Editing Middle High German texts today is led much more by the ventilation of practical necessities than by theoretical consideration. Especially lacking discussions of a basic concept of ›text‹ raises the risk of developing blind spots. The article will try to identify these blind spots as places where the traditional strategy of editing texts on the basis of the faulty-replication model persists. This will be illustrated by new editions of the ›Wunderer‹ and the ›Rosengarten‹. Furthermore, the article evolves a semiotic model of the philological praxis of editing Middle High German heroic epics. / Die Redaktion mittelhochdeutscher Texte wird heute viel mehr von der Lüftung praktischer Notwendigkeiten als von theoretischen Überlegungen geleitet. Gerade die fehlende Diskussion über einen grundlegenden Begriff von 'Text' birgt die Gefahr, dass sich blinde Flecken entwickeln. Der Artikel versucht, diese blinden Flecken als Orte zu identifizieren, an denen die traditionelle Strategie der Textredaktion auf der Grundlage des Fehlerreproduktionsmodells fortbesteht. Dies wird durch Neuauflagen des 'Wunderers' und des 'Rosengartens' illustriert. Darüber hinaus entwickelt der Artikel ein semiotisches Modell der philologischen Praxis der Edition mittelhochdeutscher Heldenepen.

Finding economical and environmentally friendly processes to recover heavy metals (HMs) from spent batteries is a research priority to move toward sustainability. Adsorption seems an acceptable procedure to replace the current separation/purification stage of hydrometallurgical techniques. Chitosan is an efficient adsorbent for HM uptake from aqueous solutions. Nevertheless, in practice, chitosan modification is unavoidable to improve its physicochemical properties. Sodium tripolyphosphate is an environmentally benign crosslinker that can be used for chitosan modification. In addition, ion-imprinting technique could potentially enhance the adsorption efficiency and selectivity of crosslinked chitosan. Considering the above, the primary purposes of this research were: investigating the adsorption efficiency of chitosan for heavy metals uptake from synthetic solutions; modifying chitosan by crosslinking alone and combined with ion-imprinting techniques to improve the physicochemical properties as well as adsorption capacity and selectivity of chitosan; evaluating and comparing the adsorption efficiency of modified chitosan beads for the adsorption of Cd(II), Ni(II) and Co(II) in single and multicomponent batch adsorption systems. Chitosan and sodium tripolyphosphate crosslinked chitosan beads were prepared to remove Cd(II) from aqueous solution in the first phase. FTIR and XRD of the synthesized beads showed partial consumption of chitosan amine groups and a decrease in crystallinity of chitosan structure over crosslinking reaction. The isotherm and thermodynamic studies showed that Langmuir isotherm was the best fit to the experimental data of Cd(II) adsorption on crosslinked chitosan and all the adsorption reactions were endothermic and spontaneous. A reduced quadratic model, constructed by the Response Surface Methodology (RSM), indicated that the Cd(II) adsorption uptake of 99.87 (mg/g) was achieved at 55 °C and 2.92 % (w/v) crosslinking degree. Then, chitosan and crosslinked chitosan beads by sodium tripolyphosphate were used for Ni(II) adsorption from aqueous media in the second phase. The BET characterization showed that increasing the crosslinking degree reduced the chitosan beads' surface area and their total pore volume. The Langmuir model described the experimental results best and showed that the maximum adsorption capacity of chitosan (80.00 mg/g) decreased after crosslinking (52.36 mg/g). In addition, a reduced quadratic model with a correlation coefficient of 0.96 was established to correlate the adsorption uptake of Ni(II) with pH and crosslinking degree. In the third phase, the adsorption of Ni(II) and Cd(II) ions from single and binary metal ions solutions onto chitosan and crosslinked chitosan beads was studied. The extended Freundlich model fitted the adsorption equilibrium data in the binary system, implying the existence of preference in the order of Ni(II) > Cd(II). Desorption studies with a mixture of NaCl and H2SO4 were also conducted during this phase, demonstrating a desorption efficiency of greater than 85 %. In the fourth phase, the removal of cadmium from aqueous solution was examined using a novel Cd(II)-imprinted crosslinked chitosan. SEM, FTIR, TGA, and BET characterizations revealed that the ion-imprinted chitosan beads had better physicochemical properties than chitosan beads and superior potential adsorption properties than non-imprinted crosslinked chitosan beads. The isotherm and thermodynamic studies revealed that the Langmuir isotherm fitted the Cd(II) experimental data the best, and the adsorption reactions were spontaneous and endothermic. The kinetics data were also best fitted by the pseudo-second-order equation. Finally, the ion-imprinted crosslinked chitosan beads were employed for the selective adsorption of Cd(II) in a competitive adsorption system of Cd(II)-Ni(II)-Co(II) in phase five. The characterization of the prepared adsorbents was performed using XRD and BET, showing a higher surface area of ion-imprinted crosslinked chitosan than non-imprinted crosslinked chitosan beads. The Extended Langmuir model fitted the experimental results obtained from the multi-component system, indicating that ion-imprinted crosslinked chitosan had a higher total metal uptake with better selectivity toward Cd(II) uptake compared to non-imprinted crosslinked chitosan. Studying the adsorption mechanism in a ternary system showed that the adsorption was governed by chemical binding and ion exchange mechanisms in the ternary system. In conclusion, crosslinking by sodium tripolyphosphate improved chitosan physiochemical properties; however, it resulted in a decrease in HM adsorption uptake. The RSM was used to assess the effect of pH, temperature, and crosslinking degree and optimize the adsorption uptake of chitosan. Also, ion-imprinting was effective in enhancing the adsorption capacity and selectivity of crosslinked chitosan for the ion used as a template (Cd(II)) in preparing ion-imprinted crosslinked chitosan.

The following work demonstrates that paternal diet controls medically important metabolic phenotypes in offspring. We observe transmission of dietary information to the zygote via sperm, and this information evades reprogramming that typically occurs after fertilization. Cytosine methylation is implicated as a major contributor to meiotic epigenetic inheritance in several transgenerational phenomena. Our extensive characterization of the sperm methylome reveals that diet does not significantly affect methylation patterns. However, we find that extensive epivariability in the sperm epigenome makes important contributions to offspring variation. Importantly, coordinate cytosine methylation and copy number changes over the ribosomal DNA locus contributes to variation in offspring metabolism. Thus, rDNA variability acts independently of postadolescent paternal diet to influence offspring metabolism. Therefore, at least two mechanisms exist for epigenetically controlling offspring metabolism: stochastic epivariation and diet acting by an unknown mechanism to further modulate metabolism. This work argues that an offspring's phenotype can no longer be viewed solely as the result of genetic interactions with the developmental environment - the additional influences of paternal environment and inherited epigenetic variability must also be considered. These findings reveal novel contributions to metabolism that could revolutionize how we think about the risk factors for human health and disease.

Au cours du développement précoce de l'embryon, une importante vague de reprogrammation épigénétique efface et rétablit les profils de méthylation d’ADN (metADN) à travers le génome. Cependant, des régions spécifiques telles que les gènes à empreinte doivent échapper à cette vague de reprogrammation et maintenir leurs profils de metADN précis par l’activité constante de l’enzyme DNMT1 (ADN méthyltransférase 1) pour assurer le bon développement embryonnaire. En utilisant un modèle de cellules souches embryonnaires (mES) de souris avec une répression inductible de Dnmt1 (Dnmt1tet/tet), nous avons précédemment montré que la perte temporaire de Dnmt1 déclenche la perte permanente des profils de metADN sur les régions à empreinte et régions similaires, ainsi que sur d'autres régions du génome. Nous ne comprenons toujours pas pourquoi certaines séquences génomiques sont incapables de rétablir leurs profils de metADN normaux après la ré-expression de Dnmt1, et comment d'autres marques épigénétiques (e.g. les modifications des histones) sont altérées. Notre hypothèse est qu’un réarrangement erroné des marques d’histones aux régions promotrices, suivant une perte temporaire du maintien de la méthylation d’ADN par DNMT1, empêchera l’expression normale dans les cellules souches embryonnaires de souris. Pour ce faire, nous avons collecté des cellules mES Dnmt1tet/tet avant l'inactivation de Dnmt1, après l'inactivation de Dnmt1, puis après la réactivation complète de l'expression de Dnmt1. Nous avons ensuite utilisé la technique ChIP-Seq pour les marques d'histones (H3K4me3, H3K27me3, H3K27ac, H3K9me3, H3K4me1), celle de RRBS pour la méthylation de l'ADN et la technique de RNA-Seq pour l'expression des gènes. En définissant une liste de 18 166 promoteurs uniques, nous les avons classés en quatre catégories (Actif, Bivalent, Déplété et Réprimé). Nous montrons que l'inactivation de Dnmt1 mène à une dérégulation drastique des marques d'histones à travers les types de promoteurs. Cependant, lors de la réactivation de Dnmt1, la plupart de ces défauts ont été corrigés. Pourtant, dans l’ensemble des catégories, nous observons des promoteurs avec des dysrégulations persistantes des marques d'histones ainsi qu'un nombre significatif de gènes avec une expression différentielle. Dans l'ensemble, nos résultats montrent qu'une absence temporaire de DNMT1 a un impact plus important sur la conservation des profils des marques d'histones et l'expression des gènes que sur le maintien des profils de metADN sur les régions promotrices, dans les cellules souches embryonnaires de souris. Cela suggère que l'absence temporaire de maintien de la méthylation d’ADN déclenche une série d'événements qui conduisent à des dérégulations permanentes de marques d'histones aux promoteurs, lesquelles ne sont pas directement associés aux altérations sous-jacentes de la méthylation d’ADN dans les régions promotrices. / During early embryo development, a major epigenetic reprogramming wave erases and re-establishes DNA methylation (DNAmet) profiles across the genome. However, specific regions such as imprinting loci must escape this reprogramming wave and maintain their precise DNAmet profiles by constant DNMT1 (DNA methyltransferase 1) activity to ensure the proper development. Using a mouse embryonic stem (mES) cell model with inducible Dnmt1 repression (Dnmt1tet/tet), we previously showed that the temporary loss of Dnmt1 triggers the permanent loss of DNAmet profiles on imprinted and imprinted-like regions, as well as on other regions across the genome. We still do not understand why particular genomic sequences are unable to re-establish their normal DNAmet profiles following Dnmt1 re-expression, and how other epigenetic marks (e.g., histone modifications) are altered. Our hypothesis is that an erroneous rearrangement of histone marks on promoter regions following a temporary lack of DNAmet maintenance by DNMT1 will prevent proper gene expression in mouse embryonic stem cells. To test this, we collected mESDnmt1tet/tet cells prior to Dnmt1 inactivation, after Dnmt1 inactivation, and following complete reactivation of Dnmt1 expression. We then performed ChIP-Seq for histone marks (H3K4me3, H3K27me3, H3K27ac, H3K9me3, H3K4me1), RRBS for DNA methylation and RNA-Seq for gene expression. By defining a list of 18 166 unique promoters we categorized them in four categories (Active, Bivalent, Depleted and Repressed). We show that inactivation of Dnmt1 lead to drastic dysregulation of histone marks across types of promoters. However, upon reactivation of Dnmt1, most of these defects were rescued. Still, across categories, we observe promoters with persistent histone mark dysregulations as well as a significant number of associated genes with differential expression. Overall, our results show that a temporary lack of DNMT1 has a greater impact on the conservation of histone mark profiles and gene expression than it has on the maintenance of DNAmet profiles on promoter regions in mouse embryonic stem cells. This suggests that the temporary lack of methylation maintenance triggers a series of events that leads to the permanent dysregulation of histone marks in promoter regions, which are not directly associated with underlying DNA methylation alterations in the promoter regions.

My diploma work is concerned with the themes of outdoor preschools and pre-school education. It searches for and is stemming from the similar subjects in foreign countries and within the Czech Republic. It shows what the benefits of children being outside are. It also searches and points out liabilities which are necessery to be taken into account. The work presents the used resources, which can lead to the foundation of the other outdoor preschools and their maintanence. The empirical study is managed as an action research. The first part of the practical section shows experiences of the outdoor preschools in general and it presents interviews with their pedagogues. The second part of the practical section deals with the opinion of experts and the non-professional community. Moving on, one then investigates the ideal level of achievement in separate competences in an ordinary preschool, and outdoor preschools. Further more, the next section is targeted at the expert's expectations and apprehensions about children staying at an outdoor preschool, taking into account their views in relation to outdoor preschools. Focus groups are being used to question the experts. The important part of the work is to analyse the legal enactments in relation to outdoor preschools motherly school.

La lipase B de Candida antarctica (CALB) est un enzyme présentant des propriétés énantiosélectives très intéressantes pour l’obtention de molécules énantio pures par dédoublement cinétique de mélanges racémiques,molécules utilisées comme synthons dans l’industrie pharmaceutique. En effet, le principe actif de nombreux médicaments est efficace sous une forme énantio pure, l’autre forme chirale pouvant se révéler délétère pour l’organisme.Les travaux de la thèse s’intéressent à mieux comprendre l’origine de l’énantiosélectivité de la lipase B de Candida antarctica, en particulier pour la résolution d’alcools secondaires par des réactions de transestérification.Nous utilisons pour la première fois la méthode de la perturbation de l’énergie libre pour estimer la différence d’énergie libre entre les intermédiaires tétraédriques obtenus avec les formes R et S d’alcools énantiomères pour une série d’alcools secondaires, dans le but de prédire in silico l’énantiosélectivité de la CALB. Les paramètres cinétiques apparents d’une réaction avec deux alcools substrats énantiopurs sont expérimentalement déterminés et permettent de définir la contribution respective du Km et du kcat de chaque énantiomère pour la définition de l’énantiosélectivité. L’étude expérimentale de l’effet d’empreinte par des molécules co-substrats est réalisée,ainsi qu’une étude par modélisation moléculaire de l’effet d’empreinte par le premier ester substrat de la réaction qui pourrait modifier la conformation du site actif de la CALB. La troisième partie porte sur l’étude de la CALB et de trois variants (T42V, S47A et T42V/S47A) chez lesquels les acides aminés dans la poche stéréospécifiques ont mutés. T42V et S47A permettent d’obtenir une augmentation de l’énantiosélectivité. L’étude propose une étude détaillée de la conformation du site actif à partir de simulations de trajectoires de dynamique moléculaire / The lipase B from Candida antarctica is an enzyme displaying enantioselective properties which are interesting to obtain enantio pure compounds by kinetic resolution of racemic mixtures, which are used as pharmaceutical intermediates and fine chemicals. Indeed, for most of the drugs, only one of the two chiral formsis efficient as bioactive compound, whereas the other chiral form may display deleterious effects. Present work concerns the understanding of the origin of Candida antarctica lipase B enantioselectivity, and more especially in case of the resolution of secondary alcohols by transesterification. We used, for the first time, the free energy perturbation method to evaluate the free energy difference between tetrahedral intermediates with R and S alcohol enantiomers for a series of secondary alcohols in order to predict in silico enantiomeric ratio of CALB-catalyzed reactions. The apparent kinetic parameters were experimentally determined for two enantio pure substrates and allow to evalute the relative contribution of both Km and kcat for R and S enantiomers in the enantiomeric ratio of CALB-catalyzed reactions. Experimental study of imprinting effect hypothesis by co-substrate molecules was done. Molecular modeling studies of imprinting effect hypothesis were performed, in which the first substrate ester of the reaction could mould the active site. At least, the third part of this thesis concerns the study of wild-type CALB and three different variants (T42V and S47A which allow to increase enantioselectivity and T42/S47A) of CALB by molecular modeling. A detailed study of the conformation of the stereo specificity pocket in the active site is presented, based on molecular dynamics simulations.

La nutrition périnatale conditionne durablement les fonctions physiologiques, avec des conséquences sur la susceptibilité à développer des maladies métaboliques à l’âge adulte. Le microbiote représente un des acteurs de cette empreinte nutritionnelle. L’objectif est de déterminer chez le porc l’impact d’une supplémentation périnatale en fructo-oligosaccharides à courte chaîne (scFOS) sur le développement des fonctions immunitaires et endocrines intestinales et les conséquences sur la santé métabolique de l’adulte en situation de déséquilibre nutritionnel.La supplémentation maternelle en scFOS, en modifiant le microbiote de la mère et de la descendance et la qualité du lait, accélère la maturation du système immunitaire intestinal des porcelets allaités.La fenêtre d’exposition (maternelle vs post-sevrage) conditionne la nature des modifications immunes induites par les scFOS. La supplémentation périnatale en scFOS modifie la réponse métabolique de l’adulte à un régime déséquilibré en stimulant la fonction endocrine intestinale et la sensibilité du pancréas au glucose, en réduisant les risques d’inflammation, et en modifiant l’homéostasie métabolique, associé à des modulations du microbiote.En résumé, la consommation périnatale de prébiotiques programme le phénotype métabolique et immunitaire de l’adulte via des modulations persistantes du microbiote. L'approche intégrée des données a permis d’identifier des acteurs moléculaires impliqués dans l’adaptation différentielle des individus à un régime déséquilibré en fonction de leur alimentation périnatale. / Perinatal scFOS supplementation modifies metabolic response to an unbalanced diet in adults by stimulating intestinal endocrine function and pancreas sensitivity to glucose, by reducing risks of inflammation, and in fine by changing metabolic homeostasis in association with modifications of microbiota.In summary, prebiotic consumption during perinatal life programs the immune and metabolic phenotype of adults through persistent modulations of intestinal microbiota. The integrated approach of data enables us to identify molecular actors involved in the differential adaptation of individuals to an unbalanced diet according to their perinatal nutrition.

<p>Metamaterials are artificially structured materials which attain their unconventional macroscopic properties from their cellular configuration rather than their constituent chemical composition. The judicious design of this cellular structure opens the possibility to program and control the optical, mechanical, acoustic, or thermal responses of metamaterials. This Ph.D. dissertation focuses on scalable design and manufacturing strategies for optical and mechanical metamaterials.<br> <br> </p> <p>The fabrication of optical metamaterials still relies heavily on low-throughput process such as electron beam lithography, which is a serial technique. Thus, there is a growing need for the development of high-throughput, parallel processes to make the fabrication of optical metamaterials more accessible and cost-effective. The first part of this dissertation presents a scalable manufacturing method, termed “roll-to-roll laser induced superplasticity” (R2RLIS), for the production of flexible optical metamaterials, specifically metallic near-perfect absorbers. R2RLIS enables the rapid and inexpensive fabrication of ultra-smooth metallic nanostructures over large areas using conventional CO₂ engravers or inexpensive diode lasers. Using low-cost metal/epoxy nanomolds, the minimum feature size obtained by R2RLIS was <40 nm, facilitating the rapid fabrication of flexible near-perfect absorbers at visible frequencies with the capability to wrap around non-planar surfaces.</p> <p> </p> <p>The existing approaches for designing mechanical metamaterials are mostly <i>ad hoc</i>, and rely heavily on intuition and trial-and-error. A rational and systematic approach to create functional and programmable mechanical metamaterials is therefore desirable to unlock the vast design space of mechanical properties. The second part of this dissertation introduces a systematic, algorithmic design strategy based on Voronoi tessellation to create architected soft machines (ASMs) and twisting mechanical metamaterials (TMMs) with programmable motion and properties. ASMs are a new class of soft machines that benefit from their 3D-architected structure to expand the range of mechanical properties and behaviors achievable by 3D printed soft robots. On tendon-based actuation, ASMs deform according to the topologically encoded buckling of their structure to produce a wide range of motions such as contraction, twisting, bending, and cyclic motion. TMMs are a new class of chiral mechanical metamaterials which exhibit compression-twist coupling, a property absent in isotropic materials. This property manifests macroscopically and is independent of the flexible material chosen to fabricate the TMM. The nature of this compression-twist coupling can be programmed by simply tuning two design parameters, giving access to distinct twisting regimes and tunable onset of auxetic (negative Poisson’s ratio) behavior. Taking a metamaterial approach toward the design of soft machines substantially increases their number of degrees of freedom in deformation, thus blurring the boundary between materials and machines.</p>