The prominent role of neutrophils during the initial phase of infection by Leishmania parasites.

Neutrophils are rapidly and massively recruited to the site of Leishmania inoculation, where they phagocytose the parasites, some of which are able to survive within these first host cells. Neutrophils can thus provide a transient safe shelter for the parasites, prior to their entry into macrophages where they will replicate. In addition, neutrophils release and synthesize rapidly several factors including cytokines and chemokines. The mechanism involved in their rapid recruitment to the site of parasite inoculation, as well as the putative consequences of their massive presence on the microenvironment of the focus of infection will be discussed in the context of the development of the Leishmania-specific immune response

Phototropin-mediated perception of light direction in leaves regulates blade flattening.

One conserved feature among angiosperms is the development of flat thin leaves. This developmental pattern optimizes light capture and gas exchange. The blue light (BL) receptors phototropins are required for leaf flattening, with the null phot1phot2 mutant showing curled leaves in Arabidopsis (Arabidopsis thaliana). However, key aspects of their function in leaf development remain unknown. Here, we performed a detailed spatiotemporal characterization of phototropin function in Arabidopsis leaves. We found that phototropins perceive light direction in the blade, and, similar to their role in hypocotyls, they control the spatial pattern of auxin signaling, possibly modulating auxin transport, to ultimately regulate cell expansion. Phototropin signaling components in the leaf partially differ from hypocotyls. Moreover, the light response on the upper and lower sides of the leaf blade suggests a partially distinct requirement of phototropin signaling components on each side. In particular, NON PHOTOTROPIC HYPOCOTYL 3 showed an adaxial-specific function. In addition, we show a prominent role of PHYTOCHROME KINASE SUBSTRATE 3 in leaf flattening. Among auxin transporters, PIN-FORMED 3,4,7 and AUXIN RESISTANT 1 (AUX1)/LIKE AUXIN RESISTANT 1 (LAX1) are required for the response while ABCB19 has a regulatory role. Overall, our results show that directional BL perception by phototropins is a key aspect of leaf development, integrating endogenous and exogenous signals

Modeling and Numerical Simulation of a Complete Hydrolelectric Production Site

For many years the EPFL Laboratory for Electrical Machines develops SIMSEN, a numerical software package for the simulation in transient and steady-state conditions of electrical power systems and adjustable speed drives, having an arbitrary topology. SIMSEN is based on a collection of modules, each corresponding to one system component (machines, converters, transformers, control devices, etc.). This contribution presents the extension of SIMSEN to the hydraulic components of a hydroelectric power plant including pump-turbine, valve, penstock, surge tank, gallery, reservoir, etc. The basic idea is to define for each hydraulic component an equivalent electric component which can be introduced in the existing electric version of SIMSEN. Doing this, it becomes possible to use the modularity of the electric version to define the complete topology of the hydroelectric power plant and the connected electrical network. This extension enables numerical simulations taking precisely into account the interactions between the hydraulic and the electric parts of the system during transients. It is therefore useful for transient and stability analyses as well as for the design optimization

Research practice development for nuclear medicine technologists: an innovative experience

Introduction - European nuclear medicine technologist’s education is delivered by Higher Education Institutions and students obtain a grade of Bachelor of Sciences (BSc), during which they are initiated to research during their studies. Once BSc nuclear medicine technologists are in professional practice, they have very few opportunities to develop a real research experience and they rather become passive users than active contributors the growth of scientific knowledge in nuclear medicine. Aim - To describe and discuss an innovative educational and professional experience aimed in strengthen research knowledge, skills and competencies of former nuclear medicine technologists student in the context of an international mobility stay

Wedgebox analysis of four-lepton events from neutralino pair production at the LHC

`Wedgebox' plots constructed by plotting the di-electron invariant mass versus the di-muon invariant mass from pp -> e^+e^- mu^+ mu^- + missing energy signature LHC events. Data sets of such events are obtained across the MSSM input parameter space in event-generator simulations, including cuts designed to remove SM backgrounds. Their study reveals several general features: (1)Regions in the MSSM input parameter space where a sufficient number of events are expected so as to be able to construct a clear wedgebox plot are delineated. (2)The presence of box shapes on a wedgebox plot either indicates the presence of heavy Higgs bosons decays or restricts the location to a quite small region of low \mu and M_2 values \lsim 200 GeV, a region denoted as the `lower island'. In this region, wedgebox plots can be quite complicated and change in pattern rather quickly as one moves around in the (\mu, M_2) plane. (3)Direct neutralino pair production from an intermediate Z^{0*} may only produce a wedge-shape since only \widetilde{\chi}_2^0\widetilde{\chi}_3^0 decays can contribute significantly. (4)A double-wedge or wedge-protruding-from-a-box pattern on a wedgebox plot, which results from combining a variety of MSSM production processes, yields three distinct observed endpoints, almost always attributable to \widetilde{\chi}_{2,3,4}^0 \to \widetilde{\chi}_1^0 \ell^+\ell^- decays, which can be utilized to determine a great deal of information about the neutralino and slepton mass spectra and related MSSM input parameters. Wedge and double-wedge patterns are seen in wedgebox plots in another region of higher \mu and M_2 values, denoted as the`upper island.' Here the pattern is simpler and more stable as one moves across the (\mu, M_2) input parameter space.Comment: 28 pages (LaTeX), 8 figures (encapsulated postscript

Active Faulting in Lake Constance (Austria, Germany, Switzerland) Unraveled by Multi-Vintage Reflection Seismic Data

Probabilistic seismic hazard assessments are primarily based on instrumentally recorded and historically documented earthquakes. For the northern part of the European Alpine Arc, slow crustal deformation results in low earthquake recurrence rates and brings up the necessity to extend our perspective beyond the existing earthquake catalog. The overdeepened basin of Lake Constance (Austria, Germany, and Switzerland), located within the North-Alpine Molasse Basin, is investigated as an ideal (neo-) tectonic archive. The lake is surrounded by major tectonic structures and constrained via the North Alpine Front in the South, the Jura fold-and-thrust belt in the West, and the Hegau-Lake Constance Graben System in the North. Several fault zones reach Lake Constance such as the St. Gallen Fault Zone, a reactivated basement-rooted normal fault, active during several phases from the Permo-Carboniferous to the Mesozoic. To extend the catalog of potentially active fault zones, we compiled an extensive 445 km of multi-channel reflection seismic data in 2017, complementing a moderate-size GI-airgun survey from 2016. The two datasets reveal the complete overdeepened Quaternary trough and its sedimentary infill and the upper part of the Miocene Molasse bedrock. They additionally complement existing seismic vintages that investigated the mass-transport deposit chronology and Mesozoic fault structures. The compilation of 2D seismic data allowed investigating the seismic stratigraphy of the Quaternary infill and its underlying bedrock of Lake Constance, shaped by multiple glaciations. The 2D seismic sections revealed 154 fault indications in the Obersee Basin and 39 fault indications in the Untersee Basin. Their interpretative linkage results in 23 and five major fault planes, respectively. One of the major fault planes, traceable to Cenozoic bedrock, is associated with a prominent offset of the lake bottom on the multibeam bathymetric map. Across this area, high-resolution single channel data was acquired and a transect of five short cores was retrieved displaying significant sediment thickness changes across the seismically mapped fault trace with a surface-rupture related turbidite, all indicating repeated activity of a likely seismogenic strike-slip fault with a normal faulting component. We interpret this fault as northward continuation of the St. Gallen Fault Zone, previously described onshore on 3D seismic data

Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Immune-mediated necrotising myopathy is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase concentrations, and autoantibodies recognising 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or the signal recognition particle (SRP). No approved therapies exist for people with immune-mediated necrotising myopathy. Previous studies have suggested that complement activation might be pathogenic in immune-mediated necrotising myopathy; therefore, zilucoplan, a complement C5 (C5) inhibitor, could be a potential therapy. We aimed to evaluate the efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive immune-mediated necrotising myopathy. METHODS: IMNM-01 was a phase 2, multicentre, randomised, double-blind, placebo-controlled study done at 15 hospital sites across the USA, the UK, France, and the Netherlands. Participants aged 18–74 years were eligible for inclusion if they had a clinically confirmed diagnosis of immune-mediated necrotising myopathy, positive serology for anti-HMGCR or anti-SRP autoantibodies, clinical evidence of weakness, serum total creatine kinase concentration of more than 1000 U/L at screening, and no change in glucocorticoids or other immunosuppressive therapies for 30 days before baseline or expected during the first 8 weeks of the study. Participants were randomly assigned (1:1) to receive daily subcutaneous zilucoplan (0·3 mg/kg) or placebo for 8 weeks by use of a computerised randomisation algorithm; with optional enrolment in the study open-label extension. Randomisation was stratified by autoantibody status. Participants and study staff were masked to treatment group assignment. Primary efficacy endpoint (in the intent-to-treat population, defined as all participants who were randomly assigned to a treatment group) was percent change from baseline to week 8 in creatine kinase concentrations. Safety analyses were performed on the safety population (participants who received at least one dose of study drug during the main study, irrespective of whether they continued to the extension period—study participants were analysed on the basis of the treatment received). This study is registered with ClinicalTrials.gov, NCT04025632. FINDINGS: Between Nov 7, 2019, and Jan 7, 2021, we randomly assigned 27 participants (13 female and 14 male) to receive zilucoplan (n=12) or placebo (n=15). All 27 participants completed the 8-week main study. At week 8 there were no significant differences between treatment groups in median percent change of creatine kinase concentrations versus baseline (–15·1% [IQR –31·1 to 3·2] in the zilucoplan group vs –16·3% [–43·8 to 5·9] in the placebo group; p=0·46) and no clinically relevant improvement over time within the treatment group despite target engagement based on mode of action. There were no unexpected adverse safety or tolerability findings. Treatment-emergent adverse events were reported in nine (75%) of 12 participants in the zilucoplan group, and in 13 (87%) of 15 participants in the placebo group, and serious treatment-emergent adverse events were reported in zero participants in the zilucoplan group and three (20%) participants in the placebo group. The most frequent treatment-emergent adverse events were headache (four [33%] participants in the zilucoplan group and four [27%] participants in the placebo group) and nausea (three [25%] participants in the zilucoplan group and three [20%] participants in the placebo group). INTERPRETATION: C5 inhibition does not appear to be an efficacious treatment modality for people with immune-mediated necrotising myopathy. Rather than being the primary driver for disease activity, complement activation might be secondary to muscle injury. FUNDING: Ra Pharmaceuticals (now part of UCB Pharma)

Membrane-Bound TNF Induces Protective Immune Responses to M. bovis BCG Infection: Regulation of memTNF and TNF Receptors Comparing Two memTNF Molecules

Several activities of the transmembrane form of TNF (memTNF) in immune responses to intracellular bacterial infection have been shown to be different from those exerted by soluble TNF. Evidence is based largely on studies in transgenic mice expressing memTNF, but precise cellular mechanisms are not well defined and the importance of TNF receptor regulation is unknown. In addition, memTNF activities are defined for a particular modification of the extracellular domain of TNF but a direct comparison of different mutant memTNF molecules has not been done in vivo

"Kultur" als Form symbolischer Gewalt: Grenzziehungsprozesse im Kontext von Migration am Beispiel der Schweiz

Die Schweiz gilt international als Modell eines gelungenen Multikulturalismus, dann nämlich wenn es das Zusammenleben der vier Sprachgruppen (Romands, DeutschschweizerInnen, TessinerInnen, RäteromanInnen) betrifft. Ein sprachlicher wie auch religiöser Pluralismus ist und war stets ein Grundbaustein des Selbstverständnisses der „Willensnation“ Schweiz. Geht es aber um MigrantInnen präsentiert sich die Geschichte anders, denn in diesem Falle erscheinen religiöse und ethnisch-kulturelle Pluralität vorwiegend als problematisch. MigrantInnen gehören entsprechend den öffentlichen und politischen Diskursen nicht zum multikulturellen Staat, vielmehr sind Prozesse kollektiver Grenzziehungen und damit Schließungsmechanismen zu beobachten, in denen Ethnizität, Religion und Kultur zu den wichtigsten Differenzierungsmerkmale werden, wie Gemeinsamkeiten gegen innen (SchweizerInnen) und Barrieren gegen außen (Ausländer, Migranten, Muslims, etc.) hergestellt werden. Ich argumentiere in diesem Kapitel, dass sich dieser „Kulturdiskurs“ im letzten Jahrzehnt verstärkt hat und gleichzeitig semantischen Verschiebungen unterworfen war. Mittels der Grenzziehungsperspektive wird historisch nachvollzogen, wie Zuwanderung und Integration in politischen Debatten und Gesetz zunehmend kulturalisiert und ethnisiert wurden. Ein Fallbeispiel aus der Forschung dient mir anschließend der Veranschaulichung dieser theoretischen Perspektive und dieses „neuen“ Essentialismus