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Background: Recognizing patients at risk for pulmonary complications (PC) is of high clinical relevance. Migration of polymorphonuclear leukocytes (PMN) to inflammatory sites plays an important role in PC, and is tightly regulated by specific chemokines including interleukin (IL)−8 and other mediators such as leukotriene (LT)B4. Previously, we have reported that LTB4 indicated early patients at risk for PC after trauma. Here, the relevance of LTB4 to indicating lung integrity in a newly established long-term porcine severe trauma model (polytrauma, PT) was explored.
Methods: mTwelve pigs (3 months old, 30 ± 5 kg) underwent PT including standardized femur fracture, lung contusion, liver laceration, hemorrhagic shock, subsequent resuscitation and surgical fracture fixation. Six animals served as controls (sham). After 72 h lung damage and inflammatory changes were assessed. LTB4 was determined in plasma before the experiment, immediately after trauma, and after 2, 4, 24 or 72 h. Bronchoalveolar lavage (BAL)-fluid was collected prior and after the experiment.
Results: Lung injury, local gene expression of IL-8, IL-1β, IL-10, IL-18 and PMN-infiltration into lungs increased significantly in PT compared with sham. Systemic LTB4 increased markedly in both groups 4 h after trauma. Compared with declined plasma LTB4 levels in sham, LTB4 increased further in PT after 72 h. Similar increase was observed in BAL-fluid after PT.
Conclusions: In a severe trauma model, sustained changes in terms of lung injury and inflammation are determined at day 3 post-trauma. Specifically, increased LTB4 in this porcine long-term model indicated a rapid inflammatory alteration both locally and systemically. The results support the concept of LTB4 as a biomarker for PC after severe trauma and lung contusion.
Der Begriff 'apokryph' taucht bei Johann Georg Hamann (1730-1788), dem 'Magus in Norden', seltener auf als man es vielleicht erwarten würde, jedenfalls so man Hamann noch immer nach dem gängigen Klischee für 'dunkel', einen 'Mystiker' oder einen 'Obskurantisten' oder gar für den Ursprung des modernen und spezifisch deutschen Irrationalismus und extremsten Feind der Aufklärung hält, gegenüber dessen "gewollter und künstlicher Dunkelheit", die er wie eine "Nebelwand um sich zog", sogar Hegels Phänomenologie des Geistes "eine wahre Ferienlektüre" sei. Ein schöpferischer Kopf also, "der manche tiefsinnigen Einfälle hatte, aber in welch geheimnisvolle Gewänder pflegte er sie zu verkleiden!" Entsprechend ist Hamanns Ruf: "Dunkelheit ist das traditionelle Prädicat, das jedem deutschen Primaner über ihn geläufig ist." Mit seiner Dunkelheit, so die unausgesprochene Annahme, möchte Hamann willentlich und wissentlich etwas verbergen, vielleicht nicht nur bei sich, sondern letztlich sogar das Licht der Aufklärung überhaupt; ein Umstand, der auf das Schönste zum griechischen apokryptein: 'verbergen, verdunkeln' (so die Übersetzung in Josef Nadlers Schlüssel zu Hamanns Werken) zu passen scheint. Entsprechend ist es, um eine weitere Bedeutung des Begriffes "apokryph" als des 'Gegen-Kanonischen' heranzuziehen, kaum verwunderlich, dass Texte Hamanns es nicht in den akademisch etablierten Kanon philosophischer Werke geschafft haben, ja sogar gegen entsprechende kanonische Texte (etwa die Metakritik über den Purismum der Vernunft gegen die Kritik der reinen Vernunft oder Golgatha und Scheblimini gegen Mendelssohns Jerusalem) gerichtet zu sein scheinen.
I summarize recent developments in the hard-thermal-loop approach to QCD. I first discuss a finite-temperature and -density calculation of QCD thermodynamics at NNLO from the hard-thermal-loop perturbation theory. I then discuss a generalization of the hard-thermal-loop framework to the magnetic scale g2T, from which a novel non-Abelian massless mode is uncovered.
Evidence of widespread wildfires in a coal seam from the middle Permian of the North China Basin
(2017)
The North China Basin is the largest coal-bearing basin in China, and has an areal extent of 800,000 km2. We analyzed 138 coal samples and in situ pillar coal samples of the middle Permian from this basin by macropetrography, microscope, scanning electron microscope, gas chromatography, and gas chromatography–mass spectrometer in order to study wildfires. High contents of inertinite (charcoal) and natural coke particles observed in coal samples indicate that vegetation in precursor mires and peats of the middle Permian coal from north China was exposed to far-ranging wildfires. In addition, high-molecular-weight polycyclic aromatic hydrocarbons were detected in the coal samples. These aromatic compounds were formed under high temperatures and provide further evidence of wildfire. These wildfires would have discharged significant CO and CO2 gases into the atmosphere and affected the paleoclimate and paleoecosystem.
Background: The Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD.
Objective: We aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy.
Methods: We conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial.
Results: We identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence.
Conclusions: Several established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.
S1P provokes tumor lymphangiogenesis via macrophage-derived mediators such as IL-1β or lipocalin-2
(2017)
A pleiotropic signaling lipid, sphingosine-1-phosphate (S1P), has been implicated in various pathophysiological processes supporting tumor growth and metastasis. However, there are only a few descriptive studies suggesting a role of S1P in tumor lymphangiogenesis, which is critical for tumor growth and dissemination. Corroborating own data, the literature suggests that apoptotic tumor cell-derived S1P alters the phenotype of tumor-associated macrophages (TAMs) to gain protumor functions. However, mechanistically, the role of TAM-induced lymphangiogenesis has only been poorly described, mostly linked to the production of lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) and VEGF-D, or transdifferentiation into lymphatic endothelial cells. Recent findings highlight a rather underappreciated role of S1P in tumor lymphangiogenesis, referring to the production of interleukin-1β (IL-1β) and lipocalin-2 (LCN2) by a tumor-promoting macrophage phenotype. In this review, we aim to provide to the readers with the current understanding of the molecular mechanism how apoptotic cell-derived S1P triggers TAMs to promote lymphangiogenesis.
The aim of our study was to reveal the differences in the species composition and soil properties of open sandy grasslands dominated by different Festuca species, Festuca vaginata and F. pseudovaginata. Due to the arid conditions, sandy grasslands are generally covered by xerothermic vegetation in which F. vaginata is a typical dominant species. Festuca pseudovaginata, a species newly described by the authors, can also gain dominance in sandy grasslands. However, species composition and soil properties of grasslands dominated by this recently discovered species are still undiscovered. Based on previous coenological studies, we hypothesised that the grasslands characterised by the endemic F. vaginata are more species-rich than those with F.pseudovaginata.
Coenological sampling was carried out in May 2009 at two study sites using the Braun-Blanquet method in quadrats of 2 m × 2 m. Five relevés were sampled in stands dominated by F. vaginata and F. pseudovaginata respectively at two study sites in Central Hungary, resulting in a total of twenty relevés. Analyses were based on the cover scores of vascular plant species and cryptogam crust and values of seven soil properties (pH [KCl], pH [H2O], humus, total N, Ca, P2O5 and K2O) measured in the 0–15 and 15–30 cm soil layers. Soil properties of the grasslands dominated by F. pseudovaginata and F. vaginata (dependent variables) were compared by linear mixed models, where ‘grassland type’ was the fixed factor and ‘site nested in grassland type’ was considered as random factor. Data were analysed by cluster analysis, fusion algorithm was a combinatorial method (minimising increase of variance), and the correlation was used as comparative function. We compared the cover of subordinate species by Mann-Whitney U test. We found that F. pseudovaginata and F. vaginata samples were well separated, and grasslands dominated by F. pseudovaginata had nearly two times more species than those dominated by F. vaginata. Based on the cluster analyses using plant cover and upper 0–15 cm soil layer data, F. pseudovaginata and F. vaginata groups could be well separated. Linear mixed models revealed that F. vaginata grasslands were typical on soils with higher pH, nitrogen, phosphorous and potassium contents compared to F. pseudovaginata grasslands, which indicates a tight connection between the properties of the upper soil layer and the vegetation in sandy grasslands.
Dort, wo es zu einem intensiven kulturellen Kontakt, Austausch und Transfer zwischen Gemeinschaften kommt, lassen sich Kategorien wie Identität und Alterität nicht immer scharf voneinander trennen, sondern erscheinen eher als "ständig zu aktualisierende soziale Konstruktionen" (NEULAND 2013: 168). Sie können zudem auch zu transkulturellen innovativen sprachlichen Schöpfungen führen. Die Sprache ist wegen ihrer identitätskonstitutiven Funktion fester Bestandteil des Modells der multiplen Sprachidentität von Marijana KRESIĆ (2007). Ausgehend von diesem Modell wird im Beitrag das enge Verhältnis von Identitätskonstruktion - Standardsprache - Sprachgebrauch diskutiert und anhand von ausgewählten Beispielen dargestellt. Die identitätskonstitutive Funktion der Sprache basiert auf der Selektion von Normen aus dem Sprachsystem, wobei der Sprechende durch die Verwendung sprachlicher Zeichen, "seine (soziale und/oder personale Identität) [begründet], d.h. er markiert, wer er als Individuum ist bzw. welcher sozialen Gruppe er zugehört" (KRESIĆ 2007: 19). Im Rahmen der Besprechung dieses Konzepts wird geprüft, wie Formen interkulturellen Sprachgebrauchs (z. B. Kiezdeutsch) in dieses Modell eingefügt werden können.
Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology
(2017)
Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOXRosa26 mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOXRosa26 mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo.
Robinia pseudoacacia L. (black locust) is a North American tree, considered controversial because of the conflict between multiple uses by humans and negative environmental impacts, which have resulted in it being listed among the most invasive species in Europe. The current management of Robinia stands in Central Europe varies locally according to national legislation, preferring either socio-economic benefits or biodiversity impacts. We collected field data from our target region of Czechia, reviewed research articles including local grey literature mostly from Central and Southern Europe, unpublished results of local projects and inquired relevant specialists. Because Robinia grows in habitats ranging from urban to forest to natural grassland, neither unrestricted cultivation nor large-scale eradication is applicable as a universal practice. In this paper we suggest a complex management strategy for Robinia stands that takes into account habitat, this species’ local ability to spread, as well as economic, cultural and biodiversity aspects. We categorized Robinia stands growing in Europe into eight groups and proposed stratified approach to the management based on decisions that reflect local context. Depending on that, the management includes (i) establishment of new plantations, (ii) maintenance or utilization of existing stands, (iii) tolerance
and (iv) conversion to original vegetation. Our complex management strategy will provide a comprehensive guideline for the management of alien trees in Europe.
In dem folgenden werkgenetischen und forschungskritischen Beitrag geht es um das sonderbare und revisionsbedürftige Schicksal, das eine von Mozart nach dessen Rückkehr aus Mannheim in Salzburg ohne Auftrag begonnene und bis Sommer 1780 fast vollendete Oper durch ihre Rezeption bei der Nachwelt bis heute erlitten hat. Für meine Hypothese, bei Mozarts Zaïde handele es sich um eine ernste (nicht-komische), höchstwahrscheinlich einaktig konzipierte Kurzoper ("Operette", W. A. M.) ohne glücklichen Ausgang, ist es ebenso unmöglich, einen "Nachweis" zu erbringen, wie für die bisher geltende, als einzig denkbare Wahrheit auftretende These, sie sei ein stark fragmentarisches, höchstwahrscheinlich dreiaktiges Singspiel, dem nicht nur die Ouvertüre und die meisten Dialoge fehlten, sondern auch die entweder in mehreren fehlenden Schlussnummern eines zweiten oder in einem dritten Akt sich vollziehen sollende glückliche Wende. Darum wird hier nicht versucht, gegen eine bestehende beanspruchte "Deutungshoheit" eine andere zu setzen, sondern lediglich angezeigt und begründet, warum es ratsam ist, eine andere Interpretationsmöglichkeit bekannter Quellen, von denen einige bisher berücksichtigt, andere vernachlässigt wurden, ins Auge zu fassen. Es kann lediglich anhand von Indizien, welche die Quellen und Teile der bisherigen Forschung aufweisen, eine neue, bisher verworfene Möglichkeit von dem über sie verhängten Verdikt befreit werden. ...
The CRISPR/Cas9 prokaryotic adaptive immune system and its swift repurposing for genome editing enables modification of any prespecified genomic sequence with unprecedented accuracy and efficiency, including targeted gene repair. We used the CRISPR/Cas9 system for targeted repair of patient-specific point mutations in the Cytochrome b-245 heavy chain gene (CYBB), whose inactivation causes chronic granulomatous disease (XCGD)—a life-threatening immunodeficiency disorder characterized by the inability of neutrophils and macrophages to produce microbicidal reactive oxygen species (ROS). We show that frameshift mutations can be effectively repaired in hematopoietic cells by non-integrating lentiviral vectors carrying RNA-guided Cas9 endonucleases (RGNs). Because about 25% of most inherited blood disorders are caused by frameshift mutations, our results suggest that up to a quarter of all patients suffering from monogenic blood disorders could benefit from gene therapy employing personalized, donor template-free RGNs.
It is well known that the media has strongly shaped the life of the people in many respects and that it exerts a sustained influence on our value systems and ways of thinking. Thus it also shows a clear extension of the human life. By far less famously however is the fact that nowadays media is the basis for all forms of mental development. This is why the relation between the people and the media is extremely tightened. Nevertheless, this ambivalent relation offers multi-complex material for the literary inspiration. Addressing the topic of the media in the literature combines two aspects ritically: On the one hand it reflects the human behaviour compared with the media and, on the other hand, it underlines emphatically the intermedial writing itself. My speech will be dedicated to the question: how these both aspects interact with each other. The narrative text of Alfred Andersch’s Erinnerte Gestalten will serve the answers to my topic. In this three prosaic texts Andersch shows the subject of the intermedial writing from different perspectives and he discusses certain human reactions to the media.
Background: To meet the requirements imposed by the time-dependency of acute stroke therapies, it is necessary 1) to initiate structural and cultural changes in the breadth of stroke-ready hospitals and 2) to find new ways to train the personnel treating patients with acute stroke. We aimed to implement and validate a composite intervention of a stroke team algorithm and simulation-based stroke team training as an effective quality initiative in our regional interdisciplinary neurovascular network consisting of 7 stroke units.
Methods: We recorded door-to-needle times of all consecutive stroke patients receiving thrombolysis at seven stroke units for 3 months before and after a 2 month intervention which included setting up a team-based stroke workflow at each stroke unit, a train-the-trainer seminar for stroke team simulation training and a stroke team simulation training session at each hospital as well as a recommendation to take up regular stroke team trainings.
Results: The intervention reduced the network-wide median door-to-needle time by 12 minutes from 43,0 (IQR 29,8–60,0, n = 122) to 31,0 (IQR 24,0–42,0, n = 112) minutes (p < 0.001) and substantially increased the share of patients receiving thrombolysis within 30 minutes of hospital arrival from 41.5% to 59.6% (p < 0.001). Stroke team training participants stated a significant increase in knowledge on the topic of acute stroke care and in the perception of patient safety. The overall course concept was regarded as highly useful by most participants from different professional backgrounds.
Conclusions: The composite intervention of a binding team-based algorithm and stroke team simulation training showed to be well-transferable in our regional stroke network. We provide suggestions and materials for similar campaigns in other stroke networks.
Background: The Hawking–Perry–Strominger (HPS) work states a new controversial idea about the black hole (BH) information paradox , where BHs maximally entropize and encode information in their event horizon area , with no “hair” thought to reveal information outside but angular momentum, mass, and electric charge only in a unique quantum gravity (QG) vacuum state. New conservation laws of gravitation and electromagnetism , appear to generate different QG vacua, preserving more information in soft photon/graviton hair implants. We find that BH photon hair implants can encode orbital angular momentum (OAM) and vorticity of the electromagnetic (EM) field. Methods: Numerical simulations are used to plot an EM field with OAM emitted by a set of dipolar currents together with the soft photon field they induce. The analytical results confirm that the soft photon hair implant carries OAM and vorticity. Results: a set of charges and currents generating real EM fields with precise values of OAM induce a “curly”, twisted, soft-hair implant on the BH with vorticity and OAM increased by one unit with respect to the initial real field. Conclusions: Soft photon implants can be spatially shaped ad hoc, encoding structured and densely organized information on the event horizon
Background: Root and tuber crops are a major food source in tropical Africa. Among these crops are several species in the monocotyledonous genus Dioscorea collectively known as yam, a staple tuber crop that contributes enormously to the subsistence and socio-cultural lives of millions of people, principally in West and Central Africa. Yam cultivation is constrained by several factors, and yam can be considered a neglected “orphan” crop that would benefit from crop improvement efforts. However, the lack of genetic and genomic tools has impeded the improvement of this staple crop.
Results: To accelerate marker-assisted breeding of yam, we performed genome analysis of white Guinea yam (Dioscorea rotundata) and assembled a 594-Mb genome, 76.4% of which was distributed among 21 linkage groups. In total, we predicted 26,198 genes. Phylogenetic analyses with 2381 conserved genes revealed that Dioscorea is a unique lineage of monocotyledons distinct from the Poales (rice), Arecales (palm), and Zingiberales (banana). The entire Dioscorea genus is characterized by the occurrence of separate male and female plants (dioecy), a feature that has limited efficient yam breeding. To infer the genetics of sex determination, we performed whole-genome resequencing of bulked segregants (quantitative trait locus sequencing [QTL-seq]) in F1 progeny segregating for male and female plants and identified a genomic region associated with female heterogametic (male = ZZ, female = ZW) sex determination. We further delineated the W locus and used it to develop a molecular marker for sex identification of Guinea yam plants at the seedling stage.
Conclusions: Guinea yam belongs to a unique and highly differentiated clade of monocotyledons. The genome analyses and sex-linked marker development performed in this study should greatly accelerate marker-assisted breeding of Guinea yam. In addition, our QTL-seq approach can be utilized in genetic studies of other outcrossing crops and organisms with highly heterozygous genomes. Genomic analysis of orphan crops such as yam promotes efforts to improve food security and the sustainability of tropical agriculture.
Thirty-seven alien plant species, pre-identified by horizon scanning exercises were prioritised for pest risk analysis (PRA) using a modified version of the EPPO Prioritisation Process designed to be compliant with the EU Regulation 1143/2014. In Stage 1, species were categorised into one of four lists – a Residual List, EU List of Minor Concern, EU Observation List and the EU List of Invasive Alien Plants. Only those species included in the latter proceeded to the risk management stage where their priority for PRA was assessed. Due to medium or high spread potential coupled with high impacts twenty-two species were included in the EU List of Invasive Alien Plants and proceeded to Stage 2. Four species (Ambrosia trifida, Egeria densa, Fallopia baldschuanica and Oxalis pes-caprae) were assigned to the EU Observation List due to moderate or low impacts. Albizia lebbeck, Clematis terniflora, Euonymus japonicus, Lonicera morrowii, Prunus campanulata and Rubus rosifolius were assigned to the residual list due to a current lack of information on impacts. Similarly, Cornus sericea and Hydrilla verticillata were assigned to the Residual List due to unclear taxonomy and uncertainty in native status, respectively. Chromolaena odorata, Cryptostegia grandiflora and Sphagneticola trilobata were assigned to the Residual List as it is unlikely they will establish in the Union under current climatic conditions. In the risk management stage, Euonymus fortunei, Ligustrum sinense and Lonicera maackii were considered a low priority for PRA as they do not exhibit invasive tendencies despite being widely cultivated in the EU over several decades. Nineteen species were identified as having a high priority for a PRA (Acacia dealbata, Ambrosia confertiflora, Andropogon virginicus, Cardiospermum grandiflorum, Celastrus orbiculatus, Cinnamomum camphora, Cortaderia jubata, Ehrharta calycina, Gymnocoronis spilanthoides, Hakea sericea, Humulus scandens, Hygrophila polysperma, Lespedeza cuneata, Lygodium japonicum, Pennisetum setaceum, Prosopis juliflora, Sapium sebiferum, Pistia stratiotes and Salvinia molesta).