Neutron diffraction and diffraction contrast imaging for mapping the TRIP effect under load path change

The transformation induced plasticity (TRIP) effect is investigated during a load path change using a cruciform sample. The transformation properties are followed by in-situ neutron diffraction derived from the central area of the cruciform sample. Additionally, the spatial distribution of the TRIP effect triggered by stress concentrations is visualized using neutron Bragg edge imaging including, e.g., weak positions of the cruciform geometry. The results demonstrate that neutron diffraction contrast imaging offers the possibility to capture the TRIP effect in objects with complex geometries under complex stress states.Fil: Polatidis, Efthymios. Paul Scherrer Institute; SuizaFil: Morgano, Manuel. Paul Scherrer Institute; SuizaFil: Malamud, Florencia. Comision Nacional de Energia Atomica. Gerencia D/area Invest y Aplicaciones No Nucleares. Departamento Haces de Neutrones del Ra10 - Cab.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Bacak, Michael. Paul Scherrer Institute; SuizaFil: Panzner, Tobias. Paul Scherrer Institute; Suiza. Swissneutronics; SuizaFil: Van Swygenhoven, Helena. Paul Scherrer Institute; Suiza. École Polytechnique Fédérale de Lausanne; SuizaFil: Strobl, Markus. Paul Scherrer Institute; Suiz

Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14-CD15(high) and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16(hi) LDGs. Clinical data on disease course, medication, and antibody status were obtained. Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group. Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

Correction: Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Triggering Subordinate Innovation Behavior:The Influence of Leaders’ Dark Personality Traits and Level 5 Leadership Behavior

The present study investigates the influence of level 5 leadership, a leadership approach based on humility and professional will, on subordinate’s innovation behavior at work. The main aim is to shed further light on the understanding of how leadership can foster innovative behavior. Further we test if the dark triad of personality, consisting of narcissism, Machiavellianism and psychopathy, affects the likelihood of being a level 5 leader. Applying partial least squares (PLS) structural equation modelling (SEM), we show that humility, but even more the interaction effect of both level 5 virtues, humility and professional will is central and in fact increases innovation behavior of subordinates. Although the influence of dark personality traits on level 5 leadership provides a mixed picture, we find evidence that narcissistic tendencies and humble behavior could coexist at the same time. This consideration contributes to the unclear relationship between narcissism and humility, two central characteristics in leadership research

The effect of work ethic on employees' individual innovation behavior

The present study examines the previously untested effect of work ethic on individual innovation behavior. These entrenched personal values that may remain unaffected by organizational constitution are suggested to shape a person's inclination to engage in innovative action. Deploying partial least squares (PLS) structural equation modeling (SEM), we show that being self‐reliant and time‐efficient positively influences employees' innovation behavior, while an attitude toward hard work and leisure has a negative impact. Moreover, self‐reliance, leisure orientation, and centrality of work are positively moderated by fair salary, a specific form of relational reward that previously has been identified as an antecedent of motivation. The work at hand thus contributes to extant research by enhancing knowledge about the antecedents of innovative behavior, showing that inherent work‐related values matter. As such, the study demonstrates the importance of considering the linkage of personal differences and motivational factors when examining the complex processes of individual innovation behavior

Defining the functional binding sites of interleukin 12 receptor beta 1 and interleukin 23 receptor to Janus kinases

The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor beta 1 (IL-12R beta 1) as one component of their receptor signaling complexes, with IL-12R beta 2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12R beta 1, whereas Jak2 binds to IL-23R and also to IL-12R beta 2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12R beta 1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12R beta 1 and Jak2 by IL-23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable

The German Copernicus Data and Exploitation platform "CODE-DE" - online data access and big data processing

Copernicus establishes an operational European Earth Observation capacity. Data from multiple sources - first and foremost the Sentinel satellite systems - feed services and provide users with reliable and up-to-date information regarding environmental and security issues. The main Sentinel Internet based data access infrastructure is implemented by ESA. In addition, several Copernicus Participating States established national "collaborative ground segments", aiming at the additional use and distribution of Copernicus datasets focusing on their national demand. Next to that the "Copernicus Data and Information Access Services" (C-DIAS) have recently been set up (Summer 2018). The five different C-DIAS platforms are contracted by ESA and EUMETSAT in the framework of a European Commission initiative. The German Copernicus Data and Exploitation Platform (CODE-DE) is an infrastructure for data access (Sentinel data, products from the Copernicus Services and national data), on-demand processing and value-added product generation. The user-friendly online data access has been operational since March 2017 and is tapped by over 1.200 registered users (August 2018), which have downloaded around 100.000 products in that timeframe. The catalogue client provides an enhanced solution to discover, view, and download available products including time, spatial and additional filters, e.g., polarization mode or cloud cover. It features a browsing to display Sentinel-2 products in full 10 m spatial resolution. In addition other satellite data (e.g. science data from our national missions) are also integrated into the portal. An on-demand processing environment for high-performance cloud processing has been operational since November 2017. The algorithms currently available are mainly those of the Sentinel tool boxes (SNAP) such as generic band math or dedicated time series algorithms. Furthermore, the results are optionally mosaicked to cover larger areas or a larger period. The capacity of the processing environment has been continuously exploited since March 2018 by selected applications, e.g. in the agricultural, maritime or snow and ice context, based on dedicated Virtual Machines (VM) using "docker". This flexible processing approach supports different use cases - allowing developers, processing experts and data experts to work on the platform in support of their own processing scenarios