The effect of an indoor-outdoor temperature difference on transient cross-ventilation

We examine the effect of an indoor-outdoor temperature difference on the transient wind-driven cross-ventilation of a room. Laboratory experiments are performed in a water flume using a reduced-scale model room. For solely wind-driven cross-ventilation with no initial temperature difference between the room and the external fluid, the ventilation rate is constant. In experiments, the mean dye concentration decays exponentially, which is expected when the room remains well-mixed. When there is an initial temperature difference but no wind, the buoyancy-driven exchange-ventilation results lie between a model that assumes the room is well-mixed and a new model that assumes no mixing between the incoming flow and the room. When both wind and buoyancy drive the flow, the relative importance of these two effects can be described by a Froude number, Fr. For buoyancy-dominated ventilation (Fr1), a temperature difference slightly reduces the ventilation rate, but only by up to 6%, a change that can be neglected in most applications. Two processes compete to ventilate the room in combined cases: the removal of fluid from a lower layer by flow through the windows and the erosion of an upper layer by entrainment into the jet that crosses the room. The relative rates of these two processes depend on the geometry of the room.This work is supported by the Engineering and Physical Sciences Research Council (EPSRC) Grand Challenge grant Managing Air for Green Inner Cities (MAGIC) [grant number EP/N010221/1]

Virtual FFR quantified with a generalized flow model using Windkessel boundary conditions ; Application to a patient-specific coronary tree.

International audienceFractional flow reserve (FFR) has proved its efficiency in improving patients diagnosis. In this paper, we consider a 2D reconstructed left coronary tree with two artificial lesions of different degrees. We use a generalized fluid model with a Carreau law and implement the Windkessel boundary conditions at the outlets. We introduce our methodology to quantify the FFR, and lead several numerical experiments. For two different finite element meshes, we compare the FFR results for Navier Stokes versus generalized flow models, and for Windkessel versus free outlets boundary conditions. We also used mixed boundary conditions. Our results highlight the fact that free outlets boundary conditions are sensitive to the FFR sensor position. The computational FFR results show that the degree of stenosis is not enough to classify a lesion, while there is a good agreement between Navier Stokes and generalized flow model in classifying the lesions

Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.

International audienceThe mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure

A Highly Intensified ART Regimen Induces Long-Term Viral Suppression and Restriction of the Viral Reservoir in a Simian AIDS Model

Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART) in a wide range of viremic conditions (103–107 viral RNA copies/mL) in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART) consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir), an integrase inhibitor (raltegravir), a protease inhibitor (ritonavir-boosted darunavir) and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL) after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*105 cells) in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR+) effector memory CD4+ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing potential cures for AIDS

Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the “COPA” pilot randomized trial

Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4+ T-cell depletion, deterioration of gut lining, and fecal microbiota composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active antiretroviral therapy (HAART)-naive HIV-1-infected adults. In a pilot double-blind, randomized, placebo-controlled study, 57 HAART-naive HIV-1-infected patients received a unique oligosaccharide mixture (15 or 30 g short chain galactooligosaccharides/long chain fructooligosaccharides/pectin hydrolysate-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) daily) or a placebo for 12 weeks. Microbiota composition improved significantly with increased bifidobacteria, decreased Clostridium coccoides/Eubacterium rectale cluster, and decreased pathogenic Clostridium lituseburense/Clostridium histolyticum group levels upon prebiotic supplementation. In addition, a reduction of soluble CD14 (sCD14), activated CD4+/CD25+ T cells, and significantly increased natural killer (NK) cell activity when compared with control group were seen in the treatment group. The results of this pilot trial highly significantly show that dietary supplementation with a prebiotic oligosaccharide mixture results in improvement of the gut microbiota composition, reduction of sCD14, CD4+ T-cell activation (CD25), and improved NK cell activity in HAART-naive HIV-infected individuals

Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

International audienceBACKGROUND: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen

Modélisation de l'écoulement sanguin coronaire à l'aide d'un modèle de fluide non Newtonien : estimation de la fraction de réserve fluide

In this thesis, we explore the possibility of virtual coronary stenosis assessment, through the simulation of Fractional Flow Reserve (FFR) measurement, that is an indispensable but binding tool during diagnosis. First, we use a 2D non Newtonian flow model, and later a weakly coupled FSI model to make a preliminary study of the main features of flow over a stenotic coronary arterial portion. We then introduce a methodology to estimate the virtual FFR in analogy with the clinical device. The FFR device was considered non-physical (integrated to the flow domain) at a first place. We led different experiments to enumerate the factors affecting the virtual FFR and computed its profiles with respect to different lesion’s parameters. Second, we consider two realistic geometries: a 2D left coronary tree obtained from the segmentation of an angiography image and a 3D bifurcation tree. We define generalized flow models inside the two geometries and consider the arterial wall to be rigid. The presence of several outlets in these new geometries led us to define a new type of boundary conditions. For the inlet, we propose a bi-sinusoidal function approaching the velocity profile recorded inside a left coronary tree. For the outlets, we implement a 2 elementWindkessel model. We led a comparative study between Navier Stokes and the flow model considered and between free outlets boundary conditions and Windkessel model in 2D and define the flow inside the 3D bifurcation tree. We also compute the virtual FFR of two artificial lesions added to the coronary tree and demonstrate that angiography alone is not enough to evaluate the severity of stenosis. Third, we investigate - through 2D and 3D modelling - one possible reason of pressure drift during FFR measurement, that is the arbitrary position and configuration of the FFR device, considered during this study extrinsic to the flow domain. We consider the same non Newtonian flow models as previously. In 2D, the FFR device is assimilated to a disk with a variable position incorporated inside the left coronary tree. While the 3D domain corresponds to a diseased arterial portion to which we introduce a deformed 3D tube (wire+sensor) with a given length and coefficient of bending. The bending effect of the tube is obtained thanks to an elastic problem based on Hooke’s law. Using a Gaussian process, we model the FFR depending on these variables - and two additional stenosis variables later - we perform a set of samples corresponding to the design space considered. The 2D data indicates a good accuracy for FFR prediction while the 4D data emphasis the fact that mi- crocatheters with important diameters overestimate lesion’s severity. The results obtained demonstrate that drift occurring because of the variable device configuration may lead to stenosis misclassification. All resolution algorithms and simulation tools were implemented under FreeFem++ software. The need of more space memory for 3D simulations led us to adopt a parallel resolution strategy using FreeFem++ MPI and MUMPS solver.Dans cette thèse, nous explorons la possibilité d’une évaluation virtuelle des sténoses à travers la simulation de l’index de la réserve coronaire - appelée FFR en anglais - qui est un outil indispensable mais contraignant lors du diagnostic. Tout d’abord, nous utilisons un modèle d’écoulement 2D non Newtonien, puis un modèle d’interaction fluide structure faiblement couplé pour établir une étude préliminaire des principales caractéristiques de l’écoulement dans une portion sclérosée. Nous introduisons ensuite une méthodologie pour estimer la FFR virtuelle par analogie avec le dispositif médical. Le capteur FFR a été, dans un premier lieu, considéré non physique (intégré au domaine d’écoulement). Nous avons mené différents tests numériques pour relever les facteurs affectant la FFR virtuelle et présenté son profil par rapport aux différents paramètres considérés pour la lésion. Deuxièmement, nous présentons deux géométries réalistes : un arbre coronaire gauche - en 2D - obtenu à partir de la segmentation d’une image angiographique et une bifurcation en 3D. Nous définissons des modèles d’écoulement généralisés à l’intérieur des deux géométries et considérons que la paroi artérielle est rigide. La présence de plusieurs sorties dans ces nouvelles géométries nous a conduit à utiliser un nouveau type de conditions aux limites. A l’entrée, nous proposons une fonction bi-sinusoïdale s’approchant du profil de vitesse sanguine enregistré pour un arbre coronaire gauche. En ce qui concerne les sorties du domaine, nous considérons un modèle Windkessel à 2 éléments. Nous avons mené une étude comparative entre le modèle de Navier Stokes et le modèle non Newtonien considéré et entre les conditions limites de sorties libres et le modèle Windkessel présenté en 2D et défini le flux à l’intérieur de l’arbre de bifurcation 3D. Nous calculons également la FFR virtuel de deux lésions artificielles ajoutées à l’arbre coronaire et démontrons que l’angiographie seule ne suffit pas pour évaluer la sévérité de la sténose. Troisièmement, nous étudions - par modélisation 2D et 3D - une des raisons possibles de la dérive de pression pendant la mesure de la réserve coronaire FFR, représentée par la position et la configuration arbitraires du capteur de pression. Le capteur est considéré durant cette étude extrinsèque au domaine de l’écoulement. Nous considérons les mêmes modèles de flux non Newtoniens que précédemment. En 2D, le capteur FFR est assimilé à un disque avec une position variable incorporée dans l’arbre coronaire gauche. Alors que le domaine 3D correspond à une portion artérielle sclérosée à laquelle on introduit un tube 3D déformé (guide + capteur) avec une longueur et un coefficient de fléchissement donnés. L’effet de fléchissement du tube est obtenu grâce à un problème élastique basé sur la loi de Hooke. À l’aide d’un processus gaussien, nous modélisons le FFR en fonction des variables du capteur - et deux autres variables de la lésion - nous effectuons un ensemble d’expériences correspondant à l’espace d’hypercube considéré. Les données 2D indiquent une bonne précision pour la prédiction de FFR tandis que les données 4D confirment le fait que les micro-cathéters avec des diamètres importants surestiment la gravité des lésions. Les résultats obtenus démontrent que la dérive qui se produit en raison de la configuration variable du dispositif FFR peut induire en erreur lors de la classification de la sténose. Tous les algorithmes de résolution et les outils de simulation ont été implémentés sous le logiciel FreeFem++. Le besoin de plus d’espace mémoire pour les simulations 3D nous a conduit à adopter une stratégie de résolution parallèle utilisant FreeFem+++ MPI et le solveur MUMPS

Modelling coronary blood flow using a non Newtonian fluid model : fractional flow reserve estimation

Dans cette thèse, nous explorons la possibilité d’une évaluation virtuelle des sténoses à travers la simulation de l’index de la réserve coronaire - appelée FFR en anglais - qui est un outil indispensable mais contraignant lors du diagnostic. Tout d’abord, nous utilisons un modèle d’écoulement 2D non Newtonien, puis un modèle d’interaction fluide structure faiblement couplé pour établir une étude préliminaire des principales caractéristiques de l’écoulement dans une portion sclérosée. Nous introduisons ensuite une méthodologie pour estimer la FFR virtuelle par analogie avec le dispositif médical. Le capteur FFR a été, dans un premier lieu, considéré non physique (intégré au domaine d’écoulement). Nous avons mené différents tests numériques pour relever les facteurs affectant la FFR virtuelle et présenté son profil par rapport aux différents paramètres considérés pour la lésion. Deuxièmement, nous présentons deux géométries réalistes : un arbre coronaire gauche - en 2D - obtenu à partir de la segmentation d’une image angiographique et une bifurcation en 3D. Nous définissons des modèles d’écoulement généralisés à l’intérieur des deux géométries et considérons que la paroi artérielle est rigide. La présence de plusieurs sorties dans ces nouvelles géométries nous a conduit à utiliser un nouveau type de conditions aux limites. A l’entrée, nous proposons une fonction bi-sinusoïdale s’approchant du profil de vitesse sanguine enregistré pour un arbre coronaire gauche. En ce qui concerne les sorties du domaine, nous considérons un modèle Windkessel à 2 éléments. Nous avons mené une étude comparative entre le modèle de Navier Stokes et le modèle non Newtonien considéré et entre les conditions limites de sorties libres et le modèle Windkessel présenté en 2D et défini le flux à l’intérieur de l’arbre de bifurcation 3D. Nous calculons également la FFR virtuel de deux lésions artificielles ajoutées à l’arbre coronaire et démontrons que l’angiographie seule ne suffit pas pour évaluer la sévérité de la sténose. Troisièmement, nous étudions - par modélisation 2D et 3D - une des raisons possibles de la dérive de pression pendant la mesure de la réserve coronaire FFR, représentée par la position et la configuration arbitraires du capteur de pression. Le capteur est considéré durant cette étude extrinsèque au domaine de l’écoulement. Nous considérons les mêmes modèles de flux non Newtoniens que précédemment. En 2D, le capteur FFR est assimilé à un disque avec une position variable incorporée dans l’arbre coronaire gauche. Alors que le domaine 3D correspond à une portion artérielle sclérosée à laquelle on introduit un tube 3D déformé (guide + capteur) avec une longueur et un coefficient de fléchissement donnés. L’effet de fléchissement du tube est obtenu grâce à un problème élastique basé sur la loi de Hooke. À l’aide d’un processus gaussien, nous modélisons le FFR en fonction des variables du capteur - et deux autres variables de la lésion - nous effectuons un ensemble d’expériences correspondant à l’espace d’hypercube considéré. Les données 2D indiquent une bonne précision pour la prédiction de FFR tandis que les données 4D confirment le fait que les micro-cathéters avec des diamètres importants surestiment la gravité des lésions. Les résultats obtenus démontrent que la dérive qui se produit en raison de la configuration variable du dispositif FFR peut induire en erreur lors de la classification de la sténose. Tous les algorithmes de résolution et les outils de simulation ont été implémentés sous le logiciel FreeFem++. Le besoin de plus d’espace mémoire pour les simulations 3D nous a conduit à adopter une stratégie de résolution parallèle utilisant FreeFem+++ MPI et le solveur MUMPS.In this thesis, we explore the possibility of virtual coronary stenosis assessment, through the simulation of Fractional Flow Reserve (FFR) measurement, that is an indispensable but binding tool during diagnosis. First, we use a 2D non Newtonian flow model, and later a weakly coupled FSI model to make a preliminary study of the main features of flow over a stenotic coronary arterial portion. We then introduce a methodology to estimate the virtual FFR in analogy with the clinical device. The FFR device was considered non-physical (integrated to the flow domain) at a first place. We led different experiments to enumerate the factors affecting the virtual FFR and computed its profiles with respect to different lesion’s parameters. Second, we consider two realistic geometries: a 2D left coronary tree obtained from the segmentation of an angiography image and a 3D bifurcation tree. We define generalized flow models inside the two geometries and consider the arterial wall to be rigid. The presence of several outlets in these new geometries led us to define a new type of boundary conditions. For the inlet, we propose a bi-sinusoidal function approaching the velocity profile recorded inside a left coronary tree. For the outlets, we implement a 2 elementWindkessel model. We led a comparative study between Navier Stokes and the flow model considered and between free outlets boundary conditions and Windkessel model in 2D and define the flow inside the 3D bifurcation tree. We also compute the virtual FFR of two artificial lesions added to the coronary tree and demonstrate that angiography alone is not enough to evaluate the severity of stenosis. Third, we investigate - through 2D and 3D modelling - one possible reason of pressure drift during FFR measurement, that is the arbitrary position and configuration of the FFR device, considered during this study extrinsic to the flow domain. We consider the same non Newtonian flow models as previously. In 2D, the FFR device is assimilated to a disk with a variable position incorporated inside the left coronary tree. While the 3D domain corresponds to a diseased arterial portion to which we introduce a deformed 3D tube (wire+sensor) with a given length and coefficient of bending. The bending effect of the tube is obtained thanks to an elastic problem based on Hooke’s law. Using a Gaussian process, we model the FFR depending on these variables - and two additional stenosis variables later - we perform a set of samples corresponding to the design space considered. The 2D data indicates a good accuracy for FFR prediction while the 4D data emphasis the fact that mi- crocatheters with important diameters overestimate lesion’s severity. The results obtained demonstrate that drift occurring because of the variable device configuration may lead to stenosis misclassification. All resolution algorithms and simulation tools were implemented under FreeFem++ software. The need of more space memory for 3D simulations led us to adopt a parallel resolution strategy using FreeFem++ MPI and MUMPS solver

Effect of Fiber Distribution on the Mechanical Behavior in Bending of Self-Compacting Mortars

The purpose of this work is to assess the steel fiber distribution effect on physical and mechanical properties of self-compacting mortar. An experimental study was conducted to see the fiber distribution during the implementation of self-compacting mortars that are fluid and on mechanical behavior in bending tensile strength. A method of placing self-compacting mortar in the molds has been developed to highlight the distribution of fibers in the cementitious matrix. The mortars are placed in prismatic molds in three layers. The amount of steel fibers differs from one layer to another. A total quantity of 90 kg /m3 was distributed in prismatic molds of dimensions 40x40x160 mm3. Straight and hooked ends steel fibers were used. The characteristics of mortars containing both types of fibers in the fresh and hardened state were measured and compared to those of self-compacting mortar without fibers. The pouring by layer allowed us to deduce that the distribution of metallic fibers has a significant effect on the hardened properties of the mortar. Indeed, the mechanical strength of the fiber-reinforced mortar depends on the nature and distribution of fibers in the cementitious matrix (mortar). A gain in bending tensile strength of 71.83% was recorded for self-compacting mortars elaborated with hooked end fibers and 52.11% for those containing straight steel fibers. Indeed, mortars containing entirely the same dosage of steel fibers (90 kg/m3) have a bending tensile strength that varies according to the fibers dosage by layers. Mortar samples with higher fiber content in the lower layer have a higher bending tensile strength than other samples with a higher fiber layer in the middle or layer above. However, it should be noted that steel fibers with hooks are much more effective than those without hooks. Indeed, the effect of fiber distribution is more significant for fibers without hooks because the hooks can slow down the movement of the fibers during the pouring of the mortar. The variation of the dosages per layer generated a difference in the deflection values for the mortars. The deflection is much higher for fiber-reinforced mortars (with hooks) compared to fiber-reinforced mortars without hooks

Recycling of Foundry Sand Wastes in Self-Compacting Mortars: Use as Cementitious Materials and Fine Aggregates

This work aims to study the possibility recycling of foundry sand wastes (FSW) as a cementations additive and fine aggregate in self-compacting mortars (SCM). For this, an experimental study was carried out to evaluate physical and mechanical properties of SCM. Firstly, sand is substituted by the foundry sand waste at dosages (0%, 10%, 30%, and 50%) by weight of the sand. Secondly cement is partially substituted by crushed foundry sand waste at different ratio (0%, 10%, 20%, 30%, and 50%) by weight of cement. The obtained results show that up to 50%, (FSW) can be used as fine aggregate for mortars without affecting the essential proprieties of mortar. However, beyond 50% of sand substitution, mortars lose their fluidity. The compressive strength of the mortars with 50% of cement substitution decreased compared to the control mortar. Value of the highest compressive strength recorded at 28 days, is of the order of 50 MPa for the mortar with 20% of cement substitution. Also, stress-strain curve show an acceptable mechanical behavior of FSW-based mortar at 50% of sand substitution