Highlights of the mini-symposium on extracellular vesicles in inter-organismal communication, held in Munich, Germany, August 2018

All living organisms secrete molecules for intercellular communication. Recent research has revealed that extracellular vesicles (EVs) play an important role in inter-organismal cell-to-cell communication by transporting diverse messenger molecules, including RNA, DNA, lipids and proteins. These discoveries have raised fundamental questions regarding EV biology. How are EVs biosynthesized and loaded with messenger/cargo molecules? How are EVs secreted into the extracellular matrix? What are the EV uptake mechanisms of recipient cells? As EVs are produced by all kind of organisms, from unicellular bacteria and protists, filamentous fungi and oomycetes, to complex multicellular life forms such as plants and animals, basic research in diverse model systems is urgently needed to shed light on the multifaceted biology of EVs and their role in inter-organismal communications. To help catalyse progress in this emerging field, a mini-symposium was held in Munich, Germany in August 2018. This report highlights recent progress and major questions being pursued across a very diverse group of model systems, all united by the question of how EVs contribute to inter-organismal communication

Solid-State Microwave Electronics

Contains research objectives and reports on status of research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

Group analysis of structure equations for stars in radiative and convective equilibrium

It is proposed to use the Lie group theory of symmetries of differential equations to investigate the system of equations describing a static star in a radiative and convective equilibrium. It is shown that the action of an admissible group induces a certain algebraic structure in the set of all solutions, which can be used to find a family of new solutions. We have demonstrated that, in the most general case, the equations admit an infinite parameter group of quasi-homologous transformations. We have found invariants of the symmetries group which correspond to the fundamental relations describing a physical characteristic of the stars such as the Hertzsprung-Russell diagram or the mass-luminosity relation. In this way we can suggest that group invariants have not only purely mathematical sense, but their forms are closely associated with the basic empirical relations.Comment: LaTeX2e, 13page

Sialylated N-glycans mediate monocyte uptake of extracellular vesicles secreted from Plasmodium falciparum-infected red blood cells

Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells

Ensuring center quality, proper patient selection and fair access to chimeric antigen receptor T-cell therapy: position statement of the Austrian CAR-T Cell Network

Chimeric antigen receptor T cells (CAR-T cells) are a novel form of cellular immunotherapy for patients with hematologic and oncologic malignancies. Known side effects of these approved cellular immunotherapies are cytokine release syndrome, immune-cell associated neurotoxicity syndrome, cytopenias, infections and long-lasting B cell aplasia. Safe administration of CAR-T cell therapy requires thorough patient selection and patient care in qualified CAR-T cell centers

Dynamics of the Universe with global rotation

We analyze dynamics of the FRW models with global rotation in terms of dynamical system methods. We reduce dynamics of these models to the FRW models with some fictitious fluid which scales like radiation matter. This fluid mimics dynamically effects of global rotation. The significance of the global rotation of the Universe for the resolution of the acceleration and horizon problems in cosmology is investigated. It is found that dynamics of the Universe can be reduced to the two-dimensional Hamiltonian dynamical system. Then the construction of the Hamiltonian allows for full classification of evolution paths. On the phase portraits we find the domains of cosmic acceleration for the globally rotating universe as well as the trajectories for which the horizon problem is solved. We show that the FRW models with global rotation are structurally stable. This proves that the universe acceleration is due to the global rotation. It is also shown how global rotation gives a natural explanation of the empirical relation between angular momentum for clusters and superclusters of galaxies. The relation $J \sim M^2$ is obtained as a consequence of self similarity invariance of the dynamics of the FRW model with global rotation. In derivation of this relation we use the Lie group of symmetry analysis of differential equation.Comment: Revtex4, 22 pages, 5 figure

Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection

Solid-State Microwave Electronics

Contains reports on two research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

Technical design of the phase I Mu3e experiment

The Mu3e experiment aims to find or exclude the lepton flavour violating decay $\mu \rightarrow eee$ at branching fractions above $10^{-16}$. A first phase of the experiment using an existing beamline at the Paul Scherrer Institute (PSI) is designed to reach a single event sensitivity of $2\cdot 10^{-15}$. We present an overview of all aspects of the technical design and expected performance of the phase~I Mu3e detector. The high rate of up to $10^{8}$ muon decays per second and the low momenta of the decay electrons and positrons pose a unique set of challenges, which we tackle using an ultra thin tracking detector based on high-voltage monolithic active pixel sensors combined with scintillating fibres and tiles for precise timing measurements.Comment: 114 pages, 185 figures. Submitted to Nuclear Instruments and Methods A. Edited by Frank Meier Aeschbacher This version has many enhancements for better readability and more detail

Particle identification studies with a full-size 4-GEM prototype for the ALICE TPC upgrade

A large Time Projection Chamber is the main device for tracking and charged-particle identification in the ALICE experiment at the CERN LHC. After the second long shutdown in 2019/20, the LHC will deliver Pb beams colliding at an interaction rate of about 50 kHz, which is about a factor of 50 above the present readout rate of the TPC. This will result in a significant improvement on the sensitivity to rare probes that are considered key observables to characterize the QCD matter created in such collisions. In order to make full use of this luminosity, the currently used gated Multi-Wire Proportional Chambers will be replaced. The upgrade relies on continuously operated readout detectors employing Gas Electron Multiplier technology to retain the performance in terms of particle identification via the measurement of the specific energy loss by ionization d$E$/d$x$. A full-size readout chamber prototype was assembled in 2014 featuring a stack of four GEM foils as an amplification stage. The performance of the prototype was evaluated in a test beam campaign at the CERN PS. The d$E$/d$x$ resolution complies with both the performance of the currently operated MWPC-based readout chambers and the challenging requirements of the ALICE TPC upgrade program. Detailed simulations of the readout system are able to reproduce the data.Comment: Submitted to NIM