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Johansson, Seiko. "Patient-derived organoid culture for 3D culture of colorectal cancer, renal cancer and osteosarcoma." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-391043.
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It is always important to choose appropriate anticancer drugs for cancer patients. At RCL, a division of Uppsala university hospital, drug resistance profiles of patients are evaluated by a cell viability assay called FMCA. However, the number of anticancer drugs that can be evaluated by the FMCA is dependent on the number of viable cancer cells from tissues that can be obtained from each individual patient. Therefore, improvement of cell viability methods is an important issue at RCL. This study was performed to improve the FMCA method by organoid culture from colorectal cancer, renal cancer and osteosarcoma to increase the number of cancer cells. As results, it was successful to expand cryopreserved patient cancer cells to organoids to acquire more cells than before expansion. Organoids showed rounded structure in microscopy images. Thereafter, FMCA was performed on organoids as well as on thawed cryopreserved cancer cells from the original sample. Those results showed that original cancer cells, cryopreserved original cancer cells and expanded organoids derived from those cryopreserved cells had similar resistance profiles. It was also discovered that the organoids secreted VEGF under the cultivation. From those results, it can be concluded that organoids are representative of the original cancer from the patients. It is however needed to improve organoid culture methods, and to further confirm organoids by protein expression analysis and DNA analysis.
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TOSCANI, CECILIA. "UNCOVERING EPIGENETIC VULNERABILITIES IN INTESTINAL CANCER DEVELOPMENT." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/697052.
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Colorectal cancer (CRC) arises from a multi-step process leading to the progressive accumulation of genetic and epigenetic mutations, thus causing deregulation in homeostasis followed by neoplastic transformation.Epigenetic and genetic alterations are able to induce a constitutive activation of the WNT signaling pathway, whose aberrant activity converges into deregulation of proliferation, differentiation and cell death pathways. The most common causes of WNT pathway hyper-activation are APC loss of function, or b-catenin constitutive activation mutations. Despite this knowledge of aberrant WNT activity, upstream interference with this signaling pathway induces adverse effects due to high cross-talk with other pathways, highlighting a need to find alternative ways to indirectly target the effectors of this pathway. Deregulated pathways in CRC provoke aberrant signaling that converges into the nucleus where transcription and chromatin-remodeling factors cooperate to maintain or modify the identity of a cell. In recent years, several studies have been focused on epigenetic players, which act by depositing specific and reversible post-translational modifications. For this reason they are being recognized as promising new targets for the development of cancer therapeutic strategies. In this context, my project takes advantage of murine 3D intestinal organoid cultures, carrying oncogenic deregulations of the WNT pathway, as a platform for pooled and arrayed RNA interference screens, to identify novel regulators that control the nuclear/transcriptional aspect of this oncogenic pathway. I also implemented the validation of selected targets in human metastatic colorectal cancer organoids to highlight their clinical relevance. Moreover, since several chromatin modifier inhibitors have been already developed, the findings of this project should prompt the development of new molecules for CRC treatment to target the novel sensitivities I identified. Finally, this project generated important technical knowledge through this pioneering approach that will open up the possibility of performing functional screens in other tissues from which organoid cultures have already been established.
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Godart, Matthias. "Interactions fonctionnelles entre voies signalétiques intrinsèques et voie des hormones thyroïdiennes dans les cellules souches et progéniteurs de l'épithélium intestinal." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1138.
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Les hormones thyroïdiennes (HTs) contrôlent plusieurs aspects du développement et de l’homéostasie intestinale. Elles agissent via des récepteurs nucléaires (TRs), facteurs de transcription modulés par la T3. Le paradigme est la métamorphose des amphibiens où elles sont responsables du remodelage du tube digestif et de l’émergence des cellules souches (Ishizuya-Oka et al, 2009). Des études précédentes ont montré que les HTs jouent un rôle fondamental en régulant la balance entre prolifération et différenciation des précurseurs épithéliaux murins. Du point de vue moléculaire, le récepteur nucléaire TRα1 contrôle plusieurs gènes du cycle cellulaire/prolifération ainsi que les voies de signalisation Wnt et Notch (rev. in Sirakov et al, 2104; Skah et al, 2017). En accord avec ces fonctions, l’expression ciblée de TRα1 dans l’épithélium intestinal (souris vil-TRα1) est suffisante pour induire des cryptes aberrantes, hyper-prolifératives et confère une sensibilité accrue au programme de tumorigénèse intestinale dépendant de la mutation dans le gène Apc (vil-TRα1/Apc+/1638N mice) (Kress et al, 2010). Le but de mon travail a été d’étudier le contrôle des cellules souches intestinales, dépendant des HTs/TRs. En effet, j’ai utilisé des souris Lgr5-EGFP-ires-CreERT2 permettant de traquer, trier et cibler les cellules souches (Barker et al, 2007) que j’ai croisées avec le modèle murin inductible au tamoxifène TRα1-LOF (Loss-of-function) (Quignodon et al, 2007). J’ai étudié les effets de l’altération de la voie HTs/TRα1 in vivo et dans des organoïdes intestinaux (ex vivo). Nos résultats indiquent que les HTs et la modulation de l’expression ou de l’activité de TRα1 affectent rapidement et fortement les cellules souches intestinales. Ce travail ouvre de nouvelles perspectives dans l’étude des signaux dépendants des HTs/ TRα1 dans la physiopathologie des cellules souches intestinalesThyroid hormones (THs) control several aspects of gut development and homeostasis. They act through the thyroid hormone nuclear receptors (TRs) that are T3-modulated transcription factors. The paradigm is the amphibian metamorphosis, where they are responsible for gut remodeling and emergence of the stem cells (Ishizuya-Oka et al, 2009). In previous studies we showed that THs play a fundamental role in regulating the balance between cell proliferation and cell differentiation of the murine intestinal epithelial precursors. From a molecular point of view the nuclear receptor TRα1 controls several proliferation/cell-cycle genes as well as the Wnt and Notch pathways (rev. in Sirakov et al, 2104; Skah et al, 2017). In accordance with these functions, targeted expression of TRα1 in the intestinal epithelium (vil-TRα1 mice) is sufficient to induce aberrant and hyper-proliferative crypts and confers increased susceptibility to Apc-mutation dependent intestinal tumorigenic program (vil-TRα1/Apc+/1638N mice) (Kress et al, 2010). The aim of my work was to study TH- and TRα1-dependent control of intestinal stem cells. Indeed, I used the Lgr5-EGFP-ires-CreERT2 mice enable tracking, sorting and targeting the stem cells (Barker et al, 2007) crossed with tamoxifen inducible TRα1 loss-of-function (Quignodon et al, 2007) mouse model (TRα1-LOF). I studied the effect of TH/TRα1 alteration in vivo and in intestinal organoids (ex vivo). In conclusion, our results indicate that HTs and modulating TRα1 expression or activity have a rapid and strong effect on the intestinal stem cells. This work opens a new perspective in the study of TH/TRα1-dependent signal on the physiopathology of the intestinal stem cells
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Dinelli, Giulia <1993>. "Matrici Naturali e Sintetiche per colture 3D di Organoidi." Master's Degree Thesis, Università Ca' Foscari Venezia, 2019. http://hdl.handle.net/10579/15246.
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Gli Organs-on-chips (OOCs) sono modelli 3D in vitro di organi umani miniaturizzati, progettati per riprodurre la biologia e fisiologia degli omologhi in vivo.
I sistemi OOCs integrano: microingegneria, tecnologie di microfluidica e principi di biomimesi per ricreare gli aspetti chiave di un organo, includendo anche criticità dell’architettura tissutale, interazioni cellula-cellula e ambiente extracellulare.
In sostanza, sono costituiti da un chip multifluidico in cui le cellule d’interesse vengono coltivate in 3D; è possibile realizzare questi sistemi a partire da cellula staminali da cui vengono ottenuti organoidi che messi in coltura su una matrice di supporto all’intero del sistema microfluidico mimano l’organo.
Nel presente studio si è voluto testare la capacità di una serie di matrici di supporto, naturali e sintetiche, a sostenere la proliferazione e il differenziamento di organoidi di fegato murino, con applicazione futura all’interno di un sistema OOCs.
Queste piattaforme creative, e la loro ulteriore integrazione in Multi-Organs-on-chips, possono portare nuovi benefici a diverse applicazioni come: lo sviluppo in vitro di modelli umani di organi sani e malati, l’indagine dei meccanismi fondamentali di eziologia delle patologie e organogenesi, valida alternativa alla sperimentazione animale per quanto riguarda la tossicità dei farmaci e lo studio di target farmacologici ed infine ideale piattaforma per lo sviluppo di nuove terapie.
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Workman, Michael J. "Generating 3D human intestinal organoids with an enteric nervous system." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416570664.
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Bagnara, Elena <1993>. "Evaluation of synthetic alternatives scaffold for 3D culture method for liver organoids." Master's Degree Thesis, Università Ca' Foscari Venezia, 2021. http://hdl.handle.net/10579/20090.
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Different Synthetic matrix alternatives were tested in this thesis to find a suitable matrix which promotes the organoids growth. Synthetic matrix are Ecofriendly biocompatible and furthermore do not show variation between batches that could be a big problem for biomedical applications.
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Anderle, Marica. "Human cerebellar organoids as an in vitro 3D model of Group 3 Medulloblastoma." Doctoral thesis, Università degli studi di Trento, 2020. http://hdl.handle.net/11572/262782.
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Medulloblastoma (MB) is a heterogeneous tumor that represents the most common malignant brain tumor of childhood. It stands as a cause for a high percentage of morbidity and mortality among cancer patients. Thanks to genome-wide analyses, MB can be divided into four significant subgroups, different from each other for diagnosis, prognosis, and metastatic recurrence. WNT subtype has the best prognosis; SHH subtype has an intermediate prognosis; Group 3 subtype is characterized by a high percentage of metastases and worst prognosis; Group 4 MB is the most common subtype, but the less understood.
Willing to increase the knowledge about the aggressiveness of the Group3 subtype, this work will focus on developing a reliable Human Group 3 MB model based on cerebellar organoids derived from human induced pluripotent stem cells (iPSC).
Three-dimensional (3D) cell culture systems have gained increasing interest in modeling, drug discovery, and tissue engineering due to their evident advantages in providing more reliable information and more predictive data before in vivo tests. The field of cell development, differentiation, and cell organization was the first to make use of cerebellar organoids, but these 3D structures are starting to be a novelty in the cancer field.
One of the innovative points of this work is the setup of a new way to modify wild type human cerebellar organoids, electroporating them with strong Group 3 MB inducers, derived from in vivo patient-specific NGS data screen. We validate that Gfi1/c-Myc and Otx2/c-Myc oncogenes give rise to MB-like organoids, which (in nude mice) can develop tumors harboring a DNA methylation signature that clusters specifically with human patient Group 3 tumors. Moreover, we identify Smarca4 as an oncosuppressor gene and discover that treatment with an EZH2 specific inhibitor, called Tazemetostat, reduces Otx2/c-Myc tumorigenicity in human organoids.
We speculate that our Medulloblastoma 3D culture system holds great promises for applications in infant tumor research, cancer cell biology, and drug discovery, being a novel human 3D reliable tool for developing personalized therapies.
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Ma, Lin. "Multi-scale 3D imaging of the microstructure in organic-rich shales." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/multiscale-3d-imaging-of-the-microstructure-in-organicrich-shales(514544f2-39f8-4fe2-b8f4-fecb27380c10).html.
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Technological advances in horizontal drilling and hydraulic fracturing have paved the way for the exploration and production of shale gas and shale oil, the fastest growing energy sector globally. The imaging and quantification of the geometry, sizes, network and distribution of extremely fine-grain minerals, organic matter and pores are a significant component for the macroscopic and microscopic characterisation of shale reservoirs but is also highly challenging. X-ray computed tomography (XCT) combined with 3D Electron Microscopy (EM) are used to address this challenge and give us information in 3D from multiple length scales over 3 orders of magnitudes: mesoscale (R1), microscale (R2), submicron-scale (R3), low-resolution nanoscale (R4) and high-resolution nanoscale (R5) with spatial resolutions of ~10micro metre, ~1micro metre, ~130 nm, ~50nm and ~5nm, respectively. The multi-scale imaging and quantification method was initially applied here to the Carboniferous Bowland Shale, the largest potential shale gas play in the UK. The appropriate length scales (both field of view and voxel size) of specified phases such as pores, organic matter, clay minerals and non-clay minerals were analysed. The low connectivity of pores and high connectivity of organic matter suggests that the 20 nm and larger pores imaged did not form connected flow paths, demonstrating that porous gas flow through this sample cannot be the main transport mechanism and diffusive transport through the organic matter and clay minerals must also be considered. Then, the variation of organic matter and pore distribution along a TOC gradient were analysis on Lublin gas-mature shale samples in Poland and Baltic oil-mature shale samples in Lithuania. The results show intergranular pores dominated in this series of samples, including organic interface pores and inter-mineral pores, which further confirm that organic matter is not the primary influencing factor for porosity, but the clay minerals. Finally, a novel multi-stage workflow of pore system is proposed relying on both image quantification and numerical modelling of geological features with studies in Jurassic Haynesville shale in the US. Three stages are divided according to pore variation, mineral variation and microfacies variation across four distinct length scales (R1-R4/R5), and permeability was simulated based on the upscaled pore system. The final computed porosity and permeability shows acceptable errors when compared with the helium porosity and press decay permeability. Beyond the lab measurements, the pore occurrence and size distribution were computed in the upscaling process. The combining of XCT and 3D-EM provides a powerful tool for the multi-scale imaging and quantification of microstructural information in shales, allowing the visualization of pores, organic matter and inorganic mineral phases over a range of scales over three orders of magnitude (~ 10 micro metre to ~ 5 nm), and the volume fraction of each phases shows a reasonable correlation to traditional physical and chemistry quantification data. The further studies, such as the variation of organic matter and pores, upscaling of porosity and permeability presented in this study, has verified the feasibility of the proposed multi-scale method and promises a bit potential for reservoir prediction and other challenges in geological studies.
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Langner, Maik. "Laterally modified microcavity systems containing organic emitters." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-67568.
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The scope of this work is an in-depth investigation of dielectric mirror microcavities with central organic dye layers, which are preferably modified in at least one lateral dimension. The large quality factor of the planar resonator in conjunction with comparatively stable and spectrally broad emitting molecules allows for a detailed analysis of several aspects of microresonator systems. Their optical properties are analyzed both with transmission and luminescence measurements as well as in the lasing regime.
The first part presents the resonant mode properties of planar and laterally structured microcavities. With the help of a high-resolution imaging micro-photoluminescence setup, working either in the spatial (near field) or vectorial (far field) regime, the polarization splitting is studied in a detuned microcavity, containing the dye 4,4'-bis[(N-carbazole)styryl]biphenyl (BSB-Cz) in a matrix of 4,4'-di(N-carbazolyl)- biphenyl (CBP). With the help of a thickness gradient, a relation between the large spectral distance of the cross-polarized states and the mode position within the stop band is investigated. In shadow-mask prepared, laterally restricted devices (5x5 µm2 square boxes), the three-dimensional confinement introduces sets of discrete modes, which experience a similar polarization splitting. The origin in this case is a different phase shift of electromagnetic waves during internal total reflection at a boundary.
By using a concentration gradient planar microcavity sample of the dye 4-(dicyanomethylene)-2-methyl-6-(4-(dimethylamino)styryl)-4H-pyran (DCM) in a tris-(8-hydroxyquinoline)aluminum (Alq3) matrix, the influence of the number of emitters on the lasing characteristics is subsequently analyzed. Depending on the pumping conditions, and thus the involvement of the Förster resonant energy transfer, an optimal composition is identified. After a qualitative evaluation of the long-term stability upon various excitation energies, the attention is focussed to the modification of the stimulated emission properties of photonic boxes. The stronger field concentration and altered density of states leads to a significant improvement of the values for the coupling factor fi and the threshold levels. Furthermore, new properties arise, namely simultaneous multimode and off-axis laser emission. With an inhomogeneous excitation of the box, it is possible to selectively excite single modes above the threshold.
The work ends with experimental results of metal structures as additional optical element in the organic microcavity layer. Here, the aim is is to understand the passive influence of these possible contact- devices on the lasing performance. For this purpose, the lasing is studied at an interface of an areal thin metal layer, which is incorporated in the organic layer.
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Li, Qian. "Organic Semiconductors Based on Triazastarphene Towards 3D : Charge Transport in Crystalline Phase." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0144.
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Depuis une trentaine d’années, les matériaux organiques semi-conducteurs sont l’objet de recherches fondamentales autant qu’appliquées. Cet intérêt s’explique par des propriétés communément absentes des matériaux inorganiques utilisés jusqu’à présent telles que leur légèreté, leur souplesse et leur mise en forme aisée par des techniques d’impression à bas coût. Cependant, la forte anisotropie de leurs propriétés électroniques, telles que la mobilité des charges, a limité leur intégration dans les appareils de la vie courante.Ainsi, le but de cette thèse est d’étudier de nouveaux concepts de structures moléculaires adaptées au transport de charge tridimensionnel (3D) en phase cristalline. Cette étude concerne la synthèse des molécules, la caractérisation de leurs propriétés optoélectroniques, la résolution de leur structure cristalline, des mesures de dispositifs électroniques ainsi que la modélisation de paramètres clés du transport de charge.Pour atteindre cet objectif, les règles de conception appliquées aux molécules linéaires appartenant à la série du TIPS-pentacene a été étendues à des molécule de symétrie C3h. Les molécules possèdent ainsi un cœur aromatique plan en forme d’étoile à trois bras auxquels sont ajoutés des substituants encombrants proches du centre. Deux empilements sont alors envisagés appelés empilement par les bras ou en colonne décalée pour lesquels un chemin de percolation des sauts de charge est attendu dans les 3 dimensions.Ainsi, 13 triazastarphenes substitués par des amines ou des phényles ont été nouvellement obtenus via des méthodes de synthèses originales et directes. De plus, des systèmes borofluorés ont pu être obtenus ainsi qu’une voie de synthèse originale d’un composé utilisé en OLED. D’autre part, la résolution des structures cristallines a permis d’identifier des empilements proches voir identiques de ceux escomptés. Par exemple, deux benzostarphenes présentent respectivement un empilement par les bras sur la moitié de la maille et un empilement en colonne décalée. Enfin, l’étude théorique a mis en évidence que le transport de charge devrait s’effectuer en 2D pour le premier cas et en 3D pour le second en phase cristalline.Finalement, ce travail décrit pour la première fois la synthèse de composés étendus et solubles en forme d’étoile basés sur un motif acridine. Au-delà des multiples études sur les propriétés de ces molécules ainsi que de leurs intégrations quelquefois réussies dans des dispositifs électroniques (OFETs ou cellules à solaires à perovskites), les nouvelles méthodes de synthèse et les empilements discutés en détails devraient contribuer à l’élaboration de nouvelles règles de conception de composé -conjugué et participer au développement de semi-conducteurs organiques de plus hautes performancesThe research in organic electronics has attracted worldwide attention due to the specific properties of organic materials such as lightness, flexibility, large scale processing ability and low production cost. Compared with inorganic materials, the strong anisotropy and low charge carrier transport mobility limit their integrations in commercial devices. This research aims at developing molecule systems leading to three-dimensional charge transport.To reach this goal, our design strategy is to expand the generally linear-shaped molecular structure into star-shaped structure with C3h symmetry. The designed molecules consist of a planar core of fused aromatic cycles to form efficient - stacking with neighboring molecules and of bulky groups located close to the center to increase the solubility of the materials and prevent 1D columnar packing. Thus, two supramolecular arrangements are speculated (arm and column packing) where charge hopping follows pathways in 3D.Based on this design, 13 triazastarphenes substituted directly by amine or phenyl groups were synthesized and thoroughly characterized. Their electronic properties were carefully determined by UV-visible absorption spectroscopy, cyclic voltammetry and DFT calculations. Results from single crystal XRD showed that the experimental packing is similar to model for few molecules. In detail, one amino-triazastarphene has shown a new 2D layer by layer packing motif, while benzo-triazastarphenes have led to column packing in one case and half arm packing for another as expected. In addition, theoretical approach highlighted 2D and 3D dimensionality for charge carrier transport for the two later examples in the crystal phase.Finally, this work is the first report about straightforward synthesis of extended C3h acridine derivatives. Even though the performances obtained from the devices (OFETs and perovskite solar cells) based on these materials did not reach state of the art performances, the novel synthetic method and the achievement of interesting molecular arrangement motifs in single crystal can contribute to the development of high-performance OSCs
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Nassor, Férid. "Etude de mécanismes de type prion impliqués dans la maladie d’Alzheimer sur un modèle de mini-cerveaux humains avec exploration par microscopie 3D." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS105.
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Les principales maladies neurodégénératives humaines, qui reposent toutes sur des mécanismes de type prion (auto-propagation d’agrégats protéiques pathogéniques), représentent un risque sociétal majeur avec une augmentation de leur prévalence directement corrélée avec l’augmentation de la longévité de la population mondiale. Il n’existe à ce jour aucun traitement curatif ni aucun modèle expérimental suffisamment pertinent pour ces maladies.L'objectif de ce travail a été d'utiliser le potentiel des mini-cerveaux humains comme modèle in vitro auto-assemblé en trois dimensions (3D) capable de restituer la complexité du cortex cérébral et d’étudier les mécanismes de type prion en développant une méthodologie de validation basée sur la microscopie 3D. Ces nouvelles structures 3D qui peuvent être obtenues à partir de cellules adultes reprogrammées de patients en cellules souches pluripotentes induites (iPSC), offrent des possibilités uniques pour accéder, observer et perturber les processus biologiques dans le cerveau humain sans les biais ni les complications des modèles animaux ou des échantillons de cerveau humain ex vivo. Ce modèle permet notamment d’observer l’apparition d’agrégats d’Aß et de Tau phosphorylée, deux protéines qui s’accumulent et se propagent de cellule en cellule dans la maladie d’Alzheimer.Nous avons été en mesure de rendre le modèle des mini-cerveaux compatible avec une future approche de criblage de molécules thérapeutiques en modifiant la méthodologie de différenciation pour augmenter leur rendement de production. D’autre part, nous avons pu tester différentes modalités de modélisation pour la Maladie d’Alzheimer, la maladie de Parkinson, la Démence Fronto-Temporale et la maladie de Creutzfeldt-Jakob : à l’aide de molécules d’induction chimique, à l’aide de cellules issues de patients, par modification génétique et par mise en contact de matériel infectieux. Ces différentes approches nous ont permis d’établir que le modèle d’organoïde cérébral permet de reproduire des aspects-clés retrouvés dans l’apparition de la pathologie chez les patients. Pour compenser l’hétérogénéité de notre modèle, nous avons réalisé une analyse in toto par imagerie, c’est-à-dire dans sa totalité sans coupes préalables. La modalité retenue pour cette acquisition est la microscopie à feuillet de lumière utilisée après marquage et clarification des mini-cerveaux. Pour ce faire, nous avons évalué et développé différentes stratégies en vue d’obtenir une plateforme d’analyse à haut contenu pour nos organoïdes cérébraux.Cette plateforme centrée autour de l’organoïde cérébral, sous-tendue par l’analyse en microscopie 3D, a été développée dans le cadre du projet « Investissements d’Avenir » 3DNeuroSecure. Ce projet a pour ambition d’apporter des solutions de calcul haute performance au domaine de la biologie, notamment avec la possibilité de traiter des informations de très grand volume, dit « exascale », telles que celles que nous obtenons avec la microscopie 3D. Le développement de cet aspect nous permettrait à terme de pouvoir établir les bases d’un outil de criblage thérapeutique par les organoïdes cérébraux pour les maladies neurodégénératives. Nous avons démontré que les mécanismes de type prion pouvaient être étudiés dans ce modèle de mini-cerveaux humains et de multiples voies de recherche fondamentale et appliquée sont désormais possibles. A plus long terme, une telle plateforme pourrait accueillir tout type d’organoïdes pour modéliser l’ensemble du corps humain et s’inscrire comme un compagnon biologique dans le cadre des futurs développements de la médecine personnaliséeHuman neurodegenerative diseases, which are all based on prion-like mechanisms (self-propagation of pathogenic protein aggregates), represent a major societal risk with the increase of their prevalence directly correlated to the increasing longevity of the world population. There is to date neither any cure nor any pertinent experimental model for their study.The objective of this work was to use the potential of human mini-brains, a self-assembled three-dimensional in vitro model able to restitute the complexity of the cerebral cortex. This model will allow us to study prion-like mechanism by developing a validation methodology based on 3D microscopy. These novel 3D structures can be obtained from reprogrammed adult cells into induced pluripotent stem cells (iPSCs) and offer unique possibilities to access, observe and disrupt biological processes in the human brain without bias nor complications as in animal models and ex vivo human brain samples. This model makes it possible to observe the development of aggregates of Aβ and hyper-phosphorylated Tau, two proteins that accumulate and propagate from cell to cell during Alzheimer’s disease.We have been to able to adapt the cerebral organoid model for a future screening approach by modifying the differentiation methodology to enhance its production ratio. We also have been able to test different modalities for disease modeling for Alzheimer’s disease, Parkinson’s disease, Fronto-Temporal Dementia and Creutzfeldt-Jakob disease: with chemical induction, with patient specific cells, through genetic modification and through contact with infectious material. These different approaches allowed us to validate that the cerebral organoid can indeed reproduce key aspects found during pathological development within patients. To compensate for the heterogeneity of the cerebral organoid, we performed an in toto analysis through microscopy, meaning in its totality without prior slicing. The chosen method of acquisition is fluorescence light-sheet microscopy used after staining and optical clearing of cerebral organoids. To do so, we have evaluated and established different strategies in order to obtain a high content screening platform for our cerebral organoid model.This platform centered around the cerebral organoid model, underpinned by 3D microscopy analysis, was developed during the “Investissements d’Avenir” project 3DNeuroSecure. This project has for ambition to bring high performance computing to the biological sciences, notably with the possibility to deal with large scale data, also called “exascale”, like the ones obtained with 3D microscopy. The development of this aspect would allow us to establish the basis for a therapeutic screening tool based on cerebral organoids for neurodegenerative diseases. We have demonstrated that prion-like mechanisms can be studied in a human mini-brain model and multiple research avenues are now opened for both fundamental and applied research. This platform could in turn become the basis for any kind of organoids derived from patients to model the whole human body and become a biological companion for personalized medicine
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Senevirathna, Wasana. "Azadipyrromethene-based Metal Complexes as 3D Conjugated Electron Acceptors for Organic Solar Cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1402062085.
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Myszczyszyn, Adam. "Studying normal and cancer stem cells in the kidney using 3D organoids and genetic mouse models." Doctoral thesis, Humboldt-Universität zu Berlin, 2021. http://dx.doi.org/10.18452/23127.
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Organoide aus adulten Mäusen sind vielversprechende Modelle für die Nierenforschung. Ihre Charakterisierung wurde jedoch nicht auf ein zufriedenstellendes Niveau gebracht. Hier habe ich ein langfristiges 3D-Maus-Organoid (Tubuloid)-Modell etabliert und charakterisiert, das die Erneuerung und die Reparatur sowie die Architektur und die Funktionalität der adulten tubulären Epithelien rekapituliert. In der Zukunft wird das Modell detaillierte Untersuchungen der Trajektorien selbsterneuernder Zellen sowohl zur teilweisen Wiederherstellung der Niere als auch zur malignen Transformation der Niere ermöglichen.
Das klarzellige Nierenzellkarzinom (ccRCC) ist der häufigste und aggressivste Nierenkrebs. Die Inaktivierung des Tumorsuppressorgens Von Hippel-Lindau (VHL) ist der Haupttreiber des ccRCCs. Zuvor hatten wir die Hochregulation der Wnt- und Notch-Signalübertragung in den CXCR4+MET+CD44+-Krebsstammzellen (CSC) aus primären humanen ccRCC-Tumoren identifiziert. Das Blockieren von Wnt und Notch in von Patienten stammenden Xenotransplantaten, Organoiden und nicht-anhaftenden Sphären unter Verwendung von niedermolekularen Inhibitoren beeinträchtigte die Selbsterneuerung der CSC und das Tumorwachstum. Um CSC-gesteuertes humanes ccRCC in genetischen Mausmodellen nachzuahmen, begann ich mit der Erzeugung von zwei Doppelmausmutanten; β-Catenin-GOF; Notch-GOF und Vhl-LOF; β-Catenin-GOF. Sowohl die β-Catenin-GOF; Notch-GOF Mausmutante als auch die Vhl-LOF; β-Catenin-GOF Mausmutante entwickelten innerhalb einiger Monate schwere Krankheitssymptome. Überraschenderweise beobachtete ich weder Tumore oder Tumorvorläuferläsionen noch höhere Zellproliferationsraten in den mutierten Nieren. Weitere Analysen ergaben, dass die Mausmutanten Merkmale chronischer Nierenerkrankung (CKD) aufwiesen.Adult mouse organoids are promising models for kidney research. However, their characterization has not been pushed forward to a satisfying level. Here, I have generated and characterized a long-term 3D mouse organoid (tubuloid) model, which recapitulates renewal and repair, and the architecture and functionality of the adult tubular epithelia. In the future, the model will allow detailed investigations of trajectories of self-renewing cells towards both the partial recreation and malignant transformation of the kidney. Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive kidney cancer. Inactivation of the Von Hippel-Lindau (VHL) tumor suppressor gene is the major driver of ccRCC. Earlier, we identified the upregulation of Wnt and Notch signaling in CXCR4+MET+CD44+ cancer stem cells (CSCs) from primary human ccRCCs. Blocking Wnt and Notch in patient-derived xenografts, organoids and non-adherent spheres using small-molecule inhibitors impaired self-renewal of CSCs and tumor growth. To mimic CSC-governed human ccRCC in genetic mouse models, I started from the generation of two double mouse mutants; β-catenin-GOF; Notch-GOF and Vhl-LOF; β-catenin-GOF. Surprizingly, I observed neither tumors or tumor precursor lesions nor higher cell proliferation rates in the mutant kidneys. Further analyses revealed that the mutant mice displayed features of chronic kidney disease (CKD). Thus, β-catenin-GOF; Notch-GOF and Vhl-LOF; β-catenin-GOF mouse mutants did not develop kidney tumors under the given experimental conditions.
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Saini, Anuj. "FROM APPLICATION OF ORGANIC THIN MULTILAYER FILMS IN 3D OPTICAL DATA STORAGE TO THEIR FABRICATION FOR ORGANIC ELECTRONIC DEVICES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1459518551.
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Sébert, Morgane. "Les effets de la thrombine sur l'épithélium colique humain, grâce aux organoïdes (modèle ex vivo, 3D)." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30006/document.
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La thrombine, une protéase à sérine connue pour être l'acteur clé de la cascade de coagulation, a été décrite pour réguler les processus apoptotiques au niveau du côlon via l'activation de récepteurs activés par des protéases ou PARs (Protease-Activated Receptors). Cependant, les effets de la thrombine sur la cellule épithéliale colique n'ont été étudiés qu'en utilisant des lignées cellulaires. Les conséquences d'une exposition à différentes doses de thrombine sur un épithélium complexe, composés de différents types cellulaires plus ou moins différenciés sont inconnues à ce jour. Un nouveau modèle cellulaire, nommé organoïde, permet de reconstituer un épithélium colique fonctionnel en 3-dimensions (3D) à partir de résections ou de biopsies humaines, et ce, grâce aux capacités d'auto-renouvellement et de différenciation des cellules souches issues des cryptes coliques. Le 1er objectif de ma thèse a été d'évaluer les effets de la thrombine sur la survie, la prolifération, l'apoptose et la différenciation de l'épithélium colique humain, en utilisant le modèle organoïde. Puis, de déterminer l'implication des récepteurs PAR1 et PAR4 activés par la thrombine dans ces effets. Ainsi, l'ajout de thrombine (à faible dose : 10mU/mL et à forte dose : 50mU/mL) sur une culture d'organoïdes établis à partir de tissus colorectaux normaux entraîne une diminution de moitié de l'activité métabolique et de la prolifération cellulaire. Ces effets sont bloqués en présence d'un antagoniste de PAR1. Le processus apoptotique est, cependant, augmenté d'un facteur 8 en réponse à la thrombine (aux deux doses). Ce processus est inhibé en présence d'antagoniste de PAR1 ou de PAR4. Concernant la différenciation épithéliale, la thrombine diminue le nombre de colonosphères (structures immatures), au profit d'une augmentation du nombre de structures apoptotiques et de colonoïdes (structures plus matures présentant des néo-cryptes). Cet effet est dû à l'activation à la fois de de PAR1 et de PAR4 dans les cellules épithéliales coliques. Mes résultats démontrent que la thrombine exogène agit sur les processus d'apoptose, de prolifération et de différenciation sur un épithélium complexe, issu de la culture de tissus humains. L'utilisation de ce modèle ex vivo permet de comparer les organoïdes pathologiques et normaux, voire de tester les effets d'approches pharmacologiques et de nouveaux médicaments sur ces cultures. Ainsi, la 2nde partie de ce travail de thèse a été d'aborder la mise en place des conditions de culture et d'imagerie nécessaires pour réaliser un screening à haut débit robuste et reproductible, HCS (High-Content Screening), appliquée aux organoïdes. Les conditions de culture d'organoïdes en plaques 96-puits ont été mises au point de même que les conditions permettant d'acquérir des images répondant aux critères nécessaires pour une analyse via un système HCS. Le système Operetta HCS couplé au logiciel d'analyse Harmony (PerkinElmer) a été utilisé pour mettre en place une procédure d'analyse permettant de reconnaître les organoïdes, de les dénombrer, de les classer selon leur état de différenciation et de suivre leur croissance tout au long de la culture. Pour conclure, ces travaux de thèse ont permis de mettre en évidence les effets de la thrombine sur l'état métabolique, l'apoptose et la différenciation de l'épithélium colique humain, grâce au modèle 3D ex vivo d'organoïdes colorectaux. L'utilisation de ce modèle complète les approches jusque-là effectuées dans des modèles de lignées de cellules épithéliales, proposant une vision intégrée du comportement d'un épithélium complexe humain. L'approche HCS initiée lors de ces travaux de thèse pourrait permettre d'analyser de façon robuste et automatisée dans ce modèle, les effets d'autres composés et avoir ainsi un impact majeur sur notre compréhension des pathologies épithéliales et sur les tests de nouvelles approches thérapeutiquesThrombin, a serine protease known for its role in the coagulation cascade, was described for its effects on the induction of apoptosis in colonic epithelial cell lines, through the activation of Protease Activated Receptors (PARs). However, the effects of thrombin on complex epithelial structures such as the human intestinal epithelium composed of different cell types and cells at different stages of differentiation, has never been investigated. A new cellular model, named organoid, enables to reconstitute a functional epithelium in 3-dimensions (3D), from human resections or biopsies, thanks to the self-renewal and differentiation properties of stem cells isolated from colonic crypts. The first objective of this thesis was to evaluate thrombin's effects on survival, proliferation, apoptosis and differentiation in human colonic epithelium, using the organoid model. Then, we aimed to determining the implication of PAR1 and PAR4 in the thrombin's effects. Thus, thrombin added (at low dose: 10mU/mL and higher dose: 50mU/mL) to organoid cultures from control patients, led to a decrease by half of metabolic activity and cell proliferation. These effects were blocked by the addition of a PAR1 antagonist. Apoptotic process was 8-fold higher in organoid cultures exposed to thrombin (both doses) and this effect was inhibited by the addition of a PAR1 or a PAR4 antagonist. As per epithelial differentiation, thrombin decreased the number of colonospheres (immature structures) favoring the increase of apoptotic structures and colonoids (budding structures considered as more mature). This effect was due to PAR1 and PAR4 activation as again, it was blocked both by PAR1 and PAR4 antagonist. Taken together, these results reveal that exogenous thrombin acts on apoptosis, proliferation and differentiation processes in complex human colonic epithelium. The use of this ex vivo model will allow to compare pathological versus normal organoid cultures, but also to test the effects of pharmacological approaches and new treatment options directly in cultured human tissues. Thus, the 2nd part of this thesis was to setup the best culture conditions and the best imaging conditions to perform a robust and reproducible screening approach, HCS (High-Content Screening), using organoid cultures. Culture conditions in 96-well plates were set up and allowed to acquire images with the HCS system. Operetta HCS coupled to an analysis software (Harmony, PerkinElmer) was used to develop a specific program enabling the recognition of organoids, their counting, their classification according to their differentiation status and enabling to follow organoid growth in cultures. To sum up, the work performed allowed to highlight the effects of thrombin on metabolic status, apoptosis and differentiation of human colon epithelium, using an ex vivo 3D organoid model. The use this model nicely completed epithelial cell line approaches, offering an integrated view of the complex behavior of human epithelium. The HCS approach initiated within this thesis should allow the automated analysis of a number of drugs and treatments. It should help our understanding of epithelial pathologies and the testing of new therapeutic approaches
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Smolka, Rastislav. "Luminiscenční nanočástice pro 3D zobrazování." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2021. http://www.nusl.cz/ntk/nusl-449374.
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The aim of this diploma thesis is to study the optical properties of new -conjugated molecules based on 1,4-di(4'-N, N-diphenylaminostyryl)benzene and their potential application in advanced imaging techniques of biological specimens, the so-called multiphoton microscopy. The thesis focuses mainly on the characterization of their optical properties and the determination of their two-photon absorption cross-section using a unique laser equipment. Furthermore, a suitable methodology for the preparation of nanoparticles from these molecules, their characterization and stability are also developed. The thesis also investigates the influence of structure on the optical properties of these molecules. The relation between the length of the conjugated system and the presence of substituents on the backbone has been shown for the optical properties of the molecules in the solvent, the position and shape of the two-photon absorption spectrum and the value of two-photon absorption cross-section. It has been shown that this substance retains its unique fluorescent properties even in the form of nanoparticles and therefore appears to be a suitable candidate for the observation of biological specimens using multiphoton fluorescence microscopy. The work contributes to the knowledge base for the design of the chemical structure of molecules with desired properties.
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Kearns, Eleanor Rose. "Multi-stimuli Metal-organic frameworks and their composites." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29561.
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Metal-Organic Frameworks (MOFs) are a versatile class of materials. Their high surface area combined with the functionality of their constituent organic ligands make them suitable for a wide range of applications. In their scale-up to industry level uses, MOFs face several roadblocks. The largest of these obstacles are large-scale green syntheses of MOFs and processing the polycrystalline powders into useable forms. This thesis examines structure-activity relationships in a family of TTF-based MOFs, and presents a green synthesis for UiO-66-NH2. Finally, 3D-printing will be examined as a method for preparing MOF-based electrocatalytic electrodes.
Chapter 3 and Chapter 4 will examine the structure-activity relationships (SARs) of charge transfer and photocyclization respectively. Herein, a family of photoactive TTF-based MOFs, generated by systematically varying the framework constituents, are used to probe the effect of structure on the intervalence charge-transfer (IVCT) and [2+2] photocyclisation processes.
Chapter 5 presents a novel one-step mechanochemical synthesis of UiO-66-NH2. This synthesis proceeds from ZrOCl2.8H2O in a 66% yield. The mechanochemical synthesis presented is more scalable than other benign syntheses of UiO-66-NH2, and importantly yields highly crystalline material with comparable surface area to UiO-66-NH2 synthesized via alternative mechanochemical routes.
Chapter 6 presents the first example of 3D-printed MOF electrodes for electrocatalysis, which expands upon previous work on 3-D printed MOF and zeolite-based composite sorbent materials. This represents a new technique for electrochemical analysis of solid analytes, as well as the development of self-supporting solid MOF-based electrodes. This research shows that the properties of the MOF are maintained once printed, and a clear electrochemical response to the analyte of interest is observed.
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Myszczyszyn, Adam [Verfasser]. "Studying normal and cancer stem cells in the kidney using 3D organoids and genetic mouse models / Adam Myszczyszyn." Berlin : Humboldt-Universität zu Berlin, 2021. http://d-nb.info/123964471X/34.
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Priadi, Eka. "Behaviour of Tiang Tongkat foundation over Pontianak soft organic soil using 3D-finite element analysis." Doctoral thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2009. http://nbn-resolving.de/urn:nbn:de:bsz:105-081293.
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Peat deposits are distributed mostly along the coast of West Kalimantan, Indonesia, particularly in and around the provincial capital of Pontianak. There are many problems with constructing over peat soil as the existence of this type of soil always generates geotechnical engineering problems for regional development. For light construction on peat land, several variations of Indonesian traditional floating wood foundations, commonly called tiang tongkat foundations, are still being used today. A tiang tongkat foundation of any dimension is constructed over different fields. The foundation was modelled as three-dimensional linear elastic and the Pontianak soft organic soil was modelled as undrained Soft-Soil-Creep Model. All of the 324 models were made to be used for simulation by means of the Plaxis 3-Dimensional Foundation Program. The purpose of this analysis is to predict the load-settlement behaviour and the capacity of traditional foundations. The comparison between field tests and numerical analysis and analytical solutions are also demonstrated.
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Anhorn, Michael J. "Nitrogen Rich Porous Organic Frameworks: Proton Conduction Behavior of 3D Benzimidazole and Azo-linked Polymers." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5448.
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Nitrogen-rich porous organic frameworks show great promise for use as acid-doped proton conducting membranes, due to their high porosity, excellent chemical and thermal stability, ease of synthesis, and high nitrogen content. Aided by very high surface area and pore volume, the material has the ability to adsorb high amounts of H3PO4 into its network, which creates a proton rich environment, capable of facile proton conduction. The morphology and chemical environment, doping behavior, and proton conduction of these materials were investigated. With such high acid-doping, ex-situ studies revealed that under anhydrous conditions, PA@BILP-16 (AC) produced a proton conductivity value of 5.8 x 10-2 S cm-1 at 60 °C and PA@ALP-6 showed a slightly higher value of 5.91 x 10-2 S cm-1 at 60 °C. With such promising results, in-situ experiments with various analogues are scheduled to be conducted in the near future.
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Forlivesi, Claudio. "Biomateriali e 3D bioprinting nella rigenerazione neurale." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/17888/.
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Il sistema nervoso centrale svolge un ruolo chiave nella raccolta, integrazione ed elaborazione delle informazioni provenienti dagli organi di senso e dall’ambiente interno dell’organismo. La sua struttura, formata da una complessa rete neurale finemente organizzata può essere soggetta a danni di vario tipo, che ne minano le funzionalità. Per far fronte a tale evenienza, negli ultimi anni, sta emergendo una nuova scienza dal carattere fortemente multidisciplinare, ovvero la medicina neurorigenerativa. Essa comprende l’ingegneria tissutale, che mira all’ingegnerizzazione dei materiali per la produzione di supporti per la rigenerazione (scaffold), la neurologia, e l’ingegneria biomedica. Scopo di questa tesi è stato quello di passare in rassegna le ricerche più recenti sui materiali impiegati per la medicina neurorigenerativa, così come le tecniche e le tecnologie emergenti per il loro processo. In particolare, i polimeri naturali e di sintesi rappresentano una reale potenzialità per possibili interventi terapeutici. D’altra parte, tecnologie di processo quali l’electrospinning e la stampa tridimensionale (3D BIOPRINTING) hanno consentito di progredire notevolmente nella fabbricazione di supporti finalizzati allo sviluppo di impianti neurorigenerativi eterologhi o coadiuvanti l’impianto autologo. In particolare, il 3D Bioprinting è una tecnologia che ha la potenzialità di consentire, in un prossimo futuro, di riprodurre con precisione sempre maggiore la delicata organizzazione spaziale e strutturale gerarchica della matrice extracellulare neuronale. I vantaggi e le applicazioni del Bioprinting sono potenzialmente vastissimi e ancora in fase di esplorazione. L’impatto di nuove tecnologie, nuovi materiali e tecniche bioigegneristiche d’avanguardia potrebbero rappresentare non solo un passo avanti nel campo della rigenerazione neurale, ma anche per la comprensione di processi fisiologici ed ancor di più patofisiologici del Sistema Nervoso Centrale.
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Hume, Robert David. "Recapitulating mammary gland development and breast cancer cell migration in vitro using 3D engineered scaffolds." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/271099.
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The adult mammary gland is comprised of a bi-layered epithelium of luminal and myoepithelial cells surrounded by an adipocyte-rich fat pad, a highly collagenous extra-cellular matrix (ECM) and a number of other stromal and endothelial cell types. Mammary stem cells (MaSCs) reside within the epithelium and these are capable of repopulating a mammary fat pad that is devoid of epithelium, upon transplantation. It was sought to recapitulate this process of MaSCs repopulating a fat pad using a synthetic fat pad, engineered from a collagen scaffold invested with adipocytes, to provide an in vitro 3D model. Fluorescently tagged murine Axin2-expressing cells were obtained from transgenic mice and seeded into these scaffolds and cultured, mimicking the process of fat pad repopulation. Immunohistochemical analysis demonstrated that Axin2+ myoepithelial cells were rarely capable of forming bi-layered structures that expressed correct myoepithelial localisation and resemblance to a luminal morphology. Breast tumours surrounded by anisotropic (directional) collagen fibres running perpendicular to the tumour boundary are more aggressive and associated with poor patient prognosis. To recapitulate this anisotropic collagen phenotype in vitro, an ice-templating technique was used to modify the structure of the collagen scaffolds producing both non-directional (isotropic) and anisotropic internal architectures. Tumour cells from various breast cancer cell lines were seeded into both isotropic and anisotropic scaffolds to investigate whether this approach could distinguish cell type-specific migratory ability and whether anisotropy affected migration efficiency. Following analysis by confocal microscopy and ImageJ, anisotropic scaffolds were observed to enhance the migratory potential of MDA-MB-231 breast cancer cells. These results highlight the importance of collagen alignment and provide a reproducible method to quantitatively measure cell migration in 3D for cells derived from different breast cancer subtypes. Building on these data, the protocol was adapted to permit the direct investigation of tumour biopsy material. Given the heterogeneity of breast tumours, it was considered important to maintain tumour architecture and stromal components. Thus, murine mammary tumour fragments from two different established mammary cancer models were utilised and cultured in anisotropic collagen scaffolds in the presence or absence of adipocytes to allow an investigation of their influence on tumour cell migration. Further experiments included addition of various therapeutic drugs followed by immunofluorescence microscopy coupled with an optical clearing technique. These data demonstrated the utility of the model in determining both the rate and capacity of tumour cells to migrate through the engineered stroma while shedding light also on the mode of migration. Moreover, the response of different mammary tumour types to chemotherapeutic drugs could be could be readily quantified. To humanize the fat pad for subsequent human tissue analysis, human mesenchymal stem cells (MSC) were obtained from reduction mammoplasties and immortalised, before differentiating them into adipocytes within anisotropic collagen scaffolds. Human breast cancer cells were fluorescently tagged for tracking using lentiviral methods and were seeded into scaffolds invested with differentiated MSCs. Both cell types were successfully co-cultured for 7 days and imaged using multiphoton methods.
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Garcia, Jordan. "DESIGN AND PROCESS OF 3D-PRINTED PARTS USING COMPOSITE THEORY." UKnowledge, 2019. https://uknowledge.uky.edu/me_etds/144.
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3D printing is a revolutionary manufacturing method that allows the productions of engineering parts almost directly from modeling software on a computer. With 3D printing technology, future manufacturing could become vastly efficient. However, it is observed that the procedures used in 3D printing differ substantially among the printers and from those used in conventional manufacturing. In this thesis, the mechanical properties of engineering products fabricated by 3D printing were comprehensively evaluated and then compared with those made by conventional manufacturing. Three open-source 3D printers, i.e., the Flash Forge Dreamer, the Tevo Tornado, and the Prusa, were used to fabricate the identical parts out of the same material (acrylonitrile butadiene styrene). The parts were printed at various positions on the printer platforms and then tested in bending. Results indicate that there exist substantial differences in mechanical responses among the parts by different 3D printers. Specimens from the Prusa printer exhibit the best elastic properties while specimens from the Flash Forge printer exhibit the greatest post-yield responses. There further exist noticeable variations in mechanical properties among the parts that were fabricated by the same printer. Depending on the positions that the parts were placed on a printer platform, the properties of resultant parts can vary greatly. For comparison, identical parts were fabricated using a conventional manufacturing method, i.e., compression molding. Results show that compression molded parts exhibit more robust and more homogeneous properties than those from 3D printing. During 3D printing, the machine code (e.g., the Gcode) would provide the processing instructions (the x, y, and z coordinates and the linear movements) to the printer head to construct the physical parts. Often times the default processing instructions used by commercial 3D printers may not yield the optimal mechanical properties of the parts. In the second part of this thesis, the orientation-dependent properties of 3D printed parts were examined. The multi-layered composite theory was used to design the directions of printing so that the properties of 3D printed objects can be optimized. Such method can potentially be used to design and optimize the 3D printing of complex engineering products. In the last part of this thesis, the printing process of an actual automobile A-pillar structure was designed and optimized. The finite element software (ANSYS) was used to design and optimize the filament orientations of the A-pillar. Actual parts from the proposed designs were fabricated using 3D printer and then tested. Consistent results have been observed between computational designs and experimental testing. It is recommended that the filament orientations in 3D-printing be “designed” or “tailored” by using laminate composite theory. The method would allow 3D printers to produce parts with optimal microstructure and mechanical properties to better satisfy the specific needs.
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Lafargue, Clément. "Dynamique non-linéaire dans les microcavités laser tridimensionnelles à base de polymères : aspects physiques et technologiques." Phd thesis, École normale supérieure de Cachan - ENS Cachan, 2013. http://tel.archives-ouvertes.fr/tel-00920272.
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Cette thèse est consacrée à l'étude fondamentale et au développement de micro-sources lasers en matériaux organiques, susceptibles de débouchés dans les technologies de l'information et les biotechnologies. Nous avons exploré l'aspect tridimensionnel (3D) de ces lasers, tant en termes de fabrication que de caractérisation. Concernant la fabrication, nous avons fait évoluer la géométrie des microlasers, auparavant quasi-bidimensionnelle (2D, issue de films fins) vers une géométrie 3D (comme des cubes). Des procédés de lithographie UV épaisse ou d'écriture directe au laser par photo-polymérisation à 2 photons ont été adaptés pour réaliser des formes sur mesure de micro-résonateurs optiques incluant un colorant. Afin d'étudier l'émission très anisotrope de ces lasers, nous avons conçu et développé un outil original, appelé scanner à angle solide (SAS), permettant de collecter l'émission d'un microlaser dans toutes les directions du demi-espace qui le surplombe, avec une grande précision. Le SAS a permis de constater que les microlasers 2D émettent principalement hors-plan. Un modèle a été développé pour expliquer cet effet et émettre des prédictions. D'autre part, différentes formes de microlasers 2D ont été analysées, à partir de leurs directions et spectres d'émission, grâce au formalisme semi-classique des orbites périodiques. En particulier, une orbite diffractive a été observée dans les triangles, ce qui ouvre la voie à une étude systématique de la diffraction par un coin diélectrique. Nous apportons également une explication à la directionalité de l'émission par des microlasers carrés. Pour finir, les premières caractérisations 3D de micro-lasers 3D ont été réalisées.
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Salaün, Mathieu. "Croissance d'oxyde métallique par photolyse dans un réseau d'interférences 3D." Phd thesis, Grenoble INPG, 2008. http://tel.archives-ouvertes.fr/tel-00612071.
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L'objectif de ce travail de thèse était d'examiner la possibilité de réaliser une croissance des structure tri-périodiques par décomposition d'une phase gazeuse dans un champ d'interférences 3D. La croissance directe de l'oxyde de chrome Cr2O3 organisée de façon tri-périodique a été prouvée. Celle-ci a lieu par décomposition photolytique du chlorure de chromyle CrO2Cl2. De plus, comme cette décomposition a été réalisée sur un substrat monocristallin de TiO2, il a été trouvé que la structuration de Cr2O3présentait des relations d'orientations cristallographiques par rapport à celle du substrat. Le processus commence par une croissance épitaxiale de l'oxyde CrO2 de structure cristalline isomorphe de celle du rutile TiO2. L'oxyde se décompose ensuite partiellement en Cr2O3, lui-même cristallographiquement orienté par rapport à CrO2. Puis une croissance de la phase Cr2O3 se poursuit selon les modulations de densité d'énergie électromagnétique du réseau d'interférences. Ce manuscrit contient aussi un rappel de la théorie du réseau d'interférences, la description du montage expérimental et la vérification de la stabilité et de sa résolution par photopolymérisation d'hybrides organo-minéraux. Une étude sur l'influence des différents paramètres de la photopolymérisation de ces hybrides est également présentée.
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Nur, Hassan Mohammed. "Fabrication of advanced ceramics and selective metallization of non-conductive substrates by inkjet printing." Thesis, Brunel University, 2002. http://bura.brunel.ac.uk/handle/2438/4823.
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Inkjet printing of ceramic components and gold conductive tracks was carried out in this study. A commercial inkjet printer, designed for printing one layer of 2D images on paper, was modified to give adequate resolution, to reverse the substrate for overprinting many layers and to accommodate the increase in thickness of 3D components during printing. Ceramic inks were prepared by wet ball milling and printed to form 3D structures. The powders used were alumina, zirconia, lead zirconate titanate (PZT) and barium titanate. The substrate used for printing the ceramic parts was an overhead transparency. Methods to stop or reduce ink flow were devised and used during printing of the ceramic parts. The alumina and zirconia powders were used for the fabrication of multi-layered laminates. The lead zirconate titanate was used to fabricate components with pillars, walls, vertical channels and x-y-z channel network. During printing of the x-y-z channel network, carbon was used as a support structure and then removed during firing. Barium titanate and carbon powders were used to form the first storey of a capacitor with a multi-storey car park structure. The printed parts were pyrolysed and fired in an oxidising environment and then characterised with scanning electron microscopy. The causes of micro structural defects found were discussed and prevention methods suggested. Organic gold powder was dissolved in methanol and then printed on three different substrates to form conductive gold tracks. The substrates used included alumina, glazed tile and microscope glass slides. The printed tracks were fired in air. The decomposition characteristics of the organic gold compound were studied with TGA and Differential Scanning Calorimetry (DSC). Scanning electron microscope was used to examine the fired gold film for defects and conductivity measurement of the tracks was carried out with a programmable multimeter.
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Vazquez, Armendariz Ana Ivonne [Verfasser]. "Establishment of murine 3D bronchioalveolar lung organoids from adult somatic stem cells for organ development and disease modeling / Ana Ivonne Vazquez Armendariz." Gießen : Universitätsbibliothek, 2018. http://d-nb.info/1170582028/34.
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Lacombe, Elsa. "Évaluation de la technologie photonique sur silicium pour le développement de liens sans fil innovants visant 40 Gb/s au-delà de 200 GHz." Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4095/document.
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Avec l’explosion du trafic de données mobiles, des débits supérieurs au Gb/s deviennent nécessaires pour l’utilisateur. Ainsi, le réseau de communication est en cour d’amélioration afin de promouvoir le déploiement de la 5G, notamment grâce au développement et à l’installation de systèmes sans fil d’onde millimétrique (mmW) à 10 Gb/s. Néanmoins, pour délivrer de tels débits, les liens fronthaul/backhaul sans fil connectés au cœur de réseau devront supporter des flux de données supérieurs à 40 Gb/s. Cet enjeu suscite un intérêt croissant pour les fréquences sub-mmW et THz (0.1 THz – 1 THz) autour desquelles des bandes passantes (BPs) de 100 GHz sont accessibles. Il serait en effet possible d’atteindre un débit de 100 Gb/s, tout en utilisant des formats de modulation simples et ainsi réduire la consommation d’énergie du système. Visant le marché de masse des applications haut-débits, la technologie Photonique sur Silicium est particulièrement attractive pour générer des BPs naturellement larges et pour sa capacité à forts niveaux d’intégration et faible cout de fabrication. Dans cette thèse, une technologie Photonique sur Silicium industrielle a donc été évaluée durant le développement d’un émetteur intégré THz fonctionnant sur la base d’une photodiode et pouvant délivrer 100 Gb/s. Le développement d’une antenne THz faible cout et compacte est également un aspect majeur de cette thèse afin de permettre la transmission point-à-point du signal THz. En effet, une antenne intégrée sur substrat organique faible cout et à faibles pertes et une lentille fabriquée par impression 3D ont été développées afin d’évaluer ces technologies de prototypage industriel au-delà de 200 GHzWith the booming of mobile data traffic, the need for higher data-rates is clearly felt. To cope with this strong demand and support the 5G roll-out, the capacity of the mobile communication network is being improved every day with many solutions, among which the development and installation of millimeterwave (mmW) wireless systems operating at up to 10 Gb/s. However, in order to deliver such high speeds to the user, the fronthaul/backhaul network sending data back to the core network would require above 40 Gb/s data-rate wireless links. This challenge generates a growing interest for sub-mmW and THz frequencies (0.1 THz – 1 THz) at which up-to 100 GHz bandwidth (BW) is accessible. In such BW, it would be possible to achieve up to 100 Gb/s data-rates while using simple modulation schemes to reduce the wireless system’s power consumption. Targeting mass-market high data-rates applications, Silicon Photonics technology seems very promising as it benefits from wide intrinsic BW and powerefficient components, as well as high integration levels and low manufacturing costs. In this context, a main aspect of this PhD project is the evaluation of an industrial Silicon Photonics technology for the development of a THz system-on-chip transmitter capable of reaching up to 100 Gb/s using a photodiode. Since THz antennas are also a hot topic for THz point-to-point transmission, a second aspect of this PhD study is the design of a low-cost and compact THz antenna-system. Hence, a planar antenna using low-loss organic packaging technology and a 3D-printed plastic lens were developed in order to assess those industrial prototyping techniques above 200 GHz
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Grosser, Gary [Verfasser]. "Der Sodium-dependent Organic Anion Transporter SOAT : Gewebeexpression, vergleichende funktionelle Charakterisierung und Generierung einer 3D-QSAR Pharmakophore / Gary Grosser." Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1064991521/34.
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Hamida, Youcef. "MAGNETISM IN A NUMBER OF METAL ORGANIC FRAMEWORKS (MOFs) WITH 1D AND 3D CHARACTERISTICS: AN EXPERIMENTAL AND ANALYTICAL STUDY." Diss., Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/195069.
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PhysicsPh.D.
Metal Organic Frameworks (MOFs) exhibit many excellent physical properties including magnetic properties for potential applications in devices. More importantly for the subject of this thesis, MOFs are ideal for the realization of low dimensional magnetism because of the large selection of ligands connecting magnetic centers in making the framework. The materials studied in this thesis include ten magnetic MOFs of the form M(L1)(L2) [M = Cu, Ni, Co, Fe, Mn; L1 = NDC, bpdc, BDC, BODC, N3; L2 = DMF, H2O, TED, bpy]. Polycrystalline powder samples as well as single crystal samples were synthesized. Their crystal structures were determined, and their magnetic and thermodynamic properties were measured and analyzed. Eight of these materials were characterized as 1D magnets and two as 3D magnets. In the 1D case it is found that above Tm [the temperature at which the magnetic susceptibility χ(T) has a peak] the magnetic behavior of MOFs (S ≥ 1) can be well described with the Classical Fisher Model (CFM). Near and below TC the spins take a more definite orientation than allowed for in the CFM and hence the Ising Model (IM) was used for fitting. Both CFM and IM yield fairly consistent intrachain couplings (J) when applied in their appropriate temperature region. To estimate the interchain exchange (J′), the susceptibility for a magnetic chain in the mean field of neighboring chains is used. In all cases, as expected, the ratio of J to J′ was less than 10%. The special case of Cu(N3)2bpy (S = ½) was analyzed with the spin ½ IM. Although the specific heat data (Ctotal) for most of the 1D MOFs showed no clear phase transition, a low temperature fit to the electron-phonon specific heats yielded apparent heavy fermion-like &gamma values on the order of several hundred mJ/mol K2. The lattice specific heat (C lattice) was estimated using a Debye-Einstein hybrid model. Subtracting Clattice from Ctotal, magnetic specific heat (CM) with a broad peak characteristic of low dimensional magnetism was obtained. The peak in CM was at temperature near that expected from χ(T) fits. The J values obtained from the magnetic specific heat fits were in good agreement with those obtained from χ(T) fits. Once the magnetic specific heat was accounted for, γtakes values in the expected range of few mJ/mol K2. For 3D MOFs [Mn(N3)2bpy and Fe(N3)2bpy], the existence of long range canted antiferromagnetic ordering was observed in both magnetic and specific heat measurements with phase transitions at 38 K and 20 K in the case of Mn(N3)2bpy and Fe(N3)2bpy, respectively. These transition temperatures are considered fairly high for molecular based materials. In both Mn(N3)2bpy and Fe(N3)2bpy, the χ(T) data fit well to the Heisenberg model for a diamond-type network. The transition can clearly be seen with an abrupt increase in the magnetization below TC and a shift to a higher temperature in the specific heat when measured under an applied magnetic field. The systematic approach in this work led to the successful estimate of C lattice resulting in meaningful fitting of χ(T) and Cmagnetic to the appropriate theoretical models in magnetism. It also led the discovery of ferrimagnets or canted antiferromagnets M(N3)2bpy with large coercivity and rather high transition temperature. The results of this study have been published in three articles in the Journal of Applied physics, and two manuscripts are under preparation for submission [1-5].
Temple University--Theses
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Hauptvogel, Ines Maria, Volodymyr Bon, Ronny Grünker, Igor A. Baburin, Irena Senkovska, Uwe Müller, and Stefan Kaskel. "A family of 2D and 3D coordination polymers involving a trigonal tritopic linker." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-138965.
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Five new coordination polymers, namely, [Zn2(H2O)2(BBC)](NO3)(DEF)6 (DUT-40), [Zn3(H2O)3(BBC)2] (DUT-41), [(C2H5)2NH2][Zn2(BBC)(TDC)](DEF)6(H2O)7 (DUT-42), [Zn10(BBC)5(BPDC)2(H2O)10](NO3)(DEF)28(H2O)8 (DUT-43), and [Co2(BBC)(NO3)(DEF)2(H2O)](DEF)6(H2O) (DUT-44), where BBC – 4,4′,4′′-(benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate, TDC – 2,5-thiophenedicarboxylate, BPDC – 4,4′-biphenyldicarboxylate, DEF – N,N-diethylformamide, were obtained under solvothermal conditions and structurally characterized. It has been shown that compounds DUT-40, DUT-41 and DUT-44 exhibit 2D layered structures with large hexagonal channels. Utilization of additional angular dicarboxylic TDC linker led to the formation of the DUT-42 compound with the structure consisting of three interpenetrated 3D networks. Using the linear co-linker dicarboxylic BPDC, DUT-43 was obtained which forms a complicated 3D architecture arising from the polycatenation of triple-layered 2D building units and 2D single layer units. The pore accessibility of the synthesized compounds in the liquid phase was proved by the adsorption of dye moleculesDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Hauptvogel, Ines Maria, Volodymyr Bon, Ronny Grünker, Igor A. Baburin, Irena Senkovska, Uwe Müller, and Stefan Kaskel. "A family of 2D and 3D coordination polymers involving a trigonal tritopic linker." Royal Society of Chemistry, 2012. https://tud.qucosa.de/id/qucosa%3A27797.
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Five new coordination polymers, namely, [Zn2(H2O)2(BBC)](NO3)(DEF)6 (DUT-40), [Zn3(H2O)3(BBC)2] (DUT-41), [(C2H5)2NH2][Zn2(BBC)(TDC)](DEF)6(H2O)7 (DUT-42), [Zn10(BBC)5(BPDC)2(H2O)10](NO3)(DEF)28(H2O)8 (DUT-43), and [Co2(BBC)(NO3)(DEF)2(H2O)](DEF)6(H2O) (DUT-44), where BBC – 4,4′,4′′-(benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate, TDC – 2,5-thiophenedicarboxylate, BPDC – 4,4′-biphenyldicarboxylate, DEF – N,N-diethylformamide, were obtained under solvothermal conditions and structurally characterized. It has been shown that compounds DUT-40, DUT-41 and DUT-44 exhibit 2D layered structures with large hexagonal channels. Utilization of additional angular dicarboxylic TDC linker led to the formation of the DUT-42 compound with the structure consisting of three interpenetrated 3D networks. Using the linear co-linker dicarboxylic BPDC, DUT-43 was obtained which forms a complicated 3D architecture arising from the polycatenation of triple-layered 2D building units and 2D single layer units. The pore accessibility of the synthesized compounds in the liquid phase was proved by the adsorption of dye molecules.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Palacios, Sebastian R. "A smart wireless integrated module (SWIM) on organic substrates using inkjet printing technology." Thesis, Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/51906.
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This thesis investigates inkjet printing of fully-integrated modules fabricated on organic substrates as a system-level solution for ultra-low-cost and eco-friendly mass production of wireless sensor modules. Prototypes are designed and implemented in both traditional FR-4 substrate and organic substrate. The prototype on organic substrate is referred to as a Smart Wireless Integrated Module (SWIM). Parallels are drawn between FR-4 manufacturing and inkjet printing technology, and recommendations are discussed to enable the potential of inkjet printing technology. Finally, this thesis presents novel applications of SWIM technology in the area of wearable and implantable electronics. Chapter 1 serves as an introduction to inkjet printing technology on organic substrates, wireless sensor networks (WSNs), and the requirements for low-power consumption, low-cost, and eco-friendly technology. Chapter 2 discusses the design of SWIM and its implementation using traditional manufacturing techniques on FR-4 substrate. Chapter 3 presents a benchmark prototype of SWIM on paper substrate. Challenges in the manufacturing process are addressed, and solutions are proposed which suggest future areas of research in inkjet printing technology. Chapter 4 presents novel applications of SWIM technology in the areas of implantable and wearable electronics. Chapter 5 concludes the thesis by discussing the importance of this work in creating a bridge between current inkjet printing technology and its future.
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BASTA, Luca. "Defect-engineered graphene functionalization via cycloaddition reaction – towards a versatile platform for nanoscale devices and 3D heterostructures." Doctoral thesis, Scuola Normale Superiore, 2022. https://hdl.handle.net/11384/126242.
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In recent years it has been shown that the outstanding properties of graphene, a direct consequence of its unique 2D structure, could be further tailored by surface functionalization with suitable materials, towards a fine tuning of the system's physical and chemical properties. In particular, the covalent functionalization of graphene using organic functional groups has been explored as a pivotal step towards the formation of graphene composites at the nanoscale. Alongside the commonly diffused approach with diazonium salts (abundant and quick but hard to control), a more selective and controlled method has been shown as very promising: 1,3-dipolar cycloaddition (1,3-DC) of azomethine ylide has been investigated for the chemical modification of graphene-like systems. However, while graphene's high specific surface area of 2630 m^2/g provides numerous possible binding sites, its chemical inertness makes it difficult to modify graphene's structure without disrupting it or introducing excessive disorder. Thus, to finely control or intentionally design the binding sites of functionalizing molecules on the surface of graphene while preserving the high quality of its unique structure remains an open challenge. A promising route in order to locally improve the reactivity of graphene is to introduce beneficial structural defects. For example, due to the defect-induced electron charge redistribution, defective graphene shows increased chemical reactivity towards addition reactions. At the same time, the precise control in defect formation would allow a fine tailoring of the surface chemistry of graphene, fundamental for the engineering of its electronic properties or for sensing applications. The most versatile approach that satisfies the requirements for a controlled introduction of structural defects in graphene is based on particle irradiation techniques. Indeed, effective defect modulations can be patterned over a large area via electron beam irradiation (EBI), utilizing scanning electron microscopy (SEM), in a very flexible way.
The PhD research presented here builds upon this idea. Covalent functionalization of different graphene-based systems has been achieved, allowing to explore various parameters of the functionalization process, including EBI defect-engineering.
Firstly, the functionalization procedure is optimized utilizing graphene nanosheets (GNS) and reduced graphene oxide (rGO) dispersed in the liquid phase, and, for the first time, a comparison of the efficiency of 1,3-DC of azomethine ylide in different dispersant solvents (NMP and DMF) is reported. The functionalization is confirmed with electron energy loss spectroscopy (EELS) and energy-dispersive X-ray spectroscopy (EDX) measurements, and new Raman features arising from the functionalization with azomethine ylide are detected. Density functional theory (DFT) models for pristine and functionalized rGO are built and characterized by evaluating the restrained electrostatic potential (RESP)-derived partial atomic charges, which highlighted the localization of the charges in the pristine rGO induced by the presence of defects (epoxy groups) in the initial structure. Furthermore, the computation of the power spectrum (PS) helps with the assignment of characteristic Raman peaks to the functionalization with the azomethine ylide. Finally, the elemental composition of pristine and functionalized graphene is investigated via x--ray photoelectron spectroscopy (XPS) measurements, allowing to confirm the stability of the functionalization (up to 180 °C) and to estimate the efficiency of the 1,3-DC on graphene. Thanks to the local inhomogeneity of the partial charges, due to the presence of oxygen functional groups in the initial structure, a higher functionalization is achieved on rGO (~ 2 times higher than on GNS).
The enhancement of the chemical reactivity measured in our defected graphene validates the interest in further exploring the possibility to control the position of defects on higher quality graphene systems. Defect patterns are designed on micromechanically exfoliated graphene flakes on silica substrates by EBI. Their distribution is analyzed with Raman spectroscopy, revealing that surface treatments of the graphene-supporting substrate have strong impact on the lateral resolution that can be achieved on the final defective pattern. Unintentional defects-rich zones are revealed in the adjacent parts of the irradiated areas, and Monte Carlo simulations of primary electrons scattering events demonstrate that these transition zones originate within the area where back-scattered electrons (BSEs) and secondary electrons (SEs) generated near the substrate surface by BSEs (by interaction with organic impurities adsorbed on the Si/SiO_2 substrate) escape from the substrate surface. These results can be exploited in order to design high spatially-resolved defect patterns on monolayer graphene flakes, introducing a selectively enhanced chemical reactivity towards the organic functionalization.
To explore this route, defect patterns are designed on exfoliated graphene flakes via low-energy (30 keV) EBI. Raman spectroscopy maps show the appearance of the characteristic D peak only in the patterned area, while AFM images confirm the spatial resolution of the pattern (~ 100 nm). The 1,3-DC of azomethine ylide in-situ involves the localization of a C=C bond of the graphene structure, which is favorable in presence of the defects, hence introducing a selective control of the chemical modification of graphene. The Raman analysis on functionalized graphene flakes exhibits new features only in the patterned area, while the unexposed area still presents the spectrum of pristine graphene, confirming the selectivity introduced via defect patterning. Moreover, AFM images of patterned graphene show an improved adhesion on the silica substrate, allowing to avoid detachment issues during the functionalization procedure in the organic solvent. DFT allows to identify the vibrational contributions of the functional groups of the azomethine ylide grafted on the graphene surface and of the modified vibrational modes of the graphene lattice in the experimental Raman spectrum. Furthermore, under laser irradiation (up to 1.6 mW) the Raman spectrum recovers towards the spectrum of non-functionalized patterned graphene, indicating the desorption of the ylide and the reversibility of the functionalization.
Then, the functionalization of epitaxial graphene (EG) on SiC is investigated, benefiting from the valuable addition of scanning tunneling microscopy (STM) and spectroscopy (STS). STM images of functionalized EG reveal the appearance of new structures, randomly arranged over the flat terraces (with lower density) and along the edges (with higher density), with an average height in the range 2 - 15 A, and a graphene surface coverage of ~ 14 %. The graphene structure is preserved after the functionalization procedure, as confirmed by atomically resolved STM images of its hexagonal lattice. STS spectra acquired on functionalization EG indicate the opening of a bandgap (of 0.13 - 0.20 eV) in the local density of states (LDOS) of these structures, in contrast with the zero-gap linear behavior measured on graphene. The Raman analysis of functionalized EG exhibit new features, together with a downshift of the G and 2D peaks. These results indicate the grafting of azomethine ylides on graphene. Finally, to increase the efficiency of the covalent functionalization of EG and, in particular, to be able to spatially design the functionalization of EG, defect patterning via EBI is explored. After patterning, Peak Force - Quantitative NanoMechanical (PF-QNM) measurements allow to identify the designed defect pattern, confirming the spatial resolution of the technique (with different electron doses and e-beam scan step sizes). Moreover, the analysis of the adhesion forces reveals that the patterning results in an enhancement of the adhesion of the graphene with the substrate, as already seen in previous experiments. Although incomplete, these are valuable results in the outlook of a deterministic and controlled chemical functionalization of EG on SiC, which would be extremely beneficial for the fabrication of high quality devices at the nanoscale. In fact, EG on SiC eliminates the need for transfer procedures and presents favorable characteristics for large-scale graphene electronics.
The results discussed here open the route for a controlled functionalization of different graphene-based systems with designed molecules, which could act both as active functional groups or passive spacers towards multi-functional sensing devices or multilayered spaced graphene systems optimized for hydrogen storage or gas sensing.
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Baillie-Johnson, Peter. "The generation of a candidate axial precursor in three dimensional aggregates of mouse embryonic stem cells." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267818.
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Textbook accounts of vertebrate embryonic development have been based largely upon experiments on amphibian embryos, which have shown that the tissues of the trunk and tail are organised from distinct precursors that existed during gastrulation. In the mouse and chick, however, retrospective clonal analyses and transplantation experiments have demonstrated that the amniote body instead arises progressively from a population of axial precursors that are common to both the neural and mesodermal tissues of the trunk and tail. For this reason, they are known as neuro-mesodermal progenitors (NMps). Detailed studies of NMps have been precluded by their lack of a unique gene expression profile and the technical difficulties associated with isolating them from the embryo. Mouse embryonic stem cells (ESCs) provide the possibility of instead deriving them in vitro. ESCs have been used to model developmental processes, partly through large cellular aggregates known as embryoid bodies. These structures do not, however, resemble the axial organisation of the embryo and they develop in a disordered manner. This thesis presents a novel culture system of small, three-dimensional aggregates of ESCs (gastruloids) that can recreate the events of early post-implantation development, including axial elongation. Gastruloids are the first ESC-based model for axial elongation morphogenesis; this body of work characterises their development and identifies a candidate population of NMps within their elongating tissues. Additionally, this work establishes a xenotransplantation assay for testing the functional properties of in vitro-derived NMp populations in the chicken embryo and applies it to NMps from gastruloid cultures. The results of this assay show that gastruloids are a credible source of NMps in vitro and therefore offer a new experimental means to interrogate their properties. The use of gastruloids to recreate embryonic development has implications for basic research as a synthetic system and for the therapeutic derivation of other embryonic progenitors through bioengineering.
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Bossard, Cédric. "Elaboration et caractérisation d’un hybride organominéral à base de polycaprolactone et de bioverre sous forme de mousse macroporeuse pour la régénération osseuse." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAC068/document.
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L’accroissement de l’espérance de vie s’accompagne d’une détérioration de l’état de santé général des seniors et d’une recrudescence des maladies chroniques. Parmi les manifestations de la sénescence, l’atteinte de l’appareil locomoteur est particulièrement invalidante et accélère considérablement l’entrée en dépendance. C’est également le cas chez les plus jeunes lors d’atteintes traumatiques ou pathologiques. Ainsi, au niveau mondial 2,2 millions de greffes osseuses sont pratiquées chaque année, mais le taux de complications post-opératoires demeure élevé et est estimé à 15 % des interventions. Ces faits dessinent les contours d’un enjeu sociétal majeur ; les matériaux d’origine animale posent des problèmes d’histocompatibilité, de pathogénicité et donc de rejet. C’est pourquoi les efforts de recherche ciblent prioritairement le développement de biomatériaux synthétiques aptes à promouvoir la régénération osseuse. Actuellement les principaux substituts osseux sur le marché sont les « céramiques » bioactives (phosphates de calcium, verres bioactifs) qui présentent comme caractéristiques d’être biocompatibles, de se lier spontanément aux tissus osseux, de promouvoir l’adhésion des cellules osseuses et enfin d’être biorésorbables. Cependant, malgré cet ensemble de caractéristiques très satisfaisantes, la fragilité de ces matériaux en limite les applications. Pour pallier ce défaut, une solution ingénieuse est de s’inspirer de la structure particulière du tissu osseux. Celle-ci mêle intimement une phase inorganique, le minéral osseux constitué de cristaux d’apatite (phosphate de calcium résorbable), à une phase organique qui est majoritairement du collagène. De manière remarquable, une telle structure associe la rigidité de la partie inorganique à la ténacité des fibres de collagène. Pour obtenir des implants aux propriétés mécaniques proches du tissu osseux, la stratégie consiste donc à combiner céramiques bioactives et matière organique. À cette fin, l’équipe Biomatériaux du Laboratoire de Physique de Clermont (LPC) a récemment mis au point un procédé innovant qui permet la synthèse de matrices tridimensionnelles d’hybrides organique-inorganique à base de verre bioactif et de polymère biocompatible aux caractéristiques variées. Dans la continuité des travaux, il était alors question d’exploiter ce procédé afin de développer un substitut osseux hybride aux propriétés optimisées. Il s’agissait tout d’abord de sélectionner le polymère le plus adéquat pour la régénération osseuse, qui s’est avéré être le polycaprolactone, puis d’optimiser la synthèse (notamment la source de calcium), la structure macroporeuse et la proportion organique-inorganique. Le matériau hybride résultant a ensuite été dopé en éléments thérapeutiques à faible dose (< 5 % de la masse totale) avec des ions strontium ou des nutriments tels que la fisétine et l’hydroxytyrosol qui possèdent un effet ostéogénique. Les mousses hybrides ainsi développées ont finalement été caractérisées in vitro afin de déterminer leurs propriétés physico-chimiques et biologiques, et in vivo afin d’évaluer leur performance. Après 3 mois d’implantation dans un défaut critique de la calvaria de souris, les résultats démontrent le potentiel de ce substitut osseux: comparé au matériau commercial de référence (os bovin traité) qui conduit à une reconstruction osseuse de 16% (± 5%), l’hybride permet une reconstruction allant de 32% (± 3%) lorsqu’il n’est pas dopé, jusqu’à 55% (± 7%) voire 58% (± 7%) lorsqu’il est dopé respectivement en fisétine ou en strontium. Ces travaux de thèse laissent entrevoir des perspectives prometteuses telles que l’association des dopants et l’impression 3D des mousses hybrides polycaprolactone-verre bioactifThe increase in life expectancy results in the decline of seniors’ health conditions and the resurgence of chronic diseases. Among the expressions of senescence, disorders of the musculoskeletal system are particularly disabling and considerably accelerate the state of dependency. This is also the case for young people who suffer from traumatic injuries or pathologic conditions. Thus, about 2.2 million bone grafts are performed worldwide every year. Yet, the level of postoperative complications remains high and is estimated at 15% of surgical operations. These facts outline a major societal concern: animal-based materials present a risk of histocompatibility issues and pathogenicity that may lead to implant failure. This is the reason why research efforts focus on the development of synthetic biomaterials capable of promoting bone regeneration. Currently, commercialised bone substitutes are mainly made of bioactive “ceramics” (calcium phosphates, bioactive glass) that are known to be biocompatible, to spontaneously bond to bone tissues, to promote bone cell adhesion and finally to be bioresorbable. However, despite these remarkable properties, the brittleness of these materials limits their applications. An ingenious solution to this brittleness can be learned from the particular structure of bone tissue. Bone tissue intimately blends an inorganic phase, the bone mineral, which is made of apatite crystals (resorbable calcium phosphates), with an organic phase that is mainly collagen. Such a structure associates the stiffness of the inorganic part with the toughness of collagen fibres. Therefore, in order to obtain implants with mechanical properties similar to that of bone, the strategy consists in combining bioactive ceramics with organic matter. To this end, the Biomatériaux team from the Laboratoire de Physique de Clermont (LPC) recently developed an innovative process that allows the synthesis of tridimensional organic-inorganic hybrids comprised of bioactive glass and biocompatible polymer. The objective of the thesis was to exploit this process in order to develop a hybrid bone substitute with optimal properties. First of all, polycaprolactone was selected as the polymer, especially because of its adequate degradation rate for long-term applications such as bone regeneration. Then, the synthesis process was improved (in particular, the calcium source was changed), the macroporous structure was optimised and the organic-inorganic ratio was chosen. Afterwards, elements that are known to induce an osteogenic effect were incorporated in the hybrid at low doses (< 5% of total weight): an inorganic doping was performed using strontium ions and an organic doping was performed using nutrients such as fisetin or hydroxytyrosol. The resultant hybrid scaffolds were eventually characterised in vitro in order to determine their physicochemical and biological properties and in vivo in order to evaluate their performance. After 3 months of implantation in a mouse calvarial critical defect, results demonstrate the potential of this bone substitute: compared to the reference commercial material (treated bovine bone) that leads to a bone reconstruction of 16% (± 5%), the hybrid allows a reconstruction going from 32% (± 3%) when it is not doped, to 55% (± 7%) and even 58% (± 7%) when it is doped respectively with fisetin or strontium. This thesis paves the way to promising perspectives like the association of doping agents and the 3D printing of polycaprolactone-bioactive glass hybrid scaffolds
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Zhao, Huiyu. "Analyse de la matière organique et ses propriétés dans l’environnement naturel en spectroscopie de fluorescence 3D traitée par PARAFAC." Thesis, Toulon, 2011. http://www.theses.fr/2011TOUL0003/document.
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Les matrices d’excitation et d’émission de fluorescence (MEEF) sont utilisées pour caractériser la matière organique naturelle (MON). Afin de mieux exploiter ces informations, un algorithme trilinéaire, PARAFAC, est employé. Après l’élimination des diffusions Rayleigh et Raman et la correction de l’effet d’écran, cette méthode permet de séparer les composants spectraux présents dans les MEEF.Ce travail présente deux études : la qualification et la quantification de la MON selon son origine environnementale et le calcul des constantes de complexation de la MON et du cuivre sous forme ionique.Les composants spectraux et leurs intensités relatives sont calculés par PARAFAC à partir 1146 échantillons regroupés suivant les missions, leur type de milieu, ou le niveau de salinité. Pour étudier ces composants, une nouvelle représentation spectrale est proposée afin de mettre en évidence leur variabilité spectrale. Les résultats montrent que le regroupement d’échantillons d’origine diverse conserve le recouvrement spectral global et les intensités relatives. Sur l’ensemble du domaine spectral, les zones correspondant aux substances humiques sont peu variables, comparées à la zone protéinique.La complexation des métaux par la MON est analysée par une technique combinant quatre outils : l’ajout logarithmique d’ions métalliques, la mesure de MEEF, la méthode PARAFAC et l’algorithme PROSECE. La mesure du quenching de fluorescence ne se limite pas seulement à la modélisation d’une intensité de fluorescence mais à celle de l’intensité relative de chaque composant PARAFAC surpassant ainsi les méthodes utilisées jusqu’à présent. Finalement, l’application de cette technique originale permet de quantifier les propriétés de complexation de la MON à l'aide d'un modèle de complexation utilisant 2 sites de complexation par composant en utilisant la totalité du signal de fluorescenceFluorescence excitation and emission matrices (EEM) are used to characterize natural organic matter (NOM). To make best use of this information, PARAFAC, a trilinear algorithm is employed. After removing Rayleigh and Raman scattering and correction of the inner filter effect, this method allows separating the spectral components present in MEEF.This work presents two studies: the characterization and quantification of NOM according to its origin and calculation of environmental complexation constants of NOM towards copper as ionic form.Spectral components and their relative intensities are calculated by PARAFAC from 1146 samples gathered according to the missions, the medium type, or the salinity level. To study these components, a new spectral representation is proposed in order to highlight their spectral variability. The results show that even when samples spectra of various origins are clustered, the overall spectral overlap and the relative intensities remain almost similar. On the whole spectral range, areas corresponding to humic substances are quite variable, compared to the protein zone.Metal complexation by NOM is analyzed by combination of four tools: metal ions logarithmic addition, MEEF measurement, the PARAFAC dissociation method and the PROSECE modelling algorithm. Fluorescence quenching measurement is not only limited to the modelling of fluorescence intensity but also to the relative intensity of each PARAFAC-dissociated component though surpassing the methods used so far. Finally, the application of this improving technique leads to quantify NOM complexation properties using a two-complexing sites complexation model for each PARAFAC-dissociated component by using the whole fluorescence signal
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Simpson, Emily. "Development and characterization of two versions of a new single particle mass spectrometer for organic aerosol analysis that incorporate a 3D ion trap." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/17414.
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Aerosol particles are ubiquitous throughout the atmosphere and play an important role in human health, climate, and the chemistry of the atmosphere. A significant mass fraction of these particles is composed of organic species, which remain poorly characterized due to the number and diversity of species present. This thesis describes the development and characterization of two versions of a new single particle mass spectrometer with a 3D ion trap for organic aerosol studies.
Version I combines CO₂ laser desorption and electron impact ionization in an ion trap. Mass spectra obtained for four species are comparable to NIST EI spectra. Tandem mass spectrometry studies are also demonstrated. The effects of vaporization energy, ionization delay time, and electron pulse width on the mass spectra and fragmentation patterns are examined. The detection limit of the instrument is found to be ~1x10⁸ molecules (350 nm diameter particle) for 2,4-dihydroxybenzoic acid.
Version II integrates CO₂ laser desorption and tunable VUV ionization in an ion trap and was used for a detailed study of oleyl alcohol, oleic acid and mixtures thereof. Both the degree of fragmentation in the mass spectra and the translational energy of the vaporized molecules are found to vary as a function of desorption energy in the pure particles and as a function of composition in the mixed particles. These changes can be described by the energy absorbed per particle during desorption. We show that these effects hinder the quantitative response of the instrument and have important implications for other two step laser desorption/ionization systems.
The final part of this thesis presents preliminary results from atmospherically relevant particles. Mass spectra of cigarette sidestream smoke, fulvic acid, meat cooking, and ammonium bisulfate aerosols are collected using both versions of the instrument. The two step desorption/ionization process only worked for two types of aerosols, while CO₂ only mass spectra were obtained for all four aerosol types. The suitability of CO₂ desorption strongly depended on particle composition, which will affect the applicability of the technique to atmospherically realistic aerosols. The results also suggest that CO₂ only laser desorption/ionization may be useful for field studies.
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Bruns, Benjamin Verfasser], Ralf [Akademischer Betreuer] [Littke, and Peter A. [Akademischer Betreuer] Kukla. "Unconventional petroleum systems in NW-Germany and the Netherlands : a 3D numerical basin modeling and organic petrography study / Benjamin Bruns ; Ralf Littke, Peter A. Kukla." Aachen : Universitätsbibliothek der RWTH Aachen, 2016. http://d-nb.info/112978746X/34.
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Rippen, Daniel Verfasser], Ralf [Akademischer Betreuer] [Littke, and Brian [Akademischer Betreuer] Horsfield. "Oil and gas shales of Northern Germany : implications from organic geochemical analyses, petrophysical measurements and 3D numerical basin modelling / Daniel Rippen ; Ralf Littke, Brian Horsfield." Aachen : Universitätsbibliothek der RWTH Aachen, 2015. http://d-nb.info/1130327094/34.
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Lee, Darryl Liang Wee. "Development of a PP-MOCVD System and its Design and Operational Parameters for Uniform Industrial Coatings on 3D Objects." Thesis, University of Canterbury. Dept. of Mechanical Engineering, 2014. http://hdl.handle.net/10092/9644.
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Increase in demand for uniform ceramic coatings on larger industrial components have led to a need for a PP-MOCVD coating system scale up. The objective of this thesis is to develop a fully functional coating system operating in the PP-MOCVD regime that is able to deposit thin film ceramic coatings on commercial or industrial components with complex 3D geometries.
This can be achieved by applying engineering and vacuum science theories, coupled with the established fundamentals of PP-MOCVD. A larger system was designed and assembled around the boundaries set by the dimensions and geometry of a stainless steel water pump impellor acting as the base substrate. Most of the components were sourced off the shelf from vacuum and fluid specialists. Components which were unavailable for various reasons were designed, and machined in-house by the departmental workshop.
Initial test depositions were conducted using small stainless steel disk substrates, heated using a resistive heater similar to the one utilised on the research scale system. The test depositions were performed with the heater and substrate combination placed in strategic locations. This is to test the overall uniformity of precursor flux in the chamber volume. The resulting coating uniformity on the disk surfaces were fair but problems such as the large collection of unreacted precursor on the chamber viewport and valve timing issues had to be addressed.
Before making any improvements to the system, each of the process areas leading to a successful deposition needed to be understood. Five process areas were developed: ‘Liquid Delivery’, ‘Atomization’, ‘Evaporation’, ‘Transport and Reactor Geometry’, and ‘Droplet Management’. Each of the process areas were analysed individually and changes were made to push for a maximum evaporation efficiency.
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The improved system provided opportunities to perform depositions that were once not possible for PP-MOCVD. Two sets of deposition tests were designed and conducted. Firstly, the improvements were justified with a series of depositions using flat stainless steel plates with dimensions 65x65x5mm. The other set of 3D case study depositions involve observing the effects of the operational parameters of PP-MOCVD on the uniformity and penetration depths of the coatings into different sized macro blind trenches.
Five geometric setup conditions were used to justify the improvements made to the system. These are: ‘Substrate positioned in the direct line of spray’, ‘Use of an unheated receptor’, ‘Use of a heated receptor’, ‘Use of an unheated receptor with a non-axial substrate setup’, and “Choked Flow’. As expected, the uniformity of the coatings on both sides of the plate varied significantly when the substrate is placed over the line of sight of the precursor spray. Similarly, the coating produced under the induced choked flow condition resulted in low conformality. The introduction of an unheated receptor plate resulted in an increase in uniformity on both sides of the plate. Further prove that PP-MOCVD is geometry independent is provided by the deposition made with the non-axial substrate placement resulting in a coating of similar result to the unheated receptor. The use of a heated receptor provided a source for a secondary evaporation of the larger precursor droplets collected resulting in an increase in coating thickness while maintaining good conformality.
The effects of temperature, pressure, injection volume, and concentration were explored in the final case study. With maximum depths of 50mm, the macro blind trenches has an aspect ratio of 1:1 and cross-sectional areas of 3x3mm, 9x9mm, and 15x15mm. The final results show that as the temperature rises, the depth penetrated into the trench decreases. This could be due to the change in rate limiting steps as homogeneous reactions begin to increase at higher temperatures. Similar trends were observed with increasing pressure. As the pressure difference between the volume of the trenches and the rest of the chamber decreases, the push needed to
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force the precursor down the trench also decreases, resulting in less depth penetration. The effects of injection volume and concentration observed, can be explained by how much precursor molecules are present during one pulse cycle. The more that is available at any given time, the more likely a reaction will occur and deeper the penetration will get. Of course a ceiling or a limit exists where the molecules in the chamber will get evacuated without being reacted.
The future work made possible as a result of the scaled up system are proposed. These include a scale up of the operational parameters to suit any given substrate geometry, improvements to the heating source to achieve greater thermal uniformity, further improvements to the overall system accessibility, and performing other depositions using different substrate materials and precursor types.
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Sengal, Asmerom Tesfamariam. "Prognostic, predictive, and therapeutic role of FGFR2 isoforms and cognate FGF ligands in endometrial cancer." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/205851/1/Asmerom%20Tesfamariam_Sengal_Thesis.pdf.
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This project investigated the role of FGFR2 isoforms (FGFR2b/FGFR2c) and their cognate FGF ligands in endometrial cancer development, prognosis, and treatment response via designing and validating an innovative BaseScope RNA in-situ hybridization assay and generating patient tumour-derived organoids. FGFR2c and high FGF18 expression were significantly associated with aggressive tumour characteristics and poor survival outcome. It was also noted FGFR2c expression is associated with progestin treatment failure in atypical hyperplasia and well-differentiated endometrial cancers. Overall, FGFR2c and FGF18 are independent prognostic biomarkers that could improve our ability to predict patient prognosis and predict response to FGFR inhibitor treatment in endometrial cancer.
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Jenson, Sage. "Digital Morphologies: Environmentally-Influenced Generative Forms." Oberlin College Honors Theses / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=oberlin1499763863308499.
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Nun, Nicholas. "Improving Skin Wound Healing Using Functional Electrospun Wound Dressings and 3D Printed Tissue Engineering Constructs." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1617985844538101.
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Richardson, Kevin Thomas. "DESIGN AND ANALYSIS OF A 3D-PRINTED, THERMOPLASTIC ELASTOMER (TPE) SPRING ELEMENT FOR USE IN CORRECTIVE HAND ORTHOTICS." UKnowledge, 2018. https://uknowledge.uky.edu/me_etds/127.
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This thesis proposes an algorithm that determine the geometry of 3D-printed, custom-designed spring element bands made of thermoplastic elastomer (TPE) for use in a wearable orthotic device to aid in the physical therapy of a human hand exhibiting spasticity after stroke. Each finger of the hand is modeled as a mechanical system consisting of a triple-rod pendulum with nonlinear stiffness at each joint and forces applied at the attachment point of each flexor muscle. The system is assumed quasi-static, which leads to a torque balance between the flexor tendons in the hand, joint stiffness and the design force applied to the fingertip by the 3D-printed spring element. To better understand material properties of the spring element’s material, several tests are performed on TPE specimens printed with different infill geometries, including tensile tests and cyclic loading tests. The data and stress-strain curves for each geometry type are presented, which yield a nonlinear relationship between stress and strain as well as apparent hysteresis. Polynomial curves are used to fit the data, which allows for the band geometry to be designed. A hypothetical hand is presented along with how input measurements might be taken for the algorithm. The inputs are entered into the algorithm, and the geometry of the bands for each finger are generated. Results are discussed, and future work is noted, providing a means for the design of a customized orthotic device.
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Loizeau, Vincent. "Prise en compte d'un modèle de sol multi-couches pour la simulation multi-milieux à l'échelle européenne des polluants organiques persistants." Thesis, Paris Est, 2014. http://www.theses.fr/2014PEST1168/document.
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Les polluants organiques persistants (POPs) sont des substances toxiques ayant la capacité de se bioaccumuler le long de la chaîne alimentaire. Une fois émis dans l'atmosphère, ils sont dispersés par le vent puis se déposent au sol. Du fait de leur persistance, ils peuvent être réémis depuis le sol vers l'atmosphère et parcourir ainsi de longues distances. Ce processus est couramment appelé « effet saut de sauterelle ». On peut donc retrouver les POPs très loin de leurs sources d'émissions. Pour pouvoir prendre des décisions visant à réduire leur impact environnemental, il est nécessaire de comprendre leur comportement dans l'atmosphère mais également dans les autres milieux, tels que le sol, la végétation ou l'eau. De nombreux modèles numériques de complexité variable ont été développés dans le but de prédire le devenir des POPs dans l'environnement. La plupart d'entre eux considèrent le sol comme un compartiment homogène, pouvant ainsi mener à une sous-estimation des réémissions du sol vers l'atmosphère. Or, du fait de la mise en place de réglementations visant à réduire les émissions anthropiques des POPs, la concentration dans l'atmosphère tend à diminuer et le sol, qui semblait jusqu'alors être seulement un réservoir, devient une source potentielle de POPs pour l'atmosphère. Il apparaît donc nécessaire de coupler les modèles de dispersion atmosphérique à un modèle de sol réaliste. Mes recherches ont permis d'étudier l'impact des interactions entre le sol et l'atmosphère sur la concentration dans les différents milieux. Pour cela, nous avons développé un modèle de sol multi-couches permettant de mieux estimer le profil de concentration dans le sol et les échanges entre ces deux milieux. Une analyse de sensibilité a été effectuée afin d'identifier les paramètres clés dans la détermination des réémissions. Puis ce modèle a été couplé à un modèle 3D de chimie-transport atmosphérique. Une étude de cas à l'échelle européenne a alors été réalisée afin d'évaluer ce modèle et d'estimer l'impact des réémissions sur les concentrations de POPs dans l'environnementPersitent Organic Pollutants (POPs) are toxic substances that bioaccumulate in the food chain. Once emitted in the atmosphere, they are transported by the wind and deposited on soil. Since they are persistent, they can be reemited from soil to atmosphere by volatilization and travel over very long distances. This process is called grasshopper effect. Thus, POPs may be found at significant levels far from their emission source. It is necessary to understand the transport and fate of these pollutants in order to support the decision making process and reduce human exposure to POPs. Regulations over the last decades lead to a decrease of anthropogenic emissions and subsequent decrease of atmospheric concentration. In this context, the soil is no longer a sink of POPs but can be a source to the atmosphere. Many numeric models aim to study the behavior of POPs in the environment. Most of them consider soil compartment as a homogeneous box, leading to an underestimation of reemissions. Then, it appears of great importance to develop more realistic soil models. The objective of my thesis was to develop such a model, with vertical transport within the soil. This model was evaluated against measured concentration soil profile. We also conducted a sensitivity analysis to identify the key parameters involved in the process of reemissions. Then, the soil model was coupled with an atmospheric transport model. A case study was finally undertaken to estimate the impacts of reemissions on global-mass balance of POPs at European scale
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Pop-Piron, Flavia-Florina. "Nouvelles architectures fonctionnelles pour la reconnaissance moléculaire, systèmes conjugués à faible Gap et matériaux pour électrode avancés." Phd thesis, Université d'Angers, 2009. http://tel.archives-ouvertes.fr/tel-01016464.
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La thèse intitulée " New Functional Architectures for Molecular Recognition, Low Band Gap Conjugated Systems and Advanced Electrode Material " est structurée en quatre chapitres traitant de a) structures supramoléculaires tels que cryptands et bis-macrocycles; b) tetrahalo-1,3-diènes chiraux stériquement encombrées; c) blocs pour la synthèse de polymères faible gap conjugués d) architectures 3D conjugués à base de bithiophènes portant des EDOTs terminaux. Dans le premier chapitre, on présente deux nouvelles séries de précurseurs macrocycliques tripodaux possédant une symétrie C3 construites à partir de 1,3,5-triazine avec des groupes fonctionnels réactifs aux extrémités des bras. Les structures supramoléculaires obtenues par des réactions de couplage acétylénique catalysées par Cu sont également présentées. Les cryptands ont été fermés par dimérisation intermoléculaire et les bis-macrocycles ont été formés par des couplages intramoléculaires suivis par dimérisation intermoléculaire. Le deuxième chapitre présente l'étude de nouveaux atropisomères à base d'EE-tetrahalo-1,3- butadiène y compris la séparation des énantiomères, la détermination des barrières de rotation et des configurations absolues. Le troisième chapitre a été consacré à la synthèse des blocs à base de benzo [2,1-b:3,4-b']- dithiophène-4,5-dione utilisés pour obtenir des polymères conjugués à faible gap pouvant fonctionner comme matériau actif dans des cellules solaires organiques. Dans le dernier chapitre on décrie la synthèse et les propriétés électroniques de différents types de nouvelles architectures 3D conjuguées à base de bithiophène comportant des unités EDOTs terminales, en vue de la génération électrochimique de réseaux microporeux électroactifs conjugués. Il est montré que la taille, la surface active et les propriétés électroniques dépendent de la nature des blocs utilisés pour la construction des bras latéraux.
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Ishiki, Hamilton Mitsugu. "Relações quantitativas entre estrutura química e atividade biológica (QSAR/QSAR-3D) de compostos com potencial atividade antituberculose." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/46/46135/tde-25042016-172925/.
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A tuberculose (TB) é uma doença causada pelo Mycobacterium tuberculosis. De acordo com estimativas da Organização Mundial da Saúde, a tuberculose é responsável pela morte de ~2 a 3 milhões de pessoas/ano no mundo e nos próximos 15 anos cerca de 1 bilhão de pessoas deverão ser infectadas, e destas, aproximadamente 35 milhões deverão morrer. Apesar de existirem vários medicamentos sendo utilizados no tratamento da doença, constatasse o crescimento no número de casos devido, principalmente, às variedades resistentes do M. tuberculosis. Considerando-se o aparecimento de cepas resistentes em TB, recomenda-se que novos medicamentos e/ou alvos biológicos alternativos devam ser intensivamente pesquisados. A ribonucleotídeo redutase (RNR), por exemplo, é uma proteína de interesse, pois catalisa uma etapa importante e única na síntese de novo dos dNTPs, reduzindo o ribonucleosídeo 5\' -difosfato ao seu correspondente desoxirribonucleosídeo 5\' -difosfato. A RNR é importante na síntese do DNA, e portanto, na divisão das células. Esta enzima importante, que possuí 16% de homologia com a RNR de mamíferos, é um alvo potencial para o desenvolvimento de novos fármacos, com provável aplicação no tratamento do câncer, da malária e do tripanossoma. Sabe-se que diferentes classes de compostos, através de diferentes mecanismos de ação, inibem a RNR, incluindo as α-(N)-heterocíclicas carboxaldeído tiossemicarbazonas, um dos inibidores mais potentes da RNR. Sabe-se que alguns derivados da tiossemicarbazona, inibidoras da RNR de células tumorais, apresentam atividade frente o M. tuberculosis atuando provavelmente através do mesmo mecanismo, envolvendo a inibição da correspondente RNR. Neste contexto, nesta tese de doutorado, foram aplicadas diferentes abordagens de QSAR/QSAR-3D no estudo de 40 derivados da 2-piridino-carboxaldeído tiossemicarbazona, inibidores da RNR de células H.Ep.-2, retirados de literatura selecionada (French & Blanz-Jr. 1974). Estes compostos foram divididos em cinco séries, a saber: séries A, B, C, D, e E contendo, respectivamente, 40, 39, 30, 23 e 22 compostos, na tentativa de tornar estas séries estruturalmente mais homogêneas. Para cada série, foram criados três grupos de treinamento e os respectivos grupos de teste (I, II e III), visando-se avaliar o poder de predição dos modelos gerados através das análises de QSAR/QSAR-3D. Para as análises de QSAR clássico, foram utilizados como variáveis independentes, os descritores mais relevantes gerados através do programa DRAGON e, pré-selecionados por PLS. Considerando-se a ausência de informações sobre a estrutura cristalográfica da enzima RNR do M. tuberculosis, os estudos de QSAR-3D foram iniciados empregando-se metodologias propostas em CoMFA e, em CoMSIA, implementadas no programa SYBYL. Além destas, foi realizada a modelagem por homologia da RNR do M. tuberculosis, utilizando-se o programa WHATIF. Para as abordagens CoMFA e CoMSIA as geometrias otimizadas através do método semi-empírico AM1 foram alinhadas átomo-a-átomo e, através da similaridade dos respectivos campos estéricos e eletrostáticos, utilizando-se o programa SEAL. Nos dois procedimentos a geometria do composto não substituído, um dos mais ativos na série, foi utilizada como molde considerando-se a ausência de informações sobre a conformação bioativa. A modelagem da RNR por homologia foi realizada utilizando-se como molde as estruturas cristalográficas, respectivamente, do C. ammoniagenes (código PDB 1KGN) e da S. typhimurium (código PDB 1R2F), sambas apresentando valores de identidade superior a 65%. Mais recentemente foram publicados os dados cristalográficos para a cadeia beta (subunidade menor) da RNR do M. tuberculosis (código PDB 1UZR). Os modelos CoMFA e CoMSIA gerados apresentaram valores aceitáveis para os coeficientes de correlação de predição, com altos valores para os coeficientes de correlação ajustados e baixos valores para os erros padrões. Os melhores modelos CoMFA e CoMSIA foram obtidos considerando o grupo com substituintes apenas na posição 5 do anel piridínico. Razoáveis coeficientes de correlação de predição para os modelos CoMSIA com altos coeficientes de correlação de ajuste e baixos valores para os erros padrões forma obtidos. Os mapas de contorno gerados em CoMFA e CoMSIA sugerem que grupos aceptores de ligações de hidrogênio próximos ao nitrogênio do anel piridínico deverá aumentar o valor da atividade inibitória. Esta observação está em boa concordância com os dados da literatura, na qual a formação de um complexo entre a TSC e o íon Ferro foi sugerido para a inibição da RNR. Estes estudos deverão permitir um melhor entendimento sobre as características estruturais desta classe de TSC inibidoras da RNR, como agentes antitumorais, em termos dos campos estéricos, eletrostáticos, hidrofóbico, doador e aceptor de ligações de hidrogênio, bem como a contribuição para o desenvolvimento racional de novos inibidores para esta importante enzima. Adicionalmente, dois compostos preparados em nosso laboratório, demonstraram atividade frente o M. tuberculosis, em testes realizados in vivo.Tuberculosis is an illness caused by Mycobacterium tuberculosis. Data from World Health Organization (WHO) estimates, that about 2-3 millions of human population died by Mycobacterium tuberculosis infection and that during the next 15 years about 1 billion will be infected and 35 million will certainly die. Although, in the clinic it was found several antiTBdrugs, these numbers will increase due several reasons including M. tuberculosis resistant strains. It has been stressed the importance of novel medicines and/or alternative biological targets research projects. It is known that Ribonucleotide reductase (RNR), is an enzyme that catalyses the rate limiting step in the de novo synthesis of dNTPs, reducing the ribonucleoside 5\'-diphosphates to the corresponding deoxyribonuc1eoside 5\' -diphosphates. RNR has a critical role in the DNA synthesis and, hence, cell division. This key enzyme, that shows 16% homology when compared with mammals RNR, is a potential target for drug design of cell growth inhibitors, with potential application in cancer therapy, antimalaria and trypanosome chemotherapy. It is known that different types of compounds or species by means of different mechanism pathways can show RNR inhibition, including α-(N)-heterocyclic carboxaldehydes thiosemicarbazones that are one of the most potent classes of RNR inhibitors. More than that, some of them, that shows activity against M. tuberculosis seems to follow the same mechanism pathways proposed to the thiosemicarbazones tumor cells activity that means, that they probably are RNR inhibitors. In this study, a series of 40 α-(N)-2-formyl-pyridine thiosemicarbazone derivatives tested against RNR of H.ep.-2-cells (human epidermoid carcinoma), taken from selected literature (French & Blanz-Jr. 1974), has quantitatively analyzed by means of several QSAR/3D-QSAR approaches. These compounds were divided into 5 individual subsets, namely A, B, C, D, and E, having 40, 39, 30, 23 e 22 compounds, respectively. This procedure has been done in order to achieve more structurally homogeneous subsets. For each set, three individual training and test sets (I,II and III) have been created in order to evaluate the predictivity power of the generated QSAR/3D-QSAR models. QSAR analysis have been done using descriptors generated by DRAGON program that have been further pre-selected by PLS procedures. Considering that crystallographic data of RNR M. tuberculosis are not available in the literature, 3D-QSAR studies have been done these applying, initially, CoMFA and CoMSIA approaches, implemented in SYBYL. Homology model studies have been performed with WHATIF program CoMFA e CoMSIA approaches used optimized geometry obtained by semi-empirical AM1 methods that have been aligned by two different methods. Rigid alignment, in which the compounds were fitted atom-by-atom onto a template, based on the root mean square fit. The N(l) and C(2) atoms of the pyridine moiety and the heavy atoms of thiosemicarbazone backbone of TSC were used as template structure. (2) Field based, in which the steric and electrostatic fields, generated by the SEAL program were considered in the alignment. In both procedures the unsubstituted 2-formylpyridine thiosemicarbazone in its syn conformation, has been taken as template. Homology RNR models were done using as template crystallographic data of ammoniagenes (1KGN) and S. typhimurium (1R2F) as template, respectively, with identity larger than 65%. More recent1y new crystallographic data have been published for the beta chain (smaller subunity) of RNR do M. tuberculosis (1UZR). CoMFA and CoMSIA generated models showed acceptable predictive correlation coefficients with high fitted correlation coefficients and low standard errors. Betler CoMFA and CoMSIA models have been derived considering a homogeneous subset of TSC substituted only at 5-position in pyridine ring. Reasonable predictive correlation coefficients for CoMSIA models with high fitted correlation coefficients and very low standard errors were obtained. The derived CoMFA and CoMSIA countour maps suggested that a hydrogen bond acceptor near the nitrogen pyridine ring could enhance inhibitory activity value. This observation is in good agreement with literature, in which a complex formation between TSC and iron ion has been suggested, to RNR inhibition. These studies are expected to enhance the understanding of the structural features of this class of TSC-RNR inhibitors as antitumor agents in terms of steric, electrostatic, hydrophobic and hydrogen donor and acceptor fields as well as to contribute to rational design of inhibitors of this key enzyme. Additionally, two compounds that have been prepared by us showed activity against M. tuberculosis using in vivo test system.
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Grall, Romain. "Nouvelles stratégies pour le traitement des tumeurs chimio et radio-résistantes : Nanodiamants hydrogénés et Solides hybrides poreux. Etude in vitro dans des systèmes 2D et 3D." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T034/document.
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Ce travail de thèse s’inscrit dans un contexte d’explosion des nanoparticules et de leur très grand potentiel pour des applications en cancérologie. Ainsi, deux classes de nanoparticules ont été étudiées afin de valider et de caractériser biologiquement ce potentiel. Premièrement les Nanodiamants hydrogénés (H-NDs) dont l’interaction avec les photons de l’irradiation comme générateur de stress oxidatif était au cœur du postulat physico-chimique. Nous avons non seulement validé cette hypothèse dans plusieurs lignées cellulaires de cancer du rein et du sein notamment, insensibles aux doses d’irradiation étudiées ; mais également identifié la sénescence comme étant la voie activée par le double traitement H-NDs et irradiation. Les Solides hybrides poreux sont également des matériaux prometteurs grâce à leur haut pouvoir d’encapsulation de molécules actives. Nous avons ainsi démontré l’absence de toxicité de ces composés seuls dans quatre lignées de cancer du poumon et du foie, élément essentiel avant d’envisager leur utilisation, chargés avec des principes actifs. Enfin, à l’heure où la réglementation internationale encourage le développement et l’utilisation de modèles alternatifs à l’expérimentation animale, nous avons mis au point un modèle de culture tridimensionnelle d’adénocarcinome mucosécrétant de poumon. Il est utilisé pour l’étude de la progression tumorale ainsi que pour la découverte de nouvelles molécules de chimiothérapieThe present work focuses on nanoparticles and their great skills for oncology therapies. Two kinds of nanoparticles have been studied in order to biologically validate and characterize their features. The use of hydrogenated Nanodiamonds (H-NDs) as radio sensitizer is based on a physic-chemical postulate where they act as oxidative stress generator through interaction with irradiation. Thus we validated this hypothesis in radio resistant kidney and breast cancer cell lines and identify senescence as the main pathway after co-treatment with H-NDs and irradiation. Metal organic frameworks are also of particular interest for drug delivery because of their very important loading capacities. Here we demonstrate the biocompatibility of the empty compounds in four lung and hepatic cancer cell lines, a main point before their involvement in drug delivery strategies. Finally, following international guidelines encouraging to make animal testing more ethic, we developed a new 3D cell culture mimicking mucinous lung adenocarcinoma. This well characterized model will be used for the study of cancer development and drug screening
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Guigue, Julien. "Influence des facteurs biotiques et abiotiques sur la dynamique de la matière organique du sol à partir de la caractérisation biogéochimique des matières organiques solubles." Thesis, Dijon, 2014. http://www.theses.fr/2014DIJOS052/document.
Full textAbstract:
Les sols sont le plus grand réservoir de carbone des écosystèmes terrestres, et la minéralisation des matières organiques par l’activité microbienne représente la majeure partie des flux de CO2 émis à la surface des continents.Dans ce travail, nous avons étudié les matières organiques extraites à l’eau (WEOM), qui correspondent à la fraction la plus réactive des matières organiques du sol (MOS). Nos objectifs étaient (i) d’identifier les liens de la dynamique du WEOM avec les communautés bactériennes, et avec les paramètres physico-chimiques du sol ; (ii) de réaliser une caractérisation chimique précise du WEOM.Il existe un lien fort entre la solubilité des MOS et les structures des communautés bactériennes, et une baisse de leur diversité impacte la dynamique des MOS et du WEOM, et provoque une baisse de la minéralisation des matières organiques. Une étude à l’échelle régionale a également permis d’identifier que les taux de MOS et d’argile contrôlent les quantités de WEOM et leur aromaticité. La caractérisation au niveau moléculaire a montré la présence d’un grand nombre de molécules ubiquistes dans le WEOM. À partir de ces analyses, nous avons également pu décrire les effets du couvert végétal et des propriétés physico-chimiques des sols sur la composition chimique du WEOMSoils are the greatest reservoir of C on the continents, and organic matter mineralisation bymicrobial activity represents the major part of the CO2 emitted by terrestrial ecosystems.In this work, we studied water-extractable organic matter (WEOM), which corresponds to themore reactive fraction of soil organic matter (SOM). Our objectives were (i) to identify therelationships of WEOM dynamics with bacterial communities, and with soil physico-chemicalparameters; (ii) to provide a precise chemical characterisation of WEOM.There is a strong link between SOM solubility and the structure of bacterial communities, andan erosion of their diversity has an impact on SOM and WEOM dynamics, and leads to adecrease in organic matter mineralisation. A study at the regional scale then allowed us to identifythat the SOM and clay contents control the quantities of WEOM and its aromaticity. TheWEOM characterisation at the molecular level revealed the presence of a large number ofubiquitous molecules in the WEOM. Based on these analyses, we were also able to describe theeffects of vegetation and soil physico-chemical properties on the chemical composition ofWEOM