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Transmissive spongiform encephalopathies, also called prion disorders, are fatal neurodegenerative diseases affecting mammals. In patients, the pathological prion protein (PrPTSE ) accumulates in CNS and causes death. Prions possess high binding affinity to surfaces. Moreover, they are highly resistant to conventional sterilization procedures which rise the risk of nosocomial transmission from patients in subclinical stage of prion disease through medical tools. In the thesis, we evaluate the efficiency of photodynamic inactivation (PDI) for prion decontamination. The PDI is induced by photoactivation of phthalocyanine (Pc) derivates AlPcOH(SO3)2, SiPc(OH)2(SO3)1-3 or ZnPc(SO3)1-3. Pc exposed to light generate reactive oxygen species, mainly singlet oxygen (O2(1 ∆g)). Production of O2(1 ∆g) in aqueous solution was confirmed by iodide method, quenching by NaN3 and oxidative degradation of uric acid. The photoactivation of Pc in infectious brain homogenate led to elimination of PrPres signal (= proteinase K-resistant PrPTSE fragment) below the detection limit of western blot by using nanomolar AlPcOH(SO3)2 concentration. The complete elimination of PrPres signal was accompanied with total protein concentration decrease by a maximum of 20% in brain homogenate No signs of protein fragmentation or...

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Climate change, water stress, and rapid population growth have increased the need to manage water resources through innovative sustainable technologies. Decentralized systems such as membrane treatment trains have become increasingly important to provide high volumes of potable water to millions of people. Pressure-driven membrane systems have dominated separation processes due to their low cost, small footprint, ease of operation, and high permeate quality. Conventionally, pressure-driven membranes are classified into microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO). MF and UF membranes operate under low pressure (< 7 bar, <~100 psi). They can separate a variety of large particles such as bacteria, natural organic matter, suspended solids, and colloids. In contrast, NF and RO membranes are more energy-intense due to operating at high pressures (7 – 80 bar, ~100 – 1200 psi) and can remove small molecules such as ions, pharmaceuticals, and heavy metals. Fouling is a primary challenge with membranes that compromises the membrane performance, increases energy consumption, and reduces the membrane lifetime. Many strategies are used to address fouling, such as pre-treatment (pH adjustment, screening, coagulation), membrane modification (chemical and morphological properties), and membrane cleaning (physical, chemical). However, such strategies increase operational expenditures, produce waste products that can impact the environment, and negatively impact membrane lifetimes. Recently, electrically conductive membranes (ECMs) have been introduced to address the challenges with traditional membranes. They contain conductive surfaces that offer self-cleaning and antifouling properties across the surface in response to electrical potential externally applied to them. ECMs are advantageous as compared to traditional membranes because (a) they are more effective in treating foulants as they target foulants at the membrane/solvent interface, (b) they are more economical and environmentally friendly as they reduce the need for chemical consumption, and (c) they can be responsive to fouling conditions as their antifouling mechanisms can be easily manipulated by changing the applied current type (positive, negative, direct current, alternating current) to match the foulant. ECMs have been formed from all categories of membranes (MF, UF, NF, MD, FO, and RO) with a range of applications. Despite the remarkable progress in demonstrating their excellent antifouling performance, there are many hurdles to overcome before they can be commercialized. Two of these are (a) a fundamental understanding of their underlying mechanisms, (b) surface materials that can withstand extreme chemical and electrical conditions. In this work, we have comprehensively discussed antifouling mechanisms with respect to surface polarization and elaborated on the impact of electrically-induced mechanisms on four major fouling categories. i.e., biofouling, organic fouling, mineral scaling, and oil wetting. In addition, we characterized surface properties of a common electrically conductive composite membrane composed of carbon nanotubes (CNTs) and polyvinyl alcohol (PVA). We then investigated the impact of cross-linkers in CNT/PVA network on transmembrane flux, electrical conductivity, hydrophilicity, and surface roughness. In addition, we proposed standard, practical, and straightforward methodologies to detect and quantify the electrochemical, physical, and mechanical stability of ECMs, using chronoamperometry and cyclic voltammetry, an evaluation of polymer leaching from membranes, and micro mechanical scratch testing, respectively. Our methods can readily be extended to all membrane-based separation processes and different membrane materials (carbonaceous materials, ceramics, metal-based, and polymers). To demonstrate the antifouling properties of ECMs, we challenged ECMs with mixed-bacterial cultures in a flow-through system. Although ECMs showed high rejection, comparable flux, and excellent self-cleaning performance under application of electrical potential, understanding the relationship between applied electrical currents and antifouling mechanisms demands a well-controlled investigation. To this end, we quantified the impact of electrochemically-induced acidic conditions, alkaline conditions, and H2O2 concentration on model bacteria, Escherichia Coli. We first quantified the electrochemical potential of CNT-based ECMs in generating stressors such as protons, hydroxyl ions, and H2O2, under a range of applied electrical currents (± 0-150 mA). Next, these individual stressors with identical magnitude were imposed on E. Coli cells and biofilms in batch and flow-through systems, respectively. This thesis guides researchers to understand the underlying antifouling mechanisms associated with ECMs, how to match the mechanisms to the application of ECMs, and offers benchmarks for making practical ECMs. / Thesis / Doctor of Philosophy (PhD)

We describe an 11 year old girl with a de novo unbalanced t(X;10) that resulted in a deletion of Xq26→Xqter and a trisomy of 10q21→10qter. Her clinical features were of distal trisomy 10q, but she lacked the cardiovascular and renal malformations observed in duplications of 10q24→10qter and had only moderate mental retardation. X inactivation was assessed on peripheral blood lymphocytes by late replication with BrdU (LR) and the human androgen receptor assay (HAR). By LR the der(X) was inactive without spreading to 10q21→10qter in all cells. The HAR assay showed skewed methylation of the paternal allele (90%). The correlation of HAR and LR suggests that the der(X) was paternally inherited and is consistent with data from other de novo balanced and unbalanced X;autosome translocations detected in females. This is the first report of parental origin of a de novo trisomy 10q.

High pressure processing (HPP) and gamma irradiation were applied to inactivate <i>Vibrio vulnificus</i> (MO624) and <i>Vibrio parahaemolyticus</i> (O3:K6 TX2103) in pure culture and in inoculated live oysters. <i>Vibrio</i> pure culture and inoculated oysters were exposed to pressures of 207 MPa (30 kpsi) to 552 MPa (80 kpsi) for 0 min to maximum of 20 min. More than 5.4 log reductions of <i>V. vulnificus</i> occurred at 345 MPa for 0 min in oysters; 345 MPa for 2 min can achieve 4 log reductions on <i>V. parahaemolyticus</i>. Dosage of 1 kGy gamma-irradiation was proved to be effective in producing <i>Vibrio</i> free oysters with comparable organoleptic quality to raw oysters. Thermal conductivity of shucked oysters was measured to be 0.58 to 0.68 W/m°C, as temperature increased from 0 to 50 °C, using a line heat source probe. The specific heat was measured by differential scanning calorimeter methods. It increased from 3.80 to 4.05 kJ/kg °C, when temperature rose from 10 to 50 °C. The thermal diffusivity was calculated employing the data of thermal conductivity, specific heat and density of shucked oysters. The results showed that, under the tested temperature range, thermal properties did not change significantly with temperature. The dielectric constant and loss factor of oysters were determined by an open-ended coaxial line probe connected to a network analyzer at frequency of 30 MHz to 3000 MHz from 1 to 55 °C. The penetration depth of dielectric heating was calculated to be 1.1 cm with the dielectric constant of 55 and loss factor of 14. A two-dimensional mathematical model was established to simulate the heat transfer of microwave heating using a fish gel. Finite difference method was utilized to solve partial differential heat transfer equations. The model was able to predict the temperature distribution in heated fish gel with an accuracy of ± 8°C. Applying the developed mathematical model, the lethality of <i>Vibrio</i> spp., artificially inoculated in live oysters, was estimated collectively by integrating the individual localized lethality of designated heating units. The predicted lethality was compared with microwave enumeration data on Vibrios in oysters. The observed maximum log reductions by microbial enumeration were 4.4 and 3.4 for <i>V. vulnificus</i> and <i>V. parahaemolyticus</i>, respectively. The lethality calculated by integrating temperature profiles was acceptable. The discrepancy between the estimated lethality and microbial test was attributed to the simplified model construction. The quality of processed oysters, including color, aroma and texture properties, was evaluated instrumentally by a digital image system, an electronic nose and universal testing machine. The performance of two electronic nose systems on their abilities to detect oyster aroma and classify the aroma data into distinct groups was evaluated using a trained sensory panel and microbial tests. Cyranose 320 system has demonstrated potential as a quality assessment tool due to its sound correlation with microbial quality data and sensory evaluation scores. According to the quality measurement results, high pressure processing conditions were recommended to be at 345 MPa for less than 3 min and 379 MPa for less than 1.5 min. Deterioration of the quality was distinct for oyster meats exposed to 60 °C or above by thermal processing. The critical thermal processing condition was identified to be 55 °C for 2 min. With careful control, microwave processing could be considered as a candidate for seafood processing to reduce potential bacterial hazard but still retain the quality of the product. / Ph. D.

Water is essential for life on earth. Human society is challenged to sustain sufficient water quantity of good quality. This objective is reflected in sustainable development goal 6, “clean water and sanitation”. Water monitoring is part of sustainable water management and aims to evaluate the physical, chemical and biological status of a water body. Regular monitoring in the catchment area of Indalsälven (Sweden) is conducted by the Indalsälven Water Conservation Association (IWCA). In this area counts of Escherichia coli (E. coli) between 0 and 500 colony forming units (CFU) were monitored from 1993 – 2022 at the closest monitoring station Enkroken. This implies that drinking water quality standards were exceeded during many occasions (≥10 E. coli CFU/100ml). It is known that survival of E. coli in aquatic environments is dependent on nutrient levels, turbidity, sedimentation, pH level, predation, microbial community composition, temperature, and solar radiation. Low water depth and clear water with poor nutrient level in Enan and Handölan, tributaries to Indalsälven, are believed to cause solar radiation to be the main driver for inactivation of E. coli. Inactivation behaviour of indicator bacteria for faecal contamination such as E. col, is assumed to reflect on other bacteria that were excreted in the same way. The objective of the research was to investigate to which extent river color and river depth under the influence of sunlight affected E. coli inactivation in pristine like conditions such as the upper catchment area of Indalsälven. In this study, conditions from the research area were mimicked in 4 laboratory experiments. Results showed that neither 10 nor 35µW/cm2 led to additional inactivation due to sunlight. In a following experiment the liquid depth was reduced, with as a result that the inactivation of bacteria started to be influenced by sunlight when the depth was reduced to 14.4cm or lower. A fourth experiment was conducted at 14.4cm depth and additional color concentration 50 and 100 mg/l Pt. Results indicated that inactivation influenced by sunlight was reduced at color level 50 or more to a level that was equal to no sunlight radiation. A median depth of 0.2 cm and median color level of 15 mg/l Pt in the catchment area of Indalsälven suggests that inactivation of E. coli is very likely influenced by the sun, upstream the measuring point Enkroken and at points where the river is as shallow 14.4cm or less. Sunlight radiation might be underestimated in the conducted laboratory experiments, therefore continuous on-site research is suggested. / <p>2022-06-19</p>

The human gut microbiota contributes to host metabolic processes. Diverse microbial metabolic enzymes can affect therapeutic agents, resulting in chemical modifications that alter drug efficacy and toxicology. These interactions may result in ineffective treatments and dose-limiting side effects, as shown by bacterial modifications of the cardiac drug digoxin and chemotherapy drug irinotecan, respectively. Yet, few drug-microbiome interactions have been characterized. Here, a platform is developed to screen for drug-microbiome interactions, validated by the isolation of a gut bacterium capable of inactivating the antineoplastic drug doxorubicin. Two hundred gut strains isolated from a healthy patient fecal sample were cultured in the presence of antibiotic and antineoplastic drugs to enrich for resistance and possible inactivation. Raoultella planticola was identified for its ability to inactivate doxorubicin anaerobically through whole cell and crude lysate assays. This activity was also observed in other Enterobacteriaceae and resulted in doxorubicin inactivation by the removal of its daunosamine sugar, likely mediated by a molybdopterin-dependent enzyme. Other potential drug-microbiome interactions were identified in this screen and can be analyzed further. This platform enables the identification of drug-microbiome interactions that can be used to study drug pharmacology, improve the efficacy of therapeutic treatments, and advance personalized medicine. / Thesis / Bachelor of Science (BSc) / The collection of microbes in the human intestinal tract, referred to as the gut microbiome, can modify therapeutic agents and change the efficacy of drug treatments. Identifying these interactions between drugs and the microbiome will help the study of drug metabolism, provide explanations for treatment failure, and enable more personalized health care. For this project, a platform was developed to isolate gut bacteria from human fecal samples and characterize bacteria that are capable of inactivating various antibiotics and anticancer drugs. Through this platform, the gut bacterium Raoultella planticola was found to inactivate doxorubicin, a commonly used anticancer drug. These results suggest that doxorubicin may be inactivated in the gut and demonstrates how this platform can be used to identify drug-microbiome interactions.

Microbubbles are small gas-filled bubbles with diameters ranging from 50 to 1 μm, and less than 200 nm are called nanobubbles. Their small sizes and large specific surface area result in a high gas dissolution rate and long lifetime in liquid. Ozone is a strong oxidant that destroys microorganisms and only produces oxygen as the final by-product in fresh water. However, due to the poor stability of aqueous ozone, critical gas waste happens during treatments which leads to a high economic loss. Microbubbles have shown promising enhancement of ozone treatment. In previous studies, ozone microbubbles exhibited excellent efficacy in the removal of organic contaminants and inactivation of microorganisms including bacteria, spores, and fungi, but few articles discuss the virus inactivation of ozone microbubbles treatment. Human noroviruses (NoVs) are the primary cause of foodborne illnesses in the US, and the development of effective inactivation methods is crucial. Because of the absence of suitable in vitro cultivation methods for NoVs and the constraints of the available infectivity models for these viruses, most of the studies about inactivation use surrogate viruses that are similar to NoVs in genetics and structure. Tulane virus is a NoV surrogate that can identify the same putative co-factor. This study focuses on the influence of treatment time, disinfectant air exposure, and the presence of organic contaminants on the inactivation efficacy of ozone microbubbles or millimeter bubbles. The results demonstrate that more than one log10 reduction was produced when the Tulane virus was exposed to ozone millimeter bubbles and ozone microbubbles for a short period of time, even in the presence of high organic load (FBS), and the protective effect of the organic load was shown when the disinfectant induced volume increased. The findings indicate that conducting further research on ozone microbubbles in aqueous applications in food-related applications is useful.

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