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Introduction: Vaginal delivery out of a breech presentation in pregnancies at term are being re-implemented into clinical practice. Still, recommendations regarding exclusion criteria leading to caesarean sections are based on expert opinions, not on evidence-based guidelines. The difference in perinatal outcome and course of delivery in births with babies in frank breech position and babies in incomplete or complete breech presentation never has been investigated in a large patient cohort.
Objective: To compare perinatal outcome of vaginally intended breech deliveries between births out of frank breech position and incomplete/complete breech presentation.
Design: Prospective cohort study.
Sample: 884 women at term with a singleton in frank breech presentation (FB) and 284 women with incomplete or complete breech presentation (CB) intending vaginal birth between January 2004 and December 2018.
Methods: Maternal and fetal outcome was compared between groups using Pearson’s Chi Square test. Birth duration parameters were analysed using logistic regression.
Results: There were no differences in cesarean section rates (FB: 25.1%, CB 22.2%, p = 0.317). Short-term fetal morbidity did not differ between groups (FB: 2.5%, CB: 2.8%, p = 0.761). In vaginal deliveries the necessity to perform manual assistance was significantly more frequent in deliveries of infants in CB (FB: 39.9%, CB: 51.6%, p = 0.0013). Cord loops (FB: 10.1%, CB: 18.0%, p = 0.0004) and cesarean sections necessary because of cord prolapses (FB: 1.4%, CB 8.1%, p = 0.005) were significantly more often in deliveries with babies in CB.
Conclusion: This study provides evidence, that perinatal morbidity is not associated with the fetal leg posture in vaginally intended breech deliveries. The higher risk for the need of manual assistance during vaginal birth in deliveries of babies out of complete or incomplete breech presentation suggests that obstetrical departments re-implementing the vaginal breech in their repertoire might start with births of babies out of frank breech presentation.
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder. In recent years, genetic studies have revealed several risk gene variants associated with ADHD; however, these variants could only be partly replicated and are responsible for only a fraction of the whole heritability of ADHD estimated from family and twin studies. One factor that could potentially explain the ‘missing heritability’ of ADHD is that childhood and adult or persistent ADHD could be genetically distinct subtypes, which therefore need to be analyzed separately. Another approach to identify this missing heritability could be combining the investigation of both common and rare gene risk variants as well as polygenic risk scores. Finally, environmental factors are also thought to play an important role in the etiology of ADHD, acting either independently of the genetic background or more likely in gene–environment interactions. Environmental factors might additionally convey their influence by epigenetic mechanisms, which are relatively underexplored in ADHD. The aforementioned mechanisms might also influence the response of patients with ADHD to stimulant and other ADHD medication. We conducted a selective review with a focus on risk genes of childhood and adult ADHD, gene–environment interactions, and pharmacogenetics studies on medication response in childhood and adult ADHD.
Uni-Highlights November 2019 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2019)
Uni-Highlights Dezember 2019 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2019)
Introduction: The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural “fear network”. We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli.
Method: 121 patients with PD/AG and 77 healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) using the disorder specific “Westphal-Paradigm”. It consists of neutral and agoraphobia-specific pictures, half of the pictures were cued to induce anticipatory anxiety.
Results: Risk allele carriers showed significantly higher amygdala activation during the perception of agoraphobia-specific stimuli than A/A homozygotes. A linear group x genotype interaction during the perception of agoraphobia-specific stimuli showed a strong trend towards significance. Patients with the one or two T alleles displayed the highest and HC with the A/A genotype the lowest activation in the inferior orbitofrontal cortex (iOFC).
Discussion: The study demonstrates an association of the NPSR1rs324981 genotype and the perception of agoraphobia-specific stimuli. These results support the assumption of a fronto-limbic dysfunction as an intermediate phenotype of PD/AG.
This position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth.
Previous studies in patients with single-sided deafness (SSD) have reported results of pitch comparisons between electric stimulation of their cochlear implant (CI) and acoustic stimulation presented to their near-normal hearing contralateral ear. These comparisons typically used sinusoids, although the percept elicited by electric stimulation may be closer to a wideband stimulus. Furthermore, it has been shown that pitch comparisons between sounds with different timbres is a difficult task and subjected to various types of range biases. The present study aims to introduce a method to minimize non-sensory biases, and to investigate the effect of different acoustic stimulus types on the frequency and variability of the electric-acoustic pitch matches. Pitch matches were collected from 13 CI users with SSD using the binary search procedure. Electric stimulation was presented at either an apical or a middle electrode position, at a rate of 800 pps. Acoustic stimulus types were sinusoids (SINE), 1/3-octave wide narrow bands of Gaussian noises (NBN), or 1/3-octave wide pulse spreading harmonic complexes (PSHC). On the one hand, NBN and PSHC are presumed to better mimic the spread of excitation produced by a single-electrode stimulation than SINE. On the other hand, SINE and PSHC contain less inherent fluctuations than NBN and may therefore provide a temporal pattern closer to that produced by a constant-amplitude electric pulse train. Analysis of mean pitch match variance showed no differences between stimulus types. However, mean pitch matches showed effects of electrode position and stimulus type, with the middle electrode always matched to a higher frequency than the apical one (p < 0.001), and significantly higher across-subject pitch matches for PSHC compared with SINE (p = 0.017). Mean pitch matches for all stimulus types were better predicted by place-dependent characteristic frequencies (CFs) based on an organ of Corti map compared with a spiral ganglion map. CF predictions were closest to pitch matches with SINE for the apical electrode position, and conversely with NBN or PSHC for the middle electrode position. These results provide evidence that the choice of acoustic stimulus type can have a significant effect on electric-acoustic pitch matching.
OXA-48 is the most common carbapenemase in Enterobacterales in Germany and one of the most frequent carbapenemases worldwide. Several reports have associated blaOXA–48 with a virulent host phenotype. To challenge this hypothesis, 35 OXA-48-producing clinical isolates of Escherichia coli (n = 15) and Klebsiella pneumoniae (n = 20) were studied in vitro, in vivo employing the Galleria mellonella infection model and by whole-genome sequencing. Clinical isolates belonged to 7 different sequence types (STs) in E. coli and 12 different STs in K. pneumoniae. In 26/35 isolates blaOXA–48 was located on a 63 kb IncL plasmid. Horizontal gene transfer (HGT) to E. coli J53 was high in isolates with the 63 kb IncL plasmid (transconjugation frequency: ∼103/donor) but low in isolates with non-IncL plasmids (<10–6/donor). Several clinical isolates were both highly cytotoxic against human cells and virulent in vivo. However, 63 kb IncL transconjugants generated from these highly virulent isolates were not more cytotoxic or virulent when compared to the recipient strain. Additionally, no genes associated with virulence were detected by in silico analysis of OXA-48 plasmids. The 63 kb plasmid was highly stable and did not impair growth or fitness in E. coli J53. In conclusion, OXA-48 clinical isolates in Germany are diverse but typically harbor the same 63 kb IncL plasmid which has been reported worldwide. We demonstrate that this 63 kb IncL plasmid has a low fitness burden, high plasmid stability and can be transferred by highly efficient HGT which is likely the cause of the rapid dissemination of OXA-48 rather than the expansion of a single clone or gain of virulence.
Das Bildnis des sogenannten "Lübecker Wunderkinds" stellt eine Kuriosität in der Porträtsammlung Holzhausen dar. Anhand zweier Porträts wird die märchenhaft anmutende, doch in Wahrheit zutiefst traurige Lebensgeschichte des Christian Heinrich Heinecken erzählt, dem seine zu jener Zeit einzigartigen Talente zum Verhängnis werden sollten.
Differences in euro-area household finances and their relevance for monetary-policy transmission
(2019)
This paper quantifies the extent of heterogeneity in consumption responses to changes in real interest rates and house prices in the four largest economies in the euro area: France, Germany, Italy, and Spain. We first calibrate a life-cycle incomplete-markets model with a financial asset and housing to match the large heterogeneity of households asset portfolios, observed in the Household Finance and Consumption Survey (HFCS) for these countries. We then show that the heterogeneity in household finances implies that responses of consumption to changes in the real interest rate and in house prices differ substantially across countries, and within countries by household characteristics such as age, housing tenure, and asset positions. The different consumption responses quantified in this paper point towards important heterogeneity in monetary-policy transmission in the euro area.
Electron microscopy (EM) demarcates itself from other structural biology techniques by its applicability to a large range of biological objects that spans from whole cells to individual macromolecules. In single-particle cryo-EM, frozen-hydrated samples, prepared by vitrification with liquid ethane, retain macromolecules in a medium that approximates their natural aqueous environment and that, in this way, preserves high-resolution structural information. Nonetheless, the sensitivity of biological specimens to the high-energy electron beam introduces restrictions on the total dose that can be used during imaging while avoiding significant radiation damage. Consequently, the signal-to-noise ratio attained in each individual image is very low, and structures with high-resolution detail must be recovered by averaging thousands of projections in random orientations. This is achieved through the use of image processing algorithms capable of aligning and classifying particle images through the evaluation of cross-correlation functions between each particle and a reference.
In recent years, several innovations took place in the field of single-particle cryo-EM, among which the development of direct electron detectors must be highlighted. Direct electron detectors have a better detective quantum efficiency (DQE) than both photographic film and CCD cameras, and offer a fast readout, compatible with the acquisition of movie stacks. Additionally, new image processing software has become available, with more sophisticated algorithms and designed to take advantage of the specific characteristics of the movies produced with direct electron detectors. These technological advances in both hardware and software catalyzed a revolution in single-particle cryo-EM, which is now routinely used for the determination of near-atomic structures. As a result, the range of macromolecules accessible to cryo-EM has increased drastically, as targets that were unsuitable before for imaging due to their small dimensions can now be adequately visualized and refined to high-resolution.
During my doctoral work, I have used single-particle cryo-EM to structurally characterize challenging membrane proteins, with a strong emphasis on protein complexes from aerobic respiratory chains. In chapter I of this thesis, I present my results on the bovine respirasome, a mitochondrial supercomplex composed of complexes I, III and IV. Chapter II is dedicated to the analysis of the structure of alternative complex III (ACIII) from Rhodothermus marinus, a bacterial quinol:cytochrome c/HiPIP oxidoreductase unrelated to the canonical cytochrome bc1 complex (complex III). In addition, in chapter III I describe the structure of KimA, a high-affinity potassium transporter that drives the transport of its substrate by using the energy stored in the form of a proton gradient. These three membrane proteins, with molecular weights ranging from 140 kDa to 1.7 MDa, illustrate the possibilities and limitations faced in single-particle cryo-EM.
The aerobic respiratory chain is responsible for the generation of a transmembrane difference of electrochemical potential that is then used by ATP synthase for the production of ATP or for driving solute transport over the membrane. They catalyze the transfer of electrons from a substrate, such as NADH or succinate, to molecular oxygen and use the chemical energy released in these redox reactions to drive the translocation of protons, or in some cases sodium ions, to the intermembrane space in mitochondria or the periplasm in bacteria.
In mitochondria, the respiratory chain is composed of four complexes: complex I (NADH:ubiquinone oxidoreductase), complex II (succinate dehydrogenase), complex III (cytochrome bc1 complex) and complex IV (cytochrome c oxidase). While it was for a long time believed that these complexes existed as single entities in the membrane, the use of milder procedures for protein purification and analysis revealed that respiratory complexes associate into well-ordered structures, known as supercomplexes. These have been proposed to offer different structural and functional advantages that are still controversial, including substrate channeling, stabilization of individual complexes and reduction of reactive oxygen species (ROS) production. The most thoroughly studied respiratory supercomplex has been the respirasome, conserved in higher eukaryotes and composed of one copy of complex I, a complex III dimer and one complex IV. By single-particle cryo-EM analysis, I retrieved a 9 Å map of the respirasome from Bos taurus, which allowed the accurate docking of atomic models of the three component complexes. The structure shows that complex III associates to the concave side of the membrane arm of complex I, while complex IV is located between the end of the complex I hydrophobic arm and complex III. Several defined protein-protein contacts are observed between the component complexes, which are mediated predominantly by supernumerary subunits and close to the membrane surfaces. The interactions established between complex I and complex III are extensive and may support the argument that the association of complex I into supercomplexes is required for the stabilization or even the biogenesis of this complex.
...
Polyketide synthases (PKSs) are large megaenzymes that occur in bacteria, fungi, and plants and produce polyketides, a class of secondary metabolites. Many polyketide natural products exhibit high biological activities e.g. as antibiotics or anti-fungal compounds. The modular architecture of assembly line PKSs makes them exciting targets for engineering approaches via the exchange of whole modules or single domains. Although many engineering attempts have been pursued over the last three decades, the resulting chimeric PKSs often exhibit decreased turnover rates or diminished product yields.
In this thesis, new approaches to engineer chimeric PKSs were explored, each targeting a different aspect of the chimeric system: First the relative contribution of protein-protein and protein-substrate recognition on the turnover of chimeric PKS was assessed, revealing the importance of protein-protein interactions between the acyl carrier protein (ACP) and the ketosynthase (KS) domain in the chain translocation step. Directed evolution experiments followed to optimize the protein-protein interaction across a chimeric interface. Additionally, different junction sites for the generation of chimeric PKSs were compared, showing the ability for recombination without interfering with the chain translocation reaction, and highlighting the use of SYNZIP domains to bridge PKS modules. To optimize chimeric PKSs even further, multipoint mutagenesis of KS domains was established, with positive effects on the activity of chimeric systems.
To support engineering attempts, several structure elucidation techniques were combined with in silico modeling to characterize the architecture of a PKS module and the domain-domain interactions within it. Preliminary results show a strong conformational flexibility of the PKS module and the great potential of these techniques to define the multitude of transient interactions in PKS modules.
Endocrine disrupting compounds (EDCs) emerged as a major concern for water quality in the last decade and have been studied extensively since. Besides typical natural and synthetic estrogens also petroleum product compounds such as some PAHs have been identified as potential EDCs, revealing endocrine disruption to be a relevant mode of action for crude oil toxicity. Hence, in the context of a comprehensive retro- or prospective risk assessment of oil spills the implementation of mechanism-specific toxicity such as endocrine disruption is of high importance. To evaluate the exposure risk for the aquatic biota, research focuses on water-soluble fractions underlying an oil slick that could be simulated via water-accommodated fractions (WAF). Against this background human (ERα-CALUX®) and yeast based (A-YES®) reporter gene bioassays were successfully optimized for the application in estrogenicity evaluation of the water-accommodated fraction (WAF) from a crude oil. Combining different approaches, the estrogenicity of the WAFs from a naphthenic North Sea crude oil was tested with and without the addition of a chemical dispersant addressing specific aspects of estrogenicity including the influence of biotransformation capacities and different salinity conditions. Both the WAF free from droplets (LEWAF) as well as the chemically dispersed WAF (CEWAF) gave indications of an ER-mediated estrogenicity with much stronger ERα agonists in the CEWAF treatment. Resulting estradiol equivalents of the WAFs were above the established effect-based trigger values for both bioassays. Results indicate that the dispersant rather increased the fraction of ER-activating crude oil compounds instead of interacting with the receptor itself. Only slight changes in estrogenic responses were observed when cells capable of active metabolism (T47D) were used instead of cells without endogenous metabolism (U2-OS) in the recombinant ER transactivation CALUX assay. With the yeast cells a higher estrogenic activity was observed in the experiments under elevated salinity conditions (6‰), which was in contrast to previous expectations due to typical decrease in dissolved PAH fraction with increasing salinity (salting-out effect) but might be related to increased cell sensitivity.
Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.
Cystathionine γ lyase (CSE) is the major source of hydrogen sulfide-derived species (H2Sn) in endothelial cells and plays an important role in protecting against atherosclerosis. Here we investigated the molecular mechanisms underlying the regulation of CSE expression in endothelial cells by fluid shear stress/flow. Fluid shear stress decreased CSE expression in human and murine endothelial cells and was negatively correlated with the transcription factor Krüppel-like factor (KLF) 2. CSE was identified as a direct target of the KLF2-regulated microRNA, miR-27b and high expression of CSE in native human plaque-derived endothelial cells, was also inversely correlated with KLF2 and miR-27b levels. One consequence of decreased CSE expression was the loss of Prx6 sulfhydration (on Cys47), which resulted in Prx6 hyperoxidation, decamerization and inhibition, as well as a concomitant increase in endothelial cell reactive oxygen species and lipid membrane peroxidation. H2Sn supplementation in vitro was able to reverse the redox state of Prx6. Statin therapy, which is known to activate KLF2, also decreased CSE expression but increased CSE activity by preventing its phosphorylation on Ser377. As a result, the sulfhydration of Prx6 was partially restored in samples from plaque containing arteries from statin-treated donors. Taken together, the regulation of CSE expression by shear stress/disturbed flow is dependent on KLF2 and miR-27b. Moreover, in murine and human arteries CSE acts to maintain endothelial redox balance at least partly by targeting Prx6 to prevent its decamerization and inhibition of its peroxidase activity.
Background and Aims: Fecal biomarkers are important non-invasive markers monitoring disease activity in inflammatory bowel disease (IBD). We compared the significance of fecal eosinophil cationic protein (fECP) and fecal calprotectin (fCal).
Methods: fECP and fCal were measured in patients with Crohn's disease (CD, n = 97), ulcerative colitis (UC, n = 53), Clostridioides difficile infection (CDI, n = 9), primary food allergy (PFA, n = 11), pollen-associated food allergy (n = 25) and non-inflammatory controls (n = 78). Results were correlated with clinical and endoscopic IBD activity scores.
Results: fECP was significantly elevated in CD, UC, CDI and PFA compared to controls. fCal was significantly increased in CD, UC and CDI. fECP had lower diagnostic accuracy than fCal (area under the curve (AUC) = 0.88) in differentiating between endoscopically active and inactive patients with IBD (AUC = 0.77, ROC analysis). In contrast to fCal, fECP correlated negatively with age and levels were also elevated in clinically and endoscopically inactive patients with IBD <45 years (endoscopically inactive IBD vs controls; AUC for fECP = 0.86; AUC for fCal = 0.62). However, in those patients with low inflammatory activity (fCal <250 mg/kg), high fECP indicated the need for treatment modification or surgery (fECP <200 µg/kg = 22%; 200–600 µg/kg = 44%; >600 µg/kg = 82%) at month 48 of follow-up.
Conclusions: fECP is a diagnostic and prognostic marker in young patients with IBD in remission.
The Arctic Svalbard Archipelago hosts the world’s northernmost cold-water ‘carbonate factories’ thriving here despite of presumably unfavourable environmental conditions and extreme seasonality. Two contrasting sites of intense biogenic carbonate production, the rhodolith beds in Mosselbukta in the north of the archipelago and the barnacle-mollusc dominated carbonate sediments accumulating in the strong hydrodynamic regime of the Bjørnøy-Banken south of Spitsbergen, were the targets of the RV Maria S. Merian cruise 55 in June 2016. By integrating data from physical oceanography, marine biology, and marine geology, the present contribution characterises the environmental setting and biosedimentary dynamics of these two polar carbonate factories. Repetitive CTD profiling in concert with autonomous temperature/salinity loggers on a long-term settlement platform identified spatiotemporal patterns in the involved Atlantic and Polar water masses, whereas short-term deployments of a lander revealed fluctuations of environmental variables in the rhodolith beds in Mosselbukta and at same depth (46 m) at Bjørnøy-Banken. At both sites, dissolved inorganic nutrients in the water column were found depleted (except for elevated ammonium concentrations) and show an overall increase in concentration and N:P ratios toward deeper waters. This indicates that a recycling system was fuelling primary production after the phytoplankton spring bloom at the time of sampling in June 2016. Accordingly, oxygen levels were found elevated and carbon dioxide concentrations (pCO2) markedly reduced, on average only half the expected equilibrium values. Backed up by seawater stable carbon and oxygen isotope signatures, this is interpreted as an effect of limited air-sea gas exchange during seasonal ice cover in combination with a boost in community photosynthesis during the spring phytoplankton bloom. The observed trends are enhanced by the onset of rhodophyte photosynthesis in the rhodolith beds during the polar day upon retreat of sea-ice. Potential adverse effects of ocean acidification on the local calcifier community are thus predicted to be seasonally buffered by the marked drop in pCO2 during the phase of sea-ice cover and spring phyto-plankton bloom, but this effect will diminish should the seasonal sea-ice formation continue to decline. Among the 25 macrobenthos taxa identified from images captured by the lander’s camera system, all but three species were calcifiers contributing to the carbonate production. Biodiversity was found to be much higher in Mosselbukta (21 taxa) compared to Bjørnøy-Banken (8 taxa), which is considered as a result of enhanced habitat diversity provided in the rhodolith beds by the bioengineering crustose alga Lithothamnion glaciale. Filter-feeding activity of selected key species did reveal group-specific but no common activity patterns. Biotic disturbance of the filtering activity was common, in contrast to abiotic factors, with hermit crabs representing the primary trigger. Motion tracking of rhodoliths revealed a high frequency of dislocation, triggered not by abiotic factors but by the activity of benthic invertebrates, in particular echinoids ploughing below or moving over the rhodoliths. The echinoid Strongylocentrotus sp. is the most abundant component of the associated fauna, thereby considerably contributing both to carbonate production and to grazing bioerosion. Together, these results portray a high degree of seasonal as well as short-term dynamics in environmental conditions that despite many similarities support distinctly different communities and biodiversity patterns in the calcifying macrobenthos at the two studied polar carbonate factories.
In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients
(2019)
Background: The potential harmful effects of particle-contaminated infusions for critically ill adult patients are yet unclear. So far, only significant improved outcome in critically ill children and new-borns was demonstrated when using in-line filters, but for adult patients, evidence is still missing.
Methods: This single-centre, retrospective controlled cohort study assessed the effect of in-line filtration of intravenous fluids with finer 0.2 or 1.2 μm vs 5.0 μm filters in critically ill adult patients. From a total of n = 3215 adult patients, n = 3012 patients were selected by propensity score matching (adjusting for sex, age, and surgery group) and assigned to either a fine filter cohort (with 0.2/1.2 μm filters, n = 1506, time period from February 2013 to January 2014) or a control filter cohort (with 5.0 μm filters, n = 1506, time period from April 2014 to March 2015). The cohorts were compared regarding the occurrence of severe vasoplegia, organ dysfunctions (lung, kidney, and brain), inflammation, in-hospital complications (myocardial infarction, ischemic stroke, pneumonia, and sepsis), in-hospital mortality, and length of ICU and hospital stay.
Results: Comparing fine filter vs control filter cohort, respiratory dysfunction (Horowitz index 206 (119–290) vs 191 (104.75–280); P = 0.04), pneumonia (11.4% vs 14.4%; P = 0.02), sepsis (9.6% vs 12.2%; P = 0.03), interleukin-6 (471.5 (258.8–1062.8) ng/l vs 540.5 (284.5–1147.5) ng/l; P = 0.01), and length of ICU (1.2 (0.6–4.9) vs 1.7 (0.8–6.9) days; P < 0.01) and hospital stay (14.0 (9.2–22.2) vs 14.8 (10.0–26.8) days; P = 0.01) were reduced. Rate of severe vasoplegia (21.0% vs 19.6%; P > 0.20) and acute kidney injury (11.8% vs 13.7%; P = 0.11) was not significantly different between the cohorts.
Conclusions: In-line filtration with finer 0.2 and 1.2 μm filters may be associated with less organ dysfunction and less inflammation in critically ill adult patients.
Trial registration: The study was registered at ClinicalTrials.gov (number: NCT02281604).
Background: Zika is of great medical relevance due to its rapid geographical spread in 2015 and 2016 in South America and its serious implications, for example, certain birth defects. Recent epidemics urgently require a better understanding of geographic patterns of the Zika virus transmission risk. This study aims to map the Zika virus transmission risk in South and Central America. We applied the maximum entropy approach, which is common for species distribution modelling, but is now also widely in use for estimating the geographical distribution of infectious diseases.
Methods: As predictor variables we used a set of variables considered to be potential drivers of both direct and indirect effects on the emergence of Zika. Specifically, we considered (a) the modelled habitat suitability for the two main vector species Aedes aegypti and Ae. albopictus as a proxy of vector species distributions; (b) temperature, as it has a great influence on virus transmission; (c) commonly called evidence consensus maps (ECM) of human Zika virus infections on a regional scale as a proxy for virus distribution; (d) ECM of human dengue virus infections and, (e) as possibly relevant socio-economic factors, population density and the gross domestic product.
Results: The highest values for the Zika transmission risk were modelled for the eastern coast of Brazil as well as in Central America, moderate values for the Amazon basin and low values for southern parts of South America. The following countries were modelled to be particularly affected: Brazil, Colombia, Cuba, Dominican Republic, El Salvador, Guatemala, Haiti, Honduras, Jamaica, Mexico, Puerto Rico and Venezuela. While modelled vector habitat suitability as predictor variable showed the highest contribution to the transmission risk model, temperature of the warmest quarter contributed only comparatively little. Areas with optimal temperature conditions for virus transmission overlapped only little with areas of suitable habitat conditions for the two main vector species. Instead, areas with the highest transmission risk were characterised as areas with temperatures below the optimum of the virus, but high habitat suitability modelled for the two main vector species.
Conclusion: Modelling approaches can help estimating the spatial and temporal dynamics of a disease. We focused on the key drivers relevant in the Zika transmission cycle (vector, pathogen, and hosts) and integrated each single component into the model. Despite the uncertainties generally associated with modelling, the approach applied in this study can be used as a tool and assist decision making and managing the spread of Zika.
Sepsis is a serious clinical condition which can cause life-threatening organ dysfunction, and has limited therapeutic options. The paradigm of limiting excessive inflammation and promoting anti-inflammatory responses is a simplified concept. Yet, the absence of intrinsic anti-inflammatory signaling at the early stage of an infection can lead to an exaggerated activation of immune cells, including monocytes and macrophages. There is emerging evidence that endogenous molecules control those mechanisms. Here we aimed to identify and describe the dynamic changes in monocyte and macrophage subsets and lung damage in CL57BL/6N mice undergoing blunt chest trauma with subsequent cecal ligation and puncture. We showed that early an increase in systemic and activated Ly6C+CD11b+CD45+Ly6G− monocytes was paralleled by their increased emigration into lungs. The ratio of pro-inflammatory Ly6ChighCD11b+CD45+Ly6G− to patrolling Ly6ClowCD11b+CD45+Ly6G− monocytes significantly increased in blood, lungs and bronchoalveolar lavage fluid (BALF) suggesting an early transition to inflammatory phenotypes during early sepsis development. Similar to monocytes, the level of pro-inflammatory Ly6ChighCD45+F4/80+ macrophages increased in lungs and BALF, while tissue repairing Ly6ClowCD45+F4/80+ macrophages declined in BALF. Levels of inflammatory mediators TNF-α and MCP-1 in blood and RAGE in lungs and BALF were elevated, and besides their boosting of inflammation via the recruitment of cells, they may promote monocyte and macrophage polarization, respectively, toward the pro-inflammatory phenotype. Neutralization of uteroglobin increased pro-inflammatory cytokine levels, activation of inflammatory phenotypes and their recruitment to lungs; concurrent with increased pulmonary damage in septic mice. In in vitro experiments, the influence of uteroglobin on monocyte functions including migratory behavior, TGF-β1 expression, cytotoxicity and viability were proven. These results highlight an important role of endogenous uteroglobin as intrinsic anti-inflammatory signal upon sepsis-induced early lung injury, which modules the early monocyte/macrophages driven inflammation.
Der Maler und Grafiker Georg Heck (1897-1982) führte ein bewegtes Leben: Seinen unbändigen Schaffensdrang konnten weder zwei Weltkriege noch der Verlust seines rechten Augenlichtes schmälern. Das Museum Giersch der Goethe-Universität präsentiert das Œuvre des Frankfurter Künstlers zwischen "Entartung" und Sezession in einer umfangreichen Retrospektive.
Aims: Patients with aortic stenosis (AS) may have concomitant heart failure (HF) that determines prognosis despite successful transcatheter aortic valve implantation (TAVI). We compared outcomes of TAVI patients with low stroke volume index (SVI) ≤35 ml/m2 body surface area in different HF classes.
Methods and results: Patients treated by transfemoral TAVI at our center (n = 1822) were classified as 1) ‘HF with preserved ejection fraction (EF)’ (HFpEF, EF ≥50%), 2) ‘HF with mid-range EF’ (HFmrEF, EF 40–49%), or 3) ‘HF with reduced EF’ (HFrEF, EF <40%). Patients with SVI >35 ml/m2 served as controls. The prevalence of cardiovascular disease and symptoms increased stepwise from controls (n = 968) to patients with HFpEF (n = 591), HFmrEF (n = 97), and HFrEF (n = 166). Mortality tended to be highest in HFrEF patients 30 days post-procedure, and it became significant after one year: 10.2% (controls), 13.5% (HFpEF), 13.4% (HFmrEF), and 23.5% (HFrEF). However, symptomatic improvement in survivors of all groups was achieved in the majority of patients without differences among groups.
Conclusions: Patients with AS and HF benefit from TAVI with respect to symptom alleviation. TAVI in patients with HFpEF and HFmrEF led to an identical, favorable post-procedural prognosis that was significantly better than that of patients with HFrEF, which remains a high-risk population.
Entwicklung und Inbetriebnahme zweier supraleitender 217 MHz CH-Strukturen für das HELIAC-Projekt
(2019)
Im Rahmen der hier vorgestellten Arbeit wurden zwei baugleiche CH-Strukturen für das im Bau befindliche HELIAC-Projekt (HELmholtz LInear ACcelerator) entwickelt und während der Produktion bis hin zu den finalen Kalttests bei 4.2 K begleitet. Zusammen mit der CH-Struktur des Demonstrator-Projektes ermöglichen sie die vollständige Inbetriebnahme und den ersten Strahltest des ersten Kryomoduls des HELIAC's, welcher aus vier Kryomodulen mit insgesamt 12 CH-Strukturen besteht. Im Vergleich zu bisherigen CH-Strukturen wurde das Design der Kavitäten im Rahmen dieser Dissertation grundlegend überarbeitet und optimiert. Durch die Entfernung der Girder und die konisch geformten Endkappen konnte die Stabilität der neuen CH-Strukturen deutlich erhöht werden, sodass die Drucksensitivität im Vergleich zur ersten CH-Kavität des Demonstrator-Projektes um ca. 80% reduziert werden konnte. Durch die nach außen gezogenen Lamellen der dynamischen Tuner konnte die mechanische Spannung sowie die benötigte Anzahl an Lamellen und damit das Risiko für das Auftreten von Multipacting reduziert werden. Das verringerte Risiko für Multipacting durch die entsprechenden Optimierungen der Kavitäten konnte durch die dauerhafte Überwindung aller Multipacting-Barrieren in den späteren Messungen verifiziert werden. Die Optimierung beider Kavitäten erfolgte dabei mit Hilfe der Simulationsprogramme CST Studio Suite und Ansys Workbench.
Beide Kavitäten wurden von der Firma Research Instruments (RI) gefertigt und während der gesamten Konstruktion durch diverse Zwischenmessungen überwacht. Nach jedem einzelnen Produktionsschritt wurden alle Einflüsse auf die Resonanzfrequenz so präzise ermittelt, dass die Zielfrequenz bei 4.2 K auf mehr als 1‰ genau erreicht werden konnte. Sowohl während der Zwischenmessungen als auch während den finalen Messungen bei 4.2 K wurden automatisierte Aufzeichnungsroutinen verwendet, welche eine sekundengenaue Auslese der Messdaten und damit eine hohe Messgenauigkeit ermöglichten. Im Hinblick auf die Komplexität der CH-Strukturen sind die geringen Abweichungen von der Zielfrequenz der direkte Beweis dafür, wie erfolgreich und präzise die Auswertungen und daraus folgenden Abschätzungen der einzelnen Zwischenmessungen waren. Insgesamt konnten bis auf die mechanischen Eigenmoden alle Ergebnisse der Simulationen durch entsprechende Messungen in guter Näherung verifiziert werden. In jeder Kavität wurden zwei dynamische Tuner verbaut, welche statische und dynamische Frequenzabweichungen im späteren Betrieb ausgleichen können. Die dynamischen Tuner wurden hinsichtlich ihrer mechanischen Stabilität und der erzeugbaren Frequenzänderung sowie ihrer mechanischen Eigenfrequenzen ausführlich mit Hilfe der Simulationsprogramme CST Studio Suite und Ansys Workbench untersucht und optimiert. Um die Ergebnisse der Simulationen zu überprüfen wurden ein eigens dafür entworfener und in der Werkstatt des Instituts für Angewandte Physik gefertigter Messaufbau verwendet, welcher es ermöglichte alle entscheidenden Eigenschaften der dynamischen Tuner präzise zu vermessen. Insgesamt stellen die ausführlichen Messungen mit Hilfe des entworfenen Aufbaus die bisher umfassendsten Messungen dynamischer Balgtuner innerhalb supraleitender CH-Strukturen dar und zeigen, mit welchen Abweichungen zwischen Simulationen und Messungen bei zukünftigen Kavitäten zu rechnen ist. Auch die Feldverteilung entlang der Strahlachse wurde während der Produktion der Kavitäten mit Hilfe der Störkörpermessmethode überprüft. Die dadurch ermittelten Werte stimmten mit einer maximalen Diskrepanz von 9% sehr gut mit den Simulationen überein.
Um eine möglichst gute Oberflächenqualität zu garantieren wurden an der Innenfläche beider Strukturen mindestens 200µm mit einer Mischung aus Fluss-, Salpeter und Phosphorsäure in mehreren Schritten abgetragen. Durch das Aufteilen der Behandlung in einzelne Schritte konnte der Einfluss der Oberflächenbehandlung auf die Resonanzfrequenz besser abgeschätzt und vorausgesehen werden. Dies führte, zusammen mit den Messungen zur Bestimmung der Drucksensitivität und der thermischen Kontraktion der Kavität beim Abkühlen, zu der hohen Übereinstimmung der gemessenen finalen Resonanzfrequenz mit der Zielfrequenz.
Die abschließenden Kalttests der beiden Kavitäten, ohne Heliummantel, wurden am Institut für Angewandte Physik der Johann Wolfgang Goethe Universität in einem vertikalen Bad-Kryostaten durchgeführt. Die erste CH-Struktur konnte erfolgreich bis zu einem maximalen Feldgradienten von 9.2 MV/m getestet werden, was einer effektiven Spannung von 3.37 MV entspricht. Die unbelastete Güte fiel dabei von anfangs 1.08 ∙ 109 auf 2.6 ∙ 108 ab. Die Vorgaben des HELIAC-Projektes liegen bei einem Beschleunigungsgradienten von 5.5 MV/m mit einer unbelasteten Güte von mindestens 3 ∙ 108. Diese Werte wurden von der ersten Kavität deutlich übertroffen, sodass sie für den Betrieb innerhalb des ersten Kryomoduls uneingeschränkt verwendet werden kann.
Bei der zweiten Kavität trat beim Abkühlen auf 4.2 K ein Vakuumleck auf, welches unter Raumtemperatur nicht detektierbar war. Aufgrund der schlechten Vakuumbedingungen innerhalb der Kavität konnten somit keine Messungen hinsichtlich der Leistungsfähigkeit durchgeführt werden, solange das Kaltleck vorhanden war. Ein erneuter Kalttest der Kavität nach Beseitigung des Lecks konnte zeitlich nicht mehr im Rahmen dieser Arbeit durchgeführt werden und ist aus diesem Grund Gegenstand nachfolgender Untersuchungen.
Insgesamt stellen die Entwicklungen, Untersuchungen und Messungen im Rahmen der hier vorgestellten Dissertation einen entscheidenden Schritt zur Inbetriebnahme des ersten Kryomoduls des HELIAC's sowie der Entwicklung weiterer CH-Kavitäten dar. Das überarbeitete Design der CH-Strukturen hat sich als erfolgreich erwiesen, weswegen es als Ausgangspunkt für die Entwicklung aller nachfolgenden CH-Strukturen des HELIAC, bis hin zur Fertigstellung des kompletten Beschleunigers, verwendet wird.
Von November 2018 bis April 2019 hat die Arbeitsstelle »Medizinethik in der Klinikseelsorge« am Fachbereich Katholische Theologie der Goethe Universität Frankfurt am Main eine partizipative Studie über Herausforderungen und Kompetenzprofile der Medizinethik in der Klinikseelsorge durchgeführt.
Im Zentrum dieser Broschüre stehen die Ergebnisse, die eine Gruppe von 19 Klinikseelsorger*innen erarbeitet hat. Welche Kompetenzen benötigen Klinikseelsorger*innen, um medizinethisch tätig zu sein? Welche Herausforderungen erleben sie im Alltag? Wie sehen sie die Zukunft der Medizinethik? Diese Broschüre präsentiert einige der Ergebnisse in aufbereiteter Form.
Transport mechanism of a multidrug resistance protein investigated by pulsed EPR spectroscopy
(2019)
In human several diseases result from malfunctions of ATP-binding cassette (ABC) systems, which form one of the largest transport system superfamily. Many ABC exporters contain asymmetric nucleotide-binding sites (NBSs) and some of them are inhibited by the transported substrate.1 For the active transport of diverse chemically substrates across biological membranes, ABC transport complexes use the energy of ATP binding and subsequent hydrolysis. In this thesis, the heterodimeric ABC exporter TmrAB2,3 from Thermus thermophilus, a functional homolog of the human antigen translocation complex TAP, was investigated by using pulsed electron-electron double resonance (PELDOR/DEER) spectroscopy. In the presence of ATP, TmrAB exists in an equilibrium between inward- and outward-facing conformations. This equilibrium can be modulated by changing the ATP concentration, showing asymmetric behaviour in the open-to-close equilibrium between the consensus and the degenerate NBSs. At the degenerate NBS the closed conformation is more preferred and closure of one of the NBSs is sufficient to open the periplasmic gate at the transmembrane domain (TMD).3 By determining the temperature dependence of this conformational equilibrium, the thermodynamics of the energy coupling during ATP-induced conformational changes in TmrAB were investigated. The results demonstrate that ATP-binding alone drives the global conformational switching to the outward-facing state and allows the determination of the entropy and enthalpy changes for this step. With this knowledge, the Gibbs free energy of this ATP induced transition was calculated. Furthermore, an excess of substrate, meaning trans-inhibition of the transporter is resulting mechanistically in a reverse transition from the outward-facing state to an occluded conformation predominantly.3 This work unravels the central role of the reversible conformational equilibrium in the function and regulation of an ABC exporter. For the first time it is shown that the conformational thermodynamics of a large membrane protein complex can be investigated. The presented experiments give new possibilities to investigate other related medically important transporters with asymmetric NBSs or other similar protein complexes.
The dissertation studied reused Roman coins (AD 100 – 400) that were found in medieval cemeteries (AD 400 – 1400) in the territory of Serbia. The evaluation process was traced through three different periods and cultural contexts: (1) in the period of Roman domination in the central Balkans (AD 1 – 400), i.e. the “primary context” of their use and circulation; (2) in the time of transition from the late antiquity to early medieval period (AD 400 – 700); and (3) in the high and late Middle Ages (AD 900 – 1400), where the last two were considered to be a “secondary context” in which the Roman coins were no longer a valid currency.
It was observed that the reused Roman coins, as a distinctive category of archaeological finds, impose a necessity for reconsideration of the relationship between the disciplines of archaeology and numismatics; encouraging a greater cooperation and discussion between the two. Considering the use and evaluation of Roman coins in their “primary context”, it is possible to presume that the strength of the political Roman system was the crucial factor in the formation and maintaining the stability of the value of Roman coins. The act of reuse should not be automatically equalized with recycling; implying only to use value, but at the same time it was not possible to assume that the value was formed only on a purely symbolical level. The (re)use of Roman coins in the funeral practices from c. AD 400 to 700 was considered to be a part of wider and occasional practice of incorporating older Roman issues in the coin pool by the “barbarian” or Byzantine authorities. It could be then concluded that the value of Roman coins was understood more as a potential attribute than as a fixed category; enabling one to simultaneously “overvalue “ and “undervalue” these objects. In the period from c. AD 900 to 1400, the reuse of Roman coins was detected only within the cemeteries of the peasantry and in a context of gradual increase of general coin use in the central Balkan communities of the Middle Ages. This was understood as an indicator that the Roman coins were not perceived as particularly valuable per se, but since the were recognized as category of objects that became more important in defining social relationships they were then incorporated in the funeral rituals and reinterpreted by the medieval population.
Objective: Studies using diffusion tensor imaging (DTI) to investigate white matter (WM) microstructure in youths with conduct disorder (CD) have reported disparate findings. We investigated WM alterations in a large sample of youths with CD, and examined the influence of sex and callous-unemotional (CU) traits.
Method: DTI data were acquired from 124 youths with CD (59 female) and 174 typically developing (TD) youths (103 female) 9 to 18 years of age. Tract-based spatial statistics tested for effects of diagnosis and sex-by-diagnosis interactions. Associations with CD symptoms, CU traits, a task measuring impulsivity, and the impact of comorbidity, and age- and puberty-related effects were examined.
Results: Youths with CD exhibited higher axial diffusivity in the corpus callosum and lower radial diffusivity and mean diffusivity in the anterior thalamic radiation relative to TD youths. Female and male youths with CD exhibited opposite changes within the internal capsule, fornix, posterior thalamic radiation, and uncinate fasciculus. Within the CD group, CD symptoms and callous traits exerted opposing influences on corpus callosum axial diffusivity, with callous traits identified as the unique clinical feature predicting higher axial diffusivity and lower radial diffusivity within the corpus callosum and anterior thalamic radiation, respectively. In an exploratory analysis, corpus callosum axial diffusivity partially mediated the association between callous traits and impulsive responses to emotional faces. Results were not influenced by symptoms of comorbid disorders, and no age- or puberty-related interactions were observed.
Conclusion: WM alterations within the corpus callosum represent a reliable neuroimaging marker of CD. Sex and callous traits are important factors to consider when examining WM in CD.
Faul sein. Den Sonntag gemütlich auf der Couch verbringen. Die To-Do-Liste zur Seite legen. Mal keinem getakteten Tagesablauf folgen. Die Zeit einfach vorbeiziehen lassen. Zur Ruhe kommen und nichts tun geht häufig mit einem negativen Gefühl einher. Von Vorwürfen der Unproduktivität bis hin zu rassistischen Ressentiments, die mit dem Nichtstun verknüpft werden: Faulheit gehört zu den Dingen, die in der kapitalistischen Gesellschaft keinerlei Wertschätzung erfahren. Neu ist die negative Konnotation des Begriffs allerdings nicht. Bereits im vierten Jahrhundert verpönt die christliche Theologie die "Trägheit" als eine der sieben Todsünden. Die abschätzige Bewertung überdauerte den christlichen Glauben, wurde sozusagen profanisiert und ist heute – in Zeiten von Überstunden, Zweit- oder auch gleich Drittjobs und ständiger Verfügbarkeit – ein No-Go. ...
Utility of the new cobas HCV test for viral load monitoring during direct-acting antiviral therapy
(2019)
Background: The COBAS AmpliPrep/COBAS TaqMan assay HCV (CAP/CTM) is widely used in clinical routine for HCV testing. Recently, the new cobas HCV test was established for high throughput testing with minimal operator intervention. As different assays may yield different quantitative/qualitative results that possibly impact treatment decisions, the aim of this study was to externally evaluate the cobas HCV test performance in comparison to CAP/CTM in a clinically relevant setting.
Methods: Serum samples were obtained from 270 patients who received direct acting antiviral therapy with different treatment regimens at two study sites (Hannover and Frankfurt) in 2016. Overall, 1545 samples (baseline, on-treatment and follow-up) were tested in parallel by both assays.
Results: The mean difference between cobas HCV and CAP/CTM for the quantification of HCV RNA was 0.008 log10 IU/ml HCV RNA (95% limits of agreement: -0.02–0.036) showing excellent agreement of both assays. With respect to clinical cut offs (HCV RNA detectable vs. target not detected and HCV RNA above the lower limit of quantification (LLOQ) vs. <LLOQ), discordant results were obtained in 9.5% and 4.6%, respectively; the greatest differences were observed during early stages of antiviral therapy (week 1, week 2 and week 4), but none were statistically significant. Overall percent agreement for SVR between cobas HCV and CAP/CTM at the 15 IU/ml cutoff was 99.2% (95%CI 92.7%-100%).
Conclusion: The performance of the new cobas HCV test was comparable to CAP/CTM in a clinical setting representing a large patient population with HCV GT 1 and 3 treated with DAAs.
leporello #2
(2019)
Diverse Quellen zu Stefan George (1868-1933) berichten von einer Geheimsprache, die der exzentrische Dichter noch in seiner Schulzeit erfunden und über Jahre hinweg weiterentwickelt haben soll. Zweck war neben dem poetischen Aspekt vor allem die Verschlüsselung von Informationen.
Ich werde im Folgenden anhand des einzig erhaltenen Fragments, zweier Verse am Ende des Gedichts "Ursprünge" von 1904, zeigen, dass das Vokabular vor allem altgriechisch mit romanischen Elementen ist. Weiterhin lässt sich nachweisen, dass die Grammatik an das damals beliebte Esperanto, eine Kunstsprache auf der Basis v.a. romanischer Sprachen (Latein) mit vereinfachter Grammatik, angelehnt ist.
Description of Hemicordulia tuiwawai sp. nov. from Kadavu Island, Fiji (Odonata: Corduliidae)
(2019)
Hemicordulia tuiwawai sp. nov. (Odonata: Corduliidae) is described and diagnosed based on material collected from Kadavu Island, Fiji; holotype: Wainitayuki River about 750 m above Baidamudamu village, -19.0916, 178.1038; 37 m a.s.l., 06 June 2016, M. Marinov leg. This species is distinguished from its congeners in the field by the contrasting colouration – dark green metallic body with bright yellow spots on the synthorax and base of the abdomen. This pattern is comparable to H. pacifica Selys, 1871. However, Hemicordulia tuiwawai sp. nov. can be recognised by the larger size and unique shape of the caudal appendages and genital hamule (in males) and vulvar scale (in females).
Records of Odonata from the southwest of Sri Aman Division and the extreme east of Serian Division in Sarawak are presented. The sampled areas are interesting not only because they are poorly known for Odonata but also because many are just to the south and west of the Lupar Line which is a division between the ancient Sunda shelf and more recent geological formations. Differences between the odonate faunas on either side of the Lupar Line are discussed. Eightyfive species of Odonata were recorded during the surveys reported on. The single most notable record is that of Coeliccia southwelli Dow & Reels, 2011, which represents a considerable extension to the known range of this species. Other interesting records include Telosticta dupophila (Lieftinck, 1933), T. species cf longigaster Dow & Orr, 2012, Podolestes parvus Dow & Ngiam, 2019 and Heliogomphus species cf olivaceous Lieftinck, 1961. Variation in the markings of Stenagrion dubium (Laidlaw, 1912) across its range is discussed and a gene tree using the COI marker is presented to illustrate the high variability of this species in this marker. However the variability in COI does not appear to be correlated with other characters.
Odonatological results of a trip across the southern Far East of Russia, from nearly the border of North Korea to Khabarovsk from July 1st to 16th, 2014, are presented. In total, 50 species were recorded, including those with limited presence in Russia, such as Paracercion calamorum, P. hieroglyphicum, P. plagiosum (for this species the 3rd Russian locality is reported), Pseudocopera tokyoensis, Stylurus annulatus (2nd Russian locality), Sinictinogomphus clavatus; Trigomphus citimus, Macromia daimoji (3rd Russian locality), M. manchurica, Deielia phaon, Lyriothemis pachygastra (2nd Russian locality). For S. annulatus, M. manchurica and D. phaon the northernmost known localities in the world are reported. D. phaon, earlier reported from one locality in Russia, have been found in five localities in Primorye and for the first time reported for Khabarovskiy Kray in general and Bol'shekhekhtsirskiy State Nature Reserve in particular. A trend of mutual exclusion of two abundant Shaogomphus postocularis epophthalmus and S. schmidti is supposed: the lowermost Ussuri River / Amur River, respectively. Variation in Paracercion spp. and Macromia amphigena fraenata is discussed.
During four field trips in Georgia, Armenia and Azerbaijan from 2010 to 2018, the author collected data of a total of 55 species (see Tab. 2 in Appendix). This study provides first insights into new or rare species in this ecoregion. Ischnura fountaineae and Cordulia aenea were found for the first time in Armenia. We also highlight the rediscovery of some species that were mentioned in the older literature but had not been confirmed since. An autochthonous population of Lestes macrostigma was discovered in Azerbaijan sixteen years after the single previous record by Dumont (2004). Original information is provided on the distribution of some rare species encountered in these countries. Finally, the identification of a puzzling Cordulegaster sp. observed in south Armenia is discussed briefly.
The Odonata collection deposited at the Museum of Comparative Zoology (MCZ) includes specimens of 634 taxa labeled as types. Fifteen of these have been incorrectly labeled as types (pseudotypes) and eight are apparently lost, leaving a total of 611 types currently deposited at MCZ. From these, 489 represent primary namebearing types (syntype/s, holotype, lectotype and neotype), 21 are probable primary types, and 101 are secondary types (paratype/s, paralectotype/s).
A checklist of 49 damselfly species from 12 families (Odonata: Zygoptera) recorded from Kon Ka Kinh National Park is provided. A first description of the female Protosticta socculus Phan & Kompier, 2016, is given. Burmargiolestes cf. laidlawi Lieftinck, 1960 and three apparently new species, two Coeliccia and one Protosticta species, are recorded, all of which are to be described in the future.
Phnom Tumpor is a scarcely accessible basalt table mountain in the Cardamom Mts. in Pursat Province of Cambodia. On top surface it bears tall evergreen forest (ca 1100 m a.s.l.), concealing a slow rivulet, O'Gran, being a chain of deep pools. It was examined odonatologically on March 1418th, 2019. Six common species were recorded in dry and burnt scrub on the Phnom Tumpor slopes and ten on the forested upper surface at O'Gran, among them Polycanthagyna erythromelas (Selys, 1891) and Macromia sp. cf. pinratani Asahina, 1987 for the first time in Cambodia. The peculiarities of the males of Coeliccia kazukoae Asahina, 1984 from Phnom Tumpor and the problem of distinguishing females of M. pinratani and M. moorei are discussed.
Survey in three protected areas of Chhattisgarh reveals the presence of 50 species of Odonata belonging to 34 genera and 9 families. Specimens were sampled from different lotic and lentic ecosystems. 17 species were exclusively found in or around running water. Larvae or exuviae of 23 species were found and photographed. Habitat availability, larval abundance, species composition and phenology are discussed.
In May 2018, 34 dragonfly species were recorded on Wolin (21), Usedom (30) and the adjacent mainland (21). The most frequent spring species in the area were Coenagrion puella, Libellula quadrimaculata, C. pulchellum, Ischnura elegans, Erythromma najas, Brachytron pratense and Cordulia aenea. C. lunulatum and Calopteryx virgo were recorded for the first time on Usedom, while Anax parthenope, Libellula fulva and Leucorrhinia caudalis were recorded for the first time on Wolin. The occurrence of Coenagrion armatum, which had been recorded in 2016 on Usedom, could not be confirmed.
The quantitative results of the survey are given for different types of water bodies (ditches, pools, ponds, lakes, bog lakes). The average number of species per water body was highest in bog lakes (7.5) and lowest (3.4) in temporary pools. In comparison to older studies from the area, the flight season started 13.7 days earlier in 2018 than in years documented prior to 1989. This might be explained by climatic changes. The species composition, however, has remained rather stable – at least on Usedom and the mainland. On Wolin, climatic factors as well as habitat loss and transformation have led to a species composition that is different from the one recorded in the first half of the 1970s.
New data on Odonata of the Preah Sihanouk Province of Cambodia obtained in March 2017 and November 2018 are presented. The presence of Onychargia atrocyana Selys, 1865 in Cambodia is confirmed. Twentyone species are added to the known fauna of the Kbal Chhay Waterfall environs, 19 species to that of Ream Peninsula and 4 to that of Koh Rong Island. The total number of species registered for Kampong Saom Peninsula amounts to 74. The presented data are rather of historical importance since most of the remaining forest has been quickly and irreversibly logged a few months ago. The validity of Gynacantha demeter Ris, 1911 as a species distinct from G. dohrnii Krüger, 1899 is doubted.
Globally urban wetlands are under high anthropogenic pressure of degradation. Urban wetlands are hotspots for species losses and rapid turnover in species assemblages. Therefore, studying such wetlands may provide an estimate of the pace of local extinction, concerning wetlanddependent species such as odonates. We undertook a study to document odonate species across a tropical urbanization gradient. We sampled six localities across the gradient across the Mula River that flows through the Pune City, India. We sampled adult odonates using a newly devised Halfcircle Point Count method from September 2016 to March 2017. We took multiple temporal replicates per site. We also sampled larvae across six sites once in November 2016. We measured site characteristics such as canopy cover, solid waste, and water turbidity to understand the level of disturbance at each site. We recorded 41 odonates, six species (primarily Gomphidae members) exclusively from the larval sampling. We did not find the localization of species in a particular site across the urbanization gradient, possibly because we sampled a relatively short stretch of the river to capture the variation. Here, we update the Odonata list of Pune including data on larvae. We demonstrate that larval sampling complements Odonata surveys, especially in recording Gomphids.
We recommend future research to include a longer timespan and extensive sampling area.
The article presents new faunistic data on 33 Odonata species, based on the material collected by the author in 2012, 2016 and 2017 and a systematic research in 2018 throughout the Nakhichevan Autonomous Republic (AR). Onychogomphus assimilis (Schneider, 1845) is a new record for the fauna of Azerbaijan. Eight species were registered for the first time for the territory of Nakhichevan AR: Lestes virens Rambur, 1842, Coenagrion scitulum (Rambur, 1842), Aeshna mixta Latreille, 1805, Anaciaeschna isoceles (Müller, 1764), Anax parthenope (Selys, 1839), Sympetrum sanguineum (Müller, 1764), Crocothemis erythraea (Brullé, 1832), and Selysiothemis nigra (Vander Linden, 1825).
Another survey of Odonata on the Indonesian island of Belitung is reported. This survey was the second survey conducted in the Belitung area with International Dragonfly Fund support and was focused to Belitung Regency's outer islands. Seventy two species were recorded during the survey. Significant records from the surveyed islands include Amphicnemis kuiperi, Mortonagrion arthuri, Mortonagrion appendiculatum, Teinobasis ruficollis, Platylestes heterostylus, Pornothemis serrata, Pornothemis starrei and Tramea phaeoneura. Almost all the records are new to the small islands surveyed, except for Mendanau Island for which there were already records of four species. A checklist of the odonate fauna of the outer islands is given in an appendix.
Contribution to the Odonata fauna of the Society Islands, French Polynesia (Insecta: Odonata)
(2019)
Following field studies in 2018 the Odonata fauna of Society Islands, French Polynesia is reviewed and the validity of all records analysed. An updated species list is provided, bringing the number of breeding species recorded from this island group to ten.
Field studies targeted Hemicordulia Selys, 1870 specimens for inclusion in the revision of the Pacific representatives of the genus. Samples were taken mainly from Tahiti and Raiatea, with some additional specimens collected from Bora Bora and Huahine. Only the Society Islands endemic H. oceanica Selys, 1871 was encountered on all four islands, being recorded from Bora Bora for the first time. At least one new species of Hemicordulia has been reported from the high mountain areas of Tahiti (Jacq et al. 2009, 2014).
The present study also emphasises the need for a revision of Zygoptera records from the French Polynesia and the rest of the Pacific. Presently, about 25 endemic species provisionally assigned to Ischnura Charpentier, 1840 and Hivaagrion Hämäläinen & Marinov, 2014 are known from the Society, Austral and Marquesas island groups (R. Englund, J. Jacq, T. Ramage, D. Polhemus, per. comm.). Only seven of them have been described so far. Detailed morphological and molecular analyses will likely prove the separate generic status of some of the species presently included under Ischnura.
Records of Odonata from Sarawak's Bintulu Division are presented. One hundred and sixtysix (or more) species are listed, of which three (Oligoaeschna amata (Förster, 1903), O. buehri (Förster, 1903) and Oligoaeschna (?) species) had not previously been recorded in Sarawak and Macromia species cf dione Lieftinck, 1971 had not previously been recorded from Borneo. Additionally this is the first published record of Prodasineura tenebricosa Lieftinck, 1937 from Sarawak, although it had been found at another location in the state prior to its discovery in Bintulu, and the first published record of Phyllothemis raymondi Lieftinck, 1950 from Borneo, although specimens from Kalimantan are present in the collections of the Naturalis Biodiversity Center, Leiden. Other notable records include "Elattoneura" longispina Lieftinck, 1937, Pericnemis dowi Orr & Hämäläinen, 2013, Linaeschna polli Martin, 1909, Burmagomphus arthuri Lieftinck, 1953, Heliogomphus borneensis Lieftinck, 1964, Merogomphus femoralis Laidlaw, 1931, Chlorogomphus species, Macromidia genialis erratica Lieftinck, 1948 and Tetrathemis flavescens Kirby, 1889. Altogether there do not appear to be any previous published records from Bintulu Division of 52 of the species listed in this paper. The status of Rhyothemis fulgens Kirby, 1889 is discussed and illustrations of its anal appendages and those of R. pygmaea (Brauer, 1867) are provided. Illustrations of the anal appendages of Tetrathemis hyalina Kirby, 1889 and T. irregularis Brauer, 1868 are also provided. Identification problems when using COIbased DNA barcoding with some species of Archibasis are discussed, and the nuclear marker ITS is shown to be a successful alternative in these cases; COI and ITS gene trees for part of the genus are included. Some COI data for Macromia species are published and the marker is used to identify larvae of M. corycia Laidlaw, 1922 and establish the relationship of another Macromia larva with M. dione, a very poorly known species from Sumatra. Macromia euterpe Laidlaw, 1915 is considered to be the same species as M. westwoodii Selys, 1874 and dropped from the list of species known from Sarawak, however formal combination of the two species is left for a peer reviewed publication. A detailed list of previously unpublished specimens from the locations covered is given in an appendix. Concise checklists for two of the locations covered Similajau National Park (54 species) and the Bukit Mina Wildlife Corridor (84 species) are given in another appendix.
This study investigates the history of Odonata studies in the Republic of Vanuatu and presents results from a two week field sampling mainly on three islands – Efate, Aneityum and Malekula. A total of 32 species are recognised as currently valid names for the country. Three new species have been collected and will be described elsewhere. Various taxonomic, faunistic and biogeographic issues are discussed in the light of the new material collected during the current study in comparison to already published research.
The general conclusion is that provisional species checklist is far from complete. The territory of Vanuatu is still highly insufficiently studied for its Odonata fauna. The local endemic genus Vanuatubasis Ober & Staniczek, 2009 is believed to be far more diverse than currently known with three described and three new species collected during the present study.
Objectives: To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs).
Methods: Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24.
Results: The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients.
Conclusions: IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
Malignant germ cell tumors (GCT) are the most common malignant tumors in young men between 18 and 40 years. The correct identification of histological subtypes, in difficult cases supported by immunohistochemistry, is essential for therapeutic management. Furthermore, biomarkers may help to understand pathophysiological processes in these tumor types. Two GCT cell lines, TCam-2 with seminoma-like characteristics, and NTERA-2, an embryonal carcinoma-like cell line, were compared by a quantitative proteomic approach using high-resolution mass spectrometry (MS) in combination with stable isotope labelling by amino acid in cell culture (SILAC). We were able to identify 4856 proteins and quantify the expression of 3936. 347 were significantly differentially expressed between the two cell lines. For further validation, CD81, CBX-3, PHF6, and ENSA were analyzed by western blot analysis. The results confirmed the MS results. Immunohistochemical analysis on 59 formalin-fixed and paraffin-embedded (FFPE) normal and GCT tissue samples (normal testis, GCNIS, seminomas, and embryonal carcinomas) of these proteins demonstrated the ability to distinguish different GCT subtypes, especially seminomas and embryonal carcinomas. In addition, siRNA-mediated knockdown of these proteins resulted in an antiproliferative effect in TCam-2, NTERA-2, and an additional embryonal carcinoma-like cell line, NCCIT. In summary, this study represents a proteomic resource for the discrimination of malignant germ cell tumor subtypes and the observed antiproliferative effect after knockdown of selected proteins paves the way for the identification of new potential drug targets.
The success of social insects is largely intertwined with their highly advanced chemical communication system that facilitates recognition and discrimination of species and nest-mates, recruitment, and division of labor. Hydrocarbons, which cover the cuticle of insects, not only serve as waterproofing agents but also constitute a major component of this communication system. Two cryptic Crematogaster species, which share their nest with Camponotus ants, show striking diversity in their cuticular hydrocarbon (CHC) profile. This mutualistic system therefore offers a great opportunity to study the genetic basis of CHC divergence between sister species. As a basis for further genome-wide studies high-quality genomes are needed. Here, we present the annotated draft genome for Crematogaster levior A. By combining the three most commonly used sequencing techniques—Illumina, PacBio, and Oxford Nanopore—we constructed a high-quality de novo ant genome. We show that even low coverage of long reads can add significantly to overall genome contiguity. Annotation of desaturase and elongase genes, which play a role in CHC biosynthesis revealed one of the largest repertoires in ants and a higher number of desaturases in general than in other Hymenoptera. This may provide a mechanistic explanation for the high diversity observed in C. levior CHC profiles.
The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet, the molecular determinants governing interactions in protein-RNA networks are not well understood. Here we investigated the relationship between the structure of an RNA and its ability to interact with proteins. Analysing in silico, in vitro and in vivo experiments, we find that the amount of double-stranded regions in an RNA correlates with the number of protein contacts. This relationship —which we call structure-driven protein interactivity— allows classification of RNA types, plays a role in gene regulation and could have implications for the formation of phase-separated ribonucleoprotein assemblies. We validate our hypothesis by showing that a highly structured RNA can rearrange the composition of a protein aggregate. We report that the tendency of proteins to phase-separate is reduced by interactions with specific RNAs.
Men and women differ in their vulnerability to a variety of stress-related illnesses, but the underlying neurobiological mechanisms are not well understood. This is likely due to a comparative dearth of neurobiological studies that assess male and female rodents at the same time, while human neuroimaging studies often don’t model sex as a variable of interest. These sex differences are often attributed to the actions of sex hormones, i.e. estrogens, progestogens and androgens. In this review, we summarize the results on sex hormone actions in the hippocampus and seek to bridge the gap between animal models and findings in humans. However, while effects of sex hormones on the hippocampus are largely consistent in animals and humans, methodological differences challenge the comparability of animal and human studies on stress effects. We summarise our current understanding of the neurobiological mechanisms that underlie sex-related differences in behavior and discuss implications for stress-related illnesses.
Die Idee und inhaltliche Ausrichtung der Ausstellung HOUSE OF NORWAY stand bereits fest, als ich Mitte März in das Frankfurter Museum Angewandte Kunst als Projektkoordinatorin für eben diese Ausstellung kam. Dass die gesamte Fläche des Museums bespielt werden sollte, erinnerte mich an die Schau The Empty House im Jahr 2013, bei der ich damals als Praktikantin mitgewirkt hatte: Auch die Performance des Konzeptkünstlers Olaf Nicolai fand im gesamten Richard-Meier-Bau statt, welcher zuvor in seinen Originalzustand von 1985 zurückversetzt worden war. HOUSE OF NORWAY war so zumindest in seiner Dimension vorangegangenen Ausstellungen nicht unähnlich – auch die Ausstellung Jil Sander. Präsens vor zwei Jahren wurde im gesamten Museumsgebäude gezeigt. ...
The ‘European Alliance Against Depression’ community-based intervention approach simultaneously targets depression and suicidal behaviour by a multifaceted community based intervention and has been implemented in more than 115 regions worldwide. The two main aims of the European Union funded project “Optimizing Suicide Prevention Programmes and Their Implementation in Europe” were to optimise this approach and to evaluate its implementation and impact. This paper reports on the primary outcome of the intervention (the number of completed and attempted suicides combined as ‘suicidal acts’) and on results concerning process evaluation analysis. Interventions were implemented in four European cities in Germany, Hungary, Portugal and Ireland, with matched control sites. The intervention comprised activities with predefined minimal intensity at four levels: training of primary care providers, a public awareness campaign, training of community facilitators, support for patients and their relatives. Changes in frequency of suicidal acts with respect to a one-year baseline in the four intervention regions were compared to those in the four control regions (chi-square tests). The decrease in suicidal acts compared to baseline in the intervention regions (-58 cases, -3.26%) did not differ significantly (χ2 = 0.13; p = 0.72) from the decrease in the control regions (-18 cases, -1.40%). However, intervention effects differed between countries (χ2 = 8.59; p = 0.04), with significant effects on suicidal acts in Portugal (χ2 = 4.82; p = 0.03). The interviews and observations explored local circumstances in each site throughout the study. Hypothesised mechanisms of action for successful implementation were observed and drivers for ‘added-value’ were identified: local partnership working and ‘in-kind’ contributions; an approach which valued existing partnership strengths; and synergies operating across intervention levels. It can be assumed that significant events during the implementation phase had a certain impact on the observed outcomes. However, this impact was, of course, not proven.
In ihrer Dankesrede für den Friedenspreis des Deutschen Buchhandels argumentierte Susan Sontag 2003, der Gegensatz zwischen "alt" und "neu" stehe im Zentrum dessen, was wir unter Erfahrung verstünden. Mehr noch: "Alt" und "neu" seien die ewigen, unumstößlichen Pole aller Wahrnehmung und Orientierung in der Welt. Ohne das Alte kämen wir nicht aus, weil sich mit ihm unsere ganze Vergangenheit, unsere Weisheit, unsere Erinnerungen, unsere Traurigkeit, unser Realitätssinn verbinde. Ohne den Glauben an das Neue wiederum kämen wir nicht aus, weil sich mit dem Neuen unsere Tatkraft, unsere Fähigkeit zum Optimismus, unser blindes biologisches Sehnen, unsere Fähigkeit zu vergessen verbinde – diese heilsame Fähigkeit, ohne die Versöhnung nicht möglich sei. Mit anderen Worten: Erst eine noch so unpräzise und temporal begrenzte Unterscheidung zwischen "alt" und "neu" gestattet es uns, soziopolitische Phänomene historisch zu vergleichen, zu ordnen, zu periodisieren, und sie schließlich als Geschichte(n) zu erzählen. "Alt" und "neu" – diese mit dem Konzept des "Fortschritts" eng verbundene Dichotomie ist grundlegend nicht nur für Kants kosmopolitische Teleologie, für Hegels Dialektik, für den "alten" und "neuen" Marxismus, sondern auch für moderne Völker-Rechtsgeschichte(n). Das zeigt auch das gut lesbare und pointierte Buch von Oona A. Hathaway und Scott J. Shapiro. Und umso interessanter sind die teleologischen Verkürzungen, die die Autoren vornehmen, um ihr Narrativ vom Neuen zu bedienen. ...
Im Jahr 2017 sind zwei Sammelbände erschienen, die aus beinahe zeitgleichen Tagungen im November 2015 zur Entwicklung des öffentlichen Rechts in Frankreich 1914–1918 hervorgegangen sind: Der eine ist der von Elina Lemaire (Universität Bourgogne – Franche-Comté) herausgegebene Band zum öffentlichen Recht während des Krieges, der andere der vom Conseil d’État selbst herausgegebene Band zu seiner Funktion und (gestaltenden) Rolle während der Kriegsjahre. Insoweit die Entwicklung des öffentlichen Rechts in Frankreich ohne den Conseil d’État kaum sinnvoll untersucht werden kann und umgekehrt eine Geschichte dieses Conseil kaum unter Auslassung seines Einflusses auf die Rechtsentwicklung geschrieben werden kann, nähern sich beide Bände aus unterschiedlichen (aber auf das öffentliche Recht fokussierten) Perspektiven gewissermaßen einem gemeinsamen Gegenstand: der Rechtsstaatlichkeit im Krieg und namentlich der Rechtsstaatlichkeit in einer Republik im Krieg. ...
Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin 17A, a key cytokine involved in the development of psoriasis. Secukinumab has shown long-lasting efficacy and safety in the complete spectrum of psoriatic disease, including disease localized to nails, scalp, palms and soles, and joints (peripheral and axial arthritis). Given the chronic and relapsing nature of psoriasis, long-term data might help to fully characterize the efficacy and safety profile of secukinumab as well as its impact on quality of life.
Es ist nicht zu übersehen, dass spätestens seit der Jahrtausendwende in den Geisteswissenschaften ein gesteigertes Bedürfnis nach einer Historisierung der eigenen Zunft existiert, bei der es nicht um die eher pflichtschuldige Übung eines einleitenden Forschungsstandes geht, von dem aus die eigene Arbeit vorangetrieben wird, sondern die die Wissensbestände des Fachs selbst zum Thema hat. Auch die Rechtsgeschichte reiht sich hier ein in einen allgemeinen Trend zu (geisteswissenschaftlicher) Wissenschaftsgeschichte und vielleicht ist es nicht verfehlt, mit Ernst-Wolfgang Böckenförde und seiner 1961 erschienenen (philosophischen) Dissertation einen gleichermaßen frühen wie wirkmächtigen rechtsgeschichtlichen Innovator zu identifizieren. ...
Täglich nutzen wir Einrichtungen, die uns selbstverständlich geworden sind. Sie gehören uns, den Bürgern, nur in einem übertragenen Sinn, und wir beherrschen sie auch nicht. Die hinter ihnen stehenden technischen und politischen Voraussetzungen verstehen wir meist nur ansatzweise. Wir verbrauchen Strom und Trinkwasser, werden mit Fernwärme, Erdgas oder Öl "versorgt", informieren uns (man beachte die Wassermetaphern) "aus allgemein zugänglichen Quellen" einschließlich des "Surfens" im Internet (Art. 5 Abs. 1 GG), steigen in öffentliche Verkehrsmittel, fahren über wohlgeglättete Straßen oder fliegen mit gebremsten Angstgefühlen von Kontinent zu Kontinent. Währenddessen werden unsere Abwässer geklärt und wird unser Müll entsorgt. Dies alles vollzieht sich durch gewaltige Netzwerke, Röhrensysteme und Kabel im Untergrund sowie über der Erde auf Verkehrsflächen und Schienen, durch Überlandleitungen, Versorgungs- und Entsorgungseinrichtungen, die wir kaum noch wahrnehmen. Wir sind auf sie angewiesen und bezahlen sie auch, mehr oder weniger stillschweigend, über Gebühren oder Steuern. Wir erwarten, dass ein weit verstandener "Staat" oder eine von ihm kontrollierte Privatwirtschaft dies alles unterhält und finanziert, einschließlich ehrgeiziger Großprojekte wie "Stuttgart 21", "Flughafen Berlin" oder "Elbphilharmonie". Was seit Ernst Forsthoffs berühmter Studie von 1938 "Daseinsvorsorge" genannt und ständig erweitert wurde, heißt seit den fünfziger Jahren – vermittelt über den Wortgebrauch der NATO – "Infrastruktur". In ihr versammeln sich alle Garantien unseres Lebensstils, aber sie bilden zugleich das "Gehäuse unserer Hörigkeit" wie man mit Max Weber sagen könnte. Insgeheim fürchten wir die damit verbundenen Abhängigkeiten, die alltäglichen Risiken, die Gefahren des Kollapses und die Verletzlichkeit gegenüber externen Angriffen. ...
Background: The prognostic factors and outcome of aneurysms appear to be dependent on its locations. Therefore, we compared left- and right- sided aneurysms in patients with aneurysmal subarachnoid hemorrhage (SAH) in terms of differences in outcome and prognostic factors.
Methods: Patients with SAH were entered into a prospectively collected database. A total of 509 patients with aneurysmal subarachnoid hemorrhage were retrospectively selected and stratified in two groups depending on side of ruptured aneurysm (right n = 284 vs. left n = 225). Midline aneurysms of the basilar and anterior communicating arteries were excluded from the analysis. Outcomes were assessed using the modified Rankin Scale (mRS; favorable (mRS 0–2) vs. unfavorable (mRS 3–6)) six months after SAH.
Results: We did not identify any differences in outcome depending on left- and right-sided ruptured aneurysms. In both groups, the significant negative predictive factors included clinical admission status (WFNS IV+V), Fisher 3- bleeding pattern in CT, the occurrence of delayed cerebral ischemia (DCI), early hydrocephalus and later shunt-dependence. The side of the ruptured aneurysm does not seem to influence patients´ outcome. Interestingly, the aneurysm side predicts the side of infarction, with a significant influence on patients´ outcome in case of left-sided infarctions. In addition, the in multivariate analysis side of aneurysm was an independent predictor for the side of cerebral infarctions.
Conclusion: The side of the ruptured aneurysms (right or left) did not influence patients’ outcome. However, the aneurysm-side predicts the side of delayed infarctions and outcome appear to be worse in patients with left-sided infarctions.
Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a potentially curative treatment option for relapsed and refractory lymphomas. Obesity displays an emerging epidemic risk factor for global mortality and is associated with an increased mortality in cancer patients. To date, the impact of obesity on the outcome of lymphoma patients undergoing auto-HSCT is understudied. We conducted a retrospective single-center study assessing 119 lymphoma patients who underwent auto-HSCT. Overall survival (OS) served as the primary endpoint whereas progression free survival (PFS), cumulative incidence of non-relapse related mortality (NRM) and cumulative incidence of relapse were analyzed as secondary endpoints. Obese patients (Body mass index, BMI≥30) had significantly lower OS (45.3% vs. 77.9%; p = 0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to non-obese patients at 48 months post-transplantation. The cumulative incidence of NRM displayed no significant differences while the cumulative incidence of relapse was significantly increased in patients with BMI≥30 (66.2% vs. 21.5%; p<0.001). Patients with a BMI<25 and overweight patients (BMI 25–30; 76.1% vs. 80.9%; p = 0.585), showed no significant difference in OS, whereas patients with BMI≥30 exhibited significant lower OS when compared to either of both groups (76.1% vs. 45.3%; p = .0.021 and 80.9% vs. 45.3%; p = 0.010). Furthermore, in a multivariate analysis, obesity was identified as an independent risk factor for death (Hazard ratio 2.231; 95% CI 1.024 to 4.860; p = 0.043). Further studies are needed to evaluate the reasons for the higher relapse rate causing higher mortality in obese patients.
Biodiversity is threatened worldwide because of ongoing habitat loss and fragmentation, overexploitation, pollution, biological invasions and a changing global climate. Due to the major importance of biological diversity for modern human living, efficient conservation and management strategies are required to protect endangered habitats and species. For this purpose, ambitious multilateral agreements on regional and global scale were declared to prevent biodiversity loss.
Efficient biomonitoring methods are required to adequately implement these biodiversity conventions. Species monitoring as a core activity in biodiversity research is an effective tool to assess the status of species and trends within habitats. Data collection can be obtained with visual, electronic or genetic surveys. Still, these monitoring programs can be expensive, laborious and inefficient for accurate species assessments. New techniques based on environmental DNA (eDNA) allows for the detection of DNA traces in environmental samples (soil, sediment, water and air samples) and open up new possibilities for species monitoring. The eDNA methodology enables detection of single species in a qualitative (presence/absence) or (semi-) quantitative way. eDNA metabarcoding approaches can be an effective community structure assessment method.
This thesis, located at the interface between experimental and applied research, illustrates the suitability of the eDNA methodology in applied biomonitoring using the example of the water-borne crayfish plague pathogen Aphanomyces astaci (Schikora 1906). The obtained results provide new insights into A. astaci sporulation dynamics in natural water courses. A. astaci sporulation is influenced by seasonal variation of water temperatures and life history traits (molting, activity, mating) of infected crayfish. The results also imply a high transmission risk of A. astaci spores during the complete year. This thesis compares two eDNA methods, which are successfully and consistently detecting A. astaci spores. Each approach is suitable for different biomonitoring tasks due to the method-specific requirements. The obtained results also reveal spatial variation in A. astaci occurance in the tested water bodies. A. astaci spore estimates are positively correlated with population density and pathogen loads of captured A. astaci- positive crayfish. eDNA results show a downstream zoospore transport of up to three kilometres distance from a distribution hot spot area of A. astaci-infected crayfish. The eDNA methodology is helpful in gaining reliable information on A. astaci occurrence in large water bodies. This information is urgently needed to initiate efficient management decisions for the conservation of European crayfish species.
eDNA-based methods such as for A. astaci detection are a useful complement for conventional monitoring and should have a strong impact on conservation policy. eDNA methodology will be helpful for the practical implementation of the main aims of key conservation agreements and thus will make important contributions to biodiversity protection.
This thesis revolves around the development of a new critical approach to contemporary anglophone postcolonial literature in the form of a concept of ‘corporate ingression.’ This term denotes a globally recurring process of biopolitical (re)structuring of a community by corporate power and its extended cultural influence on society.
Through an analysis of contemporary engagements with similarly explored events over time and space in the form of three novels (Helon Habila’s Oil on Water, Lauren Beukes’ Moxyland and David Mitchell’s The Thousand Autumns of Jacob de Zoet), this thesis explores the relevance of the concept of corporate ingression as a new approach to such imaginative works. By reading these texts closely, with and against the grain, I enter into dialogue with their discussion of corporate power as the major structural influence in the societies they explore. I also show that a comparative analysis of these texts reveals similarities between the exploration of the period of early colonialism as acted out by the various trade corporations in existence and contemporary forms of corporate dominance. This research thus concerns various contexts and explorations of corporate power and explores the concept of recurring forms of corporate ingression as a new perspective within literary postcolonial and globalisation studies.
Oil on Water (2010) as a political novel explores the complex intricacies of communities structured around corporate power and presents a full account of the stakeholders that are influenced by or connected to the Niger Delta’s oil industry. Moxyland (2008) as a futuristic cyberpunk novel nuances the destruction implied in Oil on Water as a major factor of corporate ingression by exploring corporate power’s potential for constructive influence over a community. The Thousand Autumns (2010) as a historical novel explores an instance of corporate ingression in which the Dutch East India Company in Japan, despite its significant cultural influence, is subordinate to the host state to its activity. Corporate power is explored as a fallible construction that can be controlled by a strong regime as well as benefited from.
Despite the geographic and temporal distance between the three cases, and despite their exploration of widely differing industries, circumstances and levels of success, the common factors remain recognisable. Critical analysis shows that the contrasts between especially the constructive and destructive corporate activity in the three texts is of great interest, as it highlights the potential of corporate power both for construction and destruction of value. This research also shows how each novel actively resists a binary ethical narrative, instead presenting a set of complex power dynamics within the respective communities.
With this research I show that reading corporate ingression both significantly informs the reading of various postcolonial texts, while also showing that the analysis of these texts reveals that a conventional postcolonial binary approach is insufficient to account for what these works describe and investigate. The concept of a process of corporate ingression as a new perspective on literary explorations of historical, contemporary or futuristic forms of corporate power is thus shown to be a relevant addition to current postcolonial literary scholarship.
The brain is a large complex system which is remarkably good at maintaining stability under a wide range of input patterns and intensities. In addition, such a stable dynamical state is able to sustain essential functions, including the encoding of information about the external environment and storing memories. In order to succeed in these challenging tasks, neural circuits rely on a variety of plasticity mechanisms that act as self-organizational rules and regulate their dynamics. Based on toy models of self-organized criticality, this stable state has been proposed to be a phase transition point, poised between distinct types of unhealthy dynamics, in what has become known as the critical brain hypothesis. It is not yet known, however, if and how self-organization could drive biological neural networks towards a critical state while maintaining or improving their learning and memory functions.
Here, we investigate the emergence of criticality signatures in the form of neuronal avalanches due to self-organizational plasticity rules in a recurrent neural network. We show that power-law distributions of events, widely observed in experiments, arise from a combination of biologically inspired synaptic and homeostatic plasticity but are highly dependent on the external drive. Additionally, we describe how learning abilities and fading memory emerge and are improved by the same self-organizational processes. We finally propose an application of these enhanced functions, focusing on sequence and simple language learning tasks.
Taken together, our results suggest that the same self-organizational processes can be responsible for improving the brain’s spatio-temporal learning abilities and memory capacity while also giving rise to criticality signatures under particular input conditions, thus proposing a novel link between such abilities and neuronal avalanches. Although criticality was not verified, the detailed study of self-organization towards critical dynamics further elucidates its potential emergence and functions in the brain.
Als Plasmafenster wird ein Aufbau bezeichnet, welcher zwei Bereiche unterschiedlicher Drücke voneinander trennt, Teilchenstrahlen jedoch nahezu verlustfrei passieren lässt.
Diese Anwendung einer kaskadierten Bogenentladung wurde von A. Hershcovitch vorgeschlagen.
Im Rahmen dieser Arbeit wurde ein solches Plasmafenster mit Kanaldurchmessern von 3.3 mm und 5.0 mm aufgebaut sowie die erreichbaren Druckunterschiede untersucht.
Auf der Bestimmung des Einflusses der Plasmaparametern und deren Abhängigkeit von äußeren Parametern auf die erreichbare Trennung der Druckbereiche liegt der Schwerpunkt dieser Arbeit.
Ein ausgeklügeltes optisches System ermöglicht die simultane Aufnahme mehrerer Spektren entlang der Entladungsachse, welche die gleichzeitige Bestimmung der Elektronendichte und -temperatur ermöglichen.
Für die Analyse der Plamaparameter aus über 6700 Spektren wird eine selbst entwickelte Software genutzt.
Die gemessenen Elektronendichte reicht von 8e14 cm^-3 bis zu 4.2e16 cm^-3.
Sie skaliert sowohl mit der Entladungsstromstärke als auch dem Teilchenfluss.
Für die Elektronentemperatur stellen sich Werte zwischen 1 eV und 1.3 eV ein, sie variiert nur leicht mit der Stromstärke und dem Teilchenfluss.
Wie später gezeigt wird, stimmen die hier präsentierten Daten gut mit Ergebnissen aus Simulationen und Experimenten anderer Arbeitsgruppen überein.
Als Betriebsgas wurde eine 98%Ar-2%H2 Mixtur genutzt, da die Stark-Verbreiterung der H-beta-Linie sowie die physikalischen Eigenschaften von Argon gut beschrieben sind und somit eine akkurate Elektronendichte- und -temperaturbestimmung ermöglichen.
Während die Drücke auf der Niederdruckseite einigen mbar entsprechen, werden auf der Hochdruckseite Drücke bis zu 750 mbar bei Teilchenflüsse zwischen 4.5e20 s^-1 und 18e20 s^-1 sowie Stromstärken von 45 A bis 60 A erreicht.
Die erzielten Druckverhältnisse entsprechen Werten zwischen 40 und 150, was eine Steigerung um einen Faktor von bis zu 12 gegenüber dem Druckverhältnis einer einfachen differentiellen Pumpstufe entspricht.
Zusätzlich zur Trennung der Druckbereiche kann am vorgestellten Experiment die Starkverbreiterung von Emissionslinien untersucht werden.
Vorteilhaft gegenüber anderen Aufbauten ist hier die Möglichkeit, zeitgleich Spektren unterschiedlicher Elektronendichten aufzunehmen.
Die entwickelte Software ist in der Lage, akkurate Halbwertsbreiten zu bestimmen und daher für eine solche Anwendung gut geeignet.
Alleinstellungsmerkmale dieses Aufbaus sind unter anderem die angesprochene Möglichkeit der simultanen Bestimmung von Plasmaparamertern und Linienverbreiterungen sowie der Verzicht auf Keramikisolatoren zwischen den Kühlplatten des Aufbaus.
Optische Analysen ergaben keine signifikante Schädigung der Bestandteile des Aufbaus nach einer Betriebsdauer von über 10 h; einzig die Kathodenspitzen müssen alle 5 h ausgetauscht werden.
Im Rahmen der hier vorgestellten Arbeit wurden eine Master- sowie Bachelorarbeit betreut und erfolgreich zum Abschluss gebracht.
Wie im Rahmen dieser Arbeit gezeigt, ist das entwickelte Plasmapfenster in der Lage, zwei Bereiche unterschiedlicher Drücke zu trennen und diese Trennung sicher aufrecht zu erhalten.
Die zugrundeliegenden Plasmaparameter sind erforscht und ihr Einfluss auf die Trennungseigentschaft des Plasmafensters beschrieben.
Als nächsten Schritt bietet sich die Erschließung technischer Einsatzmöglichkeiten des Plasmafensters an, so könnte dieses als Plasmastripper oder zum Schutz einer Beschleunigerstruktur vor durch Kollisionsexperimente entstandene radioaktive Isotope oder Sekundärteilchen.
Zugegeben, ich habe mich einmal lustig gemacht über die wachsende Zahl der "Handbücher", habe über die jedermann altersgemäß zukommende Festschrift gespottet, aber gleichzeitig an Handbüchern und Festschriften mitgearbeitet. Den darin steckenden Widerspruch kann ich nicht auflösen. Doch loben darf man, wenn es etwas zu loben gibt: Das vorliegende dreibändige Handbuch verdient große Bewunderung. Seine 2538 Seiten geben einen bisher nicht möglichen Überblick über die äußere und innere Geschichte der Verwaltungsgerichtsbarkeit im In- und Ausland. Die Bände sind übersichtlich gegliedert. Der erste Band enthält in kleinen, monographisch gestalteten Aufsätzen die "Vorgeschichte" im Alten Reich und im 19. Jahrhundert (Teil I), dann – nach 1871 – die ersten reichsweiten Verwaltungskontrollen, im Schwerpunkt aber in 17 Abschnitten die Geschichte der Verwaltungsgerichtsbarkeiten aller deutschen Länder und der Hansestädte bis zur Gegenwart (Teil II). Dabei steht Baden bekanntlich an der Spitze, und Preußen mit seinem Oberverwaltungsgericht bildet das Schwergewicht. Wir erfahren auf dem Weg über Hessen-Darmstadt, Württemberg und Bayern, Sachsen und Thüringen bis in die letzten Winkel kleinstaatlicher Verhältnisse, wie es unter den besonderen staatsrechtlichen Bedingungen des deutschen Föderalismus dazu kam, das noch in der Paulskirche favorisierte justizstaatliche Modell (§ 182) schrittweise durch eigenständige Verwaltungsgerichte zu ersetzen und die dort zunächst noch kompromisshaft zugelassene erstinstanzliche Dominanz der Verwaltung abzubauen. Dieser Prozess war langwierig. Nicht nur der Problemdruck der Streitfälle war in Preußen, Bremen oder Mecklenburg unterschiedlich, ebenso die Verfassungslage von Reich und Ländern nach 1871 und 1918, die parteipolitische Landschaft war ungleich, und es fehlte lange an einer obersten Instanz auf Reichsebene. Das nach dem "Anschluss" Österreichs von 1938 und dann 1941 noch gegen die NSDAP geschaffene, aber mit einem Mann aus dem "Braunen Haus" unglücklich besetzte Reichsverwaltungsgericht konnte diese Vereinheitlichung nicht leisten. ...
The relationship between past and present has been the subject of controversial debates in historical research time and again. In 2013, to give a prominent example, Philip Alston in a review essay discussed the issue of "Does the past matter?" with regard to a debate on the origins of human rights. The debate was dedicated to the controversial question of "[h]ow far back can we trace the genealogy of today’s international human rights system". In this review, I would like to rephrase this question to ask instead to what degree the present matters for historical writing. Other than in the work of Alston, this is not meant as a question on the contingency and path-dependence of history, but rather as a reflection on how historians describe and evaluate the past and what role knowledge of the present may have in this context. ...
CGC aktuell 02/2019
(2019)
Neuere Geschichten des Völkerrechts zeichnen sich dadurch aus, dass sie das Recht und dessen Wirksamkeit nicht losgelöst von sozialen und historischen Kontexten betrachten. In seinem beeindruckenden Buch "Frieden durch Recht?" über den Friedensschluss nach dem ersten Weltkrieg zeigt Marcus M. Payk (vgl. die Rezension in diesem Band), dass das Recht zwar über eine eigene Form und Logik verfügt, dessen Bindungswirkung aber nicht ohne dessen Kontexte verstanden werden kann. ...
GOeTHEO : Ausgabe 21
(2019)
Mit der vorliegenden monumentalen Monographie veröffentlicht der Verfasser, der seit Ende 2018 als Professeur agrégé de droit public an der Université Paris Saclay (Université d’Evry-Val d’Essonne) tätig ist, seine in Frankeich mehrfach ausgezeichnete thèse de doctorat aus dem Jahre 2015. Die Arbeit, die bereits vom amerikanischen Politikwissenschaftler Aurelian Craiutu begeistert rezensiert wurde (in: French Studies. A Quarterly Review 73,2 [2019] 335–336), verdient unbedingt auch einem deutschen Lesepublikum vorgestellt zu werden. Die zentrale These des Verfassers lautet, dass das englische parlamentarische System in der französischen Rechts- und politischen Kultur seit dem 18. Jahrhundert und über das ganze 19. Jahrhundert hinweg eine rechtspolitische Vorbildfunktion hatte. "Le modèle réformiste de la Constitution de l’Angleterre", lautet also das Fazit der Untersuchung, "a intellectuellement dominé la France du XIXe siècle". ...
Verstanden die europäischen Invasoren und die Angehörigen indigener Völker in Amerika sich eigentlich, wenn sie Verträge schlossen, über Rechte verhandelten, vor Gericht miteinander stritten? Fanden sie einen middle ground oder agierten sie nach dem Prinzip des code switching? Diese Fragen stehen im Mittelpunkt des von den US-amerikanischen Rechtshistorikern Brian P. Owensby und Richard J. Ross herausgegebenen Bandes Justice in a New World. Negotiating Legal Intelligibility in British, Iberian, and Indigenous America. Sieben Fallstudien rekonstruieren Momente der rechtlichen Interaktion zwischen Angehörigen indigener Gemeinschaften und Euro-Amerikanern in Anglo- und Iberoamerika zwischen dem 16. und dem 19. Jahrhundert. Sie werden gerahmt von einleitenden Überlegungen der beiden Herausgeber zur Möglichkeit des Vergleichs zwischen britischen und iberischen Rechtsräumen sowie zwei zusammenfassenden Beobachtungen. ...
Purpose: The design of biorelevant conditions for in vitro evaluation of orally administered drug products is contingent on obtaining accurate values for physiologically relevant parameters such as pH, buffer capacity and bile salt concentrations in upper gastrointestinal fluids.
Methods: The impact of sample handling on the measurement of pH and buffer capacity of aspirates from the upper gastrointestinal tract was evaluated, with a focus on centrifugation and freeze-thaw cycling as factors that can influence results. Since bicarbonate is a key buffer system in the fasted state and is used to represent conditions in the upper intestine in vitro, variations on sample handling were also investigated for bicarbonate-based buffers prepared in the laboratory.
Results: Centrifugation and freezing significantly increase pH and decrease buffer capacity in samples obtained by aspiration from the upper gastrointestinal tract in the fasted state and in bicarbonate buffers prepared in vitro. Comparison of data suggested that the buffer system in the small intestine does not derive exclusively from bicarbonates.
Conclusions: Measurement of both pH and buffer capacity immediately after aspiration are strongly recommended as “best practice” and should be adopted as the standard procedure for measuring pH and buffer capacity in aspirates from the gastrointestinal tract. Only data obtained in this way provide a valid basis for setting the physiological parameters in physiologically based pharmacokinetic models.
In the recent historiography on the canon law of the early modern Spanish Empire, legal historians have been considering many forms of normativity. Nevertheless, law still remains, and there is no reason to think otherwise, as a primary source of legal orders. In the case of canon law, many of the legislations drafted remained largely unknown due to their lack of recognitio by the Holy See and pase regio granted by the Spanish Monarch. Such texts were not printed and only circulated in manuscript form, likely resulting in a very low and uncertain degree of compliance. During the 20thcentury, gradually but fragmentally, many of these texts became known in academic publications. The book reviewed here finally gathers together in a single volume all the legislative texts drafted at church assemblies celebrated in the archdiocese of Santafé (today Bogotá) before 1625. ...
The particle-in-cell (PIC) method was developed to investigate microscopic phenomena, and with the advances in computing power, newly developed codes have been used for several fields, such as astrophysical, magnetospheric, and solar plasmas. PIC applications have grown extensively, with large computing powers available on supercomputers such as Pleiades and Blue Waters in the US. For astrophysical plasma research, PIC methods have been utilized for several topics, such as reconnection, pulsar dynamics, non-relativistic shocks, relativistic shocks, and relativistic jets. PIC simulations of relativistic jets have been reviewed with emphasis placed on the physics involved in the simulations. This review summarizes PIC simulations, starting with the Weibel instability in slab models of jets, and then focuses on global jet evolution in helical magnetic field geometry. In particular, we address kinetic Kelvin-Helmholtz instabilities and mushroom instabilities.
Background: Although mechanistic target of rapamycin (mTOR) inhibitors, such as temsirolimus, show promise in treating bladder cancer, acquired resistance often hampers efficacy. This study evaluates mechanisms leading to resistance. Methods: Cell growth, proliferation, cell cycle phases, and cell cycle regulating proteins were compared in temsirolimus resistant (res) and sensitive (parental—par) RT112 and UMUC3 bladder cancer cells. To evaluate invasive behavior, adhesion to vascular endothelium or to immobilized extracellular matrix proteins and chemotactic activity were examined. Integrin α and β subtypes were analyzed and blocking was done to evaluate physiologic integrin relevance. Results: Growth of RT112res could no longer be restrained by temsirolimus and was even enhanced in UMUC3res, accompanied by accumulation in the S- and G2/M-phase. Proteins of the cdk-cyclin and Akt-mTOR axis increased, whereas p19, p27, p53, and p73 decreased in resistant cells treated with low-dosed temsirolimus. Chemotactic activity of RT112res/UMUC3res was elevated following temsirolimus re-exposure, along with significant integrin α2, α3, and β1 alterations. Blocking revealed a functional switch of the integrins, driving the resistant cells from being adhesive to being highly motile. Conclusion: Temsirolimus resistance is associated with reactivation of bladder cancer growth and invasive behavior. The α2, α3, and β1 integrins could be attractive treatment targets to hinder temsirolimus resistance.
Is it true that speed bumps level the playing field, make financial markets more stable and reduce negative externalities of high-frequency trading (HFT) firms? We examine how the implementation of a particular speed bump – Midpoint Extended Life order (M-ELO) on Nasdaq impacted financial markets stability in terms of occurrences of mini-flash crashes in individual securities. We use high-frequency order book message data around the implementation date and apply difference-in-differences analysis to estimate the average treatment effect of the speed bump on market stability and liquidity provision. The results suggest that the introduction of the M-ELO decreases the average number of crashes on Nasdaq compared to other exchanges by 4.7%. Liquidity provision by HFT firms also improves. These findings imply that technology-based solutions by exchanges are feasible alternatives to regulatory intervention towards safer markets.
We study the accuracy and usefulness of automated (i.e., machine-generated) valuations for illiquid and heterogeneous real assets. We assemble a database of 1.1 million paintings auctioned between 2008 and 2015. We use a popular machine-learning technique—neural networks—to develop a pricing algorithm based on both non-visual and visual artwork characteristics. Our out-of-sample valuations predict auction prices dramatically better than valuations based on a standard hedonic pricing model. Moreover, they help explaining price levels and sale probabilities even after conditioning on auctioneers’ pre-sale estimates. Machine learning is particularly helpful for assets that are associated with high price uncertainty. It can also correct human experts’ systematic biases in expectations formation—and identify ex ante situations in which such biases are likely to arise.
In this study, we investigate the wealth decumulation decision from the perspective of a retiree who is averse to the prospect of fully annuitizing her accumulated savings. We field a large online survey of hypothetical product choices for phased drawdown offerings and annuities. While the demand for annuities remains low in our sample, we find significant demand for phased withdrawal products with equity-based asset allocations and flexible payout structures. Consistent with the product choice, the most important self-reported considerations for the wealth decumulation decision are low default risk in the products they purchase, the size of the withdrawal rates, and flexibility in the timing of their withdrawal. As determinants of the decision of how much wealth individuals are willing to draw down, we identify consumers’ attitudes towards future economic conditions, the extent to which they are protected against longevity risk, and their desire to leave bequests. Policy implications are discussed.
Many processes in living cells involve interaction and cooperation of multiple proteins to fulfill a specific function. To understand biological processes in their full complexity, it is not sufficient to only identify the molecules being involved but also to understand the kinetic aspects of a reaction. Mass spectrometry (MS) is a very powerful tool which allows to precisely identify the molecules of a reaction. Usually this is done with tandem-MS experiments for purpose of de-novo peptide sequencing. However, since this involves protein digestion, a statement of the in-vivo constitution of non-covalently bound protein complexes is not possible. In order to detect an intact protein complex it is necessary to analyze the biological system softly and in a near-native environment with native MS. Native MS allows the non-destructive analysis of these non-covalent protein complexes as well as to detect their components. However, up to now native MS does not offer a possibility to resolve the timing of the constitution of protein complexes on a fast time-scale. Therefore, the progress of reactions on fast time-scales is invisible. However, a method which delivers both types of information - identification of the components of a protein complex, as well as time-resolving their interaction - would be of high interest.
A suitable ionization technique for native MS is laser-induced liquid-bead ion desorption (LILBID). LILBID employs well-defined droplets which are irradiated by IR laser pulses to generate gas phase ions. The not-continuous, repetitive nature of ion generation offers itself to the development of a time-resolved (TR) native MS system which is able to investigate protein complexes on a fast time scale. The LILBID-droplets can serve as reaction vessels if they are levitated in an electrodynamic Paul-trap. This new setup would allow sample manipulation and MS analysis on precise and fast reaction time-scales. The first part of this dissertation presents the construction and characterization of a setup for TR-LILBID-MS.
An example for a complex biological system is the self-assembly of beta-amyloid (Aβ). This small peptide is the major component in plaques related to Alzheimer’s disease. Clinically relevant is especially the 42 amino acid peptide Aβ42 which aggregates from monomers to oligomers through to fibrils. The oligomers are the neurotoxic species in this process and thus of high interest. Nevertheless, standard analytical techniques are unable to detect those oligomers which makes MS an optimal tool to study the oligomerization process of Aβ with the focus on disease relevant oligomers. TR-LILBID-MS allows to follow the oligomerization of Aβ enabling to study molecules which influence this kinetic. Combining MS with ion-mobility spectrometry adds an additional dimension - the collision cross section - to the mass-to-charge ratio obtained from MS. Therewith structural alterations induced by ligands can be correlated to differences in the aggregation kinetic. This allows to draw a picture of the aggregation process of Aβ for the development of disease-relevant small oligomers on a molecular level.
Die in der vorliegenden Arbeit gewonnenen Erkenntnisse zur Reaktivität zweifach reduzierter 9,10-Dihydro-9,10-diboraanthracene [A]2– erweitern das Einsatzspektrum von Hauptgruppenverbindungen im Hinblick auf die Aktivierung kleiner Moleküle. Komplementär zu Übergangsmetallkomplexen und FLPs ermöglichen die Salze M2[A] (M+ = Li+, Na+, K+) die Entwicklung neuartiger Synthesestrategien. Als besondere Herausforderung gilt die Aktivierung des stabilen H2-Moleküls, dessen Bindung die Dianionen [A]2– homolytisch in einer konzertierten Reaktion spalten.
Untersuchungen zur Kinetik der H2-Addition an M2[A] stellten die Abhängigkeit dieses Reaktionsschritts vom borgebundenen Substituenten und vom Kation heraus. Eine geringe sterische Abschirmung der Boratome durch kleine borgebundene Substituenten (C≡CtBu, Me, H) begünstigt die H2-Aufnahme gegenüber großen Substituenten (pTol, Xyl, Et). Die maximale Ausbeute an M2[A-H2] wird für M+ = Li+ erst nach mehreren Tagen bei 100 °C erhalten, während einige Stunden bei nur 50 °C für die quantitative Bildung von K2[A-H2] ausreichen.
Unter den Salzen M2[A] eignet sich Li2[68] mit borgebundenen Me-Substituenten besonders gut für den Einsatz als Hydrierungskatalysator. Mit Li2[68] konnten das Imin Ph(H)C=NtBu, das terminale Alken Ph2C=CH2 und Anthracen erfolgreich im NMR-Maßstab hydriert werden (Katalysatorladung 37 mol%, THF-d8, 1 atm H2-Initialdruck, 100 °C, 16 h). Im Reaktionsautoklaven war für die Hydrierung von Ph(H)C=NtBu eine Verringerung der Katalysatorladung auf 10 mol% Li2[68] möglich (THF, 7 atm H2-Initialdruck, 100 °C, 18 h). Konkurrenzreaktionen begründen Einschränkungen in Bezug auf die Substratpalette, da M2[68] (M+ = Li+, Na+) mit elektronenarmen ungesättigten Verbindungen, die C=C-, C≡C-, C=O- oder C=N-Bindungen enthalten, [4+2]-Cycloadditionsprodukte bilden können. Die Reversibilität dieser Reaktion entscheidet, ob Li2[68] als Katalysator fungiert oder irreversibel in den Strukturen gebunden bleibt.
Vielseitiger sind die H2-Aktivierungsprodukte M2[A-H2] als H–-Donoren geeignet: Na2[68-H2] ersetzt Halogenid- durch H–-Substituenten in Bromethan, sowie in Chlorsilanen und PCl3; CO2 wird in Natriumformiat überführt. Unabhängig von der Anzahl der Chlorliganden werden die Produkte immer vollständig hydriert. Eine erneute Reduktion von 68 kann wieder Na2[68] bereitstellen, das H2 aufnimmt und Na2[68-H2] regeneriert, welches für neue H–-Abgaben zur Verfügung steht. Bei der experimentellen Umsetzung des Kreislaufs ist es wichtig, die beschriebenen Reaktionsschritte nacheinander auszuführen und jeweils nur stöchiometrische Mengen des Elektrophils zuzugeben. Bei Abweichungen vom schrittweisen Syntheseprotokoll finden formale nukleophile Substitutionen mit M2[68] statt und monoanionische Spezies entstehen, z. B. wenn Et3SiBr als Elektrophil anwesend ist.
Gegenüber CO2 zeigt Li2[68] eine hohe Reaktivität, durch die selektiv CO und [CO3]2– gebildet werden. Wie zuvor bei den H–-Transferreaktionen ermöglicht die Reduktion der Neutralverbindung 68 die Regeneration von Li2[68].
Die Dianionen [A]2– stechen unter anderen cyclischen Borverbindungen in niedrigen Oxidationsstufen heraus, da mit [A]2– nicht nur die Aktivierung von H2 oder CO2 gelang, sondern erstmalig über die Einbindung der Additionsprodukte in zum Teil katalytische Folgereaktionen berichtet werden konnte.
Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.
Purpose: Bacterial biofilms are a major problem in the treatment of infected dental and orthopedic implants. The purpose of this study is to investigate the cleaning effect of an electrolytic approach (EC) compared to a powder-spray system (PSS) on titanium surfaces. Materials and Methods: The tested implants (different surfaces and alloys) were collated into six groups and treated ether with EC or PSS. After a mature biofilm was established, the implants were treated, immersed in a nutritional solution, and streaked on Columbia agar. Colony-forming units (CFUs) were counted after breeding and testing (EC), and control (PSS) groups were compared using a paired sample t-test. Results: No bacterial growth was observed in the EC groups. After thinning to 1:1,000,000, 258.1 ± 19.9 (group 2), 264.4 ± 36.5 (group 4), and 245.3 ± 40.7 (group 6) CFUs could be counted in the PSS groups. The difference between the electrolytic approach (test groups 1, 3, and 5) and PSS (control groups 2, 4, and 6) was statistically extremely significant (p-value < 2.2 × 10−16). Conclusion: Only EC inactivated the bacterial biofilm, and PSS left reproducible bacteria behind. Within the limits of this in vitro test, clinical relevance could be demonstrated.
Formation of the anteroposterior and dorsoventral body axis in Caenorhabditis elegans depends on cortical flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization after formation of cell-cell contacts is not fully understood. Here, we demonstrate that planar asymmetries are established during left-right symmetry breaking: Centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) from contacts to the medial cortex, resulting in their unmixing from apical myosin. Contact localization and advection of PAR-6 requires balanced CDC-42 activation, while asymmetric retention and advection of PAR-3 can occur independently of PAR-6. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1 and opposing retention of antagonistic CDC-42 and Wnt pathway components leads to planar asymmetries. The most obvious mark of planar asymmetry, retention of PAR-3 at a single cell-cell contact, is required for proper cytokinetic cell intercalation. Hence, our data uncover how planar polarity is established in a system without the canonical planar cell polarity pathway through planar asymmetric retention of aPARs.
Die Dissertation (Universität Eichstätt-Ingolstadt) beginnt mit dem Satz "Am Ende stritt man um Akten" und endet auf Seite 483 mit eben dem gleichen Satz. Zwischen Anfang und Ende dieser akribisch gearbeiteten Publikation, die Denzler bescheiden eine "Studie" nennt, werden die massenweise in den Archiven vorhandenen Akten, die während der letzten Visitation des Reichskammergerichts von 1767–1776 produziert wurden, nach ihrer Entstehung und Funktion untersucht. Als Leitbild der Untersuchung dient der "Reformhorizont" der Aufklärung, vor dessen Hintergrund das Visitationsgeschehen in Gestalt seiner Hand- und Druckschriften analysiert wird. "Reform"-zeiten, -räume, -akteure, -verfahren sowie -inhalte geben dem engagiert geschriebenen Buch eine klare Gliederung für die Untersuchung aller Schriftgattungen von den Protokollen, Schreiben, Diktaten, Abschriften, Diarien, Korrespondenzen, Instruktionen, Berichten bis zu Gutachten und Notizen, die alle das Visitationsgeschehen in und als "Akten" repräsentieren: 562 Aktenbündel; von 1056 Sitzungen sind 13 Bände Beratungsprotokolle überliefert, die 15732 Folioseiten umfassen; 50 Visitationsbeschlüsse liegen vor; die schriftlichen Befragungen von 92 Gerichtsmitgliedern ergaben 25000 Antworten (355, 478); hinzu kommen noch die Produktion aus der visitationseigenen Druckerei sowie 200 Einzelpublikationen zur Visitation und eine visitationseigene Zeitschrift als schriftliches Untersuchungsmaterial. Daraus entsteht ein höchst umfassendes und anschauliches Bild über Medientechnik, Schriftkultur, Justizkontrolle und Dienstaufsicht im Rahmen der Visitation. Aus dem quantitativen Befund in diesem "tintenklecksenden Saeculum", wie es Schiller genannt hat, leitet Denzler die These ab, dass die Visitation von 1767 eine enorme Vermehrung und Aufwertung von Schriftlichkeit schlechthin dokumentiert (16). Vor diesem Hintergrund soll die alltägliche Bedeutung der Schriftlichkeit für die Visitation analysiert und der "Entstehungs- und Überlieferungskontext" möglichst genau im "Schriftalltag" rekonstruiert werden. Dieser "Schriftalltag" reflektiert auch den Justizalltag in seiner rechtshistorischen Bedeutung. Diesen zu beschreiben ist zwar nicht Denzlers vorrangiges Ziel, aber die Kulturgeschichte des Geschriebenen beleuchtet und ergänzt die Geschichte der Rechtspraxis am Beispiel der Visitation von 1767 in vielfältiger Weise. Das belegen auch das reiche Quellen- und Literaturverzeichnis (489–562) und die Statistiken über Personalia, Visitationskosten, Examina, Gesandtschaftsquartiere, Verfahren usw. (565–604). ...
A twentieth century-long coupled atmosphere-ocean regional climate simulation with COSMO-CLM (Consortium for Small-Scale Modeling, Climate Limited-area Model) and NEMO (Nucleus for European Modelling of the Ocean) is studied here to evaluate the added value of coupled marginal seas over continental regions. The interactive coupling of the marginal seas, namely the Mediterranean, the North and the Baltic Seas, to the atmosphere in the European region gives a comprehensive modelling system. It is expected to be able to describe the climatological features of this geographically complex area even more precisely than an atmosphere-only climate model. The investigated variables are precipitation and 2 m temperature. Sensitivity studies are used to assess the impact of SST (sea surface temperature) changes over land areas. The different SST values affect the continental precipitation more than the 2 m temperature. The simulated variables are compared to the CRU (Climatic Research Unit) observational data, and also to the HOAPS/GPCC (Hamburg Ocean Atmosphere Parameters and Fluxes from Satellite Data, Global Precipitation Climatology Centre) data. In the coupled simulation, added skill is found primarily during winter over the eastern part of Europe. Our analysis shows that, over this region, the coupled system is dryer than the uncoupled system, both in terms of precipitation and soil moisture, which means a decrease in the bias of the system. Thus, the coupling improves the simulation of precipitation over the eastern part of Europe, due to cooler SST values and in consequence, drier soil.
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 form a commercial, regulatory and monetary policy perspective.
Wir lassen die überwältigende Fülle an Werken im Arsenale hinter uns. Das Ziel sind die Giardini, der ursprüngliche und neben dem Arsenale zweite große Ausstellungsort der Kunstschau. Dort befindet sich einer der Hauptanziehungspunkte der Biennale: Im Zentralpavillon steht die in den Medien bereits oft erwähnte und gezeigte sogenannte "Blutmaschine". Ein riesiger Roboterarm mit überdimensionaler Wischschaufel, wirkt sie in ihrer Motorik dennoch ausgesprochen menschlich. Die 32 Bewegungen, die das chinesische Künstlerduo Sun Yuan und Peng Yu dem Industrieroboter "in den Leib" programmiert haben, erinnern an Winken, Tanzen, Po-Wackeln, Innehalten und Überlegen. ...
Local crowding out in China
(2019)
In China, between 2006 and 2013, local public debt crowded out the investment of private firms by tightening their funding constraints, while leaving state-owned firms’ investment unaffected. We establish this result using a purpose-built dataset for Chinese local public debt. Private firms invest less in cities with more public debt, the reduction in investment being larger for firms located farther from banks in other cities or more dependent on external funding. Moreover, in cities where public debt is high, private firms’ investment is more sensitive to internal cash flow, also when cash-flow sensitivity is estimated jointly with the probability of being credit-constrained.