Q-AIMD: A Congestion Aware Video Quality Control Mechanism

Following the constant increase of the multimedia traffic, it seems necessary to allow transport protocols to be aware of the video quality of the transmitted flows rather than the throughput. This paper proposes a novel transport mechanism adapted to video flows. Our proposal, called Q-AIMD for video quality AIMD (Additive Increase Multiplicative Decrease), enables fairness in video quality while transmitting multiple video flows. Targeting video quality fairness allows improving the overall video quality for all transmitted flows, especially when the transmitted videos provide various types of content with different spatial resolutions. In addition, Q-AIMD mitigates the occurrence of network congestion events, and dissolves the congestion whenever it occurs by decreasing the video quality and hence the bitrate. Using different video quality metrics, Q-AIMD is evaluated with different video contents and spatial resolutions. Simulation results show that Q-AIMD allows an improved overall video quality among the multiple transmitted video flows compared to a throughput-based congestion control by decreasing significantly the quality discrepancy between them

Motif pour la métamodélisation: Commentaire attribué

National audienc

A kernel transformation language for metamodel evolution and reversible model co-evolution

This report defines MicroDif, a kernel transformation language for metamodel evolution and reversible model co-evolution. To begin with, a kernel subset of Ecore is highlighted and formally defined thanks to a suitable denotational semantics. Then MicroDif is formally defined upon this subset. In a first step, the focus is put on metamodel evolution provided by a set of refactoring operators. In a second step, the focus is put on model co-evolution which is intended to be reversible thanks to a dedicated pair of transformations respectively called migration and recontextualization. Each MicroDif operator is also provided with a dedicated predicate which explains the sufficient conditions for a model to remain valid after these transformations

Relationships between sterol/phospholipid composition and xenobiotic transport in nematodes

International audienceTherapeutic failure limits prophylaxis of nematode diseases and has been mainly attributed to mutations in cellular targets of anthelmintics. Besides these specific mechanisms, alterations of drug transport also occur in parasites resistant to anthelmintics and depend on both the presence of membrane pumps such as P-glycoprotein (Pgp) and on the lipid composition of membranes. We recently showed in the nematode Haemonchus contortus, using eggs as a model, that the total cholesterol (TC) concentration alters the transport of lipophilic molecules due to membrane pumps such as P-glycoprotein and the resistance to anthelmintics. The effect of TC may depend on the presence of other lipids interacting with TC. Therefore, we analysed the lipid composition and its relationship with Pgp and resistance to anthelmintics. Better correlations were found between Pgp and free cholesterol (FC) than with TC. We also showed that the relationships between lipid composition and resistance to anthelmintics or Pgp depended on the equilibrium between FC and phospholipids (PLs), mainly PLs known to be present primarily in either the external leaflets of cell membranes or the internal leaflets. The PLs phosphatidylcholine and phosphatidylethanolamine played the most significant role, but phosphatidic acid also influenced drug resistance

A comparative study of two formal semantics of the SIGNAL language

International audienceSIGNAL is a part of the synchronous languages family, which are broadly used in the design of safety-critical real-time systems such as avionics, space systems, and nuclear power plants. There exist several semantics for SIGNAL, such as denotational semantics based on traces (called trace semantics), denotational semantics based on tags (called tagged model semantics), operational semantics presented by structural style through an inductive definition of the set of possible transitions, operational semantics defined by synchronous transition systems (STS), etc. However, there is little research about the equivalence between these semantics.In this work, we would like to prove the equivalence between the trace semantics and the tagged model semantics, to get a determined and precise semantics of the SIGNAL language. These two semantics have several different definitions respectively, we select appropriate ones and mechanize them in the Coq platform, the Coq expressions of the abstract syntax of SIGNAL and the two semantics domains, i.e., the trace model and the tagged model, are also given. The distance between these two semantics discourages a direct proof of equivalence. Instead, we transformthem to an intermediate model, which mixes the features of both the trace semantics and the tagged model semantics. Finally, we get a determined and precise semantics of SIGNAL

Mikrometastatisk kreftspredning til lungene og immunologisk premetastatisk nisje hos hunder med beinkreft

Cancer is currently ranked as a leading cause of death in humans and dogs, most often due to metastatic disease. The pre-metastatic niche (PMN) represents the metastasis-supporting microenvironmental changes that occur in a distant target organ before metastasis. The primary tumour shapes the PMN in the metastatic target organ by releasing soluble factors and extracellular vesicles. PMN-formation is an essential step in metastatic development and drives organotropism. Osteosarcoma (OS) is the most common primary bone tumour in dogs and humans, with a high metastatic rate, despite a low metastatic prevalence at diagnosis. Although most dogs develop pulmonary metastases (>90%), the prevalence of micrometastases or PMN formation at diagnosis is unknown. In this thesis, we assessed the prevalence of pulmonary micrometastases and PMN formation in dogs with OS without macroscopic metastases, focusing on macrophage and bone marrow-derived cell populations. In addition, we assessed the phenotype and transcriptomes of in vitro-generated canine monocyte-derived tumour-conditioned macrophages (TCMΦ) and compared them to classically (M1) and alternatively activated (M2) macrophages. We prospectively enrolled dogs with treatment naïve OS (n=15), which we necropsied and sampled immediately after euthanasia. We divided these dogs into those with macroscopic metastases (n=5) and not (n=10). Control dogs without cancer (n=10), systemic inflammatory diseases, allergy, or atopy, and not receiving immunomodulating drugs were enrolled retrospectively from the pathology archives. Blood from healthy dogs (n=6) was collected to generate macrophages in vitro. We performed chromogenic immunohistochemistry (IHC) with TP-3 to immunolabel micrometastasis in seven frozen lung samples from each dog with OS without metastases. We labelled samples from two dogs with OS with macroscopic metastases and two without cancer as controls. In vitro generated TCMΦ were compared to M1 and M2 macrophages using flow cytometry (CD206, CD209, CD11d, FcεRI, and LYVE-1) and RNA-sequencing. A lung sample from each of the 15 dogs with OS and ten control dogs without cancer was immunolabelled using multiplex immunofluorescence (CD204, CD206 and CD11d) to identify macrophages, their phenotype, and bone marrow-derived cells. The main findings were: - Pulmonary micrometastases could be detected with TP-3 immunohistochemistry in a subset of dogs with OS before macroscopic metastases had developed. The prevalence of micrometastases (20%) was significantly lower than expected based on post-surgical metastatic rates. - TCMΦ had a high expression of several M2-associated phenotypical markers on flow cytometry, while RNA-Seq showed upregulation of several additional M2-markers. TCMΦ had an M2-skewed cytokine and chemokine profile and exhibited several similarities to human and murine TCMΦ. - The number of CD204+ macrophages, CD206+ macrophages and monocytes, and CD11d+ bone marrow-derived cells (BMDCs) in the lungs of dogs with OS without metastases was significantly higher than in dogs without cancer. Similarly, the total nucleated cell count was higher in dogs with OS than in those without cancer. Dogs with established pulmonary metastases had significantly lower numbers of CD11d+ BMDCs than dogs with OS without metastases. In summary, this thesis provides new insight into the early phases of metastasis in dogs with OS. Furthermore, the results help bridge the knowledge gap between canine and human tumour immunology and provides new markers to study tumour-associated macrophages (TAMs) in dogs. In addition, our findings support the existence of an immunological PMN in a naturally occurring cancer model.Kreft er i dag ansett som vanligste dødsårsaken hos både mennesker og hunder, som oftest som følge av spredning av kreftsykdommen (metastatisk sykdom). Den premetastatiske nisjen (PMN) defineres som de metastasefremmende endringene som skjer i mikromiljøet i et organ der det kommer til å utvikles spredninger. Primærsvulsten danner den PMN i slike målorganer ved hjelp av løselige stoffer og ekstracellulære vesikler som føres med blodet. PMN-dannelse anses som et viktig steg i utviklingen av spredninger og er med på å bestemme hvor svulsten sprer seg. Osteosarkom (OS) er den vanligste primærsvulsten som oppstår i knoklene hos både mennesker og hunder, og har en stor evne til å metastasere på tross av en lav metastaseforekomst ved diagnosetidspunktet. Selv om de fleste hunder med OS utvikler lungemetastaser (>90%), er forekomsten av mikrometastaser og PMN dannelse ved diagnosetidspunktet ukjente. I denne avhandlingen har vi undersøkt forekomsten av mikrometastaser og PMN dannelse, med fokus på makrofager og celler fra beinmargen, hos hunder med OS uten synlige metastaser. I tillegg har vi undersøkt fenotypiske egenskaper og genuttrykket til in vitro-produserte tumorkondisjonerte makrofager (TCMΦ). Disse makrofagene ble sammenliknet med klassisk aktiverte (M1) og alternativt aktiverte (M2) makrofager. Vi rekrutterte hunder med OS som ikke hadde fått noen form for kreftbehandling (n=15) prospektivt og obduserte og samlet prøver fra disse umiddelbart etter avliving. Disse hundene ble så delt inn i to grupper; de med synlige metastaser (n=5) og de uten (n=10). Vi rekrutterte også kontrollhunder (n=10) retrospektivt fra patologiarkivene. Disse kontrollhundene var frie for systemiske inflammatoriske sykdommer og allergier, og hadde ikke stått på medisiner som kunne påvirke immunforsvaret. Vi samlet også blod fra friske hunder (n=6) for å produsere makrofager in vitro. Vi gjennomførte immunhistokjemisk (IHC) farging, med TP-3, av syv nedfryste lungeprøver fra hver av hundene med OS uten metastaser for å identifisere mikrometastaser. I tillegg farget vi prøver fra to hunder med OS med metastaser og to hunder uten kreft som kontroller. In vitro-produserte TCMΦ ble sammenliknet med M1 og M2 makrofager ved hjelp av flowcytometri (med følgende markører: CD206, CD209, CD11d, FcεRI og LYVE-1) og RNA sekvensering. Én lungevevsprøve fra hver av de 15 hundene med OS og fra de 10 kontrollhundene uten kreft ble farget ved hjelp av immunfluoresens med følgende markører: CD204, CD206 og CD11d, for å kartlegge forekomsten av makrofager og deres fenotype, samt forekomsten av celler fra beinmargen (beinmargsderiverte celler, BMDCs). Hovedfunnene våre var: -Vi påviste mikrometastaser i lungene hos kun en liten andel av hundene med OS før de hadde utviklet synlige lungemetastaser ved hjelp av TP-3 immunhistokjemi. Forekomsten av lungemikrometastaser (20%) var betydelig lavere enn forventet basert på forekomsten av lungemetastaser etter fullstendig kirurgisk fjerning av primærsvulsten. -TCMΦ hadde et høyt uttrykk av flere M2-typiske fenotypiske overflatemarkører ved flowcytometri. RNA-sekvensering viste i tillegg at ytterligere M2-typiske markører var oppregulerte i TCMΦ. Cytokin- og kjemokinprofilene til TCMΦ liknet på dem hos M2 makrofager og også på dem hos TCMΦ fra mennesker og mus. -Forekomsten av CD204+ makrofager, CD206+ makrofager og monocytter, og CD11d+ BMDCs var høyere i lungene til hundene med OS uten metastaser enn hos hundene uten kreft. I tillegg var det totale antallet kjerneholdige celler høyere hos hunder med OS enn hos dem uten kreft. Hundene med etablerte lungemetastaser hadde betydelig lavere antall CD11d+ BMDCs i lungene enn hundene med OS uten synlige metastaser. Resultatene i denne avhandlingen bidrar med ny kunnskap om de tidlige fasene av den metastatiske utviklingen hos hunder med OS. De bidrar også til å belyse kunnskapshull i tumorimmunologien hos hund, og vi har funnet nye markører som kan brukes til å studere TAMs hos hund. Funnene våre gir gode holdepunkter for å si at en immunologisk PMN faktisk forekommer hos en modell med naturlig oppstått kreftsykdom.The Research Fund for Cancer in Dogs ; Evidensia Oslo Animal HospitalacceptedVersio

Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections

The intestinal nematode Heligmosomoides bakeri has undergone 2 name changes during the last 4 decades. Originally, the name conferred on the organism in the early 20th century was Nematospiroides dubius, but this was dropped in favour of Heligmosomoides polygyrus, and then more recently H. bakeri, to distinguish it from a closely related parasite commonly found in wood mice in Europe. H. bakeri typically causes long-lasting infections in mice and in this respect it has been an invaluable laboratory model of chronic intestinal nematode infections. Resistance to H. bakeri is a dominant trait and is controlled by genes both within and outside the MHC. More recently, a significant QTL has been identified on chromosome 1, although the identity of the underlying genes is not yet known. Other QTL for resistance traits and for the accompanying immune responses were also defined, indicating that resistance to H. bakeri is a highly polygenic phenomenon. Hence marker-assisted breeding programmes aiming to improve resistance to GI nematodes in breeds of domestic livestock will need to be highly selective, focussing on genes that confer the greatest proportion of overall genetic resistance, whilst leaving livestock well-equipped genetically to cope with other types of pathogens and preserving important production traits

Contribution of laboratory tests in the diagnosis of gastrointestinal strongylosis in ruminants and choice of treatments

The clinical diagnosis of gastrointestinal strongylosis in ruminants is often difficult because of its relatively unspecific symptomatology. Moreover, as the use of prophylactic treatments is increasingly preferred over curative treatments, quantitative and accurate tests for diagnosis are required. As the gradual development of anthelmintic resistance restricts further the choice and use of molecules, laboratory diagnostic tests become useful and even often essential. Three main categories of tests are available: traditional parasitological techniques, serological assays linked to the lesions caused by the parasites, and tests for the detection of anthelmintic resistance. The principles, conditions of use and limits of interpretation of these tests are described in this brief synthesis.Le diagnostic clinique des strongyloses gastro-intestinales des ruminants est difficile dans un grand nombre de cas en raison du manque de symptomatologie très spécifique. De plus, La tendance de plus en plus grande à traiter les animaux préventivement et non plus curativement implique de disposer de moyens de diagnostic quantitatifs sensibles. Le développement progressif de phénomènes de résistance aux anthelminthiques impose des contraintes supplémentaires quant au choix et à l'utilisation des molécules. Les tests de diagnostic de laboratoire sont utiles et même souvent indispensables, dans ces démarches. Trois grandes catégories de tests sont disponibles : les tests parasitologiques classiques, les dosages sériques en relation avec les lésions occasionnées par les parasites, les tests de détection des résistances. Les principes, les conditions d'utilisation et les limites d'interprétation sont décrits dans cette courte synthèse

Efflux pump inhibitors: a progress in parasitic nematode control

Animal and human nematode infestations are controlled primarily with anthelmintics. However, their continuous administration during outbreaks represents a significant expense for livestock farms. In humans also, their high cost limits their use in poor areas where parasitic worms are most prevalent and most pathogenic. Furthermore, nematodes have developed drug resistance mechanisms, specific or not, which reduce the efficiency of treatments. Among these mechanisms, the accelerated removal of anthelmintics by efflux pumps present in cell membranes, eggshells and cuticles is a major limiting factor. This accelerated efflux is very similar to the mechanism of multidrug resistance (MDR) observed in cancer cells and protozoa. This phenomenon is all the more worrying that it applies simultaneously to several chemical families of drugs. One solution is to block the efflux pumps in parasites with inhibitors. These pumps belong to the large family of ABC transporters, which have many characteristics in common. Some have major physiological functions or protect organs from toxic agents. As much as possible, inhibitors should not have any effect on the pumps of the host and target the parasite exclusively. The diversity of these pumps is greater in nematodes than in vertebrates, and there are differences in their protein structures. Some parts of these proteins are relatively well-conserved in the animal kingdom, while other parts show little homology from one transporter to another or from one species to another. The affinity of these pumps for the substrates can vary with the mutation of a single amino acid. These differences could be used to develop inhibitors specific of nematode pumps, which could then be combined with anthelmintics.Les anthelminthiques constituent le moyen majeur de lutte contre les nématodoses animales et humaines. Administrés de façon continue en période d'infestation, ils représentent un coût considérable pour les élevages. Chez l'homme, ce coût limite leur distribution dans les zones géographiques défavorisées où pourtant les vers parasites sont les plus nombreux et les plus pathogènes. De plus, les nématodes ont développé des mécanismes de chimiorésistance, spécifiques ou non, qui réduisent l'efficacité des anthelminthiques. Parmi ces mécanismes, le rejet accéléré des molécules thérapeutiques par des pompes d'efflux est semblable au mécanisme de multi-résistance aux médicaments (MDR) des cellules cancéreuses et des protozoaires. Ces pompes sont présentes dans les membranes cellulaires, la coque des œufs et les cuticules des nématodes. Ce rejet accéléré est d'autant plus préoccupant qu'il s'applique simultanément à plusieurs familles chimiques d'antiparasitaires. Une des solutions consiste à bloquer les pompes d'efflux des parasites à l'aide d'inhibiteurs. Ces pompes appartiennent à la grande famille des transporteurs ABC dotés de nombreuses caractéristiques communes. Certains de ces transporteurs jouent des rôles physiologiques déterminants ou protègent les organes des molécules toxiques. Les inhibiteurs doivent donc être autant que possible dépourvus d'action sur les pompes de l'hôte. La variabilité des pompes est plus importante chez les nématodes que chez les vertébrés, et il existe des différences dans leur structure protéique. Certaines parties de ces protéines sont bien conservées dans le règne animal, tandis que d'autres présentent peu d'homologie d'un transporteur à l'autre ou, pour un même transporteur, d'une espèce à l'autre. L'affinité de ces pompes pour les substrats peut varier en fonction de la mutation d'un seul acide aminé. Ces différences pourraient être mises à profit pour développer des inhibiteurs spécifiques des pompes des nématodes et les utiliser en association avec les anthelminthiques