Taming Travel Time Fluctuations through Adaptive Stop Pooling

Ride sharing services combine trips of multiple users in the same vehicle and may provide more sustainable transport than private cars. As mobility demand varies during the day, the travel times experienced by passengers may substantially vary as well, making the service quality unreliable. We show through model simulations that such travel time fluctuations may be drastically reduced by stop pooling. Having users walk to meet at joint locations for pick-up or drop-off allows buses to travel more direct routes by avoiding frequent door-to-door detours, especially during high demand. We in particular propose adaptive stop pooling by adjusting the maximum walking distance to the temporally and spatially varying demand. The results highlight that adaptive stop pooling may substantially reduce travel time fluctuations while even improving the average travel time of ride sharing services, especially for high demand. Such quality improvements may in turn increase the acceptance and adoption of ride sharing services

Charakterisierung von Pathogenese und Prävention des zerebralen Vasospasmus im akuten und fixierten Hirnschnittmodell der Maus

Die Subarachnoidalblutung (SAB) nach Aneurysmaruptur geht mit einer hohen präklinischen Mortalität einher. Die Spätfolgen sind mit massiven körperlichen und psychischen Beeinträchtigungen assoziiert. Von besonderem Interesse ist der zerebrale Vasospasmus, eine Verengung großer zerebraler Arterien, die typischerweise einige Tage nach SAB auftritt und oftmals von einer zerebralen Ischämie begleitet wird. Durch diese zeitliche Abfolge eröffnet sich ein potentielles therapeutisches Zeitfenster für Präventivmaßnahmen gegen diese schwerwiegende Komplikation. Es gibt verschiedene Ansätze zur Erklärung der noch nicht vollständig nachvollzogenen pathogenetischen Hintergründe des Vasospasmus. Fokus dieser Arbeit sind Hämabbauprodukte (heme degradation products, HDPs), die im Subarachnoidalraum von SAB-Patienten zu finden sind und BK-Kaliumkanäle hemmen, welche unter physiologischen Bedingungen den Ruhetonus glatter Gefäßmuskelzellen beeinflussen. In den ersten drei Teilprojekten dieser Arbeit wurde mittels DIC-Mikroskopie die zeitliche Änderung des Gefäßdurchmessers intrakortikaler Arteriolen akuter Maushirnschnitte untersucht. Hierfür erfolgte die Applikation des vasokonstriktiv wirkenden HDPs Propentdyopent A (PDP A), sowohl bei simultaner Applikation von Rho-Kinase- bzw. Kir-Kanal-Inhibitoren, als auch an Hirnschnitten eines zellspezifischem BK-Kanal-Knockout-Modells. Eine weitere Versuchsreihe befasste sich mit der Identifikation genetischer und altersassoziierter Modulatoren der neurovaskulären Gefäßreaktion. Auch die die langfristige Wirkung von HDPs auf zerebrale Gefäße wurde untersucht. Dazu wurden mittels konfokaler Laserscanmikroskopie morphologische Veränderungen großer zerebraler Arterien an fixierten Maushirnschnitten analysiert. Die Ergebnisse sprechen dafür, dass die Pathogenese des Vasospasmus ein Zusammenspiel aus kurzfristigen und längerfristigen Prozessen ist und vom Entstehen und Verbleiben von HDPs im Subarachnoidalraum maßgeblich mitbestimmt wird

Disfluencies in German adult- and infant-directed speech

Bellinghausen C, Betz S, Zahner K, Sasdrich A, Schröer M, Schröder B. Disfluencies in German adult- and infant-directed speech. In: Proceedings of SEFOS: 1st International Seminar on the Foundations of Speech. Breathing, Pausing and The Voice. 2019: 44-46

Identifying the threshold to sustainable ridepooling

Ridepooling combines trips of multiple passengers in the same vehicle and may thereby provide a more sustainable option than transport by private cars. The efficiency and sustainability of ridepooling is typically quantified by key performance indicators such as the average vehicle occupancy or the total distance driven by all ridepooling vehicles relative to individual transport. However, even if the average occupancy is high and rides are shared, ridepooling services may increase the total distance driven due to additional detours and deadheading. Moreover, these key performance indicators are difficult to predict without large-scale simulations or actual ridepooling operation. Here, we propose a dimensionless parameter to estimate the sustainability of ridepooling by quantifying the load on a ridepooling service, relating characteristic timescales of demand and supply. The load bounds the relative distance driven and uniquely marks the break-even point above which the total distance driven by all vehicles of a ridepooling service falls below that of motorized individual transport. Detailed event-based simulations and a comparison with empirical observations from a ridepooling pilot project in a rural area of Germany validate the theoretical prediction. Importantly, the load follows directly from a small set of aggregate parameters of the service setting and is thus predictable a priori. The load may thus complement standard key performance indicators and simplify planning, operation and evaluation of ridepooling services

Xe Irradiation of Graphene on Ir(111): From Trapping to Blistering

Using X-ray photoelectron spectroscopy, thermal desorption spectroscopy, and scanning tunneling microscopy we show that upon keV Xe + irradiation of graphene on Ir(111), Xe atoms are trapped under the graphene. Upon annealing, aggregation of Xe leads to graphene bulges and blisters. The efficient trapping is an unexpected and remarkable phenomenon, given the absence of chemical binding of Xe to Ir and to graphene, the weak interaction of a perfect graphene layer with Ir(111), as well as the substantial damage to graphene due to irradiation. By combining molecular dynamics simulations and density functional theory calculations with our experiments, we uncover the mechanism of trapping. We describe ways to avoid blister formation during graphene growth, and also demonstrate how ion implantation can be used to intentionally create blisters without introducing damage to the graphene layer. Our approach may provide a pathway to synthesize new materials at a substrate - 2D material interface or to enable confined reactions at high pressures and temperatures

Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer

Fibulins (FBLNs), interacting with cell adhesion receptors and extracellular matrix (ECM) components, play multiple roles in ECM structures and tissue functions. Abnormal expression of FBLN2, one of the fibulin family members, contributes to tumor initiation and development. However, the function of FBLN2 in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we found that FBLN2 was downregulated in 9 out of 11 lung cancer cell lines compared to normal bronchial epithelial cells, which was associated with DNA hypermethylation. Primary lung squamous cell carcinoma expressed significantly more FBLN2 protein compared to adenocarcinoma ( p = 0.047). Ectopic expression of FBLN2 led to decreased cell proliferation, migration and invasion, accompanied by inactivated MAPK/ERK and AKT/mTOR pathways, while FBLN2 siRNA knockdown resulted in an opposite biological behaviour in NSCLC cells. Additionally, overexpression of FBLN2 led to dysregulation of cell adhesion molecules, ECM markers and a panel of lysate/exosome-derived-microRNAs, which are involved in cell adhesion and ECM remodelling. Taken together, our data indicate that FBLN2 is methylated and exerts a tumor suppressor function through modulation of MAPK/ERK and AKT pathways and regulation of cell adhesion and ECM genes. Moreover, FBLN2 might be a potential biomarker for the sub-classification of NSCLC

Utilisation of rehabilitation services for non-migrant and migrant groups of higher working age in Germany - results of the lidA cohort study

Background: An ageing and a shrinking labour force implies that the prevention of a premature exit from work due to poor health will become more relevant in the future. Medical rehabilitation is a health service that aims at active participation in working life. The provision of this service will be relevant for an increasing part of the ageing labour force, namely, employees with a migrant background and their different subgroups. Thus, this study examines whether first- and second-generation employees with migrant background differ from non-migrants in their utilisation of rehabilitation services and whether within the subsample of migrant employees, those persons with foreign nationality differ from those with German nationality. Methods: Socially insured employees born in 1959 or 1965 were surveyed nationwide in 2011 as part of the lidA cohort study (n=6303). Survey data of the first study wave were used to identify the dependent variable of the utilisation of rehabilitation (in- and outpatient), the independent variable of migrant status and the covariates of sociodemographic, work- and non-work-related factors. Applying bivariate statistics with tests of independence and block-wise logistic regressions, differences between the groups were investigated. Additionally, average marginal effects were computed to directly compare the adjusted models. Results: The study showed that first-generation migrants had a significantly lower likelihood of utilising outpatient rehabilitation than non-migrants (fully adj. OR 0.42, 95% CI 0.22-0.82) and that average marginal effects indicated higher differences in the full model than in the null model. No significant differences were found between the first- or second-generation migrants and non-migrants when comparing the utilisation of inpatient rehabilitation or any rehabilitation or when analysing German and foreign employees with migrant background (n=1148). Conclusions: Significant differences in the utilisation of outpatient rehabilitation between first-generation migrants and non-migrants were found, which could not be explained by sociodemographic, work- and non-work-related factors. Thus, further factors might play a role. The second-generation migrants resemble the non-migrants rather than their parent generation (first-generation migrants). This detailed investigation shows the heterogeneity in the utilisation of health services such as medical rehabilitation, which is why service sensitive to diversity should be considered

Natural variation of temperature acclimation of Arabidopsis thaliana

Acclimation is a multigenic trait by which plants adjust photosynthesis and metabolism to cope with a changing environment. Here, natural variations of photosynthetic efficiency and acclimation of the central carbohydrate metabolism were analyzed in response to low and elevated temperatures. For this, 18 natural accessions of Arabidopsis thaliana, originating from Cape Verde Islands and Europe, were grown at 22°C before being exposed to 4°C and 34°C for cold and heat acclimation, respectively. Absolute amounts of carbohydrates were quantified together with their subcellular distribution across plastids, cytosol and vacuole. Linear electron transport rates (ETRs) were determined together with the maximum quantum efficiency of photosystem II (Fv/Fm) for all growth conditions and under temperature fluctuation. Under elevated temperature, ETR residuals under increasing photosynthetic photon flux densities significantly correlated with the degree of temperature fluctuation at the original habitat of accessions, indicating a geographical east/west gradient of photosynthetic acclimation capacities. Plastidial sucrose concentrations positively correlated with maximal ETRs under fluctuating temperature, indicating a stabilizing role within the chloroplast. Our findings revealed specific subcellular carbohydrate distributions that contribute differentially to the photosynthetic efficiency of natural Arabidopsis thaliana accessions across a longitudinal gradient. This sheds light on the relevance of subcellular metabolic regulation for photosynthetic performance in a fluctuating environment and supports the physiological interpretation of naturally occurring genetic variation of temperature tolerance and acclimation

Regulatory Function of Sympathetic Innervation on the Endo/Lysosomal Trafficking of Acetylcholine Receptor

Recent studies have demonstrated that neuromuscular junctions are co-innervated by sympathetic neurons. This co-innervation has been shown to be crucial for neuromuscular junction morphology and functional maintenance. To improve our understanding of how sympathetic innervation affects nerve–muscle synapse homeostasis, we here used in vivo imaging, proteomic, biochemical, and microscopic approaches to compare normal and sympathectomized mouse hindlimb muscles. Live confocal microscopy revealed reduced fiber diameters, enhanced acetylcholine receptor turnover, and increased amounts of endo/lysosomal acetylcholine-receptor-bearing vesicles. Proteomics analysis of sympathectomized skeletal muscles showed that besides massive changes in mitochondrial, sarcomeric, and ribosomal proteins, the relative abundance of vesicular trafficking markers was affected by sympathectomy. Immunofluorescence and Western blot approaches corroborated these findings and, in addition, suggested local upregulation and enrichment of endo/lysosomal progression and autophagy markers, Rab 7 and p62, at the sarcomeric regions of muscle fibers and neuromuscular junctions. In summary, these data give novel insights into the relevance of sympathetic innervation for the homeostasis of muscle and neuromuscular junctions. They are consistent with an upregulation of endocytic and autophagic trafficking at the whole muscle level and at the neuromuscular junction

Hepatitis E virus: Efficacy of pasteurization of plasma‐derived VWF/FVIII concentrate determined by pig bioassay

Background Hepatitis E virus (HEV) is the leading cause of acute hepatitis throughout the world. Increasing blood component transfusion-associated HEV infections highlight the need for reliable virus inactivation procedures for plasma derivatives from pooled plasma donations. Study Design and Methods An animal infection study was conducted to evaluate the efficiency of HEV inactivation by pasteurization during the manufacturing process of the von Willebrand Factor/Factor VIII (VWF/FVIII) concentrate Haemate P/Humate-P (CSL Behring, Marburg, Germany). For this purpose, groups of pigs were inoculated with stabilized VWF/FVIII intermediate spiked with HEV-positive liver homogenate and exposed to increasing incubation times of 0, 3, 6, and 10 h at 60 degrees C. Animals were evaluated for virus replication over 27 days and in a subsequent trial over 92 days. Results Virus replication was detected in animals up to the 6-h pasteurization group. In contrast, pasteurization for 10 h did not reveal virus detection when the observation period was 27 days. In an additional experiment using the 10-h pasteurized material, two individuals started virus excretion and seroconverted when the observation period was extended to 92 days. Based on the total infection rate (2 of 12) of the animals inoculated with the sample pasteurized for 10 h, a virus reduction factor of at least 4.7 log(10) is calculated. Conclusion This study demonstrates that pasteurization at 60 degrees C for 10 h of an HEV-positive plasma derivative leads to the effective reduction of infectivity, resulting in a VWF/FVIII product with an appropriate margin of safety for HEV