Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

Introduction: Ischemic stroke remains one of the most debilitating diseases and is the fifth leading cause of death in the US. The ability to predict stroke outcomes within the acute period of stroke would be essential for care planning and rehabilitation. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) study collects arterial blood immediately distal and proximal to the intracranial thrombus at the time of mechanical thrombectomy. These blood samples are an innovative resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and important immune factors during mechanical thrombectomy for emergent large vessel occlusion (ELVO) and which patient demographics were predictors for stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients. Methods: The BACTRAC study is a non-probability sampling of male and female subjects (≥18 year old) treated with mechanical thrombectomy for ELVO. We evaluated 28 subjects (66 ± 15.48 years) relative concentrations of mRNA for gene expression in 84 inflammatory molecules in arterial blood distal and proximal to the intracranial thrombus who underwent thrombectomy. We used the machine learning method, Random Forest to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes. To validate the overlapping genes with outcomes, we perform ordinary least squares regression analysis. Results: Machine learning analyses demonstrated that the genes and subject factors CCR4, IFNA2, IL-9, CXCL3, Age, T2DM, IL-7, CCL4, BMI, IL-5, CCR3, TNFα, and IL-27 predicted infarct volume. The genes and subject factor IFNA2, IL-5, CCL11, IL-17C, CCR4, IL-9, IL-7, CCR3, IL-27, T2DM, and CSF2 predicted edema volume. The overlap of genes CCR4, IFNA2, IL-9, IL-7, IL-5, CCR3, and IL-27 with T2DM predicted both infarct and edema volumes. These genes relate to a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils. Conclusions: Machine learning algorithms can be employed to develop prognostic predictive biomarkers for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke

Intracellular Bacterial Infection and Invariant NKT Cells

The invariant (i) natural killer (NK)T cells represent a unique subset of T lymphocytes which express the Vα14 chain of the T cell receptor (TCR), that recognizes glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I-like antigen presentation molecule CD1d, and they participate in protection against some microbial pathogens. Although iNKT cells have originally been regarded as T cells co-expressing NKR-P1B/C (NK1.1: CD 161), they do not seem to consistently express this marker, since NK1.1 surface expression on iNKT cells undergoes dramatic changes following facultative intracellular bacterial infection, which is correlated with functional changes of this cell population. Accumulating evidence suggests that NK1.1 allows recognition of "missing-self", thus controling activation/inhibition of NK1.1-expressing cells. Therefore, it is tempting to suggest that iNKT cells participate in the regulation of host immune responses during facultative intracellular bacterial infection by controlling NK1.1 surface expression. These findings shed light not only on the unique role of iNKT cells in microbial infection, but also provide evidence for new aspects of the NK1.1 as a regulatory molecule on these cells

Aplicacion de novas ferramentas para a modelización e optimización de medios de cultivo in vitro para plantas

The main objective of this thesis is the use of experimental design and artificial intelligence techniques to improve and optimize the plants in vitro culture mediaEl objetivo principal de esta Tesis es el empleo de técnicas de diseño experimental e inteligencia artificial para la mejora de los medios de cultivo in vitro de plantas mediante modelos matemáticos que permitan su optimizaciónO obxectivo principal de esta tese e o empleo de técnicas de diseño experimental e intelixencia artificial para la mellora da composición dos medios de cultivo in vitro de prantas mediante modelos matemáticos que permitan sua optimizació

Nouvelles méthodes de séparation des champs d'ondes en sismique

The aim of this work is to bring a contribution to the wave field separation, in seismics, usingtwo advanced techniques.The first technique, based on the pattern recognition, uses the signal shape associated to theseeked echo to extract it. We show, through applications on Vertical Seismic Profiles (VSP)data, that this technique seems like a more effective filter than the low-pass frequency filter,especially when noise is not localized in a given frequency band, and do not require nor apriori information on the received signal frequency band neither on its phase. In addition, weconfirm that the pattern recognition is a good tool for P and SV polarized waves filtering, onthree components data for offset VSP. We show, in this study, that the use of the Polinedirectional filter as pre-processing on the initial data allows an identification and an automaticextraction of the P and SV training signals; the efficiency of the method is thus improved andits use made easier.The second technique, very adapted for the non-stationary signals, is based on the wavelettransform and its rebuilding formula, to detect and extract locally, in the time-scale field, aquite particular echo on the seismic recording. Filtering quality depends on the delimitation ofthe echo to be filtered in the time-scale space and the adopted filtering process. We show, on avibroseis seismic reflection recording, the efficiency of this method to filter the ground rollmade up, in our case, of two slow and fast pseudo-Rayleigh waves, with a strong energy. Wepresent the results for two different filtering processes, one based on the restoring of thetransform coefficients in the selected zone and the other on their attenuation (roll-off). Wepropose, finally, the use of this technique to extract and characterize the two pseudo-Rayleighwaves, very useful waves for geotechnic studies.L’objet de ce travail est d’apporter une contribution à la séparation d’ondes, en sismique, pardeux techniques avancées.La première technique, basée sur la reconnaissance des formes, utilise la forme du signalassocié à l’écho recherché pour l’extraire. Nous montrons, à travers des applications sur desdonnées de profils sismiques verticaux (PSV), que cette technique apparaît comme un filtreplus efficace que le filtre en fréquence passe bas- surtout lorsque le bruit n’est pas localisédans une bande de fréquence donnée- et ne nécessitant pas d’a priori sur la bande defréquences du signal reçu ni sur sa phase. Par ailleurs, nous confirmons que la reconnaissancedes formes est un bon outil de filtrage des ondes polarisées P et SV, sur des données tricomposantes de PSV à déport non nul. Nous montrons, dans cette étude, que l’utilisation dufiltre directionnel Poline, comme prétraitement sur les données initiales, permet uneidentification et une extraction automatique des signaux d’apprentissage P et SV ; l’efficacitéde la méthode se trouve ainsi améliorée et son utilisation facilitée.La deuxième technique, très adaptée pour les signaux non stationnaires, est basée sur latransformée en ondelettes et sa formule de reconstruction, pour détecter et extrairelocalement, dans le domaine temps-échelle, un écho bien particulier sur l’enregistrementsismique. La qualité du filtrage dépend de la délimitation de l’écho à filtrer dans l’espacetemps-échelle et du processus de filtrage adopté. Nous montrons, sur un enregistrementvibroseis de sismique réflexion, l’efficacité de cette méthode à filtrer le ground roll composé,dans notre cas, de deux ondes de pseudo-Rayleigh lente et rapide, de forte énergie. Nousprésentons les résultats pour deux processus de filtrage différents, l’un basé sur la remise àzéro des coefficients de la transformée dans la zone sélectionnée et l’autre sur leuratténuation. Nous proposons, enfin, l’utilisation de cette technique pour extraire et caractériserles deux ondes de pseudo-Rayleigh, ondes très utiles pour des études géotechniques

LA POPULATION REGULATRICE TNK (MODULATION DES FONCTIONS INNEES ET ADAPTATIVES PAR LES CYTOKINES, MISE EN EVIDENCE D'UNE DIVERSITE ET APPLICATION AU MODELE AUTOIMMUN DE LA SOURIS NOD (DOCTORAT : IMMUNOLOGIE))

PARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A tool for the generation of a secure access control filter

International audienceCurrently, it is well recognized that coupling graphical and formal notations offers several advantages. Indeed, even if a graphical representation permits to design a visual, synthetic and user-friendly view of the system, it may be source of ambiguity and does not permit any formal verification. Formal methods help to remedy these shortcomings by giving a precise semantics to graphical notations such that it becomes possible to verify a large range of properties and even to generate correct implementations. Nevertheless, users cannot take a full advantage of the benefits of such a combination if it is not supported by an automatic tool that liberates them from the tedious translation activity. Following this direction, the present paper describes the main functionalities of a tool that automatically generates a formal secure access control filter for information systems. The goal of the filter is to regulate the access to data of an information system according to a set of static and dynamic rules. Data are described using a UML class diagram, whereas the static and dynamic rules are modeled using \textsc{SecureUML} and UML activity diagrams respectively. Basically, the tool automatically generates the B formal specification corresponding to these diagrams and the filte

Modeling and optimizing culture medium mineral composition for in vitro propagation of actinidia arguta

The design of plant tissue culture media remains a complicated task due to the interactions of many factors. The use of computer-based tools is still very scarce, although they have demonstrated great advantages when used in large dataset analysis. In this study, design of experiments (DOE) and three machine learning (ML) algorithms, artificial neural networks (ANNs), fuzzy logic, and genetic algorithms (GA), were combined to decipher the key minerals and predict the optimal combination of salts for hardy kiwi (Actinidia arguta) in vitro micropropagation. A five-factor experimental design of 33 salt treatments was defined using DOE. Later, the effect of the ionic variations generated by these five factors on three morpho-physiological growth responses – shoot number (SN), shoot length (SL), and leaves area (LA) – and on three quality responses - shoots quality (SQ), basal callus (BC), and hyperhydricity (H) – were modeled and analyzed simultaneously. Neurofuzzy logic models demonstrated that just 11 ions (five macronutrients (N, K, P, Mg, and S) and six micronutrients (Cl, Fe, B, Mo, Na, and I)) out of the 18 tested explained the results obtained. The rules “IF – THEN” allow for easy deduction of the concentration range of each ion that causes a positive effect on growth responses and guarantees healthy shoots. Secondly, using a combination of ANNs-GA, a new optimized medium was designed and the desired values for each response parameter were accurately predicted. Finally, the experimental validation of the model showed that the optimized medium significantly promotes SQ and reduces BC and H compared to standard media generally used in plant tissue culture. This study demonstrated the suitability of computer-based tools for improving plant in vitro micropropagation: (i) DOE to design more efficient experiments, saving time and cost; (ii) ANNs combined with fuzzy logic to understand the cause-effect of several factors on the response parameters; and (iii) ANNs-GA to predict new mineral media formulation, which improve growth response, avoiding morpho-physiological abnormalities. The lack of predictability on some response parameters can be due to other key media components, such as vitamins, PGRs, or organic compounds, particularly glycine, which could modulate the effect of the ions and needs further research for confirmationXunta de Galicia | Ref. ED431D 2017/18Xunta de Galicia | Ref. ED431E 2018/07European Commission | Ref. 2012-2625 / 001-001- EM

Investigational drugs for anxiety in patients with schizophrenia

International audienc

Artificial neural networks elucidated the essential role of mineral nutrients versus vitamins and plant growth regulators in achieving healthy micropropagated plants

The design of an adequate culture medium is an essential step in the micropropagation process of plant species. Adjustment and balance of medium components involve the interaction of several factors, such as mineral nutrients, vitamins, and plant growth regulators (PGRs). This work aimed to shed light on the role of these three components on the plant growth and quality of micropropagated woody plants, using Actinidia arguta as a plant model. Two experiments using a five-dimensional experimental design space were defined using the Design of Experiments (DoE) method, to study the effect of five mineral factors (NH4NO3, KNO3, Mesos, Micros, and Iron) and five vitamins (Myo-inositol, thiamine, nicotinic acid, pyridoxine, and vitamin E). A third experiment, using 20 combinations of two PGRs: BAP (6-benzylaminopurine) and GA3 (gibberellic acid) was performed. Artificial Neural Networks (ANNs) algorithms were used to build models with the whole database to determine the effect of those components on several growth and quality parameters. Neurofuzzy logic allowed us to decipher and generate new knowledge on the hierarchy of some minerals as essential components of the culture media over vitamins and PRGs, suggesting rules about how MS basal media formulation could be modified to assess the quality of micropropagated woody plants.Xunta de Galicia | Ref. ED431E 2018/07Xunta de Galicia | Ref. ED431D2017/18European Commission | Ref. 2012-2625 / 001-001- EM