Ectoplasm & Superspace Integration Measure for 2D Supergravity with Four Spinorial Supercurrents

Building on a previous derivation of the local chiral projector for a two dimensional superspace with eight real supercharges, we provide the complete density projection formula required for locally supersymmetrical theories in this context. The derivation of this result is shown to be very efficient using techniques based on the Ectoplasmic construction of local measures in superspace.Comment: 18 pages, LaTeX; V2: minor changes, typos corrected, references added; V3: version to appear in J. Phys. A: Math. Theor., some comments and references added to address a referee reques

In vivo characterization of protein-protein interactions in the AP1 system with fluorescence correlation spectroscopy (FCS).

The aim of these studies is the quantitative investigation of protein-protein interactions in the AP1 system in vivo. First results of FCS measurements show an exchange in the nucleus of the proteins Fos-CFP and Jun-YFP in the stably mono-transfected HeLa-Cells. This is also shown by fitting the bleaching curves measured in the nucleus with an appropriate model. We obtained dissociation times between 10 and 20 seconds in the nucleus. In the autocorrelation function a free and an obstructed component of diffusion are shown. For further studies doubly transfected cells with both proteins, Fos-CFP and Jun-YFP, were prepared. These cells will now be characterized with FCCS to investigate the protein-protein interactions. In order to obtain the dissociation rates of the complex in the cell nucleus bleaching curves will be recorded on these cell lines. We also overexpressed and purified Jun-YFP and Fos-CFP for in vitro studies

Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1−/− bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1−/− in MLL—AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance

High-throughput screening of caterpillars as a platform to study host-microbe interactions and enteric immunity.

Mammalian models of human disease are expensive and subject to ethical restrictions. Here, we present an independent platform for high-throughput screening, using larvae of the tobacco hornworm Manduca sexta, combining diagnostic imaging modalities for a comprehensive characterization of aberrant phenotypes. For validation, we use bacterial/chemical-induced gut inflammation to generate a colitis-like phenotype and identify significant alterations in morphology, tissue properties, and intermediary metabolism, which aggravate with disease progression and can be rescued by antimicrobial treatment. In independent experiments, activation of the highly conserved NADPH oxidase DUOX, a key mediator of gut inflammation, leads to similar, dose-dependent alterations, which can be attenuated by pharmacological interventions. Furthermore, the developed platform could differentiate pathogens from mutualistic gastrointestinal bacteria broadening the scope of applications also to microbiomics and host-pathogen interactions. Overall, larvae-based screening can complement mammals in preclinical studies to explore innate immunity and host-pathogen interactions, thus representing a substantial contribution to improve mammalian welfare

RadioAstron Space VLBI Imaging of the jet in M87: I. Detection of high brightness temperature at 22 GHz

We present results from the first 22 GHz space very-long-baseline interferometric (VLBI) imaging observations of M87 by RadioAstron. As a part of the Nearby AGN Key Science Program, the source was observed in Feb 2014 at 22 GHz with 21 ground stations, reaching projected $(u,v)$-spacings up to $\sim11\,$G$\lambda$. The imaging experiment was complemented by snapshot RadioAstron data of M87 obtained during 2013--2016 from the AGN Survey Key Science Program. Their longest baselines extend up to $\sim25\,$G$\lambda$. For all these measurements, fringes are detected only up to $\sim$2.8 Earth Diameter or $\sim$3 G$\lambda$ baseline lengths, resulting in a new image with angular resolution of $\sim150\,\mu$as or $\sim20$ Schwarzschild radii spatial resolution. The new image not only shows edge-brightened jet and counterjet structures down to submilliarcsecond scales but also clearly resolves the VLBI core region. While the overall size of the core is comparable to those reported in the literature, the ground-space fringe detection and slightly super-resolved RadioAstron image suggest the presence of substructures in the nucleus, whose minimum brightness temperature exceeds $T_{\rm B, min}\sim10^{12}\,$K. It is challenging to explain the origin of this record-high $T_{\rm B, min}$ value for M87 by pure Doppler boosting effect with a simple conical jet geometry and known jet speed. Therefore, this can be evidence for more extreme Doppler boosting due to a blazar-like small jet viewing angle or highly efficient particle acceleration processes occurring already at the base of the outflow.Comment: 27 pages, 13 figures, accepted for publication in Ap

Off-shell supergravity-matter couplings in three dimensions

We develop the superspace geometry of N-extended conformal supergravity in three space-time dimensions. General off-shell supergravity-matter couplings are constructed in the cases N=1,2,3,4.Comment: 73 pages; V5: typos in eqs. (3.4b), (3.17) and (4.24) correcte

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology