholdsvis 98,2 og 88,2 nm. I dette størrelsesområdet bidrar partikler generert av gassblusset med en relativt lav partikkelkonsentrasjon som ikke alene kan forklare differansen i partikkelkonsentrasjon mellom bruk av elektrisk komfyr og gassbluss. Sannsynlig forklaring på differansen er en kombinasjon av forbrenning av gass og forbrenning av fett/matrester på gassblusset. For partikler >300 nm er det liten forskjell i partikkelkonsentrasjon mellom bruk av gassbluss og elektrisk komfyr. Brenning av gass på gassblusset bidrar med svært liten konsentrasjon av partikler for så store mobilitetsdiametre.Det registreres at mobilitetsdiameteren ved peak partikkelkonsentrasjon endrer seg med tiden ved bruk av gassbluss. Årsaken til dette er sannsynligvis koagulering. Partikler koagulerer og danner færre, men større partikler. Graden av koagulasjon er avhenger av kvadratet av partikkelkonsentrasjonen (Nazaroff, 2004). Høy partikkelkonsentrasjon kan være årsaken til at vi observerer en forandring i mobilitetsdiameter i våre forsøk med steking av lettsaltet sideflesk/røkt bacon på gassbluss, mens det ikke har vært observert tilsvarende endring i mobilitetsdiameter i lignende forsøk (Dennekamp et al., 2001). Ved bruk av elektrisk komfyr ligger mobilitetsdiameteren stabilt gjennom hele forsøket. Når det gjelder konsentrasjonen av totalpartikler, observeres det at konsentrasjonen er relativt lik ved steking av lettsaltet sideflesk på gassbluss og elektrisk komfyr. Konsentrasjonen av totalpartikler er vesentlig lavere ved steking av røkt bacon på gassbluss, noe som sannsynligvis kan forklares med at det røkte baconet hadde lavere fett- og vanninnhold enn det lettsaltede sideflesket.
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Tresselt, Hanne Jahreie. "Filter loss study: loss of hydrocarbons from filter when sampling and storing oil mist and oil vapour samples." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for industriell økonomi og teknologiledelse, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-15065.
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The main purpose of the thesis was to find the best way of storing samples of aerosol from drilling mud on filter.The patterns of loss depend on the properties of the base oil and the concentration of the sample. Most sample is lost during aspiration for high volatility samples, but the degree of loss during storage has similar patterns. Lower concentration samples loose more than higher concentration samples during aspiration.Filters should be taken out of the cassette before weighing rather than weighing the whole cassette with filter.Storage on cellulose acetate plus glass fibre filter combination and on double glass fibre filter have similar patterns, but more sample is lost during aspiration with a double glass fibre filter than with a cellulose acetate plus glass fibre filter combination for EDC Pearl and Sipdrill 2.0. Samples should be stored at refrigerator temperature for higher concentrations (ca. 70 mg/m3) and at room temperature for low concentrations (ca. 20 mg/m3). Plugs do not make much difference.How long a sample can be stored depends on the volatility of the sample, as high volatility (low viscosity) samples tend to lose more during aspiration.
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Hanto, Jon Sveinung. "Praktisk bruk av sikkerhetsindikatorer relatert til samhandling : Utvikling og praktisk test av indikatorsett for integrerte operasjoner i olje- og gassnæringen." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for industriell økonomi og teknologiledelse, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-15077.
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I søken etter å finne praktisk anvendbare verdier som kan inngå i et indikatorsett, har det vært viktig å finne kvantitative tall som er lette å måle, vedlikeholde, bruke og som man kan tolke entydige konkrete slutninger ut fra.Oppgaven har som formål å gi leseren et innblikk i en dypere studie hvordan man anvender et teorigrunnlag på den ene siden og undersøkelser på den andre som utgangspunkt for konkret kunne forstå og avdekke organisasjonens målepunkter for samhandling. Vurderinger er gjort under hele gjennomføringen av oppgaven, da både intervjuspørsmål og observasjoner favner ganske bredt.I oppgaven brukes teori, intervjuer og observasjoner for å argumentere for verdier som kan gjengi et nivå på sikkerhet innad i samhandlingsteam.Empirisk datainnsamling har bidratt til at denne oppgaven kan presentere et sett med indikatorer som kan reflektere sikkerheten i forhold til små team som driver med samhandling og Integrerte Operasjoner(IO) i en stor organisasjon.Gjengitt under områder forfatter i konklusjonen mener gjenspeiler sikkerhet i til et team basert på målepunktene som inngår i indikatorsettet og reflekterer sikkerhet i forhold til samhandling og Integrerte operasjoner:- Opptelling av antall mellomledere og disiplinledere som er mobilisert til samhandlingsteamet.- Gjennomsnittlig bransjeerfaring per møtedeltaker gitt antall i år.- Antall år med erfaring av gjeldende programvare.- Antall manglende kurs eller krav i gjennomsnitt per person i et påbegynt oppdrag.Disse verdiene blir vektet mot argumenterte kriterier for akseptabelt nivå av sikkerheten for samhandlingsteamet.Det er seks områder forfatter ser på som aktuelle å settes fokus på i videre arbeid med å ta oppgaven noen steg videre:1. Å teste indikatorsettet ytterligere og å bruke det aktivt over tid, optimalisere kravene og tolke trendene. Herunder også å avdekke mulige flere hovedområder som bør måles.2. Å inkludere større deler av organisasjonen i det å bruke indikatoren for små team og også å få med personell offshore da intervjuene bare ble utført onshore.3. Måle flere team mot hverandre samt å sammenstille dem i en sikkerhetsindikator for samhandling på et overordnet plan.4. Kan være å integrere operatør og vedlikeholdspersonell enda sterkere ved at flere organisasjoner måles med indikatorer som både kan sees av oppdragsgiver og oppdragsutfører.5. Kan være å inkludere andre større datasett som for eksempel et fullstendig datasett på alder av de ulike komponentene som inngår i materielle på offshoreinstallasjonen. Dette kan bidra med at man i samhandlingen kan bidra med å sette fokus på utstyr som bør fases ut.6. Forsøke å redegjøre for hvordan kroppsspråk og språklige barrierer innvirker på samhandling.
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Saggi, Karan. "Evaluation of Approaches and Methods for Establishing a Good Safety Culture." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for industriell økonomi og teknologiledelse, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-16755.
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The purpose of this thesis is to evaluate different approaches and methods used in the oil industry, based on theory, research and industrial experience. An evaluation of three oil companies’ safety culture approaches were therefore conducted; BP Norway, Conoco Phillips Norway and Wintershall Norway, in order to suggest an approach suited for establishing a “good” safety culture according to the Norwegian Framework Regulation §15. The Norwegian petroleum safety authority, Industri Energi (ABClub at BP Norway) and Samarbeid for Sikkerhet were also used to crosscheck the different organizations for similarities and differences to their safety culture approaches and methods, bringing in several aspects of the Norwegian oil industry.The evaluation was mainly based on Hale’s (2000) eight elements, which were used as rationale for a “good” safety culture, according to the Norwegian Framework Regulation § 15. The evaluation was carried out by seven in-depth interviews from the six organizations, with employees in or close to management in order to target the views from the upper management.The results show that the oil companies have implemented many decent measures to establish a “good” safety culture, but still face some challenges to get the desired effect. The different safety culture approaches have managed to address many elements regarded as essential for establishing a “good” safety culture, however, to a various extent. For instance, the results confirm that the culture approach and the behavioural based safety (BBS) approach are better in some areas compared to others, each having their advantages. While the safety culture approach more easily create trust and a common starting point in the organization, the BBS approach is better with regards to involving their employees. Both approaches have, though, demonstrated that with several tools in place the creative mistrust is easily created, regardless of the path chosen. Finally, the results show that both approaches can give lasting changes to the safety culture, however, the culture approach has a better starting point as it provides a more extensive scope. Other research on safety culture has also confirmed this, and further highlights the importance of BBS elements, as it ultimately can pose an effect on the culture.Regarding the desired effect, the assignment also demonstrates that implementation of a safety culture approach alone is not enough to get a desired effect, as many additional success factors also creates challenges, e.g. that successful implementation needs strong commitment from management, as this will positively encourage the employees to follow. Moreover, the result also confirmed that only observing statistical aberrance on safety performance gave no guarantee of a safety culture change. The reason for this is because safety culture is by meaning hard to detect, and it is therefore important to work qualitatively, e.g. by management observation and communication with employees.To conclude, the thesis has shown that it is possible to establish a “good” safety culture using a safety culture approach with various methods, in order to create a lasting change. However, the fact that the companies see their approach as the most preferable creates challenges in the practical life, in relation to implementation of a common approach for the Norwegian oil industry.
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Gerace, Salvadore. "A MODEL INTEGRATED MESHLESS SOLVER (MIMS) FOR FLUID FLOW AND HEAT TRANSFER." Doctoral diss., University of Central Florida, 2010. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/2371.
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Numerical methods for solving partial differential equations are commonplace in the engineering community and their popularity can be attributed to the rapid performance improvement of modern workstations and desktop computers. The ubiquity of computer technology has allowed all areas of engineering to have access to detailed thermal, stress, and fluid flow analysis packages capable of performing complex studies of current and future designs. The rapid pace of computer development, however, has begun to outstrip efforts to reduce analysis overhead. As such, most commercially available software packages are now limited by the human effort required to prepare, develop, and initialize the necessary computational models. Primarily due to the mesh-based analysis methods utilized in these software packages, the dependence on model preparation greatly limits the accessibility of these analysis tools. In response, the so-called meshless or mesh-free methods have seen considerable interest as they promise to greatly reduce the necessary human interaction during model setup. However, despite the success of these methods in areas demanding high degrees of model adaptability (such as crack growth, multi-phase flow, and solid friction), meshless methods have yet to gain notoriety as a viable alternative to more traditional solution approaches in general solution domains. Although this may be due (at least in part) to the relative youth of the techniques, another potential cause is the lack of focus on developing robust methodologies. The failure to approach development from a practical perspective has prevented researchers from obtaining commercially relevant meshless methodologies which reach the full potential of the approach. The primary goal of this research is to present a novel meshless approach called MIMS (Model Integrated Meshless Solver) which establishes the method as a generalized solution technique capable of competing with more traditional PDE methodologies (such as the finite element and finite volume methods). This was accomplished by developing a robust meshless technique as well as a comprehensive model generation procedure. By closely integrating the model generation process into the overall solution methodology, the presented techniques are able to fully exploit the strengths of the meshless approach to achieve levels of automation, stability, and accuracy currently unseen in the area of engineering analysis. Specifically, MIMS implements a blended meshless solution approach which utilizes a variety of shape functions to obtain a stable and accurate iteration process. This solution approach is then integrated with a newly developed, highly adaptive model generation process which employs a quaternary triangular surface discretization for the boundary, a binary-subdivision discretization for the interior, and a unique shadow layer discretization for near-boundary regions. Together, these discretization techniques are able to achieve directionally independent, automatic refinement of the underlying model, allowing the method to generate accurate solutions without need for intermediate human involvement. In addition, by coupling the model generation with the solution process, the presented method is able to address the issue of ill-constructed geometric input (small features, poorly formed faces, etc.) to provide an intuitive, yet powerful approach to solving modern engineering analysis problems.Ph.D.
Department of Mechanical, Materials and Aerospace Engineering
Engineering and Computer Science
Mechanical Engineering PhD
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Oliveira, Dami?o Valdenor de. "Biologia reprodutiva de Mimus gilvus (Aves: Mimidae) em ?rea de restinga no nordeste do Brasil." Universidade Federal do Rio Grande do Norte, 2015. http://repositorio.ufrn.br/handle/123456789/21238.
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O sabi? da praia, Mimus gilvus (Aves: Mimidae) ? um passeriforme com ampla distribui??o na Am?rica Central e do Sul. No Brasil ocorre principalmente nas ?reas de restinga e vegeta??o pr?xima a praia. Muitos atributos de sua biologia reprodutiva s?o desconhecidos, principalmente em rela??o ao sucesso reprodutivo. Nesse sentido, durante os anos de 2010-2011, 2011-2012 e 2014-2015 foram feitas visitas ? ?rea de restinga no Centro de Lan?amento da Barreira do Inferno (CLBI), localizado entre os munic?pios de Natal e Parnamirim-RN (5?54?S e 35?10?W), onde foram feitas buscas sistem?ticas buscando descrever caracter?sticas da biologia reprodutiva de M. gilvus, estimar o seu sucesso reprodutivo utilizando o m?todo de Mayfield, e identificar os principais fatores que influenciam o seu sucesso reprodutivo em ambiente de restinga. Para isso, foram utilizados 45 ninhos ativos monitorados. Apenas durante a temporada reprodutiva de 2011-2012 e 2014-2015 foram feitas visitas sistem?ticas a ?rea de estudo. O per?odo reprodutivo variou de agosto a mar?o. O tamanho da ninhada variou de dois, tr?s e seis ovos (n = 22). Ninhadas de dois ovos foram mais frequentes, sendo a m?dia de ovos colocados por ninho de 2 ? 0,51 (n = 20 ninhos). O per?odo de incuba??o foi de aproximadamente 13 ? 1,9 dias (n = 11 ninhos ). O per?odo de perman?ncia dos filhotes no ninho foi de aproximadamente 11 ? 1,6 dias (n = 9 ninhos). O sucesso aparente foi de 37,8% e o sucesso estimado pelo m?todo de Mayfield foi de 26,6 %. A preda??o foi a principal causa da perda de ninhos na ?rea de estudo. As taxas de sobreviv?ncia di?ria (TSD) obtidas foram 0,9593 para o per?odo de incuba??o e 0,9313 para o per?odo de ninhego. As estimativas de sobreviv?ncia para cada per?odo foram 0,5827 para incuba??o e 0,4571 para ninhego respectivamente. A precipita??o m?dia acumulada para cada m?s influenciou negativamente as taxas de eclos?o dos ninhos de M. gilvus. Al?m disso, o n?mero de eclos?es entre o per?odo mais chuvoso (esta??o chuvosa) e o per?odo de menor precipita??o (esta??o seca) foram diferentes. O n?mero de ninhos perdidos de M. gilvus foi menor em moitas do que em cactos, o que pode justificar o maior n?mero de ninhos dessa esp?cie encontrados em moitas. As taxas de sobreviv?ncia no per?odo de ninhego foram menores em compara??o com o per?odo de incuba??o. M. gilvus parece evitar o per?odo mais chuvoso durante sua reprodu??o, concentrado a maior parte de seus ninhos no per?odo de menor precipita??o.
The thrush beach, Mimus gilvus (Aves: Mimidae) is a passerine widely distributed in Central and South America. In Brazil occurs mainly in the areas of the resting and vegetation near the beach. In southeastern Brazil this species has disappeared, mainly due to urbanization. Many attributes of their reproductive biology are unknown, especially in relation to reproductive success. During the years 2010-2011, 2011-2012 and 2014-2015 were made visits to the area of restinga forest in Centro de Lan?amento da Barreira do Inferno (CLBI), located between the cities of Natal and Parnamirim-RN (5 ? 54'S 35 ? 10'W ) where they were made systematic searches to trying describe reproductive biology of the characteristics of M. gilvus, estimate their reproductive success using the Mayfield method, and identify the main factors that influence their reproductive success in environment the resting. For this, forty fifth active nests monitored were used. Only during the breeding season of 2011-2012 and 2014-2015 were made systematic visits to the study area. The reproductive period ranged August to March. Clutch size ranged from two, three and six eggs (n = 22). Broods of two eggs were more common, with an average of eggs laid per nest of 2 ? 0,51 (n = 20 nests). The incubation period was approximately 13 ? 1,9 days (n = 11 nests). The period of stay of the nestlings was approximately 11 ? 1,6 days (n = 9 nests). With approximately 11 days old the nestlings were able to leave the nest. The apparent success was 37,8% and the success estimated by Mayfield method was 26,6%. Predation was the main cause of loss of nests in the study area. The daily survival rates (TDS) were obtained from 0,9593 incubation and 0,9313 for nestling period respectively. Survival estimates for each period was 0,5827 for incubation and 0,4571 for nestling period. The cumulative average rainfall for each month influenced negatively the hatching rates of M. gilvus nests. In addition, the number hatch eggs among the most rainy season (rainy season) and the period of lowest rainfall (dry season) were different. The number of lost nests of M. gilvus was lower in scrubs than cactus, which may account for the largest number of nests of this species found in scrubs. Survival rates in nestling period were lower compared with the incubation period. The fact that the survival rates nests of M. gilvus be lower in the nestling period compared to the incubation period may result from increased activity of adults during this phase of the nest, which in turn would increase predation rates. M. gilvus seems to avoid the rainy season during their reproduction, concentrated most of their nests in periods of low rainfall.
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Villiers, Emilie. "Synthèses stéréocontrôlées de pseudodipeptides fluorés de mimes contraints de la proline, et d'analogues de l'Enalapril." Thesis, Rouen, INSA, 2013. http://www.theses.fr/2013ISAM0034.
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La fluorooléfine (CF=CH), motif isostère et isoélectronique de la liaison amide, peut être utilisé comme mime efficace de la liaison peptidique. De plus, ce motif confère une meilleure résistance à la dégradation enzymatique comparé à la liaison peptidique. Cette thèse s’inscrit dans notre programme de développement de nouvelles méthodologies d’accès aux fluoropseudopeptides. Dans une première partie, nous appliquons diverses stratégies originales du laboratoire vers la synthèse d’un analogue du neuropeptide 26RFa. Dans une seconde partie est présentée une stratégie générale vers l’accès à des pseudopeptides possédant un motif proline, un acide aminé extrêmement important. Ainsi, la synthèse asymétrique d’analogues fluorés de dipeptide incluant l’unité proline (AA-[(Z) ou (E)CF=C]-Pro), de conformation cisoïde ou transoïde, a été développée. Enfin, nous avons étendu cette méthodologie à la synthèse d’un analogue de l’Enalapril®, molécule biologiquement activeThe Fluoroolefin moiety (CF=CH) can be used as an effective peptide bond mimic due to isoelectronic and isosteric properties. Moreover, this moiety provides better resistance to enzymatic degradation compared to native peptide bond. This thesis is part of our program aiming at developing new methodologies towards fluoropseudopeptides. In a first part, we apply various innovative strategies from the laboratory to the synthesis of an analog of neuropeptide 26RFa. In the second part is presented an overall strategy towards fluorinated pseudopeptide including a proline residue, an amino acid extremely important. Thus, the asymmetric synthesis of fluorinated dipeptide analogues AA-[(Z) or (E) CF=C]-Pro, under cisoid or transoid conformation, has been developed. Finally, we extend this methodology to the synthesis of an analogue of biologically active Enalapril®
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Bernard, Anne-Sophie. "Etude de complexes de manganèse mimes de superoxyde dismutase sur des modèles cellulaires de l'inflammation." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066341.
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Carrel, Frédéric. "Vers de nouveaux agents anti-inflammatoires : synthèse de mimes C-saccharidiques de l'Acide Sialyl Lewis X /." [S.l.] : [s.n.], 2003. http://library.epfl.ch/theses/?nr=2766.
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Magalhães, Maria das Graças Sandi 1961. "Medos, mimos e cuidados. Leituras úteis para educar as mães = os guias maternos brasileiros (1919-1957)." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/251088.
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Orientador: Heloísa Helena Pimenta RochaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Educação
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Resumo: O mercado editorial brasileiro, em expansão nas primeiras décadas do século XX, incorporou, à sua maneira, os discursos produzidos tanto pelo movimento higienista como pelos que compreendiam a educação como forma de regenerar a nação e encaminhá-la em direção ao progresso e à modernidade. Escritos em sua maioria por pediatras, os guias maternos fizeram parte de coleções que se destinavam à educação da população. Apesar das referências nesses impressos aos procedimentos científicos em relação à criação dos filhos, a identificação dessas publicações como leituras úteis permitiu analisá-las enquanto uma das práticas médicas dirigidas às mulheres, para difundir modelos de comportamento familiar que garantissem a geração, o desenvolvimento saudável e a educação das crianças brasileiras. Este texto adota como principal referencial teórico as contribuições de Roger Chartier, em torno da história do livro e da leitura, e de Michel Foucault, no que se refere à compreensão dos mecanismos de poder sobre a população, definidos pelo autor como biopolítica. Os processos de produção e os indícios da circulação dos guias maternos foram considerados como elementos fundamentais para a compreensão da difusão das representações sobre as mulheres, as crianças e sua educação, nos moldes propostos pela medicina, como parte de um processo mais amplo de intervenção na sociedade brasileira. Ao mesmo tempo, a análise das prescrições de leitura, presentes nas características textuais e tipográficas desses impressos, permite uma aproximação das práticas propostas às mães. Por essa razão, os guias maternos que integram o corpus desta pesquisa, publicados entre 1919 e 1957, foram compreendidos tanto como objeto quanto como fonte de estudo. Entre as questões suscitadas, a principal interrogação refere-se ao espaço que esses impressos teriam ocupado no processo de difusão de práticas higiênicas que abrangiam tanto o cuidado com o corpo infantil como a educação da criança, com base nas recomendações médicas. O tratamento privilegiado dado à mulher leitora, a partir desse redimensionamento das funções maternais, em acordo com os princípios científicos, também permitiu indagar sobre as representações que teriam sido produzidas em torno da leitura feminina, veiculadas por autores e editores dos guias maternos estudados, a partir da inserção de diferentes dispositivos textuais e gráficos.
Abstract: The Brazilian publishing market in expansion since the first decades of the XX Century has incorporated at its own manner the speeches produced either by the hygienist movement as well as by those who understood upbringing as a way to regenerate a nation, leading it into progress and modernity. Written mostly by pediatricians, mother guidebooks were part of a collection that was intended for the education of the population. Despite the references contained in such publications regarding the scientific procedures related to children upbringing, identifying such publications as useful reading material allowed for analyzing them as one of the medical practices directed to women, in order to spread familial behavioral models that would guarantee the generation, the healthy development and upbringing of the Brazilian children. This work adopts, as its main theoretical reference, Roger Chartier's contributions about the history of books and reading, and Michel Foucalt's contributions to the understanding of power mechanisms over the populations, defined by the author as biopolitics. Production processes and indications of circulation of mother guidebooks were regarded to as fundamental elements to the understanding of the diffusion of representations over the women, the children and their upbringing, according to models proposed by medicine, as part of a bigger process of intervention in the Brazilian society. At the same time, the analysis of the reading prescriptions contained in the text and graphic characteristics of such printings allows for the approaching of the practices proposed to mothers. Due to this reason, mother guidebooks that form the corpus of this survey, published between 1919 and 1957, have been taken both as subject and as source of study. Among the raised issues, the main inquiry is concerned with how much space such printings might have taken in the process of diffusion of hygienic practices regarding either the care with the child's body as well as the child's upbringing based on medical recommendations. The privileged treatment given to woman readers beginning with the redesigning of maternal functions, according to scientific principles, also allowed for questioning the representations that might have been produced about the women's reading, published by authors and publishers of such guidebooks that have been studied, based on the insertion of different text and graphic devices.
Doutorado
Educação, Conhecimento, Linguagem e Arte
Doutor em Educação
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Zanon, Mariana Santos. "Distribuição, tamanho populacional e conservação de Mimus gilvus (Aves: Mimidae) no Estado do Rio de Janeiro." Universidade do Estado do Rio de Janeiro, 2010. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=1566.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoA extensão da distribuição geográfica e a abundância local se combinam para determinar o tamanho populacional total das espécies. Entretanto, tais atributos são desconhecidos para a maioria das aves. Isso representa um problema para a conservação das espécies, baseada primariamente na manutenção do número e distribuição destas. A União Internacional para a Conservação da Natureza (IUCN), por exemplo, adota a distribuição geográfica e o tamanho populacional como critérios para avaliação de ameaça de extinção de espécies. Mimus gilvus, o sabiá-da-praia, é uma ave afetada por alterações no seu hábitat e captura. No litoral oriental brasileiro, habita exclusivamente restingas, e seu desaparecimento vem sendo divulgado para alguns remanescentes de restinga fluminenses. Essa ave é categorizada como Em Perigo em avaliações dos estados do Rio de Janeiro e Espírito Santo. O objetivo geral do presente estudo foi prover uma atualização da distribuição geográfica de M. gilvus no estado do Rio de Janeiro e fornecer uma estimativa do tamanho atual de sua população remanescente neste estado. Duas metodologias foram aplicadas: transecções lineares e amostragem por pontos (marcados ao longo de transecções). As transecções foram realizadas em 15 remanescentes de restinga. O esforço de busca pela espécie foi complementado por meio de visitas fortuitas, gerando uma soma de 21 áreas exploradas. Um total de 40 pontos foi amostrado em quatro remanescentes onde a presença da espécie havia sido confirmada. Os dados de presença e ausência permitiram a geração de um mapa de extensão de ocorrência atual de M. gilvus no estado do Rio de Janeiro. Adicionalmente, produziu-se um mapa de extensão de ocorrência original de M. gilvus, para comparação. A extensão de ocorrência da espécie foi calculada segundo definição da IUCN. A partir dos dados de abundância populacional gerados por transecções e pontos, calculou-se a densidade populacional de M. gilvus para cada remanescente onde a espécie esteve presente. A espécie foi encontrada em apenas quatro (19%) das 21 áreas amostradas. Sua densidade populacional média foi de 37 indivíduos/km2 (transecções) e de 52 indivíduos/km2 (pontos). Os valores de extensão de ocorrência estimados foram de 760 km2 (atual) e 2143 km2 (original). Combinando-se a extensão de ocorrência e a densidade média populacional, foram obtidos valores de tamanho populacional máximo de 29640 (transecções) e 39520 indivíduos (pontos) e mínimo considerando a probabilidade de ocorrência da espécie de 8299 (transecções) e 17784 indivíduos (pontos). No estado do Rio de Janeiro, M. gilvus sofreu redução dos limites de sua extensão de ocorrência ao leste, e surgiram vazios na porção central de sua extensão de ocorrência original. De acordo com as quantificações dos critérios propostos pela IUCN, confirmou-se a categoria regional de ameaça Em Perigo (EN) para M. gilvus. Isso reflete a intensa pressão antrópica sobre as restingas e, possivelmente, também está associado com a captura de ninhegos. Portanto, pressões antrópicas levam a espécie a uma situação de isolamento populacional e de extinções locais, provavelmente irreversível. Recomendam-se uma efetiva proteção formal dos remanescentes de restinga e educação ambiental para mitigar as pressões sobre a espécie e evitar mais extinções locais.