Une méthode pour l'évaluation de la qualité des images 3D stéréoscopiques.

Dans le contexte d'un intérêt grandissant pour les systèmes stéréoscopiques, mais sans méthodes reproductible pour estimer leur qualité, notre travail propose une contribution à la meilleure compréhension des mécanismes de perception et de jugement humains relatifs au concept multi-dimensionnel de qualité d'image stéréoscopique. Dans cette optique, notre démarche s'est basée sur un certain nombre d'outils : nous avons proposé un cadre adapté afin de structurer le processus d'analyse de la qualité des images stéréoscopiques, nous avons implémenté dans notre laboratoire un système expérimental afin de conduire plusieurs tests, nous avons crée trois bases de données d'images stéréoscopiques contenant des configurations précises et enfin nous avons conduit plusieurs expériences basées sur ces collections d'images. La grande quantité d'information obtenue par l'intermédiaire de ces expérimentations a été utilisée afin de construire un premier modèle mathématique permettant d'expliquer la perception globale de la qualité de la stéréoscopie en fonction des paramètres physiques des images étudiée.In a context of ever-growing interest in stereoscopic systems, but where no standardized algorithmic methods of stereoscopic quality assessment exist, our work stands as a step forward in the understanding of the human perception and judgment mechanisms related to the multidimensional concept of stereoscopic image quality. We used a series of tools in order to perform in-depth investigations in this direction: we proposed an adapted framework to structure the process of stereoscopic quality assessment, we implemented a stereoscopic system in our laboratory for performing various tests, we created three stereoscopic datasets with precise structures, and we performed several experimental studies using these datasets. The numerous experimental data obtained were used in order to propose a first mathematical framework for explaining the overall percept of stereoscopic quality in function of the physical parameters of the stereoscopic images under study.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Human factors in the perception of stereoscopic images

Research into stereoscopic displays is largely divided into how stereo 3D content looks, a field concerned with distortion, and how such content feels to the viewer, that is, comfort. However, seldom are these measures presented simultaneously. Both comfortable displays with unacceptable 3D and uncomfortable displays with great 3D are undesirable. These two scenarios can render conclusions based on research into these measures both moot and impractical. Furthermore, there is a consensus that more disparity correlates directly with greater viewer discomfort. These experiments, and the dissertation thereof, challenge this notion and argue for a more nuanced argument related to acquisition factors such as interaxial distance (IA) and post processing in the form of horizontal image translation (HIT). Indeed, this research seeks to measure tolerance limits for viewing comfort and perceptual distortions across different camera separations. In the experiments, HIT and IA were altered together. Following Banks et al. (2009), our stimuli were simple stereoscopic hinges, and we measured the perceived angle as a function of camera separation. We compared the predictions based on a ray-tracing model with the perceived 3D shape obtained psychophysically. Participants were asked to judge the angles of 250 hinges at different camera separations (IA and HIT remained linked across a 20 to 100mm range, but the angles ranged between 50° and 130°). In turn, comfort data was obtained using a five-point Likert scale for each trial. Stimuli were presented in orthoscopic conditions with screen and observer field of view (FOV) matched at 45°. The 3D hinge and experimental parameters were run across three distinct series of experiments. The first series involved replicating a typical laboratory scenario where screen position was unchanged (Experiment I), the other presenting scenarios representative of real-world applications for a single viewer (Experiments II, III, and IV), and the last presenting real-world applications for multiple viewers (Experiment V). While the laboratory scenario revealed greatest viewer comfort occurred when a virtual hinge was placed on the screen plane, the single-viewer experiment revealed into-the-screen stereo stimuli was judged flatter while out-of-screen content was perceived more veridically. The multi-viewer scenario revealed a marked decline in comfort for off-axis viewing, but no commensurate effect on distortion; importantly, hinge angles were judged as being the same regardless of off-axis viewing for angles of up to 45. More specifically, the main results are as follows. 1) Increased viewing distance enhances viewer comfort for stereoscopic perception. 2) The amount of disparity present was not correlated with comfort. Comfort is not correlated with angular distortion. 3) Distortion is affected by hinge placement on-screen. There is only a significant effect on comfort when the Camera Separation is at 60mm. 4) A perceptual bias between into the depth orientation of the screen stimuli, in to the screen stimuli were judged as flatter than out of the screen stimuli. 5) Perceived distortion not being affected by oblique viewing. Oblique viewing does not affect perceived comfort. In conclusion, the laboratory experiment highlights the limitations of extrapolating a controlled empirical stimulus into a less controlled “real world” environment. The typical usage scenarios consistently reveal no correlation between the amount of screen disparity (parallax) in the stimulus and the comfort rating. The final usage scenario reveals a perceptual constancy in off-axis viewer conditions for angles of up to 45, which, as reported, is not reflected by a typical ray-tracing model. Stereoscopic presentation with non-orthoscopic HIT may give comfortable 3D. However, there is good reason to believe that this 3D is not being perceived veridically. Comfortable 3D is often incorrectly converged due to the differences between distances specified by disparity and monocular cues. This conflict between monocular and stereo cues in the presentation of S3D content leads to loss of veridicality i.e. a perception of flatness. Therefore, correct HIT is recommended as the starting point for creating realistic and comfortable 3D, and this factor is shown by data to be far more important than limiting screen disparity (i.e. parallax). Based on these findings, this study proposes a predictive model of stereoscopic space for 3D content generators who require flexibility in acquisition parameters. This is important as there is no data for viewing conditions where the acquisition parameters are changed

The role of STEAP2 in aggressive prostate cancer traits and androgen responses

The prognosis of localised prostate cancer is generally promising, as many tumours remain dormant and therefore do not require immediate intervention. In contrast, once metastasised, the prognosis for aggressive prostate cancer is often poor, highlighting the need for novel, effective treatment approaches. The expression of the six transmembrane epithelial antigen of the prostate2 (STEAP2) cell surface protein is increased in aggressive prostate cancer compared to normal prostate tissue. In vitro studies have shown STEAP2 to aid in prostate cancer progression, and as such this molecule shows promise as a potential novel therapeutic target in the treatment of advanced disease. The aim of this thesis was to develop a comprehensive understanding of the mechanistic role of STEAP2 in promoting aggressive prostate cancer traits and evaluate if its knock-out has the capacity to reduce the invasive potential of prostate cancer cells in vitro. As prostate cancer is a largely androgen dependent disease, this thesis also aimed to evaluate the effects of STEAP2 inhibition on the expression of the androgen receptor and androgen-regulated genes. This study developed and optimised a protocol for generating a set of 3D prostate cancer spheroids to provide more representative models of the in vivo prostate cancer environment. In this thesis, one commercial anti-STEAP2 polyclonal antibody and a panel of anti-STEAP2 monoclonal antibodies were selected for proof-of-concept studies where their effects on reducing prostate cancer cell viability were assessed. Receptor internalisation of STEAP2 was evaluated upon anti-STEAP2 monoclonal antibody binding to determine its suitability for use with antibody-drug conjugate technology. STEAP2 expression was knocked out using CRISPR/Cas9 genome engineering technology in two prostate cancer cell lines to evaluate its impact on cell proliferation, migration and invasion. Furthermore, gene expression profiling was conducted to explore interactions between STEAP2, the androgen receptor and a panel of androgen-regulated genes (PSA, FKBP5, GPRC6A and TMPRSS2) following: 1) anti-STEAP2 antibody treatment, 2) STEAP2-knockout and 3) the growth of prostate cancer cells in androgen-depleted conditions. The data presented in this thesis demonstrate that inhibition of STEAP2 by both the polyclonal anti-STEAP2 antibody and lead anti-STEAP2 monoclonal antibody significantly reduced prostate cancer cell viability. STEAP2 receptor internalisation was triggered following treatment of prostate cancer cells with the anti-STEAP2 monoclonal antibody, demonstrating its potential utility with antibody-drug conjugate technology in the future. STEAP2 knockout prostate cancer cells exhibited decreased cell proliferation, migration and invasion in comparison to wild-type cells. These promising findings highlight the therapeutic value of STEAP2-knockout in inhibiting invasive tumour cell traits. Gene expression data from both STEAP2-knockout cells and androgen-depleted cells suggest that STEAP2 may be involved in crosstalk between the androgen receptor and androgen-regulated genes. STEAP2 could therefore provide a novel target in conjunction with current conventional androgen deprivation therapy. In conclusion, the in vitro findings presented herein suggest STEAP2 as a viable target for the development of more tailored and personalised therapeutic agents to improve the clinical management of men with aggressive prostate cancer

Circulating biomarkers in cancer progression and treatment

Cancers consist of diverse clonal cell populations. In addition to cancer-stroma interactions, different cancer cell subpopulations can influence each other’s treatment responses. This thesis describes a novel model to track interaction between cancer subpopulations and the host in response to drug treatment. Moreover, studies in this thesis suggest that combined serial analyses of DNA and microRNAs in the circulation provide a molecular footprint of cancer that is crucial for adequate monitoring of cancer progression as well as treatment responses in real time with a minimally invasive procedure

Improving treatment of glioblastoma: new insights in targeting cancer stem cells effectively

Glioblastoma is the most common primary malignant brain tumour in the adult population. Despite multimodality treatment with surgery, radiotherapy and chemotherapy, outcomes are very poor, with less than 15% of patients alive after two years. Increasing evidence suggests that glioblastoma stem cells (GSCs) are likely to play an important role in the biology of this disease and are involved in treatment resistance and tumour recurrence following standard therapy. My thesis aims to address two main aspects of this research area: 1) optimization of methods to evaluate treatment responses of GSCs and their differentiated counterparts (non-GSCs), with a particular focus on a tissue culture model that resembles more closely the tumoral niche; 2) characterization of cell division and centrosome cycle of GSCs, investigating possible differences between these cells and non-GSCs, that would allow the identification of targets for new therapeutic strategies against glioblastomas. In the first part of my project, I optimized a clonogenic survival assay, to compare sensitivity of GSCs and non-GSCs to various treatments, and I developed the use of a 3-dimentional tissue culture system, that allows analysis of features and radiation responses of these two subpopulations in the presence of specific microenvironmental factors from the tumoral niche. In the second part, I show that GSCs display mitotic spindle abnormalities more frequently than non-GSCs and that they have distinctive features with regards to the centrosome cycle. I also demonstrate that GSCs are more sensitive than non-GSCs to subtle changes in Aurora kinase A activity, which result in a rapid increase in polyploidy and subsequently in senescence, with a consistent reduction in clonogenic survival. Based on these findings, I propose that kinases involved in the centrosome cycle need to be explored as a novel strategy to target GSCs effectively and improve outcomes of glioblastoma patients

The potential for autonomic neuromodulation to reduce perioperative complications and pain: a systematic review and meta-analysis

BACKGROUND: Autonomic dysfunction promotes organ injury after major surgery through numerous pathological mechanisms. Vagal withdrawal is a key feature of autonomic dysfunction, and it may increase the severity of pain. We systematically evaluated studies that examined whether vagal neuromodulation can reduce perioperative complications and pain. METHODS: Two independent reviewers searched PubMed, EMBASE, and the Cochrane Register of Controlled Clinical Trials for studies of vagal neuromodulation in humans. Risk of bias was assessed; I2 index quantified heterogeneity. Primary outcomes were organ dysfunction (assessed by measures of cognition, cardiovascular function, and inflammation) and pain. Secondary outcomes were autonomic measures. Standardised mean difference (SMD) using the inverse variance random-effects model with 95% confidence interval (CI) summarised effect sizes for continuous outcomes. RESULTS: From 1258 records, 166 full-text articles were retrieved, of which 31 studies involving patients (n=721) or volunteers (n=679) met the inclusion criteria. Six studies involved interventional cardiology or surgical patients. Indirect stimulation modalities (auricular [n=23] or cervical transcutaneous [n=5]) were most common. Vagal neuromodulation reduced pain (n=10 studies; SMD=2.29 [95% CI, 1.08-3.50]; P=0.0002; I2=97%) and inflammation (n=6 studies; SMD=1.31 [0.45-2.18]; P=0.003; I2=91%), and improved cognition (n=11 studies; SMD=1.74 [0.96-2.52]; P<0.0001; I2=94%) and cardiovascular function (n=6 studies; SMD=3.28 [1.96-4.59]; P<0.00001; I2=96%). Five of six studies demonstrated autonomic changes after vagal neuromodulation by measuring heart rate variability, muscle sympathetic nerve activity, or both. CONCLUSIONS: Indirect vagal neuromodulation improves physiological measures associated with limiting organ dysfunction, although studies are of low quality, are susceptible to bias and lack specific focus on perioperative patients

Sulfur Mustard Toxicity Following Dermal Exposure: Role of Oxidative Stress, and Antioxidant Therapy

Objective: Sulfur mustard (bis-2-(chloroethyl) sulfide) is a chemical warfare agent (military code: HD) causing extensive skin injury. The mechanisms underlying HD-induced skin damage are not fully elucidated. This review will critically evaluate the evidence showing that oxidative stress is an important factor in HD skin toxicity. Oxidative stress results when the production of reactive oxygen (ROS) and/or reactive nitrogen oxide species (RNOS) exceeds the capacity of antioxidant defense mechanisms. Methods: This review will discuss the role of oxidative stress in the pathophysiology of HD skin toxicity in both in vivo and in vitro model systems with emphasis on the limitations of the various model systems. Evidence supporting the therapeutic potential of antioxidants and antioxidant liposomes will be evaluated. Antioxidant liposomes are effective vehicles for delivering both lipophilic (incorporated into the lipid bilayers) and water-soluble (encapsulated in the aqueous inner-spaces) antioxidants to skin. The molecular mechanisms interconnecting oxidative stress to HD skin toxicity are also detailed. Results: DNA repair and inflammation, in association with oxidative stress, induce intracellular events leading to apoptosis or to a programmable form of necrosis. The free radical, nitric oxide (NO), is of considerable interest with respect to the mechanisms of HD toxicity. NO signaling pathways are important in modulating inflammation, cell death, and wound healing in skin cells. Conclusions: Potential future directions are summarized with emphasis on a systems biology approach to studying sulfur mustard toxicity to skin as well as the newly emerging area of redox proteomics

ANTICANCER EFFECT OF INDANONE-BASED THIAZOLYL HYDRAZONE DERIVATIVE ON P53 MUTANT COLON CANCER CELL LINES: IN VITRO AND IN VIVO STUDY

Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, irinotecan, a topoisomerase I inhibitor, is an important anticancer drug approved for patients with advanced or recurrent colorectal cancer. Considering the low response rate and the events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anticancer activity against most of the tested colon cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, N-Indan-1-ylidene-N\u27-(4-Biphenyl-4-yl-thiazol-2-yl)-hydrazine (ITH-6) is found to be more effective than irinotecan against p53 mutant colon cancer cells, HT-29, COLO 205, and KM 12 than p53 wild-type colon cancer cell line such as HCT 116. Mechanistic studies reveal that ITH-6 arrests these cancer cell lines in G2/M phase of the cell cycle, induces apoptosis, and causes an increase in ROS level with a significant reduction in the GSH level. The cell cycle arrest is related to the inhibition of tubulin polymerization in the mitotic phase. Moreover, ITH-6 inhibits the expression of NF-kB p65 and Bcl-2, which proves its cytotoxic action. The downregulation of NF-kB p65 can be further proved by immunofluorescence. Moreover, CRISPR/Cas9 was applied to establish NF-kB p65 gene knockout HT-29 cell model to validate the target of ITH-6. In addition, ITH-6 significantly decreased tumor size, growth rate and tumor volume in mice bearing HT-29 and KM 12 tumor xenografts. Overall, the results suggest that ITH-6 could be a potential anticancer drug candidate for p53 mutant colon cancers