Pathogens such as <i>Listeria</i>, <i>Shigella</i>, <i>Brucella</i>, <i>Salmonella</i>, <i>Mycobacterium tuberculosis</i> and <i>methicillin-resistant Staphylococcus aureus</i> (MRSA) can traverse into mammalian cells, such as phagocytic macrophages. Once inside, these bacteria can survive and reproduce, causing chronic infections. It is of utmost importance to develop novel antibiotics with broad spectrum activity to control these deadly bacteria. Broad spectrum activity will allow for targeting of pathogens with different structures and cell membrane components.<div>This work focuses on the synthesis of a dual antibiotic agent, composed of a cationic amphiphilic polyproline helix (CAPH) possessing cell penetrating and nonmembrane lytic antimicrobial capabilities (P14LRR), and a derivative of the polymyxin B (PMX) antibacterial peptide. This dual antibiotic conjugate was created to be a tool to potentially clear intracellular pathogenic bacteria. Overall, the reduction of the disulfide bond linking the two antibiotics within the reducing environment of cells would release the individual antimicrobial agents, and could have improved cell membrane penetration and intracellular synergistic activity. Herein, the synthesis of the dual antibiotic agent, P14LRR-PMX, is discussed. </div>

Penetrating brain injury resulting from nail-gun use is a well-characterized entity, one that is increasing in frequency as nail guns become more powerful and more readily available to the public. We present a case and offer management strategies for a 50-year-old male with two intracranial penetrating nail gun injuries. Nail gun brain injuries are commonly intentionally self-inflicted. Suicide should be considered when straight nails cause wounds to the chest, head, or abdomen. The primary preoperative concern is formation of a traumatic pseudoaneurism, which prompts both preoperative and follow-up cerebral angiography. Surgery for combined intracranial and extracranial injury may require the collaborative expertise of colleagues from the fields of ophthalmology, otolaryngology, and oral maxillofacial surgery. A rational management strategy should permit these patients to be discharged with no additional injury.

Background: Cerebrovascular injury (CVI) is a potentially devastating complication of gunshot wounds to the head (GSWH), with yet unclear incidence and prognostic implications. Few studies have also attempted to define CVI risk factors and their role in patient outcomes. We aimed to describe 10 years of CVI from GSWH and characterize these injury patterns. Methods: Single-institution data from 2009 to 2019 were queried to identify patients presenting with dural-penetrating GSWH. Patient records were reviewed for GSWH characteristics, CVI patterns, management, and follow-up. Results: Overall, 63 of 297 patients with GSWH underwent computed tomography angiography (CTA) with 44.4% showing CVI. The middle cerebral artery (22.2%), dural venous sinuses (15.9%), and internal carotid artery (14.3%) were most frequently injured. Arterial occlusion was the most prominent injury type (22.2%) followed by sinus thrombosis (15.9%). One fifth of patients underwent delayed repeat CTA, with 20.1% showing new/previously unrecognized CVI. Bihemispheric bullet tracts were associated with CVI occurrence (P = 0.001) and mortality (P = 0.034). Dissection injuries (P = 0.013), injuries to the vertebrobasilar system (P = 0.036), or the presence of ≥2 concurrent CVIs (P = 0.024) were associated with increased risk of mortality. Of patients with CVI on initial CTA, 30% died within the first 24 hours. Conclusions: CVI was found in 44.4% of patients who underwent CTA. Dissection and vertebrobasilar injuries are associated with the highest mortality. CTA should be considered in any potentially survivable GSWH. Longitudinal study with consistent CTA use is necessary to determine the true prevalence of CVI and optimize the use of imaging modalities.

The ability of cell-penetrating peptides to cross plasma membranes has been explored for various applications, including the delivery of bioactive molecules to inhibit disease-causing cellular processes. The uptake mechanisms by which cell-penetrating peptides enter cells depend on the conditions, such as the cell line the concentration and the temperature. To be used as therapeutics, each novel cell-penetrating peptide needs to be fully characterized, including their physicochemical properties, their biological activity and their uptake mechanism. Our group has developed a series of highly performing, non-toxic cell-penetrating peptides, all derived from the original sequence of transportan 10. These analogs are called PepFects and NickFects and they are now a diverse family of N-terminally stearylated peptides. These peptides are known to form noncovalent, nano-sized complexes with diverse oligonucleotide cargoes. One bottleneck that limits the use of this technology for gene therapy applications is the efficient release of the internalized complexes from endosomal vesicles. The general purpose of this thesis is to reveal the mechanisms by which our in house designed peptides enter cells and allow the successful transport of biofunctional oligonucleotide cargo. To reach this goal, we used both biophysical and cell biology methods. We used spectroscopy methods, including fluorescence, circular dichroism and dynamic light scattering to reveal the physicochemical properties. Using confocal and transmission electron microscopy we observed and tracked the internalization and intracellular trafficking. Additionally we tested the biological activity in vitro and the cellular toxicity of the delivery systems. We conclude that the transport vectors involved in this study are efficient at perturbing lipid membranes, which correlates with their remarkable capacity to transport oligonucleotides into cells. The improved and distinct capacities to escape from endosomal vesicles can be the result of their different structures and hydrophobicity. These findings extend the knowledge of the variables that condition intracellular Cell-penetrating peptide mediated transport of nucleic acids, which ultimately translates into a small step towards successful non-viral gene therapy.

L’objectif de la thèse est d’améliorer les différents traitements et de proposer une visualisation claire et intuitive à l’opérateur des données en sortie d’un géoradar (radargramme) afin de pouvoir localiser de manière précise les réseaux de canalisations enfouis. Notamment, nous souhaitons mettre en évidence les hyperboles présentes dans les radargrammes car celles-ci sont caractéristiques de la présence d'une canalisation. Dans un premier temps nous nous sommes intéressés à la suppression de l’information inutile (clutter) pouvant gêner la détection des hyperboles. Nous avons ainsi proposé une méthode de filtrage du clutter et du bruit des radargrammes. Ensuite, nous avons travaillé sur l’élaboration d’une méthode permettant de détecter automatiquement les hyperboles dans un radargramme ainsi qu’une estimation de sa fonction mathématique dans des conditions quasi-temps réel. Et enfin nous avons également proposé une méthode de séparation de source permettant de distinguer le clutter et le signal utile du radargramme tout en ayant un impact minimal sur les hyperboles. Ces derniers travaux ouvrent d’autres possibilités pour le filtrage, le rehaussement ou la détection automatique d’hyperboles. / The thesis objective is to improve the different processing in order to make the data acquired by ground penetrating radar (B-scan) more understandable for the operators. Consequently, it will facilitate the pipe localisation. More particularly, we wish to highlight the hyperbolas in the B-scan because they point out the presence of a pipe. First of all, we are interested in removing all the useless information which might hide the hyperbolas. We proposed a filtering method removing unwanted reflections and noise. Then, we worked on an automatic hyperbola detection method and an estimation of their mathematical functions in quasi real time. Finally, we proposed a source separation method to distinguish the unwanted reflections from the hyperbolas with a minimal impact on them. This last work opens interesting perspectives in filtering, hyperbolas enhancement and hyperbola detection.

Antarctic debris-covered glaciers are potential archives of long-term climate change. However, the geomorphic response of these systems to climate forcing is not well understood. To address this concern, I conducted a series of field-based and numerical modeling studies in the McMurdo Dry Valleys of Antarctica (MDV), with a focus on Mullins and Friedman glaciers. I used data and results from geophysical surveys, ice-core collection and analysis, geomorphic mapping, micro-meteorological stations, and numerical-process models to (1) determine the precise origin and distribution of englacial and supraglacial debris within these buried-ice systems, (2) quantify the fundamental processes and feedbacks that govern interactions among englacial and supraglacial debris, (3) establish a process-based model to quantify the inventory of cosmogenic nuclides within englacial and supraglacial debris, and (4) isolate the governing relationships between the evolution of englacial /supraglacial debris and regional climate forcing. Results from 93 field excavations, 21 ice cores, and 24 km of ground-penetrating radar data show that Mullins and Friedman glaciers contain vast areas of clean glacier ice interspersed with inclined layers of concentrated debris. The similarity in the pattern of englacial debris bands across both glaciers, along with model results that call for negligible basal entrainment, is best explained by episodic environmental change at valley headwalls. To constrain better the timing of debris-band formation, I developed a modeling framework that tracks the accumulation of cosmogenic 3He in englacial and supraglacial debris. Results imply that ice within Mullins Glacier increases in age non-linearly from 12 ka to ~220 ka in areas of active flow (up to >> 1.6 Ma in areas of slow-moving-to-stagnant ice) and that englacial debris bands originate with a periodicity of ~41 ka. Modeling studies suggest that debris bands originate in synchronicity with changes in obliquity-paced, total integrated summer insolation. The implication is that the englacial structure and surface morphology of some cold-based, debris-covered glaciers can preserve high-resolution climate archives that exceed the typical resolution of Antarctic terrestrial deposits and moraine records.

Les travaux présentés dans cette thèse portent sur les résolutions des problèmes direct et inverse associés à l’étude du radar de sol (GPR). Ils s’inscrivent dans un contexte d’optimisation des performances et d’amélioration de la qualité de l’imagerie. Un état de l’art est réalisé et l’accent est mis sur les méthodes de simulation et les techniques d’imagerie appliquées dans le GPR. L’étude de l’utilisation de la méthode du Galerkin discontinue (GD) pour la simulation GPR est d’abord réalisée. Des scénarios complets de GPR sont considérés et les simulations GD sont validées par comparaison avec des données obtenues par CST-MWS et des mesures. La suite de l’étude concerne la résolution du problème inverse en utilisant le Linear Sampling Method (LSM) pour l’application GPR. Une étude avec des données synthétiques est d’abord réalisée afin de valider et tester la fiabilité du LSM. Finalement, le LSM est adapté pour des applications GPR en prenant en compte les caractéristiques du rayonnement de l’antenne ainsi que ses paramètres S. Finalement, une étude est effectuée pour prouver la détectabilité de la jonction d‘un câble électrique souterrain dans un environnement réel. / The work presented in this thesis deals with the resolutions of the direct and inverse problems of the ground radar (GPR). The objective is to optimize GPR’s performance and its imaging quality. A state of the art of ground radar is realized. It focused on simulation methods and imaging techniques applied in GPR. The study of the use of the discontinuous Galerkin (GD) method for the GPR simulation is first performed. Some scenarios complete of GPR are considered and the GD simulations are validated by comparing the same scenarios’ modeling with CST-MWS and the measurements. Then a study of inverse problem resolution using the Linear Sampling Method (LSM) for the GPR application is carried out. A study with synthetic data is first performed to test the reliability of the LSM. Then, the LSM is adapted for the GPR application by taking into account the radiation of antenna. Finally, a study is designed to validate the detectability of underground electrical cables junction with GPR in a real environment.

abstract: Water is one of, if not the most valuable natural resource but extremely challenging to manage. According to old research in the field, many Water Distribution Systems (WDSs) around the world lose above 40 percent of clean water pumped into the distribution system because of unfortune leaks before the water gets anywhere from the fresh water resources. By reducing the amount of water leaked, distribution system managers can reduce the amount of money, resources, and energy wasted on finding and repairing the leaks, and then producing and pumping water, increase system reliability and more easily satisfy present and future needs of all consumers. But having access to this information pre-amatively and sufficiently can be complex and time taking. For large companies like SRP who are moving tonnes of water from various water bodies around phoenix area, it is even more crucial to efficiently locate and characterize the leaks. And phoenix being a busy city, it is not easy to go start digging everywhere, whenever a loss in pressure is reported at the destination. Keeping this in mind, non-invasive methods to geo-physically work on it needs attention. There is a lot of potential in this field of work to even help with environmental crisis as this helps in places where water theft is big and is conducted through leaks in the distribution system. Methods like Acoustic sensing and ground penetrating radars have shown good results, and the work done in this thesis helps us realise the limitations and extents to which they can be used in the phoenix are. The concrete pipes used by SRP are would not be able to generate enough acoustic signals to be affectively picked up by a hydrophone at the opening, so the GPR would be helpful in finding the initial location of the leak, as the water around the leak would make the sand wet and hence show a clear difference on the GPR. After that the frequency spectrum can be checked around that point which would show difference from another where we know a leak is not present. / Dissertation/Thesis / Masters Thesis Mechanical Engineering 2019

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