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

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called ‘superballs’, that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide–alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range

IL-33-mediated protection against experimental cerebral malaria is linked to induction of Type 2 innate lymphoid cells, M2 macrophages and regulatory T cells

Author Summary Cerebral malaria (CM) caused by the parasite Plasmodium sp . is a fatal disease, especially in children. Currently there is no effective treatment. We report here our investigation on the role of a recently discovered cytokine IL-33, in treating experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. IL-33 protects the mice against ECM. The protection is accompanied by a reduction of Th1 response and the enhancement of type 2 cytokine response. We also found that IL-33 mediates its protective effect by inducing a population of type 2 innate lymphoid cells (ILC2), which then polarize macrophages to alternatively-activated phenotypes (M2). M2 in turn expand regulatory T cells (Tregs) which suppress the deleterious Th1 response. Our report therefore reveals hitherto unrecognised mechanisms of the regulation of ECM and provide a novel function of IL-33

Specific Receptor Usage in Plasmodium falciparum Cytoadherence Is Associated with Disease Outcome

Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving several host receptors and a major parasite-derived variant antigen (PfEMP1) expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these have been inconclusive. In this study we have examined the cytoadherence patterns of 101 patient isolates from varying clinical syndromes to CD36 and ICAM-1, and have used variant ICAM-1 proteins to further characterise this adhesive phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

Placental malaria (PM) is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs) and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI) enhanced C5a receptor expression (CD88) on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10), chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta) and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function

Synthèse et évaluation biologique de glycoclusters contre la virulence bactérienne

Because of the appearance of more and more bacteria resistant to antibiotics, it is an urgent need to find new antibacterials. Several approaches have developed in the last few years such as antivirulence. This strategy is based on the weakening of the bacteria rather than killing it. Therefore, we interested in this principle and we developed new antibacterials to combat the bacterial virulence. We based our approach on multivalent scaffolds, as the multivalency is well know to improve the inhibition and/or activation of biological processes. We synthesized new multimeric compounds such as glycofullerenes, glycopillararenes and glycorotaxanes. We showed that these molecules are good inhibitors of glycosyltransferases and lectins, multivalent effects were observed in several cases.(DOCSC02) -- FUNDP, 201