Search

Background and Objectives: Carotid revascularization to prevent future vascular events is reasonable in patients with high-grade carotid stenosis. Currently, several biomarkers to predict carotid plaque development and progression have been investigated, among which microRNAs (miRs) are promising tools for the diagnosis of atherosclerosis. Methods and Results: A total of 49 participants were included in the study, divided into two main populations: Population 1 comprising symptomatic and asymptomatic inpatients, and Population 2 comprising asymptomatic outpatients. The study consisted of two main phases: a preliminary discovery phase and a validation phase, applying different techniques. MiR-profiles were performed on plasma and plaque tissue samples obtained from 4 symptomatic and 4 asymptomatic inpatients. MiRs emerging from profiling comparisons, i.e. miR-126-5p, miR-134-5p, miR-145-5p, miR-151a-5p, miR-34b, miR-451a, miR-720 and miR-1271-5p, were subjected to validation through RT-qPCR analysis in the total cohort of donors. Comparing asymptomatic and symptomatic inpatients, significant differences were reported in the expression levels of c-miRs for miR-126-5p and miR-1271-5p in blood, being more expressed in symptomatic subjects. In contrast, simultaneous evaluation of the selected miRs in plaque tissue samples did not confirm data obtained by the miR profiling, and no significant differences were observed. Using Receiver-Operating Characteristic (ROC) analysis, a circulating molecular signature (mir-126-5p, miR-1271-5p, albumin, C-reactive protein, and monocytes) was identified, allowing the distinction of the two groups in Population 1 (AUC = 0.795). Conclusions: Data emerging from this thesis suggest that c-miRs (i.e. miR-126-5p, miR-1271-5p) combined with selected haemato-biochemical parameters (albumin, C-reactive protein, and monocytes) produced a good molecular 'signature' to distinguish asymptomatic and symptomatic inpatients. C-miRs in blood do not necessarily reflect the expression levels of the same miRs in carotid plaque tissues since different mechanism can influence their expression.

Additional file 1: Table S1. Characteristics of the patient population. Table S2. Differentially expressed transcripts. Table S3. List of the selected miRNAs with their relative fold-changes (FC). Figure S1. Characterization by TME and NTA of EVs. Figure S2. EV characterization by flow cytometry. Figure S3. Representative western blot and quantification graph for TOMM20.

The main objective of this thesis was to study the reactivity of diesel exhaust soot under oxidizing conditions. The two studied diesel soot are collected from the same motor bench. This survey appears in a project titled "modelling of a catalysed diesel particulate filter" in which several laboratories (LTAC Metz, LRS Paris VI and LCA Saint-Avold) had collaborated with an industrial partner (Renault SA).Firstly, the soot samples have been characterized by various analytic techniques in order to determine their structural and chemical characteristics as well as their thermal behaviour. We also put in evidence the existence of an interaction between soot and adsorbed compounds during thermal treatment in inert atmosphere (formation of a microporous carbonaceous layer).Concerning the reactivity of non catalysed soot under air, the kinetic parameters have been determined thanks to thermogravimetric analyses. The values obtained for the combustion of the carbonaceous matrix are near for all soot samples (Ea = 140-170 kJ.mol-1, n ~ 0.25, nO2 ~ 0.72). Nor the quantity of soluble organic fraction (SOF), volatile organic fraction (VOF), the mineral inclusions and the thermal treatment seems to influence the combustion process.the effect of a Pt/ZrO2-CeO2 catalyst on the oxidization of soot under air and under a mixture containing 10 % of oxygen and 700 ppm of NO2/Ar has been studied by thermogravimetry. For the catalysed reaction, the activation energy decreases and the order of the reaction of soot (n) increases. There is a change of reaction mechanism. In the case of the reaction under air, it seems that contact between soot and catalyst is necessary whereas in presence of NO2 the catalyst is active even without contact.Finally, the formation of the reaction intermediates (R-NOx) created during the reaction of soot with NO2 has been put forward by thermogravimetry. The nature of these compounds has been determined by infrared spectrometry in agreement with the literature results. Some possible formation and decomposition mechanisms of these species have been proposed thanks to the analysis of gases obtained during soot-NO2 reaction and the thermodesorption of the R-NOx and ROx formed., L'objectif principal de cette thèse était d'étudier la réactivité des suies d'échappement d'un véhicule diesel sous atmosphère oxydante. Les suies diesel présentées ici proviennent de deux lots obtenus sur un même banc moteur. Cette étude s'inscrit dans un projet intitulé " modélisation d'un filtre à particule catalysé " pour lequel plusieurs laboratoires (LTAC Metz, LRS Paris VI et LCA Saint-Avold) associés à Renault SA ont collaboré.Tout d'abord les échantillons de suies ont été caractérisés par diverses techniques analytiques. C'est ainsi que nous avons pu déterminer les caractéristiques structurales et chimiques des suies ainsi que leur comportement thermique. Nous avons aussi mis en évidence l'existence d'interactions entre les suies et les composés adsorbés à leur surface lors de traitement thermique en atmosphère inerte (formation d'une couche carbonée microporeuse).Concernant la réactivité des suies non catalysée sous air, les paramètres cinétiques ont été déterminés grâce à des analyses thermogravimétriques. Quel que soit l'échantillon de suie utilisé, les valeurs obtenues pour la combustion de la matrice carbonée des suies sont proches (Ea = 140-170 kJ.mol-1, n ~ 0,25, nO2 ~ 0,72). Ni la quantité de fraction organique soluble (FOS), volatile (FOV), ni les inclusions minérales et le traitement thermique ne semblent avoir d'influence sur les paramètres cinétiques de la combustion des suies.L'effet d'un catalyseur de type Pt/ZrO2-CeO2 sur l'oxydation des suies sous air et sous un mélange contenant 10 % d'oxygène et 700 ppm de NO2 dans l'argon a été étudié en thermobalance. En présence de catalyseur, l'énergie d'activation diminue et l'ordre de la réaction par rapport à la masse de suie augmente. Il y a un changement de mécanisme de réaction. Dans le cas de la réaction sous air, il semble que le contact entre les suies et le catalyseur soit nécessaire alors qu'en présence de NO2 le catalyseur est actif même sans contact.Enfin, la formation d'intermédiaires réactionnels (R-NOx) créés lors de la réaction des suies et du NO2 a été mise en évidence par thermogravimétrie. La nature de ces composés a été déterminée par spectroscopie infrarouge en réflexion diffuse en accord avec les résultats de la littérature. Des mécanismes possibles de formation et de décomposition de ces espèces ont été proposés grâce à l'analyse des gaz émis lors de la réaction suies-NO2 et la thermodésorption des R-NOx et R-Ox formés.

The main objective of this thesis was to study the reactivity of diesel exhaust soot under oxidizing conditions. The two studied diesel soot are collected from the same motor bench. This survey appears in a project titled "modelling of a catalysed diesel particulate filter" in which several laboratories (LTAC Metz, LRS Paris VI and LCA Saint-Avold) had collaborated with an industrial partner (Renault SA).Firstly, the soot samples have been characterized by various analytic techniques in order to determine their structural and chemical characteristics as well as their thermal behaviour. We also put in evidence the existence of an interaction between soot and adsorbed compounds during thermal treatment in inert atmosphere (formation of a microporous carbonaceous layer).Concerning the reactivity of non catalysed soot under air, the kinetic parameters have been determined thanks to thermogravimetric analyses. The values obtained for the combustion of the carbonaceous matrix are near for all soot samples (Ea = 140-170 kJ.mol-1, n ~ 0.25, nO2 ~ 0.72). Nor the quantity of soluble organic fraction (SOF), volatile organic fraction (VOF), the mineral inclusions and the thermal treatment seems to influence the combustion process.the effect of a Pt/ZrO2-CeO2 catalyst on the oxidization of soot under air and under a mixture containing 10 % of oxygen and 700 ppm of NO2/Ar has been studied by thermogravimetry. For the catalysed reaction, the activation energy decreases and the order of the reaction of soot (n) increases. There is a change of reaction mechanism. In the case of the reaction under air, it seems that contact between soot and catalyst is necessary whereas in presence of NO2 the catalyst is active even without contact.Finally, the formation of the reaction intermediates (R-NOx) created during the reaction of soot with NO2 has been put forward by thermogravimetry. The nature of these compounds has been determined by infrared spectrometry in agreement with the literature results. Some possible formation and decomposition mechanisms of these species have been proposed thanks to the analysis of gases obtained during soot-NO2 reaction and the thermodesorption of the R-NOx and ROx formed., L'objectif principal de cette thèse était d'étudier la réactivité des suies d'échappement d'un véhicule diesel sous atmosphère oxydante. Les suies diesel présentées ici proviennent de deux lots obtenus sur un même banc moteur. Cette étude s'inscrit dans un projet intitulé " modélisation d'un filtre à particule catalysé " pour lequel plusieurs laboratoires (LTAC Metz, LRS Paris VI et LCA Saint-Avold) associés à Renault SA ont collaboré.Tout d'abord les échantillons de suies ont été caractérisés par diverses techniques analytiques. C'est ainsi que nous avons pu déterminer les caractéristiques structurales et chimiques des suies ainsi que leur comportement thermique. Nous avons aussi mis en évidence l'existence d'interactions entre les suies et les composés adsorbés à leur surface lors de traitement thermique en atmosphère inerte (formation d'une couche carbonée microporeuse).Concernant la réactivité des suies non catalysée sous air, les paramètres cinétiques ont été déterminés grâce à des analyses thermogravimétriques. Quel que soit l'échantillon de suie utilisé, les valeurs obtenues pour la combustion de la matrice carbonée des suies sont proches (Ea = 140-170 kJ.mol-1, n ~ 0,25, nO2 ~ 0,72). Ni la quantité de fraction organique soluble (FOS), volatile (FOV), ni les inclusions minérales et le traitement thermique ne semblent avoir d'influence sur les paramètres cinétiques de la combustion des suies.L'effet d'un catalyseur de type Pt/ZrO2-CeO2 sur l'oxydation des suies sous air et sous un mélange contenant 10 % d'oxygène et 700 ppm de NO2 dans l'argon a été étudié en thermobalance. En présence de catalyseur, l'énergie d'activation diminue et l'ordre de la réaction par rapport à la masse de suie augmente. Il y a un changement de mécanisme de réaction. Dans le cas de la réaction sous air, il semble que le contact entre les suies et le catalyseur soit nécessaire alors qu'en présence de NO2 le catalyseur est actif même sans contact.Enfin, la formation d'intermédiaires réactionnels (R-NOx) créés lors de la réaction des suies et du NO2 a été mise en évidence par thermogravimétrie. La nature de ces composés a été déterminée par spectroscopie infrarouge en réflexion diffuse en accord avec les résultats de la littérature. Des mécanismes possibles de formation et de décomposition de ces espèces ont été proposés grâce à l'analyse des gaz émis lors de la réaction suies-NO2 et la thermodésorption des R-NOx et R-Ox formés.

In this paper a continuous-time low-pass analog filter based on the Cascoded Super Source Follower (C-SSF) architecture, implemented in a 28-nm bulk CMOS process, is presented. The target application is the transceiver analog baseband for the next-generation IEEE 802.11ax WiFi standard. To comply with the high-selectivity requirements, a 6th-order Chebyshev transfer function has been implemented as a cascade of three biquadratic cells. The high quality factors required by such topology have been achieved by cascoding the feedback transistor in the standard SSF cell, reducing the quality factor dependence on the output conductance of the source follower transistor. Designed with the Inversion-Coefficient (IC) methodology, the filter is able to operate for channel bandwidths ranging from 10 MHz to 20 MHz by changing its bias current. Measurement results show that the filter has a minimum noise power of -55.1 dBm and a maximum IIP3 of 14 dBm consuming 49 mu W, i.e. 8.17 mu W per pole, occupying an area of 0.0099 mm(2).

Blood circulating microRNAs (c‐miRs) are potential biomarkers to trace aging and longevity trajectories to identify molecular targets for anti‐aging therapies. Based on a cross‐sectional study, a discovery phase was performed on 12 donors divided into four groups: young, old, healthy, and unhealthy centenarians. The identification of healthy and unhealthy phenotype was based on cognitive performance and capabilities to perform daily activities. Small RNA sequencing identified 79 differentially expressed c‐miRs when comparing young, old, healthy centenarians, and unhealthy centenarians. Two miRs, that is, miR‐19a‐3p and miR‐19b‐3p, were found increased at old age but decreased at extreme age, as confirmed by RT‐qPCR in 49 donors of validation phase. The significant decrease of those miR levels in healthy compared to unhealthy centenarians appears to be due to the presence of isomiRs, not detectable with RT‐qPCR, but only with a high‐resolution technique such as deep sequencing. Bioinformatically, three main common targets of miR‐19a/b‐3p were identified, that is, SMAD4, PTEN, and BCL2L11, converging into the FoxO signaling pathway, known to have a significant role in aging mechanisms. For the first time, this study shows the age‐related increase of plasma miR‐19a/b‐3p in old subjects but a decrease in centenarians. This decrease is more pronounced in healthy centenarians and was confirmed by the modified pattern of isomiRs comparing healthy and unhealthy centenarians. Thus, our study paves the way for functional studies using c‐miRs and isomiRs as additional parameter to track the onset of aging and age‐related diseases using new potential biomarkers., Small RNA deep sequencing on plasma‐derived RNA from 12 donors (young and old subjects, healthy, and unhealthy centenarians) was performed: 79 differentially expressed c‐miRs were identified. MiR‐19a/b‐3p increased at old age but decreased at extreme age, as confirmed by RT‐qPCR in 49 subjects. The decrease was more relevant in healthy centenarians, also confirmed by the modified pattern of isomiRs. Three common targets of miR‐19a/b‐3p were identified converging into the FoxO signaling pathway.

An appraisal of recent data highlighting aspects inspired by the new Geroscience perspective are here discussed. The main findings are summarized as follows: i) liver has to be considered an immunological organ, and new studies suggest a role for the recently described cells named telocytes; ii) the liver-gut axis represents a crucial connection with environment and life style habits and may influence liver diseases onset; iii) the physiological aging of liver shows relatively modest alterations. Nevertheless, several molecular changes appear to be relevant: a) an increase of microRNA-31-5p; -141-3p; -200c-3p expressions after 60 years of age; b) a remodeling of genome-wide DNA methylation profile evident until 60 years of age and then plateauing; c) changes in transcriptome including the metabolic zones of hepatocyte lobules; d) liver undergoes an accelerated aging in presence of chronic inflammation/liver diseases in a sort of continuum, largely as a consequence of unhealthy life styles and exposure to environmental noxious agents. We argue that chronic liver inflammation has all the major characteristics of "inflammaging" and likely sustains the onset and progression of liver diseases. Finally, we propose to use a combination of parameters, mostly obtained by omics such as transcriptomics and epigenomics, to evaluate in deep both the biological age of liver (in comparison with the chronological age) and the effects of donor-recipient age-mismatches in the context of liver transplants.

Introduction L-a-alanine has aroused considerable interest for use in radiation ESR dosimetry. In this work, we examined the energy response of alanine ESR films in the low energy X-photon energy range between 1 keV and 40 keV. Dose measurements through a reference ionization chamber and a semiconductor detection system were also performed to complement ESR measurements. Methods Commercial alanine ESR films were used. All ESR signal measurements were also done using an XBand (9.7 GHz) Bruker spectrometer. The dosimeters were irradiated at the "Livio Scarsi" Laboratory (LAX) of the University of Palermo, where X-ray beams in the 1–40 keV energy range are produced using a Seifert SN60 tube. Reference dosimetry measurements were made using a plane parallel chamber with thin polyethylene membranes. X-ray fluxes and energy spectra were measured with an innovative system based on semiconductor detectors (CdTe, Si) and digital pulse processing (DPP) electronics. Results The response of alanine to low-energy X-rays was characterized experimentally. The response as function of dose, the dependence of the ESR signal on the photon energy as well as the stability of the signal with time were investigated. Comparison of the ESR response to high energy photons was also carried out. The relative effectiveness is lower if compared to high-energy photons. Conclusion Alanine dosimeters show very interesting dosimetric features also for these low-energy X-ray beams. To our knowledge, these data have not been previously reported and they may be extremely relevant, e.g., when mapping the high-gradient treatment fields used in microbeam radiation therapy (MRT) with synchrotron radiation.