IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes

Intraepithelial lymphocytes (IEL) respond to IL-15 complexed with IL-15Ra but how this intrinsically affects IEL is unclear. Here the authors use proteomics analyses of the main mouse IEL subsets and identify PIM kinases as essential for IEL proliferation, metabolism and effector function downstream of IL-15

Energy deposition studies for the Upgrade II of LHCb at the CERN Large Hadron Collider

The Upgrade II of the LHCb experiment is proposed to be installed during the CERN Long Shutdown 4, aiming to operate LHCb at 1.5x$10^{34}cm^{-2}s^{-1}$ that is 75 times its design luminosity and reaching an integrated luminosity of about $400 fb^{-1}$ by the end of the High Luminosity LHC era. This increase of the data sample at LHCb is an unprecedented opportunity for heavy flavour physics measurements. A first upgrade of LHCb, completed in 2022, has already implemented important changes of the LHCb detector and, for the Upgrade II, further detector improvements are being considered. Such a luminosity increase will have an impact not only on the LHCb detector but also on the LHC magnets, cryogenics and electronic equipment placed in the IR8. In fact, the LHCb experiment was conceived to work at a much lower luminosity than ATLAS and CMS, implying minor requirements for protection of the LHC elements from the collision debris and therefore a different layout around the interaction point. The luminosity target proposed for the Upgrade II requires to review the layout of the entire insertion region in order to ensure safe operation of the LHC magnets and to mitigate the risk of failure of the electronic devices. The objective of this paper is to provide an overview of the implications of the Upgrade II of LHCb in the experimental cavern and in the tunnel with a focus on the LHCb detector, electronic devices and accelerator magnets

Evolution of protoplanetary disks from their taxonomy in scattered light: spirals, rings, cavities, and shadows

The variety of observed protoplanetary disks in polarimetric light motivates a taxonomical study to constrain their evolution and establish the current framework of this type of observations. We classified 58 disks with available polarimetric observations into six major categories (Ring, Spiral, Giant, Rim, Faint, and Small disks) based on their appearance in scattered light. We re-calculated the stellar and disk properties from the newly available GAIA DR2 and related these properties with the disk categories. More than a half of our sample shows disk sub-structures. For the remaining sources, the absence of detected features is due to their faintness, to their small size, or to the disk geometry. Faint disks are typically found around young stars and typically host no cavity. There is a possible dichotomy in the near-IR excess of sources with spiral-disks (high) and ring-disks (low). Like spirals, shadows are associated with a high near-IR excess. If we account for the pre-main sequence evolutionary timescale of stars with different mass, spiral arms are likely associated to old disks. We also found a loose, shallow declining trend for the disk dust mass with time. Protoplanetary disks may form sub-structures like rings very early in their evolution but their detectability in scattered light is limited to relatively old sources (more than 5 Myr) where the recurrently detected disk cavities allow to illuminate the outer disk. The shallow decrease of disk mass with time might be due to a selection effect, where disks observed thus far in scattered light are typically massive, bright transition disks with longer lifetime than most disks. Our study points toward spirals and shadows being generated by planets of fraction-to-few Jupiter masses that leave their (observed) imprint on both the inner disk near the star and the outer disk cavity.This work has been supported by the project PRININAF 2016 The Cradle of Life - GENESIS-SKA (General Conditions in Early Planetary Systems for the rise of life with SKA). A.G. acknowledges the support by INAF/Frontiera through the "Progetti Premiali" funding scheme of the Italian Ministry of Education, University, and Research. We acknowledge funding from ANR of France under contract number ANR-16-CE31-0013 (Planet Forming disks). P.P. acknowledges support by NASA through Hubble Fellowship grant HST-HF2-51380.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS 5-26555

: Géoprospective territoriale à l'île de La Réunion

16 p.National audienceThe objective of this paper is to present an approach for experimenting territorial prospective analysis based on spatial modelling. This approach is carried out in the framework of the DESCARTES project which aims at developing a spatial simulation tool to support the design and analysis of different scenarios for land-use allocation in Reunion Island in terms of environmental services. The spatial modelling tool is composed of two complementary applications: (i) the Ocelet modelling language and its land dynamics simulation environment, and (ii) the Margouill@ platform. The first demonstrator, a model of farm land consumption by urbanization, was developed and presented during workshops in order to test the role of the spatial simulation tool in support of a collaborative innovation process among stakeholders, and to foster new research on social learning, spatial simulation of environmental services, and scale change issues.L'objectif de cet article est de présenter une démarche de construction d'un exercice de prospective territoriale basé sur un outil de modélisation spatiale. Cette démarche est mise en œuvre dans le cadre du projet ANR DESCARTES dont l'objectif est de construire un outil de simulation cartographique pour analyser différents scénarios d'affectation de l'usage des sols à l'Ile de La Réunion, en termes de services environnementaux. La plateforme de simulation cartographique est composée de deux applications complémentaires (i) le langage de modélisation Ocelet et son environnement de simulation de paysages dynamiques, et (ii) la plateforme Margouill@. Le développement puis la présentation, en atelier, d'un premier démonstrateur sur la consommation des terres agricoles par l'urbanisation a permis de tester l'outil cartographique comme support d'un processus d'innovation collective entre les parties prenantes, et d'ouvrir de nouveaux champs de recherche sur l'analyse de la démarche par les apprentissages, la spatialisation et la simulation prospective des services écosystémiques, et la prise en compte du changement d'échelle

Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma

JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS. A two-stage Simon design was used. JX-594 was administered intra-venously at the dose 1.109 every 2 weeks for the first 3 injections and then every 3 weeks. Cyclophosphamide was given orally at the dose of 50 mg BID 1 week on 1 week off. The primary endpoint was the 6-month non progression rate. 20 patients were included (arm 1:15, arm 2:5). The two most frequent toxicities were grade 1 fatigue and fever and grade 2 fatigue and grade 2 lymphopenia in arms 1 and 2, respectively. In arm 1, 12 patients were assessable for the efficacy analysis. None of them were progression-free at 6 months indicating that the first stage of the Simon's design was not satisfied. One patient out 4 assessable for efficacy was progression-free at 6 months in arm 2. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as CXCL10 and soluble CD8 antigen in arm 1. Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS

Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts