NCube/papyrus huggingface dataset:
Consommateurs de pornographie juvénile et agresseurs sexuels, du pareil au même? Comparaisons sur le plan développemental et comportemental

Objectives. The primary objective of this master’s thesis involves the study of similarities between three types of sexual offenders (child pornography offenders, child pornography offenders with victim and sexual offenders) according to different developmental, psychological and behavioural factors. The objective will also determine with which group the child pornography offenders with victim share the most similarities. In addition, it will address the importance of the different factors taken into account into belonging to one of the three groups of sexual offenders. Methodology. The sample consists of 50 child pornography offenders (CP), 52 child pornography offenders with victim (CPV) and 40 sexual offenders (n= 146). All of these men were the subject of a study on sexual behaviour conducted by the Centre d’intervention en délinquance sexuelle de Laval (CIDS); chi-squared analysis as well as comparative analysis were conducted in order to determine the most significant and applicable factors. Analyses of multinomial logistic regressions were thereafter applied in order to determine the significance of the different factors into belonging to one of the three groups of sexual offenders. Results. Analyses suggest that child pornography offenders and child pornography offenders with victim are significantly different from sexual offenders when it comes to the issues of relationship with their father, to drug use, consumption of legal pornography as well as to their extramarital activities. Moreover, only one factor distinguishes child pornography offenders with victims from the group of child pornography offenders; they are more likely to have a criminal record which includes more non-sexual criminal convictions. Additionally, according to results, we can argue that child pornography offenders with victim exhibit patterns more likely to relate to child pornography offenders than to the group of sexual offenders.

Keyphrases: Internet, Délinquance sexuelle, Child pornography, Sexual assault, Sexual offending, Risk factors
Détection de matériaux énergétiques dans les eaux naturelles souterraines par spectroscopie de résonance des plasmons de surface portable

Over the last few years, energetic materials such as 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) have been used and show a probable environmental impact on military bases, the surrounding population, fauna and flora, caused by military training involving munitions. On shooting ranges, soils near the firing positions and around targets require special monitoring, since the quantities of explosives residues found can be significant, and these compounds can be transported to surface water and groundwater by precipitation. However, the current procedure to detect energetic materials in natural water is complex, long and poorly adapted to. These operations require highly specialized personnel and increase the risk of cross contamination. Therefore, it is difficult to ensure a fast and continuous monitoring of the contaminants. Here, the objective is to develop a technique for identifying and quantifying explosives and their degradation products in natural water. Also, this test has to be in-situ, inexpensive and fast. Surface plasmon resonance (SPR) has been proposed to probe energetic materials. A bis-aniline-cross-linked gold nanoparticles (AuNPs) matrix is used as a molecular imprinted polymer (MIP) on gold film to selectively capture the target compound. The association of the target such as TNT or RDX to the MIP with π-donor-acceptor interactions have allow the detection of explosives by following SPR refractive changes. Plasmon coupling effects between the AuNPs and the gold film could also increase the SPR signals. The optimal sensor was then used on site to detect RDX in underground water of a Canadian military base. The utilisation of MIP based assay will provide a tool for the extraction and pre-concentration of TNT or RDX on the detector’s surface and will allow the detection of lower concentrations in natural water.

Keyphrases: SPR, TNT, RDX, MIP, Energetic materials, Molecularly imprinted polymer, Natural water, Surface plasmon resonance
Investigation of the effects of ceramide-C16 and n-decane on the polymorphism of phosphatidylethanolamine : a 2H and 31P solid-state NMR and differential scanning calorimetry study

Ceramide C16 (CerC16), a mid-chain sphingolipid bearing a hexadecanoyl chain, is involved in several diseases such as diabetes, obesity, Parkinson, and certain type of cancers. In the first part of my M.Sc. project, I employed differential scanning calorimetry (DSC) and sequential 2H and 31P static solid-state NMR spectroscopy to study the role of CerC16 ( ≤ 20 mol%) in modifying the polymorphism of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE). The results demonstrate that CerC16 has major impacts. It broadens the gel‒fluid lamellar (Lβ‒Lα) phase transition and shifts it toward higher temperatures.  This effect leads to the creation of a wide Lβ/Lα coexistence region in the phase diagram of the system. CerC16 also broadens the Lα‒inverted hexagonal (HII) phase transition and shifts it towards lower temperatures. When CerC16 proportion in POPE bilayers is ≥ 12-13 mol%, the two transitions overlap, leading to a three-phase coexistence line in the phase diagram.  Such a phenomenon leads to a direct Lβ‒HII phase transition. Globally, CerC16 can have a wide range of effects on membrane properties, from varying its fluidity to modulating its curvature.  Alkanes of various chain lengths are able to promote the Lα‒HII transition of different phosphatidylethanolamines (PE). In the second part of my M.Sc. thesis, I investigated the impacts of 10 mol% n-decane-d22, a short alkane, on the polymorphism of POPE, using sequential 2H and 31P solid-state NMR spectroscopy. The results show that although, n-decane causes a significant downshift in the onset temperature of the Lα‒HII transition, it does not shift considerably the end of the transition.  As a consequence, a very broad Lα‒HII transition is obtained. It is inferred that n-decane molecules are found within the lower part of the POPE acyl chains in the Lα phase. This location increases the chain packing stress and consequently, initiates the Lα‒HII transition at lower temperatures. Upon increasing temperature, more and more n-decane molecules are transferred to the HII phase; the relocation not only decreases the chain packing stress in the Lα phase, but also allows the decane molecules to fill the interstitial void spaces between the HII cylinders.

Keyphrases: Polymorphism, Gel, Liquid Crystalline, Inverted Hexagonal, Phase Diagram
Nano-encapsulation : distribution d'un médicament dans une population de micelles polymères et mécanisme de perméabilisation de liposomes photosensibles

Drug encapsulation is a thriving field, as potential therapeutic improvements are significant. In this framework, we have studied the distribution of a drug, SN-38, by infrared spectroscopy at the nanometric scale, in a population of drug-loaded polymeric micelles. The drug/polymer ratio was measured by comparing the wavelength intensities of the drug and the polymer. We were unable to obtain a satisfactory signal from an isolated micelle. By studying a film left by the evaporation of a suspension of charged micelles, we found no difference in the drug to polymer ratio of the population in a 5% interval around the theoretical composition (10% drug w/w), apart from a few clusters, possibly artefacts from the sample preparation. In a second step, we investigated the parameters influencing the release of a fluorescent probe (sulforhodamine B, SRB) encapsulated in photosensitive liposomes. This release is caused by the photoactivated isomerization of a monoalkylated azobenzene derivative (azo) in the bilayer. azobenzene, when illuminated with UV radiation, passes from a trans-plane conformation to a more voluminous cis conformation, which disrupts the bilayer and makes it more permeable. The liposomes are composed of this azo and cholesterol sulfate (SC) in SC/azo 3/1 (mol/mol) proportions. These lipids are in the liquid-ordered phase (lo). We observed a very rapid release during the isomerization itself, and then a passive leak in the presence of azo-cis, greater than in the presence of azo-trans. It has been demonstrated that the presence of azo-trans decreases the order of a bilayer formed of SC and a monoalkyle, sharper in presence of azo-cis. By replacing the SC with other lipids, we tested the behaviour of azo in other phases. The isomerization is slower in the gel phase and more rapid in the disordered lamellar fluid phase (ld), compared to the lo phase. In the ld phase, it seems that the mobility of the lipids makes it possible to accommodate the cis isomer without changing the permeability of the bilayer. Our gel phase system did not allow us to make reproducible SRB release measurements.

Keyphrases: Permeability, cholesterol sulfate, azobenzene, sterosomes, isomerization, photorelease, polymeric micelles
Développement d’une plateforme de criblage par SPR pour la caractérisation d’inhibiteurs de la DHFR R67

The objective of the research project is to develop a method for inhibitor screening based on a portable Surface Plasmon Resonance (SPR) device, an emerging technology.  The target is R67 dihydrofolate reductase (R67 DHFR), an enzyme that confers bacterial resistance to the antibiotic trimethoprim. Here, the target enzyme is linked to a thin gold surface having specific plasmonic (optical) properties that vary as a function of the mass of bound molecules. This allows monitoring binding to the surface-linked R67 DHFR, and thus permits identification of inhibitors. However, the mass of the low-affinity inhibitors typically identified in early stages of screening (i.e. 500-1000 g/mol) is too low to produce a significant SPR signal. To address this shortcoming, a competitive assay will be developed: a gold nanoparticle carrying a substrate analog will bind the surface-immobilized R67 DHFR, resulting in a strong SPR signal due to its high mass. Then, upon screening for potential inhibitors, the bound nanoparticle will be displaced from the target enzyme if a molecule provides sufficient affinity. By those means, it will be possible to indirectly monitor the binding of an inhibitor to the target.  This goal of this project is to test and validate the SPR screening approach applied to R67 DHFR.

Keyphrases: Medicinal chemistry, Enzymology, Screening platform development, Surface plasmon resonance, R67 dihydrofolate reductase, Biophysics
Altérations des cellules de Schwann périsynaptiques à la jonction neuromusculaire : implications pour la sclérose latérale amyotrophique

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease causing the death of diagnosed people within two to five years. Notably, ALS is a disease characterized by motor neuron degeneration and destruction of the neuromuscular junction (NMJ). Although the contribution of glial cells in the CNS to disease development and progression is now well established, the properties of glial cells at the NMJ, perisynaptic Schwann cells (PSCs), remains ill defined. PSCs are involved in a variety of NMJ functions, including its establishment during development, the regulation of its synaptic transmission and maintenance and its repair in the context of injury. It has been proposed that muscarinic receptors (mAChRs) regulate these functions in PSCs. Since no characterization of these cells in the context of NMJ function has been made in ALS, the objective of this thesis was to conduct a comprehensive assessment of the NMJ in a SOD1 (G37R) mouse model. Most specifically, we have focused on the ability of PSCs to detect synaptic transmission and to promote NMJ repair. Our results suggest that a high level of mAChRs activation is a key element for the synchronization of PSCs with their associated synapse and to enable them to repair the NMJ in ALS. Overall, these results are essential to update the vision of the NMJ in ALS and are the first to put in the spotlight not only functional alterations of PSCs, but also the physiological impact of such alterations. In addition, the results of this thesis could have major implications for the advancement of knowledge in the field of research on ALS, placing PSCs directly on the list of potential therapeutic targets. Therefore, the quality of life of patients with this disease could be improved by further work derived from this thesis.

Keyphrases: amyotrophic lateral sclerosis, neuromuscular junction, perisynaptic Schwann cell, muscarinic receptor, electrophysiology, immunohistochemistry
Magnetic resonance imaging of resting cerebral oxygen metabolism : applications in Alzheimer’s disease

The BOLD contrast employed in functional MRI studies is an ambiguous signal composed of changes in blood flow, blood volume and oxidative metabolism. In situations where the vasculature and metabolism may have been affected, such as in aging and in certain diseases, the dissociation of the more physiologically-specific components from the BOLD signal becomes crucial. The latest generation of calibrated functional MRI methods allows the estimation of both resting blood flow and absolute oxygen metabolism. The work presented here is based on one such proof-of-concept approach, dubbed QUO2, whereby taking into account, within a generalized model, both arbitrary changes in blood flow and blood O2 content during a combination of hypercapnia and hyperoxia breathing manipulations, yields voxel-wise estimates of resting oxygen extraction fraction and oxidative metabolism. In the first part of this thesis, the QUO2 acquisition protocol and data analysis were revisited in order to enhance the temporal stability of individual blood flow and BOLD responses, consequently improving reliability of the model-derived estimates. Thereafter, an assessment of the within and between-subject variability of the optimized QUO2 measurements was performed on a group of healthy volunteers. In parallel, an analysis was performed of the sensitivity of the model to different sources of random and systematic errors, respectively due to errors in measurements and choice of assumed parameters values. Moreover, the various impacts of the oxygen concentration administered during the hyperoxia manipulation were evaluated through a simulation and experimentally, indicating that a mild hyperoxia was beneficial. Finally, the influence of Alzheimer’s disease in vascular and metabolic changes was explored for the first time by applying the QUO2 approach in a cohort of probable Alzheimer’s disease patients and age-matched control group. Voxel-wise and region-wise differences in resting blood flow, oxygen extraction fraction, oxidative metabolism, transverse relaxation rate constant R2* and R2* changes during hypercapnia were identified. A series of limitations along with recommended solutions was given with regards to the delayed transit time, the susceptibility artifacts and the challenge of performing a hypercapnia manipulation in cohorts of elderly and Alzheimer’s patients.

Keyphrases: Calibrated fMRI, Hyperoxia, Hypercapnia, Accuracy and precision, Resting oxidative metabolism, Oxygen extraction fraction at rest, Cerebral blood flow, Vascular and metabolism health, Alzheimer’s disease
Interactions multisensorielles chez les musiciens

Playing a musical instrument requires the integration of information from multiple senses. The long-term sensory training from playing a musical instrument for many years has effects on cortical networks and behavioral abilities. Touch is a sensory modality that seems to be altered by musical training, but little research has focused on the tactile abilities of musicians. The objective of this thesis is to assess non-musical unisensory and multisensory tactile abilities in musicians using behavioral methodologies. The first study aimed at evaluating simple auditory, tactile, and audiotactile reaction times in musicians. Reaction times of 16 musicians and 19 controls were evaluated. The results of this study suggest that musicians have significantly faster response times for auditory, tactile, and audiotactile stimulations. The second study aimed at evaluating the integration of temporal and spectral audiotactile information in musicians. Audiotactile interactions of 13 musicians and 17 controls were evaluated using multisensory illusions. The results of this research suggest that only temporal audiotactile interactions are different for musicians. The third study aimed at assessing temporal tactile localization in musicians using tactile temporal order judgement task. Temporal tactile localization was evaluated in 17 musicians and 20 members of a control group. The results of this study suggest that musicians have a higher error rate to localize tactile stimulations when their arms are crossed but generally have faster reaction times for this task. All of these results suggest that musicians have altered tactile abilities. Overall, these results suggest that long-term musical training alters specific unisensory and multisensory tactile abilities. Further studies are required to better understand the factors of musical training leading to these changes and why certain interactions remain unchanged.

Keyphrases: audiotactile, tactile, interactions multisensorielles, sensory training, musicians, multisensory illusions, multisensory interaction, frames of reference
High-Density Lipoproteins (HDL) Functionality in Degenerative Cardiac Disease - 
Novel Cardioprotective Roles of HDL and Strategies to Target HDL Dysfunction

Background: The recent failure of drugs targeted to high-density lipoprotein (HDL) cholesterol levels has led to the conclusion that HDL function rather than HDL quantity is the key player in cardiovascular pathologies. The augmentation of functional HDL through administration of reconstituted HDL (rHDL) or apolipoprotein A-I (apoA-I) seems a promising strategy to in coronary artery disease (CAD) and aortic valve stenosis (AVS). However, clinically applicable biomarkers reflecting functionality of HDL are lacking. In addition, little is known on the mechanisms governing the cardioprotective effects of HDL-based approaches as well as rHDL and apoA-I possible conversion into dysfunctional molecules. Finally, data regarding potential secondary effects of such therapy are sparse. Thus, the present project explored the value of cholesterol esterification as biomarker for cardioprotective HDL effects, assessed whether rHDL exerts beneficial effects in endothelial repair, and investigated potential side-effects of HDL-based therapies as well as HDL-preserving strategies in AVS.   Method and results: We explored the value of cholesterol esterification during maturation of HDL particles, as a biomarker for cardioprotective HDL effects in 267 patients with stable CAD. In addition, the effect of rHDL on vascular repair mechanism was assessed in 33 patients with a recent acute coronary syndrome (ACS), and the contribution of different plasma proteases to apoA-I degradation was compared in patients with AVS as well as in a rabbit model of AVS. Using the same population and experimental model, we also assessed possible impact of apoA-I administration on haemorrhagic disorders in patients with AVS. Cholesterol esterification was found to be a strong and independent predictor of atherosclerotic burden in patients with CAD. Administration of rHDL prevented endothelial progenitor cells decline in patients with a recent ACS. While apoA-I administration did not negatively affect haemorrhagic disorders in AVS, it was found that the cysteine protease cathepsin S is the key protease responsible for 70% of apoA-I degradation in humans.  Conclusion: The present data indicate that cholesterol esterification is a useful biomarker mirroring severity of atherosclerotic disease. Thus, targeting cholesterol esterification might be a promising therapeutic strategy to reduce cardiovascular risk. Our data further indicate that an improvement of cardiovascular repair mechanisms following myocardial injury might be amongst the mechanisms by which exogenous HDL exerts its cardioprotective actions. The latter is also a particularly promising strategy in the treatment of AVS and its efficacy could be further enhanced by inhibition of the cysteine protease cathepsin S.

Keyphrases: Coagulation, High-density lipoproteins, Apolipoprotein A-I, Lecithin cholesterol acyltransferase, Coronary artery disease, Aortic valve stenosis, Cardiovascular risk, Endothelial progenitor cells
Structural and Biochemical Characterization of VirB8 Protein in Type IV Secretion Systems

Secretion is the passage of macromolecules across cellular membranes. In bacteria, secretion is essential for virulence and survival. Gram-negative bacteria use specialized envelope-spanning multiprotein complexes to secrete macromolecules called type IV secretion system (T4SS). T4SSs mediate the secretion of monomeric proteins, multisubunit protein toxins and nucleoprotein complexes. Also, they contribute to the horizontal spread of plasmid-encoded antibiotic resistance genes. Consequently, they are potential targets for antivirulence drugs. Gram- negative bacteria have two membranes that the secretion complex spans. As a result, the T4SS consists of proteins inserted in the membranes and of soluble proteins that face into or out of the bacterial cell. The details of channel assembly and structure are not known, although recent advances have revealed the structure of the core secretion channel. VirB8 is an inner membrane protein of the complex that interacts with many other T4SS subunits and works as nucleation factor for T4SS channel assembly. Biophysical studies and NMR experiments in particular were conducted to characterize the structural aspects of VirB8 interactions. Dynamic regions of VirB8 during monomer-to-dimer transition were identified by NMR spectroscopy. X-ray crystal and NMR analyses revealed structural differences at the helical regions (α-1 and α-4) of wild-type VirB8 and its monomeric variant VirB8M102R. Fragment screening identified small molecules binding to the wild-type and monomeric variant. In silico docking analyses suggested that the surface groove in the VirB8 structure is important for effective binding of the small molecules. NMR experiments and biochemical assays demonstrated that the β-sheet domain (β1 in particular) is the binding interface of VirB8 for the interaction with VirB10. The identified interface has functional importance for T4SS-mediated conjugation. In addition, I used NMR spectroscopy to identify changes in the structure of VirB8 upon interaction with VirB5. Altogether, structural and biochemical studies on periplasmic and full length VirB8 enabled us to characterize the sequence of interactions between VirB8 and other VirB proteins during T4SS complex assembly and function. The results of this research may lead to an innovative strategy for the development of novel antimicrobial drugs.

Keyphrases: Antibiotic resistance, Crystal structure, NMR assignment, Type IV secretion system, VirB8