Reliable infarction of the middle cerebral artery territory in C57BL/6 mice using pterygopalatine artery ligation and filament optimization – The PURE-MCAo model

Current techniques for inducing intraluminal filamentous middle cerebral artery occlusion (fMCAo) in mice produce highly variable results and often cause additional infarcts in the posterior cerebral artery (PCA) territory. The aim of the current study was to develop a novel procedure to overcome these shortcomings. Male C57BL/6 mice were subjected to 60 min of fMCAo with cerebral blood flow monitored by laser Doppler flowmetry. The influence of the length of the occlusion filament coating and the combination of common carotid artery (CCA) or pterygopalatine artery (PPA) ligation on lesion volume and functional outcome 24 h after reperfusion was evaluated. The use of appropriate filament and PPA ligation while maintaining CCA perfusion prevented the development of infarcts in the PCA area, resulted in pure MCA infarcts (68.3 ± 14.5 mm3) and reduced the variability of infarct volumes by more than half (from 26–38% to 14% standard deviation/mean). Using an improved fMCAo procedure, we were able to produce PCA area-unaffected reproducible (PURE) infarcts exclusively in the MCA territory. Thus PURE-MCAo reduced outcome variability by more than 50%. Our results may thus help to reduce the number of animals in preclinical stroke research and to increase the reproducibility of the fMCAo model

In vivo synergistic enhancement of MIF‐mediated inflammation in acute lung injury by the plant ortholog ArabidopsisMDL1

Recent research has uncovered Arabidopsis thaliana proteins that are similar to the human inflammatory cytokine MIF. Plant MIF/D-dopachrome tautomerase (D-DT)-like proteins (MDLs) can interact with human MIF, yet the significance of these findings in living organisms has not been investigated. Given MIF's key role in acute respiratory distress syndrome promoting pulmonary inflammation, pathology, and leukocyte infiltration, here we set out to investigate the interplay between MIF and MDL1, one of three A. thaliana MIF orthologs, in an in vivo mouse model of MIF-induced acute lung injury (ALI). Human MIF and MDL1 were administered to C57BL/6 mice via inhalation, individually or in combination. Inhalation of MIF promoted various parameters of lung injury as evaluated by flow cytometry, immunofluorescence microscopy, RT-qPCR, and ELISA, while MDL1 inhalation alone had no effect. Intriguingly, combined treatment with MIF and MDL1 synergistically enhanced pulmonary infiltration of neutrophils and monocytic cells, accompanied by an upregulation of pro-inflammatory cytokine genes. Thus, the plant-derived MIF ortholog MDL1 potentiates MIF-induced inflammation in ALI. These data support the growing evidence of interactions between plant-derived compounds and human inflammatory mediators and illustrate how they may impact human health

What if … there were no special schools?

Inclusive education is a human right that involves restructuring the school system and closing special schools. However, there is uncertainty about whether all or only some students in an inclusive system should attend regular primary schools and whether all or only some special schools should be closed. This question is usually only discussed in terms of the best possible care and education and the challenge of transportation to school and travel distances is neglected. This article attempts to take both into account. The federal state of Bavaria in Germany does not yet have a fully developed inclusive school system. Using school statistics data for the entire Bavarian primary school population in 2020 (N > 445,000) and geographical data, we simulate deterministically what the Bavarian primary school system could look like with various underlying inclusion models. We analyse the resulting student numbers, support rates of primary schools and school travel distances of former special school students in an urban-rural comparison in four different simulated inclusion models. The results show that all models are potentially feasible. The student numbers at each primary school resulting from the closure of special schools would in most cases not change significantly, whereas the support rate (i.e., the percentage of students with SEN per primary school) would. Schooling close to home favours students in rural areas in particular and significantly reduces their journeys to school by up to 30 km, while for students in urban areas, all inclusive models would be possible. The pedagogical and systemic consequences of the simulated inclusion models are discussed.Inklusive Bildung ist ein Menschenrecht, das die Umstrukturierung des Schulsystems und die Schließung von Sonderschulen fordert. Es ist ein offener Streit, ob alle oder nur einige Schüler:innen in einem inklusiven Schulsystem reguläre Grundschulen besuchen sollten und ob alle oder nur einige Sonderschulen geschlossen werden sollten. Diese Frage wird in der Regel nur im Hinblick auf die bestmögliche Bildung und Betreuung diskutiert, wobei die Herausforderung des Fahrtwegs zur Schule vernachlässigt wird. Dieser Artikel versucht, beides zu berücksichtigen. Der Freistaat Bayern in Deutschland verfügt noch nicht über ein inklusives Schulsystem. Unter Verwendung von Schulstatistikdaten für die gesamte bayerische Grundschulschülerschaft im Jahr 2020 (N > 445.000) und geografischen Daten simulieren wir deterministisch, wie das bayerische Grundschulsystem mit verschiedenen zugrunde liegenden Inklusionsmodellen aussehen könnte. Wir analysieren die resultierenden Schülerzahlen, Förderquoten der Grundschulen und Schulwege in einem urban-ruralen Vergleich in vier verschiedenen simulierten Inklusionsmodellen. Die Ergebnisse zeigen, dass alle Modelle grundsätzlich umsetzbar wären. Die Grundschulgrößen würden sich durch Sonderschulschließungen in den meisten Fällen nicht signifikant ändern, während die Förderquote (der prozentuale Anteil von Lernenden mit Förderbedarf pro Grundschule) dies tun würde. Wohnortnahe Inklusion kommt insbesondere Schüler:innen auf dem Land zugute und reduziert ihre Schulwege um bis zu 30 km, während für Schüler:innen in der Stadt alle inklusiven Modelle möglich wären. Pädagogische und systemische Konsequenzen der simulierten Inklusionsmodelle werden diskutiert

Cryptocurrencies, a controversial innovation? Unpacking argumentation analysis in economic geography

In this paper, we analyze the global controversy surrounding the innovation of cryptocurrencies, developing an analytical framework to assess the empirical structure of arguments. By unpacking an argumentation analysis of a comprehensive set of scholarly, media, and industry publications, we identify six key dimensions of disagreement, comprising 42 distinct arguments. These dimensions include the raison d’être, environmental impact, social inclusion, susceptibility to illegal activities, economic impact, and potential for decentralization and democratization. Our findings reveal entrenched positions supported by robust scholarly research and empirical evidence. Cryptocurrencies represent a controversial innovation, for which global resolution remains elusive. While the controversy may appear unbounded, we plead for a geographical approach, emphasizing that localized institutional contexts are crucial for exploring potential trajectories of the controversy. Finally, our analysis illustrates the potential of argumentation analysis to properly disentangle complex societal disagreements, and it therefore promises to enrich the methodological pluralism in economic geography

Learning regular cross-trial shifts of the target location in serial search involves awareness – An eye-tracking study

People can learn and use both static and dynamic (cross-trial) regularities in the positioning of target items during parallel, ‘pop-out’ visual search. Static target-location learning also works in serial search, however, acquiring dynamic regularities is hindered by the demands of item-by-item scanning. Also, questions have been raised regarding whether explicit awareness is necessary for using dynamic regularities to optimize performance. The present study re-examined if dynamic regularities can be learned in serial search when regular shifts of the target location occur frequently, and if such learning correlates with awareness of the dynamic rule. We adopted the same regularity used by Yu et al. (2023) to demonstrate dynamic learning in parallel search: a cross-trial shift of the target location in a (counter-)clockwise direction within a circular array in 80 % of the trials, compared to irregular shifts in the opposite direction (10 %) or some other random direction (10 %). The results showed that about 70 % of participants learned the dynamic regularity, with performance gains correlating with awareness: the more accurately they estimated the likelihood of the target shifting in the frequent direction, the greater their gains. Importantly, part of the gains accrued already early during the search: a large proportion of the very first and short-latency eye movements were directed to the predicted location, regardless of the target appeared there. We discuss whether this rule-driven behavior is causally mediated by conscious control

Ethiopic Palimpsests

While spectacular scholarly breakthroughs and technological advances have led to a surge in recent scholarship on palimpsests, their existence within the Ethiopic manuscript tradition has hitherto received virtually no attention. Nonetheless, at least sixteen Ethiopic palimpsests have been identified, with many more to be found within collections inaccessible at present. Those available for study exhibit strong tendencies towards having biblical commentaries overwritten and being manufactured around the seventeenth century, though the only such manuscript to have undergone multi-spectral imaging thus far (Berlin, Staatsbibliothek zu Berlin, Petermann II Nachtrag 24) is of slightly later date. This manuscript contains no less than ten discrete scriptiones inferiores, but in this regard it likely constitutes an outlier to palimpsesting as practised within the Ethiopic tradition more broadly

Data depth functions for non-standard data by use of formal concept analysis

In this article we introduce a notion of depth functions for data types that are not given in standard statistical data formats. We focus on data that cannot be represented by one specific data structure, such as normed vector spaces. This covers a wide range of different data types, which we refer to as non-standard data. Depth functions have been studied intensively for normed vector spaces. However, a discussion of depth functions for non-standard data is lacking. In this article, we address this gap by using formal concept analysis to obtain a unified data representation. Building on this representation, we then define depth functions for non-standard data. Furthermore, we provide a systematic basis by introducing structural properties using the data representation provided by formal concept analysis. Finally, we embed the generalised Tukey depth into our concept of data depth and analyse it using the introduced structural properties. Thus, this article presents the mathematical formalisation of centrality and outlyingness for non-standard data and increases the number of spaces in which centrality can be discussed. In particular, we provide a basis for defining further depth functions and statistical inference methods for non-standard data

Step‐by‐Step Towards Biological Homochirality – from Prebiotic Randomness To Perfect Asymmetry

The history of life's formation and the origin of its stereochemistry are nearly as multifaceted as the life itself. In this review, we focus on analyzing the step-by-step path leading to what we can define as “life” in parallel to what we know about the emergence of enantiomeric imbalance and subsequent transition to full homochirality. We start at the level of assembly of the building blocks of life from inorganic molecules and build up to the polymerization and formation of nucleic acids and peptides. We report and analyze different theories at various stages of this development and try to elucidate the most plausible theory

Impact of Pulmonary Hypertension on Outcomes After Transcatheter Tricuspid Valve Edge-to-Edge Repair

Background Data regarding the association of pulmonary hypertension (PH) and outcomes in patients undergoing transcatheter tricuspid valve edge-to-edge repair (T-TEER) are scarce. Objectives The aims of this study were: 1) to investigate the impact of PH on outcomes after T-TEER; and 2) to shed further light on the role of precapillary- and postcapillary PH in patients undergoing T-TEER for relevant tricuspid regurgitation (TR). Methods The study included patients from EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation; NCT06307262) who underwent T-TEER for relevant TR from 2016 until 2023 with available invasive evaluation of systolic pulmonary artery pressure (sPAP) using right heart catheterization. Study endpoints were procedural TR reduction, improvement in NYHA function class, and a combined endpoint of death or heart failure hospitalization (HFH) at 2 years. Results Among a total of 1,230 patients (mean age 78.6 ± 7.0 years, 51.4% women), increasing sPAP was independently associated with increasing rates of 2-year death or HFH (HR: 1.027; 95% CI: 1.003-1.052; P = 0.030; median survival follow-up 343 days [Q1-Q3: 114-645 days]). No significant survival differences were observed for patients with pre- vs postcapillary PH. Sensitivity analysis revealed an sPAP value of 46 mm Hg as the optimized threshold for the prediction of death or HFH. Being observed in 526 patients (42.8%), elevated sPAP (>46 mm Hg) was associated with more severe heart failure symptoms at baseline and follow-up. Importantly, NYHA functional class significantly improved and TR severity was significantly reduced irrespective of PH. Conclusions PH is an important outcome predictor in patients undergoing T-TEER for relevant TR. In contrast to previous studies, no significant differences were observed for patients with precapillary and postcapillary PH in terms of survival free from HFH