En thérapie génique, la stratégie du leurre moléculaire consiste à utiliser un acide nucléique courtcontenant une séquence spécifiquement reconnue par un facteur de transcription cible, ce qui permetson piégeage intracellulaire et conduit à inhiber l’expression des gènes sous sa dépendance.L’efficacité thérapeutique de cette stratégie est notamment liée à la biostabilité de l’acide nucléique età la possibilité de multicibler des facteurs de transcription qui coopèrent dans des dérégulationscellulaires à l’origine de nombreuses pathologies. Nous avons développé une technologie deproduction in vitro de minicercles d’ADN de moins de 250 paires de base pour interagir avec plusieursprotéines, fonctionnalisables chimiquement et résistants aux exonucléases. Un double ciblage dufacteur de transcription NF-κB par un minicercle permet l’inhibition in cellulo d’un système rapporteurde la transcription NF-κB dépendante, en faveur d’une activité leurre moléculaire du minicercle.Le cisplatine est une molécule anticancéreuse dont la cible pharmacologique est l’ADN. Dansplusieurs lignées cellulaires cancéreuses, la baisse d’activité transcriptionnelle de NF-κB a été reliée àune augmentation de la sensibilité des cellules au cisplatine. Nous avons étudié in cellulo si lemécanisme d’inhibition de NF-κB par le cisplatine pouvait dépendre de la platination de son siteconsensus à l’aide d’une application originale de la stratégie leurre moléculaire. Nous montrons queles adduits du cisplatine contrairement à ceux du transplatine (isomère inactif) diminuent lareconnaissance de NF-κB pour son site consensus in vitro et in cellulo.La stratégie leurre moléculaire de multiciblage avec un minicercle d’ADN sera développée au niveaucellulaire pour faire la preuve de concept de cette approche et démontrer son efficacité biologique. / In gene therapy, decoy strategy consists in using short nucleic acid containing a sequence specificallyrecognized by a transcription factor in order to trap it and in turn to inhibit the expression of genesunder its control. The therapeutic efficacy of this strategy is related to the biostability of the nucleicacid and the possibility to target several transcription factors that cooperate to induce cellderegulations responsible in human diseases. We have developed a technology to product in vitroDNA minicircle less than 250 base pairs which can interact with several proteins, chemicallyfunctionalizable and resistant to exonucleases. A dual targeting of the transcription factor NF-κB by aminicircle allows inhibition in cellulo of a NF-κB-dependent transcription reporter system consistentwith a decoy activity induced by the minicircle.Cisplatin is an anticancer drug whose pharmacological target is DNA. In several cancer cell lines, thedecrease of transcriptional activity of NF-κB has been linked to an increase in the sensitivity of cells tocisplatin. We studied in cellulo whether the mechanism of inhibition of NF-κB by cisplatin could dependon the platination of its consensus sequence using a novel application of the decoy strategy. We showthat cisplatin adducts, unlike those of transplatin (inactive isomer), decreases recognition of NF-κB toits consensus sequence in vitro and in cellulo.Decoy strategy with minicircle DNA will be developed to make the proof of concept of this approach atthe cellular level and further to demonstrate its biological effectiveness.

Energy functions are found to be a key of protein structure prediction. In this work, we propose a novel 3-dimensional energy function based on hydrophobic-hydrophilic properties of amino acid where we consider at least three different possible interaction of amino acid in a 3-dimensional sphere categorized as hydrophilic versus hydrophilic, hydrophobic versus hydrophobic and hydrophobic versus hydrophilic. Each of these interactions are governed by a 3-dimensional parameter alpha used to model the interaction and 3-dimensional parameter beta used to model weight of contribution. We use Genetic Algorithm (GA) to optimize the value of alpha, beta and Z-score. We obtain three energy scores libraries from a database of 4332 protein structures obtained from Protein Data Bank (PDB) server. Proposed energy function is found to outperform nearest competitor by 40.9% for the most challenging Rosetta decoy as well as better in terms of the Z-score based on Moulder and Rosetta decoy sets.

Reported in this dissertation are the results of investigations performed at the New Orleans Center for Mass Spectrometry at the University of New Orleans. The projects that are detailed in the coming pages take on a variety of subjects, but a common thread is that each employs matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to solve a problem. Fundamental aspects of MALDI in-plume ionization are implicated in the introduction of a newly developed electron-transfer secondary ionization matrix. The remaining projects are related to the ever expanding field of proteomics. Mass spectrometry was used to investigate the site specificity of a newly developed bilin-lyase enzyme, a new approach was developed to distinguish between A-ring and D-ring attachment of bilins, and F. grandis protein expression pattern was investigated in several tissues. All obtained results were acquired using a MALDI TOF/TOF mass spectrometer. The sensitivity, mass accuracy, mass resolution and the ability to perform collision induced decomposition (CID) experiments were all valuable features that served to raise the quality of data, and thereby improved the detail of inferences to be drawn for the different projects.

We are currently experiencing a rapid development of quantum information, a new branch of science, being an interdisciplinary of quantum physics, information theory, telecommunications, computer science, and many others. This new science branch was born in the middle of the eighties, developed rapidly during the nineties, and in the current decade has brought a technological breakthrough in creating secure quantum key distribution (QKD), quantum secret sharing, and exciting promises in diverse technological fields. Recent QKD experiments have achieved high rate QKD at 200 km distance in optical fiber. Significant QKD results have also been achieved in free-space. Due to the rapid broadband access deployment in many industrialized countries and the standing increasing transmission security treats, the natural development awaiting quantum communications, being a part of quantum information, is its migration into commercial switched telecom networks. Such a migration concerns both multiuser quantum key distribution and multiparty quantum secret sharing that have been the main goal of my PhD studies. They are also the main concern of the thesis. Our research efforts in multiuser QKD has led to a development of the five-user setup for transmissions over switched fiber networks in a star and in a tree configuration. We have achieved longer secure quantum information distances and implemented more nodes than other multi-user QKD experiments. The measurements have shown feasibility of multiuser QKD over switched fiber networks, using standard fiber telecom components. Since circular architecture networks are important parts of both intranets and the Internet, Sagnac QKD has also been a subject of our research efforts. The published experiments in this area have been very few and results were not encouraging, mainly due to the single mode fiber (SMF) birefringence. Our research has led to a development of a computer controlled birefringence compensation in Sagnac that open the door to both classical and quantum Sagnac applications. On the quantum secret sharing side, we have achieved the first quantum secret sharing experiment over telecom fiber in a five-party implementation using the "plug & play" setup and in a four-party implementation using Sagnac configuration. The setup measurements have shown feasibility and scalability of multiparty quantum communication over commercial telecom fiber networks.

The popularity of the internet has made the use of web applications ubiquitous and essential to the daily lives of people, businesses and governments. Web servers and web applications are commonly used to handle tasks and data that can be critical and highly valuable, making them a very attractive target for attackers and a vector for successful attacks that are aimed at the application layer. Existing misuse and anomaly-based detection and prevention techniques fail to cope with the volume and sophistication of new attacks that are continuously appearing, which suggests that there is a need to provide new additional layers of protection. This work aims to design a new layer of defense based on deception that is employed in the context of web application-layer traffic with the purpose of detecting and preventing attacks. The proposed design is composed of five deception strategies: Deceptive Comments, Deceptive Request Parameters, Deceptive Session Cookies, Deceptive Status Codes and Deceptive JavaScript. The strategies were implemented as a software artifact and their performance evaluated in a testing environment using a custom test script, the OWASP ZAP penetration testing tool and two vulnerable web applications. Deceptive Parameter strategy obtained the best security performance results, followed by Deceptive Comments and Deceptive Status Codes. Deceptive Cookies and Deceptive JavaScript got the poorest security performance results since OWASP ZAP was unable to detect and use deceptive elements generated by these strategies. Operational performance results showed that the deception artifact could successfully be implemented and integrated with existing web applications without changing their source code and adding a low operational overhead.