Quantifying non-Markovianity of continuous-variable Gaussian dynamical maps

We introduce a non-Markovianity measure for continuous-variable open quantum systems based on the idea put forward in H.-P. Breuer, that is, by quantifying the flow of information from the environment back to the open system. Instead of the trace distance we use here the fidelity to assess distinguishability of quantum states. We employ our measure to evaluate non-Markovianity of two paradigmatic Gaussian channels: the purely damping channel and the quantum Brownian motion channel with Ohmic environment. We consider different classes of Gaussian states and look for pairs of states maximizing the backflow of information. For coherent states we find simple analytical solutions, whereas for squeezed states we provide both exact numerical and approximate analytical solutions in the weak coupling limit

Intracellular and intercellular transport of RNA organelles in CXG repeat disorders: The strength of weak ties

RNA is a vital biomolecule, the function of which is tightly spatiotemporally regulated. RNA organelles are biological structures that either membrane-less or surrounded by membrane. They are produced by the all the cells and indulge in vital cellular mechanisms. They include the intracellular RNA granules and the extracellular exosomes. RNA granules play an essential role in intracellular regulation of RNA localization, stability and translation. Aberrant regulation of RNA is connected to disease development. For example, in microsatellite diseases such as CXG repeat expansion disorders, the mutant CXG repeat RNA’s localization and function are affected. RNA is not only transported intracellularly but can also be transported between cells via exosomes. The loading of the exosomes is regulated by RNA-protein complexes, and recent studies show that cytosolic RNA granules and exosomes share common content. Intracellular RNA granules and exosome loading may therefore be related. Exosomes can also transfer pathogenic molecules of CXG diseases from cell to cell, thereby driving disease progression. Both intracellular RNA granules and extracellular RNA vesicles may serve as a source for diagnostic and treatment strategies. In therapeutic approaches, pharmaceutical agents may be loaded into exosomes which then transport them to the desired cells/tissues. This is a promising target specific treatment strategy with few side effects. With respect to diagnostics, disease-specific content of exosomes, e.g., RNA-signatures, can serve as attractive biomarker of central nervous system diseases detecting early physiological disturbances, even before symptoms of neurodegeneration appear and irreparable damage to the nervous system occurs. In this review, we summarize the known function of cytoplasmic RNA granules and extracellular vesicles, as well as their role and dysfunction in CXG repeat expansion disorders. We also provide a summary of established protocols for the isolation and characterization of both cytoplasmic and extracellular RNA organelles

Förderung digitaler Kompetenzen in der wirtschaftswissenschaftlichen Hochschullehre

Die digitale Transformation verändert die zukünftigen beruflichen Handlungsfelder der Studierenden, weshalb die domänenspezifische Förderung digitaler Kompetenzen in den Fokus rückt. Eine Facette im betriebswirtschaftlichen Bereich stellen hierbei ERP-Anwendungen dar, die digital strukturiert Geschäftsprozesse in Unternehmen steuern. Im Beitrag wird das didaktische Design eines Onlinekurses und dessen Entwicklungsprozess vorgestellt. Digitale Kompetenzen sollen hier über didaktische Elemente des problembasierten, begleitungsorientierten und selbstregulierten Lernens gefördert werden. Ergebnisse der ersten Testung in Form einer Persona-Analyse illustrieren, dass die Bandbreite der didaktischen Designelemente die Heterogenität der Studierenden aufnehmen kann.The digital transformation is changing the future professional fields of students. Therefore, fostering digital competencies is an urgent pedagogical challenge within study programs. However, digital competencies must be operationalized in a domain-specific manner. In this paper, we present an online course to foster digital competencies in the Business domain especially by using ERP systems. In detail, the learning design elements of the onlinecourse and their development will be explained. Based on this, results of the first testing phase with a persona analysis are offered. The results illustrate the fit of the learning design elements with the characteristic of the students

Stereoscopic X-ray imaging, cone beam CT, and couch positioning in stereotactic radiotherapy of intracranial tumors: preliminary results from a cross-modality pilot installation

Background: To assess the accuracy and precision of a fully integrated pilot installation of stereoscopic X-ray imaging and kV-CBCT for automatic couch positioning in stereotactic radiotherapy of intracranial tumors. Positioning errors as detected by stereoscopic X-ray imaging are compared to those by kV-CBCT (i.e. the accuracy of the new method is verified by the established method), and repeated X-ray images are compared (i.e. the precision of new method is determined intra-modally). Methods: Preliminary results are reported from a study with 32 patients with intracranial tumors. Patients were treated with stereotactic radiotherapy guided by stereoscopic X-ray imaging and kV-CBCT. Patient positioning was automatically corrected by a robotic couch. Cross-modal discrepancies in position detection were measured (N = 42). Intra-modal improvements after correction and re-verification by stereoscopic X-ray imaging were measured (N = 70). The accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were confirmed in phantom measurements (N = 12 shifts of a ball bearing phantom, N = 24 shifts of a head phantom). Results: After correction based on stereoscopic X-ray imaging 95% of residual mean errors were below 0.4, 0.4, 0.5, and 0.7 mm (lateral, longitudinal, vertical, radial, respectively). Stereoscopic X-ray imaging and CBCT were in close agreement with an average discrepancy of 0.1, 0.5, 0.3 and 0.8 mm, respectively. 95% of discrepancies were below 0.8, 1.2, 1.0, and 1.4 mm, respectively. After correction and re-verification by stereoscopic X-ray imaging, the remaining intra-modal residual error was consistent with zero (p = 0.31, p = 0.48, p = 0.81 in lateral, longitudinal, and vertical direction;p-values from two-tailed t-test). The inherent technical accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were found to be of the order of 0.1 mm in controlled phantom settings. Conclusions: In a routine clinical setting, both stereoscopic X-ray imaging and CBCT were able to reduce positioning errors by an order of magnitude. The end-to-end precision of the system, measured from the discrepancy (mean) between ExacTrac and CBCT, in a clinical setting seems to be about 0.8 mm radially, including couch positioning. The precision (measured from repeatability of ExacTrac, intra-modal) was found to be about 0.7 mm radially in a clinical setting

Adiponectin protects against Toll-like receptor 4-mediated cardiac inflammation and injury

Aims Adiponectin (APN) is an immunomodulatory and cardioprotective adipocytokine. Toll-like receptor (TLR) 4 mediates autoimmune reactions that cause myocarditis resulting in inflammation-induced cardiac injury. Here, we investigated whether APN inhibits inflammation and injury in autoimmune myocarditis by interfering with TLR4 signalling. Methods and results APN overexpression in murine experimental autoimmune myocarditis (EAM) down-regulated cardiac expression of TLR4 and its downstream targets tumour necrosis factor (TNF)α, interleukin (IL)-6, IL-12, CC chemokine ligand (CCL)2, and intercellular adhesion molecule (ICAM)-1 resulting in reduced infiltration with cluster of differentiation (CD)3+, CD14+, and CD45+ immune cells as well as diminished myocardial apoptosis. Expression of TLR4 signalling pathway components was unchanged in hearts and spleens of APN-knockout (APN-KO) mice. In vitro APN had no effect on TLR4 expression in cardiac and immune cells but induced dissociation of APN receptors from the activated TLR4/CD14 signalling complex. APN inhibited the expression of a TLR4-mediated inflammatory phenotype induced by exogenous and endogenous TLR4 ligands as assessed by attenuated nuclear factor (NF)-κB activation and reduced expression of TNFα, IL-6, CCL2, and ICAM-1. Accordingly, following TLR4 ligation, splenocytes from APN-KO mice showed enhanced expression of TNFα, IL-6, IL-12, CCL2, and ICAM-1, whereas dendritic cells (DCs) from APN-KO mice demonstrated increased activation and T-cell priming capacity. Moreover, APN diminished TLR4-mediated splenocyte migration towards cardiac cells as well as cardiomyocyte apoptosis after co-cultivation with splenocytes. Mechanistically, APN inhibited TLR4 signalling through cyclooxygenase (COX)-2, protein kinase A (PKA), and meiosis-specific serine/threonine kinase (MEK)1. Conclusion Our observations indicate that APN protects against inflammation and injury in autoimmune myocarditis by diminishing TLR4 signalling thereby attenuating inflammatory activation and interaction of cardiac and immune cell

Implications for the Binding of the Protein G5P to DNA

Microorganisms accumulate molar concentrations of compatible solutes like ectoine to prevent proteins from denaturation. Direct structural or spectroscopic information on the mechanism and about the hydration shell around ectoine are scarce. We combined surface plasmon resonance (SPR), confocal Raman spectroscopy, molecular dynamics simulations, and density functional theory (DFT) calculations to study the local hydration shell around ectoine and its influence on the binding of a gene-S-protein (G5P) to a single-stranded DNA (dT(25)). Due to the very high hygroscopicity of ectoine, it was possible to analyze the highly stable hydration shell by confocal Raman spectroscopy. Corresponding molecular dynamics simulation results revealed a significant change of the water dielectric constant in the presence of a high molar ectoine concentration as compared to pure water. The SPR data showed that the amount of protein bound to DNA decreases in the presence of ectoine, and hence, the protein-DNA dissociation constant increases in a concentration- dependent manner. Concomitantly, the Raman spectra in terms of the amide I region revealed large changes in the protein secondary structure. Our results indicate that ectoine strongly affects the molecular recognition between the protein and the oligonudeotide, which has important consequences for osmotic regulation mechanisms

Adiponectin expression in patients with inflammatory cardiomyopathy indicates favourable outcome and inflammation control

Aims Circulating adiponectin (APN) is an immunomodulatory, pro-angiogenic, and anti-apoptotic adipocytokine protecting against acute viral heart disease and preventing pathological remodelling after cardiac injury. The purpose of this study was to describe the regulation and effects of APN in patients with inflammatory cardiomyopathy (DCMi). Methods and results Adiponectin expression and outcome were assessed in 173 patients with DCMi, 30 patients with non-inflammatory DCM, and 30 controls. Mechanistic background of these findings was addressed in murine experimental autoimmune myocarditis (EAM), a model of human DCMi, and further elucidated in vitro. Adiponectin plasma concentrations were significantly higher in DCMi compared with DCM or controls, i.e. 6.8 ± 3.9 µg/mL vs. 5.4 ± 3.6 vs. 4.76 ± 2.5 µg/mL (P< 0.05, respectively) and correlated significantly with cardiac mononuclear infiltrates (CD3+: r2= 0.025, P= 0.038; CD45R0+: r2= 0.058, P= 0.018). At follow-up, DCMi patients with high APN levels showed significantly increased left ventricular ejection fraction improvement, decreased left ventricular end-diastolic diameter, and reduced cardiac inflammatory infiltrates compared with patients with low APN levels. A multivariate linear regression analysis implicated APN as an independent prognostic factor for inhibition of cardiac inflammation. In accordance with these findings in human DCMi, EAM mice exhibited elevated plasma APN. Adiponectin gene transfer led to significant downregulation of key inflammatory mediators promoting disease. Mechanistically, APN acted as a negative regulator of T cells by reducing antigen specific expansion (P< 0.01) and suppressed TNFα-mediated NFκB activation (P< 0.01) as well as release of reactive oxygen species in cardiomyocytes. Conclusion Our results implicate that APN acts as endogenously upregulated anti-inflammatory cytokine confining cardiac inflammation and progression in DCM

SchussenAktivplus: reduction of micropollutants and of potentially pathogenic bacteria for further water quality improvement of the river Schussen, a tributary of Lake Constance, Germany

The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities

AKT inhibition impairs PCNA ubiquitylation and triggers synthetic lethality in homologous recombination-deficient cells submitted to replication stress

Translesion DNA synthesis (TLS) and homologous recombination (HR) cooperate during S-phase to safeguard replication forks integrity. Thus, the inhibition of TLS becomes a promising point of therapeutic intervention in HR-deficient cancers, where TLS impairment might trigger synthetic lethality (SL). The main limitation to test this hypothesis is the current lack of selective pharmacological inhibitors of TLS. Herein, we developed a miniaturized screening assay to identify inhibitors of PCNA ubiquitylation, a key post-translational modification required for efficient TLS activation. After screening a library of 627 kinase inhibitors, we found that targeting the pro-survival kinase AKT leads to strong impairment of PCNA ubiquitylation. Mechanistically, we found that AKT-mediated modulation of Proliferating Cell Nuclear Antigen (PCNA) ubiquitylation after UV requires the upstream activity of DNA PKcs, without affecting PCNA ubiquitylation levels in unperturbed cells. Moreover, we confirmed that persistent AKT inhibition blocks the recruitment of TLS polymerases to sites of DNA damage and impairs DNA replication forks processivity after UV irradiation, leading to increased DNA replication stress and cell death. Remarkably, when we compared the differential survival of HR-proficient vs HR-deficient cells, we found that the combination of UV irradiation and AKT inhibition leads to robust SL induction in HR-deficient cells. We link this phenotype to AKT ability to inhibit PCNA ubiquitylation, since the targeted knockdown of PCNA E3-ligase (RAD18) and a non-ubiquitylable (PCNA K164R) knock-in model recapitulate the observed SL induction. Collectively, this work identifies AKT as a novel regulator of PCNA ubiquitylation and provides the proof-of-concept of inhibiting TLS as a therapeutic approach to selectively kill HR-deficient cells submitted to replication stress.Fil: Villafañez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: García, Iris Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Carbajosa González, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pansa, Maria Florencia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mansilla, Sabrina Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Llorens de Los Ríos, María Candelaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Angiolini, Virginia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; ArgentinaFil: Guantay, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Jacobs, Heinz. Tumor Biology And Immunology-netherlands Cancer Institu; Países BajosFil: Madauss, Kevin P.. Glaxosmithkline; Reino UnidoFil: Gloger, Israel. Glaxosmithkline; Reino UnidoFil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin