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International audience; Consider a stochastic wireless device-to-device (D2D) caching network with nodes that are harvesting energy from external sources at random times. Each node is equipped with a cache memory, where the node prefetches maximum distance separable (MDS) coded packets of the files from a given library. When a node requests a file from this library, neighbouring nodes are asked to send the relevant missing subfiles over noisy channels. This work presents different selection strategies to determine which neighbouring nodes should transmit which missing subfiles. The strategies can roughly be divided into three categories: sequential strategies where transmission stops when the requesting node has correctly decoded enough subfiles; coordinated strategies where the requesting node is informed about the other nodes' cache contents and centrally decides which node should send which file; and adaptive strategies where the requesting node sequentially decides on which files should be sent in function of the subfiles that it previously decoded correctly. Our numerical simulations show that at moderate energy levels or when there are many file requests, sequential strategies perform significantly worse than coordinated or adaptive strategies. On the other hand, at high energy levels sequential strategies (or even completely decentralized strategies) perform as well or even better. These latter strategies should thus be prefered as they come with less synchronization overhead and delay. The same applies for environments with only few transmission errors (i.e., in high quality channels).

Natural ribonucleoside-5&rsquo, monophosphates are building blocks for nucleic acids which are used for a number of purposes, including food additives. Their analogues, additionally, are used in pharmaceutical applications. Fludarabine-5&acute, monophosphate, for example, is effective in treating hematological malignancies. To date, ribonucleoside-5&rsquo, monophosphates are mainly produced by chemical synthesis, but the inherent drawbacks of this approach have led to the development of enzymatic synthesis routes. In this study, we evaluated the potential of human deoxycytidine kinase (HsdCK) as suitable biocatalyst for the synthesis of natural and modified ribonucleoside-5&rsquo, monophosphates from their corresponding nucleosides. Human dCK was heterologously expressed in E. coli and immobilized onto Nickel-nitrilotriacetic acid (Ni-NTA) superflow. A screening of the substrate spectrum of soluble and immobilized biocatalyst revealed that HsdCK accepts a wide range of natural and modified nucleosides, except for thymidine and uridine derivatives. Upon optimization of the reaction conditions, HsdCK was used for the synthesis of fludarabine-5&acute, monophosphate using increasing substrate concentrations. While the soluble biocatalyst revealed highest product formation with the lowest substrate concentration of 0.3 mM, the product yield increased with increasing substrate concentrations in the presence of the immobilized HsdCK. Hence, the application of immobilized HsdCK is advantageous upon using high substrate concentration which is relevant in industrial applications.

Especially in biomanufacturing, methods to design optimal experiments are a valuable technique to fully exploit the potential of the emerging technical possibilities that are driving experimental miniaturization and parallelization. The general objective is to reduce the experimental effort while maximizing the information content of an experiment, speeding up knowledge gain in R&D. The approach of model-based design of experiments (known as MBDoE) utilizes the information of an underlying mathematical model describing the system of interest. A common method to predict the accuracy of the parameter estimates uses the Fisher information matrix to approximate the 90% confidence intervals of the estimates. However, for highly non-linear models, this method might lead to wrong conclusions. In such cases, Monte Carlo sampling gives a more accurate insight into the parameter's estimate probability distribution and should be exploited to assess the reliability of the approximations made through the Fisher information matrix. We first introduce the model-based optimal experimental design for parameter estimation including parameter identification and validation by means of a simple non-linear Michaelis-Menten kinetic and show why Monte Carlo simulations give a more accurate depiction of the parameter uncertainty. Secondly, we propose a very robust and simple method to find optimal experimental designs using Monte Carlo simulations. Although computational expensive, the method is easy to implement and parallelize. This article focuses on practical examples of bioprocess engineering but is generally applicable in other fields.

Today, there is a real need to strengthen the communication security to anticipate the development of quantum computing and the eventual attacks arising from it. This work explores two complementary techniques that provide confidentiality to data transmitted over wireless networks. In the first part, we focus on lattice-based public-key cryptography, which is one of the most promising techniques for the post-quantum cryptography systems. In particular, we focus on the Goldreich-Goldwasser-Halevi (GGH) cryptosystem, for which we propose a new scheme using GLD lattices. In the second part of this work, we study the security of multi-user cache-aided wiretap broadcast channels (BCs) against an external eavesdropper under two secrecy constraints: individual secrecy constraint and joint secrecy constraint. We compute upper and lower bounds on secure capacity-memory tradeoff considering different cache distributions. To obtain the lower bound, we propose different coding schemes that combine wiretap coding, superposition coding and piggyback coding. We prove that allocation of the cache memory to the weaker receivers is the most beneficial cache distribution scenario., Aujourd’hui, le renforcement de la sécurité des systèmes de communications devient une nécessité, par anticipation du développement des ordinateurs quantiques et des nouvelles attaques qui en découleront. Cette thèse explore deux techniques complémentaires permettant d’assurer la confidentialité des données transmises sur des liens sans-fils. Dans la première partie de ce travail, nous nous intéressons au schéma de cryptographie à clé publique basée sur des réseaux de points, qui représente une des techniques les plus prometteuses pour la cryptographie post-quantique. En particulier, nous considérons le cryptosystème Goldreich-Goldwasser-Halevi (GGH), pour lequel nous proposons un nouveau schéma utilisant les GLD. Dans la seconde partie de ce travail, nous étudions la sécurité des canaux de diffusion multi-utilisateur, ayant accès à des mémoires de caches, en présence d'un espion. Nous considérons deux contraintes de sécurité: la contrainte de sécurité individuelle et la contrainte de sécurité jointe. Nous dérivons des bornes supérieure et inférieure pour le compromis sécurisé capacité-mémoire en considérant différentes distributions de cache. Afin d'obtenir la borne inférieure, nous proposons plusieurs schémas de codage combinant codage wiretap, codage basé sur la superposition et codage piggyback. Nous prouvons qu'il est plus avantageux d'allouer la mémoire de cache aux récepteurs les plus faibles.

Today, there is a real need to strengthen the communication security to anticipate the development of quantum computing and the eventual attacks arising from it. This work explores two complementary techniques that provide confidentiality to data transmitted over wireless networks. In the first part, we focus on lattice-based public-key cryptography, which is one of the most promising techniques for the post-quantum cryptography systems. In particular, we focus on the Goldreich-Goldwasser-Halevi (GGH) cryptosystem, for which we propose a new scheme using GLD lattices. In the second part of this work, we study the security of multi-user cache-aided wiretap broadcast channels (BCs) against an external eavesdropper under two secrecy constraints: individual secrecy constraint and joint secrecy constraint. We compute upper and lower bounds on secure capacity-memory tradeoff considering different cache distributions. To obtain the lower bound, we propose different coding schemes that combine wiretap coding, superposition coding and piggyback coding. We prove that allocation of the cache memory to the weaker receivers is the most beneficial cache distribution scenario.; Aujourd’hui, le renforcement de la sécurité des systèmes de communications devient une nécessité, par anticipation du développement des ordinateurs quantiques et des nouvelles attaques qui en découleront. Cette thèse explore deux techniques complémentaires permettant d’assurer la confidentialité des données transmises sur des liens sans-fils. Dans la première partie de ce travail, nous nous intéressons au schéma de cryptographie à clé publique basée sur des réseaux de points, qui représente une des techniques les plus prometteuses pour la cryptographie post-quantique. En particulier, nous considérons le cryptosystème Goldreich-Goldwasser-Halevi (GGH), pour lequel nous proposons un nouveau schéma utilisant les GLD. Dans la seconde partie de ce travail, nous étudions la sécurité des canaux de diffusion multi-utilisateur, ayant accès à des mémoires de caches, en présence d'un espion. Nous considérons deux contraintes de sécurité: la contrainte de sécurité individuelle et la contrainte de sécurité jointe. Nous dérivons des bornes supérieure et inférieure pour le compromis sécurisé capacité-mémoire en considérant différentes distributions de cache. Afin d'obtenir la borne inférieure, nous proposons plusieurs schémas de codage combinant codage wiretap, codage basé sur la superposition et codage piggyback. Nous prouvons qu'il est plus avantageux d'allouer la mémoire de cache aux récepteurs les plus faibles.

Contraction of muscle reflects its physiological state. Methods to quantify contraction are often complex, expensive and tailored to specific models or recording conditions, or require specialist knowledge for data extraction. Here we describe an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes and pharmacological responses. MUSCLEMOTION allowed rapid and easy measurement of contractility in (i) single cardiomyocytes from primary adult heart and human pluripotent stem cells, (ii) multicellular 2D-cardiomyocyte cultures, 3D engineered heart tissues and cardiac organoids/microtissues in vitro and (iii) intact hearts of zebrafish and humans in vivo. Good correlation was found with conventional measures of contraction in each system. Thus, using a single method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell- and animal models and human echocardiograms.

Einleitung: Zöliakie ist eine systemische, durch Gluten ausgelöste Immunerkrankung, die sich mit einem Malabsorptionssyndrom, aber auch mit vielfältigen Symptomen in nahezu allen Organen manifestiert und mit einer Prävalenz von etwa 1 % in der kaukasischen Bevölkerung auftritt. MICA, ein atypisches MHC-Klasse-I-Molekül, spielt eine tragende Rolle in der Pathogenese der Zöliakie, indem es als Ligand für intraepitheliale Lymphozyten, die bei der Erkrankung vermehrt in das Dünndarmepithel einwandern, zur Zelllyse und damit zu der zöliakietypischen Zottenatrophie beiträgt. Einige MICA-Allele, zusammengefasst als MICA-A.5.1-Allele, tragen eine Guanininsertion, die in einer Trunkierung der Transmembrandomäne resultiert und in MDCK-Zellen zu einer Sortierung in die apikale anstatt in die basolaterale Membran führt. Methoden: Zöliakiepatienten und Kontrollen wurden mittels DNA-Sequenzierung auf das Vorliegen der MICA-A5.1-Allele untersucht. Anhand von Patienteninterviews wurde die klinische Präsentation der Zöliakie analysiert und mit dem MICA-Genotyp korreliert. Die Lokalisation von MICA wurde in Duodenalbiopsien der sequenzierten Patienten spezifisch mit Immunhistochemie dargestellt. Mit Immunfluoreszenzfärbungen an Biopsien und Caco-2-Zellen wurde die subzelluläre Lokalisation von MICA und MICB, einem nahezu sequenzhomologen Protein, untersucht. In Western-Blot-Analysen wurden die MICA/B-Proteinlevel von Patienten mit Zöliakie und refraktärer Zöliakie sowie Kontrollen verglichen. Ergebnisse: Bei Zöliakiepatienten liegt das Allel A5.1 signifikant häufiger vor als bei Kontrollen, immunhistochemisch zeigte sich bei A5.1-positiven Patienten eine Sortierung von MICA in die apikale Membran. Eine Auswirkung auf die klinische Präsentation der Zöliakie bestätigte sich nicht. In Duodenalbiopsien fand sich bei allen Individuen ein apikales Immunfluoreszenzsignal von MICA und MICB unabhängig vom MICA-Genotyp, das mit alkalischer Phosphatase, rab3b-positiven Vesikeln und IgA enthaltenden Strukturen kolokalisiert. In MICA-Allel-A5.1-negativen Caco-2-Zellen zeigte sich ebenfalls eine apikale MICA/B-Fraktion, die mit alkalischer Phosphatase, aber auch mit Lipid rafts kolokalisiert. Die intrazellulär vorliegende MICA/B-Fraktion konnte keinem untersuchten Zellkompartiment zugeordnet werden. In Western-Blot-Analysen bestätigte sich eine gesteigerte Expression von MICA/B nur in Patienten mit refraktärer Zöliakie gegenüber Kontrollen. Unabhängig vom Genotyp zeigte sich eine kleinere, 38 anstatt 43 kDa große MICA/B-Fraktion. Schlussfolgerung: Die MICA-A5.1-Allele scheinen bei Kontrollen und Patienten eine Sortierung von MICA in die apikale Membran ohne Auswirkung auf die klinische Präsentation der Zöliakie zu bewirken. Die jedoch in allen Gruppen beobachtete apikale Lokalisation von MICA und MICB und die Kolokalisation mit sekretorischen Strukturen und Lipid rafts deuten auf eine zusätzliche Funktion von MIC-Proteinen neben der Interaktion mit den intraepithelialen Lymphozyten hin. Die im Western-Blot beobachtete, vom Genotyp unabhängige 38 kDa große MICA/B-Fraktion ist möglicherweise ein Hinweis auf eine posttranslationale Prozessierung der Proteine. Um diese Hypothesen zu untersuchen, wären als Gegenstand weiterer Studien funktionelle Analysen von MICA und MICB vonnöten, um z.B. eine luminale Sekretion näher beleuchten zu können., Introduction: Celiac disease is a systemic immune disease induced by gluten which causes a malabsorption syndrome, but also manifests with many symptoms in almost all organ systems. The prevalence is about 1 % in the Caucasian population. MICA, an atypical MHC class I molecule, plays an important role in disease pathogenesis by acting as a ligand for intraepithelial lymphocytes, which in celiac disease infiltrate small intestine epithelium leading to cell lysis and thereby causing villous atrophy typical of the disease. There are four MICA alleles, collectively, MICA A5.1 alleles, carrying a guanine insertion leading to a truncation of the protein within the transmembrane domain. In MDCK cell lines this results in sorting of MICA to the apical instead of the basolateral cellular membrane. Methods: By DNA sequencing, celiac disease patients and healthy controls were tested for the presence of MICA A5.1 alleles. Patients were interviewed to analyze the disease’s clinical presentation in each individual; the results were correlated with the respected MICA genotype. MICA localization in duodenal biopsies was shown by immunohistochemistry staining. Subcellular localization of MICA and MICB, a protein almost homologue to MICA in structure and sequence, was analyzed in human duodenal biopsies and Caco-2 cell lines by immunofluorescence staining. Western blot analysis was performed in celiac disease and refractory celiac disease patients and in controls to compare MICA/B protein levels. Results: MICA alleles A5.1 are significantly higher in patients with celiac disease than in controls. Immunohistochemistry showed an apical sorting of MICA in patients carrying MICA A5.1. There was no indication that apical MIC-A does affect clinical presentation of the disease. An apical immunofluorescence staining of MICA and MICB together was found in all human duodenal biopsy samples, in both MICA A5.1 positive and negative patients, and co-localized with alkaline phosphatase, rab3b-positive vesicles and IgA-containing structures. Furthermore, MICA A5.1 negative Caco-2-cells showed this apical staining signal as well; in this case immunofluorescence revealed a co- localization of MICA/B not only with alkaline phosphatase, but with lipid rafts. The cell compartment holding intracellular MICA/B could not be identified. Western blot analysis showed higher expression levels of MICA/B in refractory celiac disease patients compared with controls only. An amount of MICA/B with a molecular weight of 38 kDa instead of 42 kDa was found in both MICA A5.1 positive and negative samples, regardless of MICA genotype. Conclusion: MICA A5.1 alleles appear to cause MICA shifting in the apical membrane without affecting clinical presentation in celiac disease. Apical localization of MICA and MICB and their co-localization with secretory structures and lipid rafts observed in all samples indicate an additional function of MICA/B other than acting as a ligand only. The amount of 38 kDa- MICA/B might suggest posttranslational modification of MICA/B proteins. In order to test these hypotheses, further functional studies, for example luminal secretion of MICA/B, have to be performed.