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The gamma rhythm has been implicated in neuronal communication, but causal evidence remains indirect. We measured spike output of local neuronal networks and emulated their synaptic input through optogenetics. Opsins provide currents through somato-dendritic membranes, similar to synapses, yet under experimental control with high temporal precision. We expressed Channelrhodopsin-2 in excitatory neurons of cat visual cortex and recorded neuronal responses to light with different temporal characteristics. Sine waves of different frequencies entrained neuronal responses with a reliability that peaked for input frequencies in the gamma band. Crucially, we also presented white-noise sequences, because their temporal unpredictability enables analysis of causality. Neuronal spike output was caused specifically by the input’s gamma component. This gamma-specific transfer function is likely an emergent property of in-vivo networks with feedback inhibition. The method described here could reveal the transfer function between the input to any one and the output of any other neuronal group.
Summary We introduce fsbrain, an R package for the visualization of neuroimaging data. The package can be used to visualize vertex-wise and region-wise morphometry data, parcellations, labels and statistical results on brain surfaces in three dimensions (3D). Voxel data can be displayed in lightbox mode. The fsbrain package offers various customization options and produces publication quality plots which can be displayed interactively, saved as bitmap images, or integrated into R notebooks.
Availability and Implementation The software, source code and documentation are available under the MIT license at https://github.com/dfsp-spirit/fsbrain. Releases can be installed directly from the Comprehensive R Archive Network (CRAN).
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.
Visual scene perception is mediated by a set of cortical regions that respond preferentially to images of scenes, including the occipital place area (OPA) and parahippocampal place area (PPA). However, the differential contribution of OPA and PPA to scene perception remains an open research question. In this study, we take a deep neural network (DNN)-based computational approach to investigate the differences in OPA and PPA function. In a first step we search for a computational model that predicts fMRI responses to scenes in OPA and PPA well. We find that DNNs trained to predict scene components (e.g., wall, ceiling, floor) explain higher variance uniquely in OPA and PPA than a DNN trained to predict scene category (e.g., bathroom, kitchen, office). This result is robust across several DNN architectures. On this basis, we then determine whether particular scene components predicted by DNNs differentially account for unique variance in OPA and PPA. We find that variance in OPA responses uniquely explained by the navigation-related floor component is higher compared to the variance explained by the wall and ceiling components. In contrast, PPA responses are better explained by the combination of wall and floor, that is scene components that together contain the structure and texture of the scene. This differential sensitivity to scene components suggests differential functions of OPA and PPA in scene processing. Moreover, our results further highlight the potential of the proposed computational approach as a general tool in the investigation of the neural basis of human scene perception.
The development of binocular vision is an active learning process comprising the development of disparity tuned neurons in visual cortex and the establishment of precise vergence control of the eyes. We present a computational model for the learning and self-calibration of active binocular vision based on the Active Efficient Coding framework, an extension of classic efficient coding ideas to active perception. Under normal rearing conditions, the model develops disparity tuned neurons and precise vergence control, allowing it to correctly interpret random dot stereogramms. Under altered rearing conditions modeled after neurophysiological experiments, the model qualitatively reproduces key experimental findings on changes in binocularity and disparity tuning. Furthermore, the model makes testable predictions regarding how altered rearing conditions impede the learning of precise vergence control. Finally, the model predicts a surprising new effect that impaired vergence control affects the statistics of orientation tuning in visual cortical neurons.
Active efficient coding explains the development of binocular vision and its failure in amblyopia
(2020)
The development of vision during the first months of life is an active process that comprises the learning of appropriate neural representations and the learning of accurate eye movements. While it has long been suspected that the two learning processes are coupled, there is still no widely accepted theoretical framework describing this joint development. Here, we propose a computational model of the development of active binocular vision to fill this gap. The model is based on a formulation of the active efficient coding theory, which proposes that eye movements as well as stimulus encoding are jointly adapted to maximize the overall coding efficiency. Under healthy conditions, the model self-calibrates to perform accurate vergence and accommodation eye movements. It exploits disparity cues to deduce the direction of defocus, which leads to coordinated vergence and accommodation responses. In a simulated anisometropic case, where the refraction power of the two eyes differs, an amblyopia-like state develops in which the foveal region of one eye is suppressed due to inputs from the other eye. After correcting for refractive errors, the model can only reach healthy performance levels if receptive fields are still plastic, in line with findings on a critical period for binocular vision development. Overall, our model offers a unifying conceptual framework for understanding the development of binocular vision.
Hintergrund: Die Erstversorgung von Wunden und kleinere chirurgische Eingriffe gehören neben der hochspezialisierten Medizin zu den allgemein notwendigen Grundleistungen der Notfallversorgung in den Kliniken. Die Vergütung der ambulanten Notfallleistungen für gesetzlich Versicherte erfolgt derzeit nach dem Einheitlichen Bewertungsmaßstab (EBM), welchem die betriebswirtschaftliche Aufwandserfassung des niedergelassenen Sektors als Kalkulationsgrundlage dient. Krankenhäuser haben im Vergleich zu Arztpraxen wesentlich höhere Vorhaltungskosten.
Ziel der Arbeit: In dieser Arbeit wird das entstehende Kosten-Erlös-Verhältnis der ambulanten Wundversorgung in einer Notaufnahme durch die Vergütung nach EBM analysiert.
Material und Methoden: Die Daten wurden in der Notaufnahme des Universitätsklinikums Frankfurt am Main über 12 Monate erhoben. Eingeschlossen wurden alle Patienten, die in diesem Zeitraum eine Wundversorgung mittels Naht erhielten. Die Kosten wurden der Abrechnung nach EBM 01210 (bzw. 01212) mit der Zusatzpauschale für kleinchirurgische Eingriffe EBM 02301 gegenübergestellt.
Ergebnisse: Im Beobachtungszeitraum wurden 1548 Patienten versorgt; das entspricht 19,52 % aller unfallchirurgischen Fälle. Den Kosten einer Standardwundversorgung in Höhe von 45,40 € steht eine Vergütung von 31,83 € gegenüber. Die Berechnung des Gesamterlöses weist einen Defizitbetrag von 13,57 € pro ambulantem Fall auf; dies entspricht einem Jahresdefizit von 21.006,36 €.
Diskussion: Es konnte gezeigt werden, dass ohne Betrachtung der relevanten Vorhaltekosten in keinem Fall eine Kostendeckung erreicht werden kann.
Die bisherige Vergütung der ambulanten Wundversorgung nach EBM erscheint unzureichend. Eine Anpassung bzw. Zusatzvergütung scheint notwendig, um eine ausreichende Versorgungsqualität in Zukunft sicherstellen zu können.
Animals extract behaviorally relevant signals from “noisy” environments. To investigate signal extraction, echolocating provides a rich system testbed. For orientation, bats broadcast calls and assign each echo to the corresponding call. When orienting in acoustically enriched environments or when approaching targets, bats change their spectro-temporal call design. Thus, to assess call adjustments that are exclusively meant to facilitate signal extraction in “noisy” environments, it is necessary to control for distance-dependent call changes. By swinging bats in a pendulum, we tested the influence of acoustic playback on the echolocation behavior of Carollia perspicillata. This paradigm evokes reproducible orientation behavior and allows a precise definition of the influence of the acoustic context. Our results show that bats dynamically switch between different adaptations to cope with sound-based navigation in acoustically contaminated environments. These dynamics of echolocation behavior may explain the large variety of adaptations that have been reported in the bat literature.
The firing pattern of ventral midbrain dopamine neurons is controlled by afferent and intrinsic activity to generate prediction error signals that are essential for reward-based learning. Given the absence of intracellular in vivo recordings in the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. By establishing stable in vivo whole-cell recordings of >100 spontaneously active midbrain dopamine neurons in anaesthetized mice, we identified the repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. We demonstrate that dopamine neuron in vivo activity deviates from a single spike pacemaker pattern by eliciting transient increases in firing rate generated by at least two diametrically opposing biophysical mechanisms: a transient depolarization resulting in high frequency plateau bursts associated with a reactive, depolarizing shift in action potential threshold; and a prolonged hyperpolarization preceding slower rebound bursts characterized by a predictive, hyperpolarizing shift in action potential threshold. Our findings therefore illustrate a framework for the biophysical implementation of prediction error and sensory cue coding in dopamine neurons by tuning action potential threshold dynamics.
The plant family Brassicaceae includes some of the most studied hosts of plant microbiomes, targeting microbial diversity, community assembly rules, and effects on host performance. Compared to bacteria, eukaryotes in the brassicaceous microbiome remain understudied, especially under natural settings. Here, we assessed the impact of host identity and age on the assembly of fungal and oomycete root communities, using DNA metabarcoding of roots and associated soil of three annual co-habiting Brassicaceae collected at two time points. Our results showed that fungal communities are more diverse and structured than those of oomycetes. In both cases, plant identity and sampling time had little influence on community variation, whereas root/soil compartment had a strong effect by exerting control on the entry of soil microorganisms into the roots. The enrichment in roots of specific fungi suggests a specialization towards the asymptomatic colonization of plant tissues, which could be relevant to host’s fitness and health.
Von A bis Å. (Fast) alles über die Frankfurter Skandinavistik. Ausgabe 1 ; Wintersemester 2020/21
(2020)
Cross sections of the process 𝑒+𝑒−→𝜋0𝜋0𝐽/𝜓 at center-of-mass energies between 3.808 and 4.600 GeV are measured with high precision by using 12.4 fb−1 of data samples collected with the BESIII detector operating at the BEPCII collider facility. A fit to the measured energy-dependent cross sections confirms the existence of the charmoniumlike state 𝑌(4220). The mass and width of the 𝑌(4220) are determined to be (4220.4±2.4±2.3) MeV/𝑐2 and (46.2±4.7±2.1) MeV, respectively, where the first uncertainties are statistical and the second systematic. The mass and width are consistent with those measured in the process 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓. The neutral charmonium-like state 𝑍𝑐(3900)0 is observed prominently in the 𝜋0𝐽/𝜓 invariant-mass spectrum, and, for the first time, an amplitude analysis is performed to study its properties. The spin-parity of 𝑍𝑐(3900)0 is determined to be 𝐽𝑃=1+, and the pole position is (3893.1±2.2±3.0)−𝑖(22.2±2.6±7.0) MeV/𝑐2, which is consistent with previous studies of electrically charged 𝑍𝑐(3900)±. In addition, cross sections of 𝑒+𝑒− → 𝜋0𝑍𝑐(3900)0 → 𝜋0𝜋0𝐽/𝜓 are extracted, and the corresponding line shape is found to agree with that of the 𝑌(4220).
Digitale Technologien begünstigen den Einsatz einer dynamischen Preisgestaltung, also von Preisen, die für ein prinzipiell gleiches Produkt unangekündigt variieren. Dabei werden in der öffentlichen Diskussion unterschiedliche Ausgestaltungsformen dynamischer Preise oftmals vermischt, was eine sinnvolle Analyse der Vor- und Nachteile der dynamischen Preisgestaltung erschwert. Das Ziel des Beitrags ist die Darstellung der ökonomischen Grundlagen und die Diskussion sowie Klassifikation der Ausgestaltungsmöglichkeiten der dynamischen Preisgestaltung. Darüber hinaus erfolgt eine Bewertung der Vor- und Nachteile der dynamischen Preisgestaltung aus Käufer- und Verkäufersicht. Abschließend werden Implikationen für die betriebswirtschaftliche Forschung diskutiert.
Mehr Nachhaltigkeit im deutschen Leitindex DAX : Reformvorschläge im Lichte des Wirecard-Skandals
(2020)
Im Rahmen der Aufarbeitung des Wirecard-Skandals wird auch eine Änderung der Kriterien zur Aufnahme in den deutschen Leitindex DAX diskutiert. Die bislang von der Deutschen Börse vorgesehenen Maßnahmen gehen in die richtige Richtung, sind aber nicht weitreichend genug. Es bedarf eines deutlichen Zeichens, dass sich künftig nur solche Unternehmen für den DAX qualifizieren können, die ein zumindest befriedigendes Maß an Nachhaltigkeit gemessen durch einen ESG-Risk-Score (Environment, Social, Governance) in ihrer Geschäftstätigkeit erreichen. Eine Simulation verdeutlicht, dass nach ESG-Kriterien seit langem kritisch betrachtete Unternehmen dem DAX nicht mehr angehören würden. Damit könnte mehr Kapital in nachhaltig wirtschaftende Unternehmen und Sektoren fließen.
Libra — a global virtual currency project initiated by Facebook — has been the subject of many controversial discussions since its announcement in June 2019. This paper provides a differentiated view on Libra, recognising that different development scenarios of Libra are conceivable. Libra could serve purely as an alternative payment system in combination with a dedicated payment token, the Libra coin. Alternatively, the Libra project could develop into a broader financial infrastructure for advanced financial services such as savings and loan products operating on the Libra Blockchain. Based on a comparison of the Libra architecture with other cryptocurrencies, the opportunities and challenges for the development of the respective Libra ecosystems are investigated from a commercial, regulatory and monetary policy perspective.
Heavy quarks are useful probes to investigate the properties of the Quark-Gluon Plasma (QGP) produced in heavy-ion collisions at the LHC, since they are produced in initial hard scattering processes. To single out the signals that are characteristic of the QGP, it is nevertheless crucial to understand the primordial heavy-quark production in vacuum, and to disentangle hot from cold nuclear matter effects. Moreover, observations of collective effects in high-multiplicity pp and p-Pb collisions show surprising similarities with those in heavy-ion collisions. Heavy-flavour production in such collisions could give further insight into the underlying processes. The heavy-flavour production can be studied with e+e− pairs from correlated semileptonic decays of heavy-flavour hadrons. Compared to single heavy-flavour measurements, the dielectron yield contains information about the initial kinematical correlations between the charm and anti-charm quarks, which is otherwise not accessible, and is sensitive to soft heavy-flavour production. We report results on correlated e+e− pairs in pp collisions recorded by the ALICE detector at different collision energies. The production of heavy quarks is discussed by comparing the yield of dielectrons from heavy-flavour hadron decays as a function of invariant mass, pair transverse momentum and distance of closest approach to the primary vertex with different Monte Carlo event generators. The heavy-flavour production cross sections are also presented. Results from high-multiplicity pp collisions at √s=13 TeV and the status of the p-Pb analysis at √sNN=5.02 TeV are reported as well.
A comprehensive study of sillenite Bi12SiO20 single-crystal properties, including elastic stiffness and piezoelectric coefficients, dielectric permittivity, thermal expansion and molar heat capacity, is presented. Brillouin-interferometry measurements (up to 27 GPa), which were performed at high pressures for the first time, and ab initio calculations based on density functional theory (up to 50 GPa) show the stability of the sillenite structure in the investigated pressure range, in agreement with previous studies. Elastic stiffness coefficients c11 and c12 are found to increase continuously with pressure while c44 increases slightly for lower pressures and remains nearly constant above 15 GPa. Heat-capacity measurements were performed with a quasi-adiabatic calorimeter employing the relaxation method between 2 K and 395 K. No phase transition could be observed in this temperature interval. Standard molar entropy, enthalpy change and Debye temperature are extracted from the data. The results are found to be roughly half of the previous values reported in the literature. The discrepancy is attributed to the overestimation of the Debye temperature which was extracted from high-temperature data. Additionally, Debye temperatures obtained from mean sound velocities derived by Voigt-Reuss averaging are in agreement with our heat-capacity results. Finally, a complete set of electromechanical coefficients was deduced from the application of resonant ultrasound spectroscopy between 103 K and 733 K. No discontinuities in the temperature dependence of the coefficients are observed. High-temperature (up to 1100 K) resonant ultrasound spectra recorded for Bi12MO20 crystals revealed strong and reversible acoustic dissipation effects at 870 K, 960 K and 550 K for M = Si, Ge and Ti, respectively. Resonances with small contributions from the elastic shear stiffness c44 and the piezoelectric stress coefficient e123 are almost unaffected by this dissipation.
Weimarer Beiträge 66/2020
(2020)
Die Weimarer Beiträge sind eine Zeitschrift für Literaturwissenschaft, aktuelle ästhetische Theorie und Kulturwissenschaft. Zu Ihren Schwerpunkten gehören moderne Literatur im Rahmen anderer Künste und Medien, die Wechselbeziehungen von Literatur, philosophischer und ästhetischer Reflexion sowie die kritische Analyse der Gegenwartskultur.
Decades of work have demonstrated that mRNAs are localized and translated within neuronal dendrites and axons to provide proteins for remodeling and maintaining growth cones or synapses. It remains unknown, however, whether specific forms of plasticity differentially regulate the dynamics and translation of individual mRNA species. To address these issues, we targeted three individual synaptically-localized mRNAs, CamkIIa, Beta actin, Psd95, and used molecular beacons to track endogenous mRNA movements and reporters and Crispr-Cas9 gene editing to track their translation. We found widespread alterations in mRNA behavior during two forms of synaptic plasticity, long-term potentiation (LTP) and depression (LTD). Changes in mRNA dynamics following plasticity resulted in an enrichment of mRNA in the vicinity of dendritic spines. Both the reporters and tagging of endogenous proteins revealed the transcript-specific stimulation of protein synthesis following LTP or LTD. The plasticity-induced enrichment of mRNA near synapses could be uncoupled from its translational status. The enrichment of mRNA in the proximity of spines allows for localized signaling pathways to decode plasticity milieus and stimulate a specific translational profile, resulting in a customized remodeling of the synaptic proteome.
Kaum ein Text von Johannes R. Becher hat in der Weimarer Republik für so viel Furore gesorgt wie sein zweiter Roman "(CHCl=CH)3As (Levisite) oder Der einzig gerechte Krieg (1926)", stand er doch im Mittelpunkt des gegen den Autor eingeleiteten Hochverratsprozesses, der den öffentlichen Protest verschiedener Schriftsteller gegen die Unterdrückung freier Meinungsäußerung zur Folge hatte. Als Levisite 1926 erschien, ermittelten die Behörden bereits einige Zeit gegen den Kommunisten Johannes R. Becher. [...] Da die Forschungsarbeiten zu Becher schwerpunktmäßig aus der DDR-Germanistik stammen, kritisieren die vorliegenden Studien oftmals die Form, in der die ideologische Botschaft artikuliert wird. Geprägt von der Skepsis gegenüber experimenteller Sprachgestaltung, wie sie in der Formalismusdebatte am deutlichen zum Ausdruck kommt, bemerken sie im Buch einen "krasse[n] Widerspruch zwischen dem sprachexperimentellen Charakter der Dichtung und den politischen Intentionen des Dichters", der die Arbeiterklasse als Leserschaft daher eher abschrecke. Dabei ist der Roman aus dieser Perspektive nur sehr schwer zu fassen. Hierfür ist ein Ansatz vonnöten, der in der Lage ist, die ästhetische Form und den Inhalt zusammenzudenken, und der das Werk zudem im Kontext des Hochverratsprozesses gegen Becher beleuchtet. Denn "Levisite" ist als bewusster Skandalroman angelegt und in dieser Weise als performativ-politisches Statement, das im fiktionalisierten Rückbezug auf den Autor dessen Entscheidung für den Kommunismus legitimiert. Das Problem, wie man Kunst und Leben zusammenbringen soll, beschäftigt die Frühe Moderne seit den naturalistischen Manifesten. Becher selbst vertritt Zeit seines Lebens ein Konzept, nach dem beide Dimensionen unmittelbar ineinander übergehen oder sich gegenseitig befruchten. Bechers Werk wird also nur verständlich, wenn man die Selbstinszenierungsstrategien seines Autors mit in den Blick nimmt. Dies gilt auch für die einer solchen Egozentrik scheinbar eher abträgliche politisch-engagierte Literatur der 1920er Jahre, wie sich am Beispiel von "Levisite" besonders gut zeigen lässt. Im Gegensatz zum konventionellen Bild der proletarisch-revolutionären Literatur, das vom Sozialistischen Realismus und der Arbeiterliteratur geprägt ist, erinnert der Roman den heutigen Leser daran, dass es eine kommunistische Avantgarde auch außerhalb der Theaterexperimente eines Erwin Piscator oder Bertolt Brecht gab. Er zeigt eine kommunistische Bewegung, die noch auf der Suche nach dem idealen Weg ist, um die politischen Machtstrukturen durch Kunst verändern zu können. Bechers Antwort auf diese Frage hat viel mit ihm selbst zu tun, weil sich die intendierte Wirkung des Buchs nicht unbedingt dadurch entfaltet, dass sich der Leser die Protagonisten zum Vorbild nimmt. Der Roman ist vielmehr das wichtigste Instrument Bechers, die Wahrnehmung seiner eigenen Person in der Weimarer Republik zu beeinflussen und sich selbst als Exempel des politisch verfolgten Schriftstellers zu inszenieren, womit der Inhalt der Romanhandlung in der Realität Bestätigung findet.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV by the BESIII detector at the BEPCII, we measure the branching fractions of the singly Cabibbo-suppressed decays 𝐷→𝜔𝜋𝜋 to be ℬ(𝐷0→𝜔𝜋+𝜋−)=(1.33±0.16±0.12)×10−3 and ℬ(𝐷+→𝜔𝜋+𝜋0)=(3.87±0.83±0.25)×10−3, where the first uncertainties are statistical and the second ones systematic. The statistical significances are 12.9𝜎 and 7.7𝜎, respectively. The precision of ℬ(𝐷0→𝜔𝜋+𝜋−) is improved by a factor of 2.1 over prior measurements, and ℬ(𝐷+→𝜔𝜋+𝜋0) is measured for the first time. No significant signal for 𝐷0→𝜔𝜋0𝜋0 is observed, and the upper limit on the branching fraction is ℬ(𝐷0→𝜔𝜋0𝜋0)<1.10×10−3 at the 90% confidence level. The branching fractions of 𝐷→𝜂𝜋𝜋 are also measured and consistent with existing results.
Using 2.93 fb−1 of 𝑒+𝑒− collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the absolute branching fractions of 14 hadronic 𝐷0(+) decays to exclusive final states with an 𝜂, e.g., 𝐷0→𝐾−𝜋+𝜂, 𝐾0𝑆𝜋0𝜂, 𝐾+𝐾−𝜂, 𝐾0𝑆𝐾0𝑆𝜂, 𝐾−𝜋+𝜋0𝜂, 𝐾0𝑆𝜋+𝜋−𝜂, 𝐾0𝑆𝜋0𝜋0𝜂, and 𝜋+𝜋−𝜋0𝜂; 𝐷+→𝐾0𝑆𝜋+𝜂, 𝐾0𝑆𝐾+𝜂, 𝐾−𝜋+𝜋+𝜂, 𝐾0𝑆𝜋+𝜋0𝜂, 𝜋+𝜋+𝜋−𝜂, and 𝜋+𝜋0𝜋0𝜂. Among these decays, the 𝐷0→𝐾−𝜋+𝜂 and 𝐷+→𝐾0 𝑆𝜋+𝜂 decays have the largest branching fractions, which are ℬ(𝐷0→𝐾−𝜋+𝜂) = (1.853±0.025stat±0.031syst)% and ℬ(𝐷+→𝐾0𝑆𝜋+𝜂) = (1.309±0.037stat±0.031syst)%, respectively. The charge-parity asymmetries for the six decays with highest event yields are determined, and no statistically significant charge-parity violation is found.
Surface temperature is a fundamental parameter of Earth’s climate. Its evolution through time is commonly reconstructed using the oxygen isotope and the clumped isotope compositions of carbonate archives. However, reaction kinetics involved in the precipitation of carbonates can introduce inaccuracies in the derived temperatures. Here, we show that dual clumped isotope analyses, i.e., simultaneous ∆47 and ∆48 measurements on the single carbonate phase, can identify the origin and quantify the extent of these kinetic biases. Our results verify theoretical predictions and evidence that the isotopic disequilibrium commonly observed in speleothems and scleractinian coral skeletons is inherited from the dissolved inorganic carbon pool of their parent solutions. Further, we show that dual clumped isotope thermometry can achieve reliable palaeotemperature reconstructions, devoid of kinetic bias. Analysis of a belemnite rostrum implies that it precipitated near isotopic equilibrium and confirms the warmer-than-present temperatures during the Early Cretaceous at southern high latitudes.
Digital spatial processes have been widely explored and investigated in subject-specific geographic research. So far, however, this research has not been sufficiently reflected in classrooms or teacher education, and remains unconnected to notions of geographical digital literacy. Viral constructions of space – realities shaped in everyday life that are experienced and (re-)produced by students and teachers alike through social media – present an opportunity for Geography education to adapt to the digital society. This paper attempts to connect viral constructions of space, the digital society and the knowledge teachers need to include viral constructions of space in the classroom using Mishra and Koehler’s (2006) TPACK model, a well-established means for summarizing teachers’ technological, pedagogical and content knowledge for a specific topic. The paper focuses on content knowledge, identifies five sub-types of viral constructions of space, and extracts nine descriptors of teachers’ content knowledge. By focusing on content knowledge, the paper presents a starting point for future investigations of pedagogical and technological teacher knowledge as well as their intersections. It also raises awareness of viral constructions of space as both a new essential topic in the Geography classroom and a phenomenon already shaping learning environments for spatial acquisition.
Background: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.
Methods: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research (GENDAAR).
Results: Discovery analyses in ABIDE revealed significant main effects across the intrinsic functional connectivity (iFC) of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples – EU-AIMS LEAP.
Limitations: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.
Conclusions: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
Competing Interest Statement: ADM receives royalties from the publication of the Italian version of the Social Responsiveness Scale Child Version by Organization Speciali, Italy. JKB has been a consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice, Roche, and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, or royalties. CFB is director and shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and received book royalties from Guildford Press and Sage. DM has been a consultant to, and advisory board member, for Roche and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speakers fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. JT is a consultant to Roche. The remaining authors declare no competing interests.
The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). 77 cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
Background: Autism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined.
Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling.
Results: Results showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD.
Conclusion: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the bat Carollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioural outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1-12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.
Leider erhielten wir erst im vergangenen Jahr Kenntnis davon, dass Erika Brokmann, die langjährige Geschäftsführerin des Forum Vormärz Forschung, am 24. Dezember 2017 im Alter von 90 Jahren verstorben ist. [...] Erika Brokmann war an der Gründung des Forum Vormärz Forschung maßgeblich beteiligt. Sie war Mitorganisatorin der Gründungsversammlung am 16. April 1994 und wurde dort zur ersten Geschäftsführerin des Vereins gewählt.
Der Tumormarker Sialinsäure
(2020)
Die vorliegende Übersicht zum Tumormarker Sialinsäure wird im Rahmen der Serie „Tumormarker“ des Zentralblatts für Arbeitsmedizin, Arbeitsschutz und Ergonomie publiziert, die sich mit dem immer häufigeren Gebrauch der Bestimmung von spezifischen Markern bei sog. Manager-Vorsorgen und Check-up-Untersuchungen beschäftigt. Sialinsäure eignet sich grundsätzlich nicht für solche Vorsorgen, sondern ist ein Marker zur Therapie‑, Verlaufs- und Rezidivkontrolle von Mundhöhlenkarzinomen. Hier zeigt dieser eine hohe Sensitivität und Spezifität, wobei der Marker aber auf keinen Fall als Screeningparameter zur Frühdiagnostik eingesetzt werden soll.
Selectivity remains a challenge for ATP-mimetic kinase inhibitors, an issue that may be overcome by targeting unique residues or binding pockets. However, to date only few strategies have been developed. Here we identify that bulky residues located N-terminal to the DFG motif (DFG-1) represent an opportunity for designing highly selective inhibitors with unexpected binding modes. We demonstrate that several diverse inhibitors exerted selective, noncanonical binding modes that exclusively target large hydrophobic DFG-1 residues present in many kinases including PIM, CK1, DAPK, and CLK. By use of the CLK family as a model, structural and biochemical data revealed that the DFG-1 valine controlled a noncanonical binding mode in CLK1, providing a rationale for selectivity over the closely related CLK3 which harbors a smaller DFG-1 alanine. Our data suggest that targeting the restricted back pocket in the small fraction of kinases that harbor bulky DFG-1 residues offers a versatile selectivity filter for inhibitor design.
Gegenstand des vorliegenden Aufsatzes ist es, einige Aspekte des Versuchs, den in Deutschland neu geprägten Begriff der "Ästhetik" nach Frankreich zu importieren, in der Zeit um 1850 zu beleuchten, einer Periode, in der die Ästhetik sich als philosophische Wissenschaft in Frankreich allmählich etabliert. Seit Mitte des 18. Jahrhunderts stieß der Begriff "esthétique", der als direkte Übersetzung des deutschen Wortes "Ästhetik" geprägt wurde, auf zähen Widerstand. Schon ein schneller Blick auf die Wortgeschichte zeugt von dieser Resistenz. Zwar tauchte der Terminus "esthétique" bereits 1753 auf, aber dieser erste Beleg, der im Werk des französischsprachigen Mitglieds der Berliner Akademie der Wissenschaften Louis de Beausobre erschien, blieb lange Zeit isoliert und ohne Widerhall. In der "Encyclopédie" von Diderot und d'Alembert ist bezeichnenderweise unter "esthétique" kein Eintrag zu finden. Erst in zwei Nachbildungen der "Encyclopédie" - in die "Encyclopédie d'Yverdon" von Fortunato Bartolomeo de Felice und ins "Supplément à l'Encyclopédie" von Charles-Joseph Panckoucke - wurde ein solcher Artikel eingeführt. Dieser Importversuch blieb aber bis Anfang des 19. Jahrhunderts so gut wie folgenlos. 1835 wurde das Lemma zum ersten Mal in der sechsten Ausgabe des "Dictionnaire de l'Académie Française" aufgenommen. Den ersten wichtigen Beleg für einen regelrechten Einbürgerungsversuch liefert aber erst der zweite Band des "Dictionnaire des sciences philosophiques" von 1845. Dort ist ein Eintrag zur "esthétique" zu finden, der von Charles Bénard gezeichnet ist. Damit wurde dem Wort "esthétique" in der Sprache der französischen Philosophie sozusagen sein erster Taufschein erstellt. Wer genau war der Autor dieses langen Artikels und was hat ihn veranlasst, einen solchen Eintrag zu schreiben? Wie konnte die Ästhetik als besonderes Teilgebiet der Philosophie um 1850 neue Befürworter finden? Auf welche Hindernisse stießen ihre Fürsprecher? Auf diese Fragen sollen im Folgenden einige Antworten skizziert werden.
Am Fall Husserl soll aufgezeigt werden, wie das wiederholte Von-vorn-Beginnen unweigerlich in eine bestimmte Form des Philosophierens mündet. Dies zu verfolgen erfordert aber weniger eine philosophische als eine poietologische Perspektive. Die konstante Beschäftigung mit dem Anfang führt zu besonderen Schreibformen und entwirft ganze Lebensentwürfe. Dem entspricht ein Lektüremodus, der besonderen Wert auf diejenigen "höchst artistische[n] Volten und Manöver" legt, die im Umgang mit Anfangs- und Ursprungsszenarien zu beobachten sind, und der die daraus erwachsenden praxeologischen Bestimmungen und poetologischen Entwürfe als notwendiger Bestandteil dieser Bemühungen versteht. Es geht also weder darum, die philosophischen Aporien rund um den richtigen Anfang zu lösen, noch darum, ein Theoriemodell des Anfangens zu entwerfen, das in der Literaturwissenschaft aufzunehmen und anzuwenden wäre. Im Fokus stehen soll vielmehr das Zusammenspiel von Epistemologie und Po(i)etologie, das sich über das Anfangsproblem präsentiert und für das sich die "unendliche Aufgabe" von Husserls Phänomenologie, aufgrund der Ernsthaftigkeit ihres Rückfragens und der daraus resultierenden Denk- und Schreibpraxis, besonders eignet. Um die textuellen Konsequenzen der Anfangsaufgabe herausarbeiten zu können, soll in einem zweiten, sich von Husserl lösenden Schritt auf einen Autor zurückgegangen werden, der in der literaturwissenschaftlichen Forschung bereits vielfach als ein ständig neu beginnender und nie zum Schluss kommender beschrieben wurde: Franz Kafka. [...] Im Folgenden sollen also diese beiden Sachverhalte untersucht werden: Zum einen: Welche poetologischen Perspektiven auf das Anfangsproblem schlagen sich in Husserls vielfältigen Fragestellungen und Reflexionsfiguren nieder (III)? Zum anderen: Inwiefern kann Kafkas Form des ständigen Neubeginnens als konsequente Fortführung der Husserl'schen Problemstellung verstanden werden (IV)?
Background: The current COVID-19 pandemic has led to a surge of research activity. While this research provides important insights, the multitude of studies results in an increasing fragmentation of information. To ensure comparability across projects and institutions, standard datasets are needed. Here, we introduce the “German Corona Consensus Dataset” (GECCO), a uniform dataset that uses international terminologies and health IT standards to improve interoperability of COVID-19 data, in particular for university medicine.
Methods: Based on previous work (e.g., the ISARIC-WHO COVID-19 case report form) and in coordination with experts from university hospitals, professional associations and research initiatives, data elements relevant for COVID-19 research were collected, prioritized and consolidated into a compact core dataset. The dataset was mapped to international terminologies, and the Fast Healthcare Interoperability Resources (FHIR) standard was used to define interoperable, machine-readable data formats.
Results: A core dataset consisting of 81 data elements with 281 response options was defined, including information about, for example, demography, medical history, symptoms, therapy, medications or laboratory values of COVID-19 patients. Data elements and response options were mapped to SNOMED CT, LOINC, UCUM, ICD-10-GM and ATC, and FHIR profiles for interoperable data exchange were defined.
Conclusion: GECCO provides a compact, interoperable dataset that can help to make COVID-19 research data more comparable across studies and institutions. The dataset will be further refined in the future by adding domain-specific extension modules for more specialized use cases.
Non-forest ecosystems, dominated by shrubs, grasses and herbaceous plants, provide ecosystem services including carbon sequestration and forage for grazing, yet are highly sensitive to climatic changes. Yet these ecosystems are poorly represented in remotely-sensed biomass products and are undersampled by in-situ monitoring. Current global change threats emphasise the need for new tools to capture biomass change in non-forest ecosystems at appropriate scales. Here we assess whether canopy height inferred from drone photogrammetry allows the estimation of aboveground biomass (AGB) across low-stature plant species sampled through a global site network. We found mean canopy height is strongly predictive of AGB across species, demonstrating standardised photogrammetric approaches are generalisable across growth forms and environmental settings. Biomass per-unit-of-height was similar within, but different among, plant functional types. We find drone-based photogrammetry allows for monitoring of AGB across large spatial extents and can advance understanding of understudied and vulnerable non-forested ecosystems across the globe.
Nach wie vor ist die Geschichte der ästhetischen und auch der poetologischen Debatten in der ersten Hälfte des 19. Jahrhunderts, was ihre Breite und Heterogenität angeht, ein blinder Fleck der Forschung. Das überrascht angesichts der Dynamik der Verschiebungen innerhalb der Paradigmata des Schönen nach 1800, die der erstarkenden Bedeutung des Sehens im Horizont medialer Formerweiterungen ebenso Rechnung trägt wie der philosophischen Ausrichtung der Phänomenologie, der wachsenden Bedeutung der Psychologie und auch dem steigenden Einfluss von wissenschaftlichen Ordnungen auf die Künste. Allenthalben verschaffen sich neue Konzepte des Schönen, der Kontinuität, der Brüchigkeit und der Kritik, des Verhältnisses von Idee und Realität, von Phänomen und System, von Erscheinung und Abstraktion Ausdruck und werden wiederum in Ästhetik 'betrachtet' und eingeordnet.
Wie immer man Vischers Argumentation einordnet, deutlich machen sollte man sich zunächst, dass sie nicht allein kunstphilosophisch orientiert ist, sondern den Austausch mit sich seit den 1830er Jahren zusehends pluralisierenden und von der Zeitordnung, die Hegels Geschichtsphilosophie vorgibt, emanzipierenden literatur- und kunsthistoriografischen Diskursen sucht, womöglich sogar das Ergebnis literatur- und kunstgeschichtlicher Revisionen dieses Zeitraums ist. Dies würde bedeuten, dass es nicht allein (und vielleicht nicht einmal primär) das Gebiet der philosophischen Ästhetik (Kunstphilosophie) ist, innerhalb dessen Vischers Moderne ihre Konturen gewinnt. Im Mittelpunkt stehen würde demgegenüber die empirisch orientierte, d. h. an Einzelwerk und -künstler interessierte Kunst- und Literaturforschung. Wenn wir im Weiteren diese These verfolgen, so nicht so sehr aus dem Interesse heraus, den Anteil kunstphilosophischer Konzeption im Denken Vischers tatsächlich marginalisieren zu wollen. Interessant ist vielmehr die Möglichkeit, in heuristischer Absicht die Elemente der kunst- und literaturgeschichtlichen Rede als eigenständige Diskursformationen in der Betrachtung scharfstellen zu können. Mit diesem Ziel soll es zunächst darum gehen, das Verhältnis von Romantik und Moderne im Haushalt der hegelianischen Literatur- und Kunstgeschichtsschreibung um 1840 zu bestimmen. Gefragt werden soll zudem: Wie lässt sich Vischers im Plan zu einer neuen Gliederung der Ästhetik entworfenes Moderne-Ideal in diesen Rahmen integrieren (Kap. I)? In einem zweiten Schritt wird schließlich ganz konkret jenen Spuren nachgegangen, die Vischers Argumentation im Einflussgebiet kunst- und literaturgeschichtlicher Diskursmuster seiner Zeit zu verorten erlauben (Kap. II). Abschließend wollen wir die Ergebnisse in eine Konturierung des Moderne-Begriffes einbringen (Kap. III).
Im Folgenden möchte ich Mundts Schrift in ihren Hauptmomenten vorstellen und dabei schlaglichtartig derartige Schnittstellen erhellen: die Idee einer großen, die modernen Differenzerfahrungen aufhebenden Vermittlung und deren politische Implikationen (1.); die Möglichkeiten einer politischen Artikulation im Rahmen der philosophischen Ästhetik des Vormärz (2.); die dynamische Begriffsordnung der "Aesthetik", deren Bewegungsemphase und das zugleich bemerkbare Erproben formativer Kräfte (3.); Phantasie und Idealisierung (4.) und schließlich den für Mundts Schrift wichtigen Begriff des Bildes (5.). Die Verbindungslinien, die sich zwischen Mundts "Aesthetik" und der Ästhetik des Jahrhunderts zeigen werden, sind dann zugleich Ausweis von Kontinuitäten, die sich zwischen den beiden Jahrhunderthälften, zwischen Vormärz und Nachmärz erstrecken.
Im 15. Abschnitt seiner Aesthetik kommt Theodor Mundt auf den Humor als 'burleske Philosophie' zu sprechen. Als erster deutscher Ästhetiker hatte der von dem berühmt-berüchtigten Verbotsbeschluss des Bundestags vom 10. Dezember 1835 gegenüber dem sogenannten Jungen Deutschland hart getroffene Autor 1837 in seiner Abhandlung Die Kunst der deutschen Prosa systematisch die "zeitgemäße Stellung" der deutschen Prosa und damit deren Vorrangstellung gegenüber der Poesie begründet. [...] Richtete Mundt in dieser Abhandlung den Fokus noch auf die "Emancipation der Prosa", ist es in der Aesthetik nun "das Prinzip der Unmittelbarkeit" als "Philosophie der That". Mundt selbst spricht im Vorwort selbstbewusst von dem "von mir neu aufgestellte[n] Prinzip der Aesthetik". [...]
Vischers Freiheitsbedürfnis war unersättlich, und er war ständig auf der Suche nach Trost und Orientierung in einer orientierungslosen Zeit. Vischer hoffte, dies nicht nur in der Kunstschönheit in fernen Ländern zu finden, sondern vor allem in der Literatur, der Dichtung und der Philosophie. Der erste Teil des Goethe'schen Faust und Hegels Philosophie sollten daher in der zerrissenen, stürmischen Vormärzzeit zum Rettungsanker für ihn werden. Vischer wird sich von diesen Reisebegleitern nie gänzlich befreien, sie werden mehr oder weniger ausdrücklich sein ganzes Leben an seiner Seite sein, wenn er sich auf die Suche nach einem (unmöglichen) Gleichgewicht zwischen den beiden Seelen in seiner gespaltenen Brust macht: der systematischen (mit offensichtlichen Anklängen an Hegel) und der zerrissenen (die klar auf den Faust anspielt). Wir wollen, von der ersten ausgehend, beide analysieren.
Background In the pandemic, testing for SARS-CoV-2 by RT-PCR in one of the pillars on which countermeasures are based. Factors limiting the output of laboratories interfere with the effectiveness of public health measures. Conserving reagents by pooling samples in low-probability settings is proposed, but may cause dilution and loss of sensitivity.
Methods We tested an alternate approach (FACT) by simultaneously incubating multiple respiratory swabs in a single tube. This protocol was evaluated by serial incubation of a respiratory swab in up to 10 tubes. The analytics validity of this concept was demonstrated in a five-sample mini pool set-up. It was consequently applied in the testing of 50 symptomatic patients (five-sample pools) as well as 100 asymptomatic residents of a nursing home (ten-sample pools).
Results Serial incubation of a respiratory swab in up to 10 tubes did not lead to a significant decline in viral concentration. The novel FACT-protocol did not cause a false negative result in a five-sample mini-pool setup, with non-significantly differing Ct values between single sample and mini-pool NAT. In two routine applications, all mini pools containing positive patient samples were correctly identified.
Conclusions Our proposed FACT-protocol did not cause a significant loss in analytic or diagnostic sensitivity compared to single sample testing in multiple setups. It reduced the amount of reagents needed by up to 40%, and also reduced hands-on time. This method could enhance testing efficiency, especially in groups with a low pretest-probability, such as systemically relevant professional groups.
It becomes more and more obvious that deregulation of host metabolism play an important role in SARS-CoV-2 pathogenesis with implication for increased risk of severe course of COVID-19. Furthermore, it is expected that COVID-19 patients recovered from severe disease may experience long-term metabolic disorders. Thereby understanding the consequences of SARS-CoV-2 infection on host metabolism can facilitate efforts for effective treatment option. We have previously shown that SARS-CoV-2-infected cells undergo a shift towards glycolysis and that 2-deoxy-D-glucose (2DG) inhibits SARS-CoV-2 replication. Here, we show that also pentose phosphate pathway (PPP) is remarkably deregulated. Since PPP supplies ribonucleotides for SARS-CoV-2 replication, this could represent an attractive target for an intervention. On that account, we employed the transketolase inhibitor benfooxythiamine and showed dose-dependent inhibition of SARS-CoV-2 in non-toxic concentrations. Importantly, the antiviral efficacy of benfooxythiamine was further increased in combination with 2DG.
"Berührungsfurcht" : soziale Imaginationen der Unterklassigen in der Kanon-Literatur der Moderne
(2020)
Die gutbürgerliche Literatur verwahrt sich mit allem, was ihr eigen ist - Sprache, Aisthesis, Kreativität, Imagination, Wissen und Bildung - gegen den Übergriff des Anderen und Fremden in Gestalt des sozial Niederen und Subalternen im eigenen Erfahrungsbereich, durchsetzt mit Empathie und Aggression. Aus der Sicht der noblen Literatur fällt der Blick auf die schäbigen Volkssänger, von denen sich Gustav Aschenbach, Thomas Manns Identifikationsfigur im "Tod in Venedig", auf der Hotelempore des Lido bedrängt fühlt, auf die elenden "Schalen von Menschen" in den Straßen und Krankenanstalten von Paris in Rilkes "Malte Laurids Brigge", auf die im Gerede sprachlosen Scheusale von Haushälterin und Hausbesorger in Canettis "Blendung", auf die im 'Jargon' agierende chassidische Schauspieler-Bagage, die Kafka so vehement gegen den Prager Kulturzionismus verteidigt. Die kulturelle Hybris gegenüber den Subalternen und Deklassierten folgt der Spur eines elitären Gestus, auch im politischen Handeln: Verachtung, Abscheu, Angst und Erschrecken angesichts der 'Deplorables', des bedauernswerten Elends der sozial Deklassierten und minder Kultivierten. [...] Das entsprechende Bildrepertoire an einsinnigen Klischees begegnet, ästhetisch nuanciert, in der literarischen Zeitgenossenschaft um 1900 bei Autoren unterschiedlichster Weltanschauung und Schreibweise. Und seitdem, was im Folgenden aufzuzeigen ist, in fast jedem uns vertrauten Text moderner, als bürgerlich verbürgter deutscher Literatur, der sich dem sozial Anderen außerhalb des eigenen Lebens- und Erfahrungsbereichs zuwendet, mehr oder weniger emphatisch oder verdrossen. Bei diesem kleinen Streifzug durch einige Kanon-Texte der Moderne kann es nicht um ihre sozialpsychologische und sozialhistorische Erklärbarkeit gehen. Vielmehr interessieren, als kleiner Nachtrag zur Lektüre der uns wohl bekannten Werke, gewisse Wege und Abwege der sozialen Imagination: der moralisch und ästhetisch oft verquere Umgang mit einem Fremden, das nicht nur in anderen Ländern und Kulturen zu suchen, sondern daheim, hier und jetzt, zu entdecken ist. In der Ferne so nah, voller "Berührungsfurcht", wenn nicht panischem Erschrecken vor dem Anderen.
Cancer‐associated venous thromboembolism (VTE) is a frequent, potentially life‐threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer‐associated thrombosis (CAT); factor Xa–inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low‐molecular‐weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo‐controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis—expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real‐world evidence studies, including investigator‐initiated research.
Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis
(2020)
Highlights
• Hypoxia decreases NCOA4 transcription in primary human macrophages.
• NCOA4 mRNA is a target of miR-6862-5p.
• Lowering NCOA4 increases FTMT abundance under hypoxia.
• FTMT and FTH protect from ferroptosis.
• Tumor cells lack the hypoxic decrease of NCOA4 and fail to stabilize FTMT.
Abstract
Cellular iron, at the physiological level, is essential to maintain several metabolic pathways, while an excess of free iron may cause oxidative damage and/or provoke cell death. Consequently, iron homeostasis has to be tightly controlled. Under hypoxia these regulatory mechanisms for human macrophages are not well understood. Hypoxic primary human macrophages reduced intracellular free iron and increased ferritin expression, including mitochondrial ferritin (FTMT), to store iron. In parallel, nuclear receptor coactivator 4 (NCOA4), a master regulator of ferritinophagy, decreased and was proven to directly regulate FTMT expression. Reduced NCOA4 expression resulted from a lower rate of hypoxic NCOA4 transcription combined with a micro RNA 6862-5p-dependent degradation of NCOA4 mRNA, the latter being regulated by c-jun N-terminal kinase (JNK). Pharmacological inhibition of JNK under hypoxia increased NCOA4 and prevented FTMT induction. FTMT and ferritin heavy chain (FTH) cooperated to protect macrophages from RSL-3-induced ferroptosis under hypoxia as this form of cell death is linked to iron metabolism. In contrast, in HT1080 fibrosarcome cells, which are sensitive to ferroptosis, NCOA4 and FTMT are not regulated. Our study helps to understand mechanisms of hypoxic FTMT regulation and to link ferritinophagy and macrophage sensitivity to ferroptosis.
Purpose: Neonatal surgery for abdominal wall defects is not performed in a centralized manner in Germany. The aim of this study was to investigate whether treatment for abdominal wall defects in Germany is equally effective compared to international results despite the decentralized care.
Methods: All newborn patients who were clients of the major statutory health insurance company in Germany between 2009 and 2013 and who had a diagnosis of gastroschisis or omphalocele were included. Mortality during the first year of life was analysed.
Results: The 316 patients with gastroschisis were classified as simple (82%) or complex (18%) cases. The main associated anomalies in the 197 patients with omphalocele were trisomy 18/21 (8%), cardiac anomalies (32%) and anomalies of the urinary tract (10%). Overall mortality was 4% for gastroschisis and 16% for omphalocele. Significant factors for non-survival were birth weight below 1500 g for both groups, complex gastroschisis, volvulus and anomalies of the blood supply to the intestine in gastroschisis, and female gender, trisomy 18/21 and lung hypoplasia in omphalocele.
Conclusions: Despite the fact that paediatric surgical care is organized in a decentralized manner in Germany, the mortality rates for gastroschisis and omphalocele are equal to those reported in international data.
Objectives: To analyze the performance of radiological assessment categories and quantitative computational analysis of apparent diffusion coefficient (ADC) maps using variant machine learning algorithms to differentiate clinically significant versus insignificant prostate cancer (PCa). Methods: Retrospectively, 73 patients were included in the study. The patients (mean age, 66.3 ± 7.6 years) were examined with multiparametric MRI (mpMRI) prior to radical prostatectomy (n = 33) or targeted biopsy (n = 40). The index lesion was annotated in MRI ADC and the equivalent histologic slides according to the highest Gleason Grade Group (GrG). Volumes of interest (VOIs) were determined for each lesion and normal-appearing peripheral zone. VOIs were processed by radiomic analysis. For the classification of lesions according to their clinical significance (GrG ≥ 3), principal component (PC) analysis, univariate analysis (UA) with consecutive support vector machines, neural networks, and random forest analysis were performed. Results: PC analysis discriminated between benign and malignant prostate tissue. PC evaluation yielded no stratification of PCa lesions according to their clinical significance, but UA revealed differences in clinical assessment categories and radiomic features. We trained three classification models with fifteen feature subsets. We identified a subset of shape features which improved the diagnostic accuracy of the clinical assessment categories (maximum increase in diagnostic accuracy ΔAUC = + 0.05, p < 0.001) while also identifying combinations of features and models which reduced overall accuracy. Conclusions: The impact of radiomic features to differentiate PCa lesions according to their clinical significance remains controversial. It depends on feature selection and the employed machine learning algorithms. It can result in improvement or reduction of diagnostic performance.
Marie Holzman, 1922–1941
(2020)
Marie Holzman, geboren am 22. April 1922 in Jena, war die ältere Tochter des seit 1922/23 in Kaunas (Litauen) ansässigen Gründers und Inhabers der Verlagsbuchhandlung Pribačis Max Holzman (1889–1941) sowie der aus Jena stammenden Malerin und Kunsterzieherin Helene Czapski-Holzman (1891–1961). Nach dem deutschen Überfall auf die Sowjetunion wurde sie am 29. Oktober 1941 in Kaunas ermordet. Ihre Mutter hat zwei von ihrer Tochter aus dem Litauischen übersetzte Erzählungen bewahrt. Unlängst gelangten die beiden Manuskripte ans Exilarchiv der DNB in Frankfurt/M.
Deconfinement of Mott localized electrons into topological and spin–orbit-coupled Dirac fermions
(2020)
The interplay of electronic correlations, spin–orbit coupling and topology holds promise for the realization of exotic states of quantum matter. Models of strongly interacting electrons on honeycomb lattices have revealed rich phase diagrams featuring unconventional quantum states including chiral superconductivity and correlated quantum spin Hall insulators intertwining with complex magnetic order. Material realizations of these electronic states are, however, scarce or inexistent. In this work, we propose and show that stacking 1T-TaSe2 into bilayers can deconfine electrons from a deep Mott insulating state in the monolayer to a system of correlated Dirac fermions subject to sizable spin–orbit coupling in the bilayer. 1T-TaSe2 develops a Star-of-David charge density wave pattern in each layer. When the Star-of-David centers belonging to two adyacent layers are stacked in a honeycomb pattern, the system realizes a generalized Kane–Mele–Hubbard model in a regime where Dirac semimetallic states are subject to significant Mott–Hubbard interactions and spin–orbit coupling. At charge neutrality, the system is close to a quantum phase transition between a quantum spin Hall and an antiferromagnetic insulator. We identify a perpendicular electric field and the twisting angle as two knobs to control topology and spin–orbit coupling in the system. Their combination can drive it across hitherto unexplored grounds of correlated electron physics, including a quantum tricritical point and an exotic first-order topological phase transition.