Traitement d'images bas niveau intégré dans un capteur de vision CMOS

Le traitement d images classique est basé sur l évaluation des données délivrées par un système à basede capteur de vision sous forme d images. L information lumineuse captée est extraiteséquentiellement de chaque élément photosensible (pixel) de la matrice avec un certain cadencementet à fréquence fixe. Ces données, une fois mémorisées, forment une matrice de données qui estréactualisée de manière exhaustive à l arrivée de chaque nouvelle image. De fait, Pour des capteurs àforte résolution, le volume de données à gérer est extrêmement important. De plus, le système neprend pas en compte le fait que l information stockée ai changé ou non par rapport à l imageprécédente. Cette probabilité est, en effet, assez importante. Ceci nous mène donc, selon l activité de la scène filmée à un haut niveau de redondances temporelles. De même, la méthode de lectureusuelle ne prend pas en compte le fait que le pixel en phase de lecture a la même valeur ou non que lepixel voisin lu juste avant. Cela rajoute aux redondances temporelles un taux de redondances spatialesplus ou moins élevé selon le spectre de fréquences spatiales de la scène filmée. Dans cette thèse, nousavons développé plusieurs solutions qui visent contrôler le flot de données en sortie de l imageur enessayant de réduire les redondances spatiales et temporelles des pixels. Les contraintes de simplicité etd intelligence des techniques de lecture développées font la différence entre ce que nousprésentons et ce qui a été publié dans la littérature. En effet, les travaux présentés dans l état de l artproposent des solutions à cette problématique, qui en général, exigent de gros sacrifices en terme desurface du pixel, vu qu elles implémentent des fonctions électroniques complexes in situ.Les principes de fonctionnement, les émulations sous MATLAB, la conception et les simulationsélectriques ainsi que les résultats expérimentaux des techniques proposées sont présentés en détailsdans ce manuscrit.The classical image processing is based on the evaluation of data delivered by a vision sensor systemas images. The captured light information is extracted sequentially from each photosensitive element(pixel) of the matrix with a fixed frequency called frame rate. These data, once stored, form a matrixof data that is entirely updated at the acquisition of each new image. Therefore, for high resolutionimagers, the data flow is huge. Moreover, the conventional systems do not take into account the factthat the stored data have changed or not compared to the previously acquired image. Indeed, there is ahigh probability that this information is not changed. Therefore, this leads, depending on the "activity"of the filmed scene, to a high level of temporal redundancies. Similarly, the usual scanning methodsdo not take into account that the read pixel has or not the same value of his neighbor pixel read oncebefore. This adds to the temporal redundancies, spatial redundancies rate that depends on the spatialfrequency spectrum of the scene. In this thesis, we have developed several solutions that aim to controlthe output data flow from the imager trying to reduce both spatial and temporal pixels redundancies. Aconstraint of simplicity and "Smartness" of the developed readout techniques makes the differencebetween what we present and what has been published in the literature. Indeed, the works presented inthe literature suggest several solutions to this problem, but in general, these solutions require largesacrifices in terms of pixel area, since they implement complex electronic functions in situ.The operating principles, the emulation in MATLAB, the electrical design and simulations and theexperimental results of the proposed techniques are explained in detail in this manuscriptSAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Effets de l'environnement sur la plasticité des neurones olfactifs durant le développement (étude anatomique, moléculaire, physiologique et comportementale)

Dans le but d évaluer l impact d une exposition postnatale sur une population spécifique de neurones olfactifs, nous avons exposé au Lyral des souris transgéniques dont les neurones récepteurs olfactifs MOR23 expriment la protéine fluorescente, GFP. Nous avons évalué l impact d une exposition précoce sur la population des neurones MOR23, en utilisant plusieurs méthodes. Par des observations anatomiques, nous montrons que le nombre de neurones olfactifs exprimant MOR23 diminue chez les sujets traités. Cette baisse concerne principalement les neurones matures. Ensuite, des analyses en qPCR quantitatives sur de petits échantillons de cellules isolées indiquent que les neurones MOR23 des souris exposées expriment davantage de récepteurs, de canaux couplés aux nucléotides cycliques (CNGA2) et de phosphodiestérase (PDE1C). La surexpression du récepteur MOR23 par neurone est transitoire. Enfin, cette surexpression est corrélée avec les propriétés électriques des neurones en réponse au ligand du récepteur MOR23 étudiées en patch-clamp. Afin d écarter tout effet aspécifique inhérent à une éventuelle toxicité du Lyral, nous avons réalisé des enregistrements d électroolfactogramme (EOG), une étude transcriptomique (41 gènes) et une étude d immunohistochimie sur la muqueuse olfactive montrant que l EO reste intact après exposition de trois semaines au Lyral. Nous montrons également que l effet est dépendant du couple ligand-récepteur. Enfin, par des observations comportementales, nous montrons que les souris exposées développent une préférence pour le Lyral et passent plus de temps à l explorer.Ensemble, ces résultats suggèrent que les neurones olfactifs font preuve d une certaine plasticité et sont capables de s adapter à l environnementIn order to investigate the consequences of postnatal odorant exposure on a specific population of olfactory sensory neurons (OSNs), we have taken the following experimental approach. MOR23-GFP mice were daily exposed to Lyral for 21 days starting at birth and three lines of investigations were carried out. Using anatomical analysis we observe that the density of OSNs expressing MOR23 decreases after odorant exposure. This decrease concerns primarily matures OSN (MOR23-OMP+). In order to study molecular changes within individual OSNs, mRNA levels for olfactory signaling pathway components were quantitatively analyzed using qPCR on GFP-labeled neurons (7 per mouse). mRNAs for CNGA2, PDE1C and MOR23 olfactory receptor were up-regulated in exposed mice, whereas ACIII transcript levels remained stable. This effect is not permanent: we observed an anatomical and a molecular recovery. Patch-clamp recordings on MOR23 dendritic knobs correlate with qPCR datas. To exclude any aspecific effect due to a possible Lyral toxicity we performed EOG, immunohistochemistry and qPCR on total olfactory epithelium (OE). These experiments show that 3 weeks of Lyral exposure does not damage the OE. Then qPCR on isolated cells reveals that the effect is couple ligand-receptor dependant: M71 neurons are not affected by acetophenone exposure. Finally, we performed behavioral experiments on mice from both groups. Exposed mice favored their exposure odor in olfactory preference test and spend more time exploring Lyral than non-exposed mice. These observations suggest that the environment can induce plasticity in olfactory sensory neuronsDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Mise en évidence de transporteurs de la résistance pléiotropique dans la muqueuse olfactive et leur implication dans la réponse aux odorants chez les rongeurs

La résistance pléiotropique (MDR) est une propriété de certaines cellules relative à la capacité de rejeter ou d évacuer une très large variété de substances potentiellement toxiques. Les pompes à l origine de ce rejet sont des protéines membranaires appartenant à la superfamille ABC (ATP-Binding Cassette). Deux membres de cette famille ABC confèrent la propriété de résistance pléiotropique, P-gp (P-glycoprotein) et MRP1 (Multidrug Resistance-associated Protein). Nous avons mené une étude fonctionnelle sur l activité de ces deux transporteurs dans la muqueuse olfactive à la fois chez le rat et la souris. Nous avons employé le test fluorométrique à la calcéine-AM sur des tranches coronales de la muqueuse olfactive incubées en présence d inhibiteurs spécifiques des transporteurs de la résistance pléiotropique, vérapamil et cyclosporine A comme inhibiteurs de Pgp ainsi que probénécide et MK571 comme inhibiteurs de MRP1. Chacun de ces quatre inhibiteurs provoque une augmentation significative de l intensité de la fluorescence.Afin de savoir si les transporteurs de la résistance pléiotropique peuvent être impliqués dans la réponse olfactive nous avons examiné les réponses évoquées par des odorants seuls ou mélangés à l aide d enregistrements d électro-olfactogrammes (EOG). En présence des deux inhibiteurs de MRP1, l amplitude maximale des EOG est significativement réduite pour chaque stimulus odorant testé, tandis que les inhibiteurs de Pgp n ont qu un effet modéré ou nul. L expression des gènes codant pour Pgp et MRP1 dans l épithélium olfactif ont ensuite été confirmées par RT-PCR. L ensemble de ces résultats suggère que les transporteurs MRP1 et Pgp sont présents et fonctionnels dans l épithélium olfactif principal des rongeurs et sont impliqués dans la réponse aux odorants. Leur fonction précise dans l olfaction reste à éluciderMultidrug resistance (MDR) is a property of various cells associated with the capacity to reject or efflux a wide range of potentially harmful substances out of the cell. Pumps that effect such efflux are membrane proteins and belong to the ATP- binding cassette (ABC) superfamily. Among the members of the ABC family two are conferring MDR, P-glycoprotein (Pgp) and the multidrug resistance-associated protein (MRP1). In this study we investigated the functional activity of MDR transporters in olfactory mucosa of two species, rat and mouse. We used the fluorometric calcein-AM uptake assay on olfactory mucosal slices incubated with specific inhibitors of the MDR-transporters, verapamil and cyclosporin A as Pgp-inhibitors, and probenecid and MK571 as MRP-inhibitors. All four inhibitors caused significant increases in fluorescence intensities. To test if MDR transporters may be involved in the olfactory response we examined odorant evoked responses to single and mixed odorants by means of electro-olfactograms recordings (EOG). In the presence of the two MRP inhibitors, maximum EOG amplitudes were significantly reduced for all odorants tested, while Pgp inhibitors had only a moderate or no effect. Expression of Pgp and MRP1 encoding genes in the olfactory epithelium was further confirmed by RT-PCR. The results together suggest that MRP and Pgp transporters are present and functional in the main olfactory epithelium of rodents and are implicated in the olfactory response. The precise functional role in olfaction remains to be elucidated.DIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

When the nose must remain responsive: glutathione conjugation of the mammary pheromone in the newborn rabbit

In insects, xenobiotic-metabolizing enzymes were demonstrated to regulate pheromones inactivation, clearing them from the olfactory periphery and keeping receptors ready for stimulation renewal. Here, we investigate whether similar processes could occur in mammals, focusing on the pheromonal communication between female rabbits and their newborns. Lactating rabbits emit in their milk a volatile aldehyde, 2-methylbut-2-enal, that elicits searching-grasping in neonates; called the mammary pheromone (MP), it is critical for pups which are constrained to find nipples within the 5 min of daily nursing. For newborns, it is thus essential to remain sensitive to this odorant during the whole nursing period to display several actions of sucking. Here, we show that the MP is enzymatically conjugated to glutathione in newborn olfactory epithelium (OE), in accordance with the high mRNA expression of glutathione transferases evidenced by quantitative reverse transcription-PCR. This activity in the nose is higher than in the liver and in OE of newborns compared with weanlings (no more responsive to the pheromone). Therefore, the results pinpoint the existence of a high level of MP-glutathione conjugation activity in the OE of young rabbits, especially in the developmental window where the perceptual sensitivity toward the MP is crucial for survival

The Lyon Clinical Olfactory Test: Validation and Measurement of Hyposmia and Anosmia in Healthy and Diseased Populations

The LCOT is a self-administered test designed to assess olfactory deficits. Altogether, 525 subjects contributed to the validation. Elderly participants were well represented in this sample. In a validation study (study 1), 407 healthy and 17 anosmic volunteers between 15 and 91 years of age underwent threshold, supraliminal detection, and identification testing. Cutoff values for normosmia and hyposmia were calculated and applied in a second study in a group of patients with smell complaints and in a group of Alzheimer patients with age-matched controls. Incidence of smell deficit was estimated at 5.6% in the healthy population of study 1, and at 16% in the elderly control group of study 2. Assessment of the ability of each subtest to discriminate between groups showed that LCOT is relevant to differentiating between perception and identification deficits and between Alzheimer's and hyposmic patients

Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral olfactory responses in rats.

International audienceA large set of xenobiotic-metabolizing enzymes (XMEs), such as the cytochrome P450 monooxygenases (CYPs), esterases and transferases, are highly expressed in mammalian olfactory mucosa (OM). These enzymes are known to catalyze the biotransformation of exogenous compounds to facilitate elimination. However, the functions of these enzymes in the olfactory epithelium are not clearly understood. In addition to protecting against inhaled toxic compounds, these enzymes could also metabolize odorant molecules, and thus modify their stimulating properties or inactivate them. In the present study, we investigated the in vitro biotransformation of odorant molecules in the rat OM and assessed the impact of this metabolism on peripheral olfactory responses. Rat OM was found to efficiently metabolize quinoline, coumarin and isoamyl acetate. Quinoline and coumarin are metabolized by CYPs whereas isoamyl acetate is hydrolyzed by carboxylesterases. Electro-olfactogram (EOG) recordings revealed that the hydroxylated metabolites derived from these odorants elicited lower olfactory response amplitudes than the parent molecules. We also observed that glucurono-conjugated derivatives induced no olfactory signal. Furthermore, we demonstrated that the local application of a CYP inhibitor on rat olfactory epithelium increased EOG responses elicited by quinoline and coumarin. Similarly, the application of a carboxylesterase inhibitor increased the EOG response elicited by isoamyl acetate. This increase in EOG amplitude provoked by XME inhibitors is likely due to enhanced olfactory sensory neuron activation in response to odorant accumulation. Taken together, these findings strongly suggest that biotransformation of odorant molecules by enzymes localized to the olfactory mucosa may change the odorant's stimulating properties and may facilitate the clearance of odorants to avoid receptor saturation

Human milk nutritional composition across lactational stages in Central Africa

The African region encompasses the highest undernutrition burden with the highest neonatal and infant mortality rates globally. Under these circumstances, breastfeeding is one of the most effective ways to ensure child health and development. However, evidence on human milk (HM) composition from African women is scarce. This is of special concern, as we have no reference data from HM composition in the context of food insecurity in Africa. Furthermore, data on the evolution of HM across lactational stages in this setting lack as well. In the MITICA study, we conducted a cohort study among 48 Central-African women and their 50 infants to analyze the emergence of gut dysbiosis in infants and describe the mother-infant transmission of microbiota between birth and 6 months of age. In this context, we assessed nutritional components in HM of 48 lactating women in Central Africa through five sampling times from week 1 after birth until week 25. Unexpectedly, HM-type III (Secretor + and Lewis genes -) was predominant in HM from Central African women, and some nutrients differed significantly among HM-types. While lactose concentration increased across lactation periods, fatty acid concentration did not vary significantly. The overall median level of 16 detected individual human milk oligosaccharides (HMOs; core structures as well as fucosylated and sialylated ones) decreased from 7.3 g/l at week 1 to 3.5 g/l at week 25. The median levels of total amino acids in HM dropped from 12.8 mg/ml at week 1 to 7.4 mg/ml at week 25. In contrast, specific free amino acids increased between months 1 and 3 of lactation, e.g., free glutamic acid, glutamine, aspartic acid, and serine. In conclusion, HM-type distribution and certain nutrients differed from Western mother HM

A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays

Background: A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element nanoparticles has been made. Here, we directly compare the irradiation-induced (10 Gy of 6-MV X-ray photon) production of hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the following metal oxide nanoparticles: Al2O3, SiO2, Sc2O3, TiO2, V2O5, Cr2O3, MnO2, Fe3O4, CoO, NiO, CuO, ZnO, ZrO2, MoO3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb4O7, Dy2O3, Er2O3 and HfO2. We also examine DNA damage due to these NPs in unirradiated and irradiated conditions. Results: Without any X-rays, several NPs produced more radicals than water alone. Thus, V2O5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO2 NPs produced around 10-times more superoxide anions and Tb4O7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V2O5 NPs produced nearly 10-times more hydroxyl radicals than water. Changes in radical concentrations were determined by subtracting unirradiated values from irradiated values. These were then compared with irradiation-induced changes in water only. Irradiation-specific increases in hydroxyl radical were seen with most NPs, but these were only significantly above the values of water for V2O5, while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO2 showed a trend of irradiation-specific increase in superoxides, while V2O5, MnO2, CoO, CuO, MoO3 and Tb4O7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V2O5, NiO, CuO, MoO3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO2, Fe3O4 and CoO were slightly protective against irradiation-induced DNA damage. Conclusions: Beyond identifying promising metal oxide NP radiosensitisers and radioprotectors, our broad comparisons reveal unexpected differences that suggest the surface chemistry of NP radiosensitisers is an important criterion for their success

Functional Evidence of Multidrug Resistance Transporters (MDR) in Rodent Olfactory Epithelium

Background: P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. Principal Findings: Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices. Calcein-AM uptake was measured as fluorescence intensity changes in the presence of Pgp or MRP specific inhibitors. Epifluorescence microscopy measured time course analysis in the olfactory epithelium revealed significant inhibitor-dependent calcein uptake in the presence of each of the selected inhibitors. Furthermore, intracellular calcein accumulation in olfactory receptor neurons was also significantly increased in the presence of either one of the Pgp or MRP inhibitors. The presence of Pgp or MRP1 encoding genes in the olfactory mucosa of rat and mouse was confirmed by RT-PCR with appropriate pairs of speciesspecific primers. Both transporters were expressed in both newborn and adult olfactory mucosa of both species. To assess a possible involvement of MDR transporters in the olfactory response, we examined the electrophysiological response to odorants in the presence of the selected MDR inhibitors by recording electroolfactograms (EOG). In both animal species

Food Insecurity and Maternal Diet Influence Human Milk Composition between the Infant's Birth and 6 Months after Birth in Central-Africa

Although the World Health Organization (WHO) and UNICEF recommend that infants should be exclusively breastfed for the first 6 months of life, evidence is scarce on how the mother’s undernourishment status at delivery and maternal dietary factors influence human milk (HM) composition during the first 6 months of life in regions with high food insecurity. The maternal undernourishment status at delivery, maternal diet, and HM nutrients were assessed among 46 women and their 48 vaginally born infants in Bangui at 1, 4, 11, 18, and 25 weeks after birth through 24-h recalls and food consumption questionnaires from December 2017 to June 2019 in the context of the "Mother-to-Infant TransmIssion of microbiota in Central-Africa" (MITICA) study. High food insecurity indexes during the follow-up were significantly associated with them having lower levels of many of the human milk oligosaccharides (HMOs) that were measured and with lower levels of retinol (aß-coef = −0.2, p value = 0.04), fatty acids (aß-coef = −7.2, p value = 0.03), and amino acids (aß-coef = −2121.0, p value < 0.001). On the contrary, women from food-insecure households displayed significantly higher levels of lactose in their HM (aß-coef = 3.3, p value = 0.02). In parallel, the consumption of meat, poultry, and fish was associated with higher HM levels of many of the HMOs that were measured, total amino acids (aß-coef = 5484.4, p value < 0.001), and with lower HM levels of lactose (aß-coef = −15.6, p value = 0.01). Food insecurity and maternal diet had a meaningful effect on HM composition with a possible impact being an infant undernourishment risk. Our results plead for consistent actions on food security as an effective manner to influence the nutritional content of HM and thereby, potentially improve infant survival and healthy growth