Human mesenchymal stem cell (MSC) therapy has shown neuroprotective effects and improvement on recovery from neonatal intraventricular hemorrhage (IVH). This study focused on histological evaluations of human amniotic fluid MSC therapy during early prenatal life in a preterm IVH rabbit model. IVH was diagnosed at 24 h of age with ultrasound and animals were randomized into subgroups with confirmed IVH and an IVH negative control group. Animals with confirmed IVH received vehicle only or MSCs at two different doses via intraperitoneal administration. The animals were sacrificed at 48 h post administration. The severity of IVH was histologically analyzed via staining of endogenous peroxidase activity in cryosections and the distribution of red blood cells and cell-free hemoglobin was scored. Primary antibodies targeting human epitopes were validated in IHC assays of frozen MSC pellet. An anti-human nuclear mitotic apparatus (hNuMA) antibody labeled the majority of cells in the MSC pellet and did not cross-react with rabbit NuMA when tested in the nontreated rabbit brain. Significant levels of red blood cells and cell-free hemoglobin were found in the IVH confirmed group, whereas the control group showed no hemorrhage. The MSC therapy groups showed similar scoring results as the IVH-vehicle group. Anti-hNuMA immunolabeling did not detect any cells in the brain of MSC treated rabbits. However, extracellular (nonnuclear) immunolabeling was detected, located in the midbrain of the animals that received MSCs, indicating the presence of MSC nuclear debris. The preterm rabbit model was proven successful for inducing IVH, whereas MSC treatment did not affect the degree of hemorrhage. To increase the possibility to detect the MSCs post administration, future studies should include prelabeling of the MSCs with a suitable cell tracker and analyses at time points closer to the administration of MSCs. / Human mesenkymal stamcellsterapi har visat neuroprotektiva effekter samt förbättring av återhämtning efter neonatal intraventrikulär blödning (IVH). Denna studie fokuserade på histologiska utvärderingar av stamcellsterapi med humana mesenkymala stamceller (MSC) från fostervatten under tidigt prenatalt liv i en prematur IVH-kaninmodell. IVH diagnostiserades med ultraljud vid 24 tim. ålder och djuren delades slumpmässigt in i undergrupper med konfirmerad IVH och en IVH-negativ kontrollgrupp. Djur med konfirmerad IVH mottog endast bärmedel eller MSC i två olika doser via intraperitoneal administration. Djuren avlivades 48 tim. post administration. Graden av IVH analyserades histologiskt genom färgning av peroxidasaktivitet i kryosnitt av hjärna och distributionen av erytrocyter samt fritt hemoglobin graderades. Primärantikroppar riktade mot humana epitop validerades i immunhistokemiska analyser av fryst MSC-pellet. En anti-human nukleär mitotisk apparat (hNuMA) antikropp märkte majoriteten av cellerna i MSC-pelleten och korsreagerade inte med kanin-NuMA under försök i obehandlad kaninhjärna. Signifikanta nivåer av erytrocyter och fritt hemoglobin påvisades i gruppen med konfirmerad IVH, medan kontrollgruppen inte visade någon blödning. Samtliga IVH-grupper; IVH-vehicle och de som mottog MSC- terapi, visade liknande blödningsgrad. Anti-hNuMA-immuninmärkning kunde inte detektera några celler i de MSC-behandlade kaninhjärnorna. Dock detekterades extracellulär (icke-nukleär) immuninmärkning lokaliserad i mitthjärnan hos de djur som mottog MSC, vilket indikerar närvaro av nukleär MSC-debris. Den prematura kaninmodellen bevisades vara framgångsrik för induktion av IVH, men MSC-terapi påverkade inte blödningsgraden. För att öka sannolikheten att detektera MSC efter administration, borde framtida studier inkludera förmärkning av MSC med en lämplig cellmarkör samt analyser vid tidpunkter närmare administrationen av MSC.

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Made available in DSpace on 2016-04-28T19:58:49Z (GMT). No. of bitstreams: 1 Dissertacao Adriane Roberta Ribeiro de Macedo.pdf: 654593 bytes, checksum: c29eac6f38caf415d4c87c648592285d (MD5) Previous issue date: 2005-11-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present dissertation has as objective to reflect on the process of construction of the narrative speech of Cacos para um vitral, workmanship of Adélia Prado, published in 1980. thus, we elaborate the following question: Knowing that the organization give to the composition to the romance Cacos para um vitral deives a digialogical construction, equivalent and multi-meaming, where is discursive dimension modality retakes the similar literal logic to the composition of stain glass window? Ahead of the object and the problematic one considered, we raise two hypotheses, first, the architextura of the composition of the stain glass window, second, the metalinguistic method cooperates with the assembly of double metaphor: stain glass window text. The research discloses, among other conclusions, that the organization of the text is brock up in direction, approaching the process of construction of the text and the composition of stain glass window / A presente dissertação tem como objetivo refletir sobre o processo de construção do discurso narrativo de Cacos para um vitral, obra de Adélia Prado, publicada em 1980. para tanto, elaboramos a seguinte pergunta: sabendo que a organização dada ao romance Cacos para um vitral deriva uma construção dialógica, equivalente e plurissignificativa, em que dimensão esta modalidade retoma a lógica textual similar à composição de um vitral? Diante do objetivo e da problemática propostos, levantamos duas hipóteses: primeira a arquitextura do romance Cacos para um vitral, retoma a modalidade discursiva metafórica da composição do vitral; segunda o método metalingüístico coopera com a montagem da dupla metáfora: texto-vitral. A pesquisa revela, entre outras conclusões, que a organização do texto é fragmentada no sentido de romper com as estruturas da linearidade. A metalinguagem é empregada no sentido operativo, aproximando o processo de construção do texto e a composição do vitral

Dans le but de déchiffrer l’évolution tectono-métamorphique des massifs de Belledonne, des Grandes Rousses et du Pelvoux nous avons effectué une étude multidisciplinaire (Structures, pétrologies, géochronologies, géochimies, et isotopes radiogéniques). Les résultats obtenus permettent de reconnaitre six évènements tectono-métamorphiques responsables de la structuration de ce segment de la chaîne varisque. Le premier événement, Dx, correspond à un épisode de collision précoce et se produit vers ca.380 Ma. Il est responsable de l’obduction vers l’E du complexe ophiolitique de Chamrousse, ainsi que d’un métamorphisme de MP-BT. Vers 350 Ma, un évènement magmatique permet la formation de l’unité magmatique bi-modal de Rioupéroux-Livet. Entre 350 et 330 Ma, la mise en place de nappes vers l’E (D₁) se caractérisé par un métamorphisme barrovien. Cet événement est également responsable de la mise en place de nombreux granites liés à la fusion partielle de la croûte. L’évènement transpressif senestre D₂ se produit immédiatement après, vers 320-300 Ma. Il se caractérise par le plissement de la pile de nappes non migmatitiques, et par le développement d’une foliation verticale S₂. Dans la croûte partiellement fondue, il est marqué par une fabrique verticales (S₂), par des zones de cisaillements (C₂ et C’₂), qui s’organisent en structure de type S-C-C’. Synchrone à la déformation tardi-D₂ (305-300 Ma), l’événement D₃ est responsable de la formation d.une foliation plate (S₃) à la transition entre les migmatites et les roches non fondues. Les structures D₂ et D₃ sont interprétées comme étant relatives au fluage latéral de la croûte partiellement fondue. L’événement D₂ s’accompagne également de la mise en place de nombreux granites peralumineux, formés lors de la fusion partielle de la croûte. Enfin, l’intrusion d’un granite à cordiérite au Permien constitue le dernier évènement observé dans cette portion de la chaîne varisque. / In order to decipher the Variscan tectono-thermal evolution of the Belledonne-Pelvoux area we perform a multidisciplinary study (structural, petrology, geochronology, geochemistry and radiogenic isotopes). The results allow us to recognize six tectono-thermal events responsible for the building of the studied portion of the Variscan orogen. The first, Dx corresponds to an earlier collisional event at ca. 380 Ma that was responsible for the obduction of the Chamrousse ophiolitic unit toward the East and MP-BT metamorphism. At ca. 350 Ma, a magmatic event is responsible for the formation of the bi-modal magmatism of the Rioupéroux-Livet unit. Between ca.350-330 Ma an eastward nappe-staking event (D₁) responsible of a barrovian metamorphism occurred. It is coeval with the emplacement of numerous continental crust derived plutons. This event is followed at ca. 320-300 Ma by a D2 NW-SE directed shortening in a sinistral transpressive regime. This event is characterized by folding of the unmolten nappe pile and development of a subvertical S₂ foliation. In the partially molten crust, the D₂ event is characterized by the formation of steeply dipping S₂ and shear zones (C₂ and C’₂) organized as S-C-C’-like pattern. Coeval with the late-D₂ deformation (ca. 305-300Ma) a D₃ event responsible for the development of a flat laying S₃ foliation at the boundary between the molten and unmolten domains is documented. The late-D₂ and D₃ events are interpreted to be relative to the lateral flow of the partially-molten crust. The D₂ event is coeval with the emplacement of the manly Stephanian peraluminous granitoids, formed by melting of the continental crust. Finally, a Cordierite- bearing granite indicate the existence of a Permian magmatism.

Objective: To quantify and compare histopathological differences regarding atherosclerosis and granular media calcinosis (GMC) of ascending aortic aneurysms (AAA), which are associated with aortic stenosis (AS) or aortic regurgitation (AR). Additionally, a subanalysis of patients with bicuspid or tricuspid aortic valve (BAV or TAV), which were contained within the AS and AR group, was conducted. Patients and Methods: From 01/2012 till 12/2015 84 ascending aortic tissue samples were obtained and divided into their convex and concave half during aortic surgery. Aortic surgery was indicated due to AAA in association to AS (AS-AAA group: n = 43) or AR (AR-AAA group: n = 41). Both groups contained 19 patients with TAV. Convex and concave halves of all samples were stained with three different histologic dyes: hematoxylin-eosin (HE) was used as general stain for atherosclerosis, von-Kossa (vKossa) stain and alizarin-red (Ared) stain were used as calcinosis specific dyes. HE stained samples were analyzed using a semi-quantitative score, while calcinosis quantification was carried out by a binary, pixel guided contrast analysis via computer software. Results: In the AR-AAA group, atherosclerosis was two and a half times more often detectable in the concave halves of the tissue samples as in the AS-AAA group (AR-AAA concave: 15 (36%) vs. AS-AAA concave: 6 (13%), p ≤ 0,01). Regarding GMC, tissue samples from AS-AAAs showed a 4,2-4,5% higher mean GMC deposit than their AR-AAA counterparts (p ≤ 0,001). Furthermore, BAV patients within the AS-AAA group showed a 2,1-2,4% higher mean deposit of GMC than their TAV peers (p ≤ 0,002). These finding of higher GMC deposition was consistent for BAV patients contained in the AAA-AR group. Conclusion: AR-AAA are, in comparison with AS-AAA, more prone to develop atherosclerosis. Atherosclerosis will most likely present at the concave curvature of the ascending aorta. AS-AAAs present significant higher mean GMC deposits than AR-AAAs. Combined with a bicuspid morphology of the aortic valve, GMC deposition in AAAs is elevated in comparison to AAAs with TAV morphology. Therefore AS-AAAs with BAV have the highest tendency to develop heavy GMC deposition, compromising the biomechanical structure of the aortic wall.

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<p>Human noroviruses (HuNoVs) are the leading cause of an acute form of non-bacterial gastroenteritis, where strains belonging to genogroup (G) II are dominant. Upon expression with the baculovirus culture system, virus-like particles (VLPs) of HuNoVs are expected to assemble into T = 3 icosahedral capsid particles resembling the structure of the infectious virion particles. However, some strains were found to assemble into either T = 1 or T = 4 capsids, or a combination of two different capsid forms. In this study, we showed that VLPs of the Virginia 1997 387 (VA387) GII.4 outbreak strain assembled into T = 1, T = 3, and T = 4 capsids upon expression in insect cell culture, the first case for a naturally occurring HuNoV strain to assemble into all three capsid states. TEM analysis revealed that T = 1 icosahedral particles were the most abundant in purified samples, which contrasts previous findings where either T = 3 or T = 4 were the most abundant. We resolved the cryo-EM structures of the T = 1 shell (S) domain, T = 3, and T = 4 particles to 2.24, 2.44, and 3.43 Å, respectively, making them the most resolved norovirus (NoV) structures to date. Single particle cryo-EM 3D analysis showed that the protruding (P) domain of T = 1 and T = 4 VLPs are highly dynamic. Additionally, we showed that T = 3 VLPs are resistant while T = 1 and T = 4 VLPs are sensitive to digestion in the presence of trypsin. This suggested that T = 1 and T = 4 capsids are less stable among the VLPs, which is consistent with the highly dynamic P domain inferred from our cryo-EM 3D analysis. During infection, HuNoVs travel through the gastrointestinal (GI) tract where they encounter a broad range of variable conditions that include pH, ionic strength, and host defenses (e.g., proteases). Our analyses suggest that virions are T = 3 particles as they can survive the GI tract upon exiting the host. We determined the first cryo-EM structure of T = 3 VLPs in complex with the known HuNoV host cell receptor, histo-blood group antigen (HBGA), to a resolution of 2.51 Å, demonstrating that NoV VLPs can serve as a platform in the structural characterization of small ligand molecules. Lastly, we identified a histidine residue retained in the S domain of all identified caliciviruses critical in the assembly of capsids. Our structures and their characterization will contribute to the development of therapeutic agents to combat noroviruses. </p>

<p dir="ltr">Generative Image-to-Image Translation (I2IT) involves transforming an input image from one domain to another. Typically, this transformation retains the content in the input image while adjusting the domain-dependent style elements. Generative I2IT finds utility in a wide range of applications, yet its effectiveness hinges on adaptations to the unique characteristics of the data at hand. This dissertation pushes the boundaries of I2IT by applying it to stain-related problems in computational pathology. Particularly, the main contributions span two major applications of stain translation: H&E-to-H&E and H&E-to-IHC, each with its unique requirements and challenges. More specifically, the first contribution addresses the generalization challenge posed by the high variability in H&E stain appearances to any task-specific machine learning models. To this end, the Generative Stain Augmentation Network (G-SAN) is introduced to augment the training images in any downstream task with random and diverse H&E stain appearances. Experimental results demonstrate G-SAN’s ability to enhance model generalization across stain variations in downstream tasks. The second key contribution in this dissertation focuses on H&E-to-IHC stain translation. The major challenge in learning accurate H&E-to-IHC stain translation is the frequent and sometimes severe inconsistencies in the groundtruth H&E-IHC image pairs. To make training more robust to these inconsistencies, a novel contrastive learning based loss, named the Adaptive Supervised PatchNCE (ASP) loss is presented. Experimental results suggest that the proposed ASP-based framework outperforms the state-of-the-art in H&E-to-IHC stain translation by significant margins. Additionally, a new dataset for H&E-to-IHC translation – the Multi-IHC Stain Translation (MIST) dataset, is released to the public, featuring paired images from H&E to four different IHC stains. For future directions of generative I2IT in stain translation problems, a proof-of-concept study of applying the latest diffusion model based I2IT methods to the problem of virtual H&E staining is presented.</p>

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With the evolution of GPU performance, the interest of using AI for all kinds of purposes has risen. Companies today put a great amount of resources to find new ways of using AI to increase the value of their products or automating processes. An area in the wood industry where AI is widely used and studied is in defect detection. In this thesis, the combination of using AI and hyperspectral images is studied and evaluated in the case of segmenting defects in hardwood with a U- Net network structure. The performance is compared to another known method usually used when dealing with high-dimensional data: PLS-DA. This thesis also compares the use of RGB image data in combination with AI, to further analyze the usefulness that the hyperspectral data provide. The results showed signs of improvement when using hyperspectral images com- pared to RGB images when detecting blue stain and red heartwood defects. De- tection of the defects rot and knots did however show no sign of improvements. Due to the annotations being more accurate in the RGB data, the results from the hyperspectral data-fed networks would suggest that blue stain and red heartwood could be of interest regarding further investigation. Computational performance is shown to vary across the different reduction meth- ods, and the results from this thesis provides some insight that might aid in the reasoning regarding how to choose an appropriate reduction method.