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Paleoearthquakes and historic earthquakes are the most important source of information for the estimation of long-term earthquake recurrence intervals in fault zones, because corresponding sequences cover more than one seismic cycle. However, these events are often rare, dating uncertainties are enormous, and missing or misinterpreted events lead to additional problems. In the present study, I assume that the time to the next major earthquake depends on the rate of small and intermediate events between the large ones in terms of a clock change model. Mathematically, this leads to a Brownian passage time distribution for recurrence intervals. I take advantage of an earlier finding that under certain assumptions the aperiodicity of this distribution can be related to the Gutenberg-Richter b value, which can be estimated easily from instrumental seismicity in the region under consideration. In this way, both parameters of the Brownian passage time distribution can be attributed with accessible seismological quantities. This allows to reduce the uncertainties in the estimation of the mean recurrence interval, especially for short paleoearthquake sequences and high dating errors. Using a Bayesian framework for parameter estimation results in a statistical model for earthquake recurrence intervals that assimilates in a simple way paleoearthquake sequences and instrumental data. I present illustrative case studies from Southern California and compare the method with the commonly used approach of exponentially distributed recurrence times based on a stationary Poisson process.
A doppelalgebra is an algebra defined on a vector space with two binary linear associative operations. Doppelalgebras play a prominent role in algebraic K-theory. We consider doppelsemigroups, that is, sets with two binary associative operations satisfying the axioms of a doppelalgebra. Doppelsemigroups are a generalization of semigroups and they have relationships with such algebraic structures as interassociative semigroups, restrictive bisemigroups, dimonoids, and trioids.
In the lecture notes numerous examples of doppelsemigroups and of strong doppelsemigroups are given. The independence of axioms of a strong doppelsemigroup is established. A free product in the variety of doppelsemigroups is presented. We also construct a free (strong) doppelsemigroup, a free commutative (strong) doppelsemigroup, a free n-nilpotent (strong) doppelsemigroup, a free n-dinilpotent (strong) doppelsemigroup, and a free left n-dinilpotent doppelsemigroup. Moreover, the least commutative congruence, the least n-nilpotent congruence, the least n-dinilpotent congruence on a free (strong) doppelsemigroup and the least left n-dinilpotent congruence on a free doppelsemigroup are characterized.
The book addresses graduate students, post-graduate students, researchers in algebra and interested readers.
Cell-free protein synthesis as a novel tool for directed glycoengineering of active erythropoietin
(2018)
As one of the most complex post-translational modification, glycosylation is widely involved in cell adhesion, cell proliferation and immune response. Nevertheless glycoproteins with an identical polypeptide backbone mostly differ in their glycosylation patterns. Due to this heterogeneity, the mapping of different glycosylation patterns to their associated function is nearly impossible. In the last years, glycoengineering tools including cell line engineering, chemoenzymatic remodeling and site-specific glycosylation have attracted increasing interest. The therapeutic hormone erythropoietin (EPO) has been investigated in particular by various groups to establish a production process resulting in a defined glycosylation pattern. However commercially available recombinant human EPO shows batch-to-batch variations in its glycoforms. Therefore we present an alternative method for the synthesis of active glycosylated EPO with an engineered O-glycosylation site by combining eukaryotic cell-free protein synthesis and site-directed incorporation of non-canonical amino acids with subsequent chemoselective modifications.
Background/Aims: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far. Methods: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR. Results: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade. Conclusion: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade.
ShapeRotator
(2018)
The quantification of complex morphological patterns typically involves comprehensive shape and size analyses, usually obtained by gathering morphological data from all the structures that capture the phenotypic diversity of an organism or object. Articulated structures are a critical component of overall phenotypic diversity, but data gathered from these structures are difficult to incorporate into modern analyses because of the complexities associated with jointly quantifying 3D shape in multiple structures. While there are existing methods for analyzing shape variation in articulated structures in two-dimensional (2D) space, these methods do not work in 3D, a rapidly growing area of capability and research. Here, we describe a simple geometric rigid rotation approach that removes the effect of random translation and rotation, enabling the morphological analysis of 3D articulated structures. Our method is based on Cartesian coordinates in 3D space, so it can be applied to any morphometric problem that also uses 3D coordinates (e.g., spherical harmonics). We demonstrate the method by applying it to a landmark-based dataset for analyzing shape variation using geometric morphometrics. We have developed an R tool (ShapeRotator) so that the method can be easily implemented in the commonly used R package geomorph and MorphoJ software. This method will be a valuable tool for 3D morphological analyses in articulated structures by allowing an exhaustive examination of shape and size diversity.
The variabilities of the semidiurnal solar and lunar tides of the equatorial electrojet (EEJ) are investigated during the 2003, 2006, 2009 and 2013 major sudden stratospheric warming (SSW) events in this study. For this purpose, ground-magnetometer recordings at the equatorial observatories in Huancayo and Fuquene are utilized. Results show a major enhancement in the amplitude of the EEJ semidiurnal lunar tide in each of the four warming events. The EEJ semidiurnal solar tidal amplitude shows an amplification prior to the onset of warmings, a reduction during the deceleration of the zonal mean zonal wind at 60 degrees N and 10 hPa, and a second enhancement a few days after the peak reversal of the zonal mean zonal wind during all four SSWs. Results also reveal that the amplitude of the EEJ semidiurnal lunar tide becomes comparable or even greater than the amplitude of the EEJ semidiurnal solar tide during all these warming events. The present study also compares the EEJ semidiurnal solar and lunar tidal changes with the variability of the migrating semidiurnal solar (SW2) and lunar (M2) tides in neutral temperature and zonal wind obtained from numerical simulations at E-region heights. A better agreement between the enhancements of the EEJ semidiurnal lunar tide and the M2 tide is found in comparison with the enhancements of the EEJ semidiurnal solar tide and the SW2 tide in both the neutral temperature and zonal wind at the E-region altitudes.
One of the crucial components in seismic hazard analysis is the estimation of the maximum earthquake magnitude and associated uncertainty. In the present study, the uncertainty related to the maximum expected magnitude mu is determined in terms of confidence intervals for an imposed level of confidence. Previous work by Salamat et al. (Pure Appl Geophys 174:763-777, 2017) shows the divergence of the confidence interval of the maximum possible magnitude m(max) for high levels of confidence in six seismotectonic zones of Iran. In this work, the maximum expected earthquake magnitude mu is calculated in a predefined finite time interval and imposed level of confidence. For this, we use a conceptual model based on a doubly truncated Gutenberg-Richter law for magnitudes with constant b-value and calculate the posterior distribution of mu for the time interval T-f in future. We assume a stationary Poisson process in time and a Gutenberg-Richter relation for magnitudes. The upper bound of the magnitude confidence interval is calculated for different time intervals of 30, 50, and 100 years and imposed levels of confidence alpha = 0.5, 0.1, 0.05, and 0.01. The posterior distribution of waiting times T-f to the next earthquake with a given magnitude equal to 6.5, 7.0, and7.5 are calculated in each zone. In order to find the influence of declustering, we use the original and declustered version of the catalog. The earthquake catalog of the territory of Iran and surroundings are subdivided into six seismotectonic zones Alborz, Azerbaijan, Central Iran, Zagros, Kopet Dagh, and Makran. We assume the maximum possible magnitude m(max) = 8.5 and calculate the upper bound of the confidence interval of mu in each zone. The results indicate that for short time intervals equal to 30 and 50 years and imposed levels of confidence 1 - alpha = 0.95 and 0.90, the probability distribution of mu is around mu = 7.16-8.23 in all seismic zones.
In this chapter, an overview of systematic eradication of basic science foci in European universities in the last two decades is given. This happens under the slogan of optimisation of the university education to the needs and demands of the society. It is pointed out that reliance on “market demands” brings with it long-term deficiencies in the maintenance of basic and advanced knowledge construction in societies necessary for long-term future technological advances. University policies that claim improvement of higher education towards more immediate efficiency may end up with the opposite effect of affecting its quality and long term expected positive impact on society.
The increasing availability of earth observations necessitates mathematical methods to optimally combine such data with hydrologic models. Several algorithms exist for such purposes, under the umbrella of data assimilation (DA). However, DA methods are often applied in a suboptimal fashion for complex real-world problems, due largely to several practical implementation issues. One such issue is error characterization, which is known to be critical for a successful assimilation. Mischaracterized errors lead to suboptimal forecasts, and in the worst case, to degraded estimates even compared to the no assimilation case. Model uncertainty characterization has received little attention relative to other aspects of DA science. Traditional methods rely on subjective, ad hoc tuning factors or parametric distribution assumptions that may not always be applicable. We propose a novel data-driven approach (named SDMU) to model uncertainty characterization for DA studies where (1) the system states are partially observed and (2) minimal prior knowledge of the model error processes is available, except that the errors display state dependence. It includes an approach for estimating the uncertainty in hidden model states, with the end goal of improving predictions of observed variables. The SDMU is therefore suited to DA studies where the observed variables are of primary interest. Its efficacy is demonstrated through a synthetic case study with low-dimensional chaotic dynamics and a real hydrologic experiment for one-day-ahead streamflow forecasting. In both experiments, the proposed method leads to substantial improvements in the hidden states and observed system outputs over a standard method involving perturbation with Gaussian noise.
Rapid population and economic growth in Southeast Asia has been accompanied by extensive land use change with consequent impacts on catchment hydrology. Modeling methodologies capable of handling changing land use conditions are therefore becoming ever more important and are receiving increasing attention from hydrologists. A recently developed data-assimilation-based framework that allows model parameters to vary through time in response to signals of change in observations is considered for a medium-sized catchment (2880 km(2)) in northern Vietnam experiencing substantial but gradual land cover change. We investigate the efficacy of the method as well as the importance of the chosen model structure in ensuring the success of a time-varying parameter method. The method was used with two lumped daily conceptual models (HBV and HyMOD) that gave good-quality streamflow predictions during pre-change conditions. Although both time-varying parameter models gave improved streamflow predictions under changed conditions compared to the time-invariant parameter model, persistent biases for low flows were apparent in the HyMOD case. It was found that HyMOD was not suited to representing the modified baseflow conditions, resulting in extreme and unrealistic time-varying parameter estimates. This work shows that the chosen model can be critical for ensuring the time-varying parameter framework successfully models streamflow under changing land cover conditions. It can also be used to determine whether land cover changes (and not just meteorological factors) contribute to the observed hydrologic changes in retrospective studies where the lack of a paired control catchment precludes such an assessment.
Left-right (L-R) asymmetry in the body plan is determined by nodal flow in vertebrate embryos. Shinohara et al. (Shinohara K et al. 2012 Nat. Commun. 3, 622 (doi:10.1038/ncomms1624)) used Dpcd and Rfx3 mutant mouse embryos and showed that only a few cilia were sufficient to achieve L-R asymmetry. However, the mechanism underlying the breaking of symmetry by such weak ciliary flow is unclear. Flow-mediated signals associated with the L-R asymmetric organogenesis have not been clarified, and two different hypotheses-vesicle transport and mechanosensing-are now debated in the research field of developmental biology. In this study, we developed a computational model of the node system reported by Shinohara et al. and examined the feasibilities of the two hypotheses with a small number of cilia. With the small number of rotating cilia, flow was induced locally and global strong flow was not observed in the node. Particles were then effectively transported only when they were close to the cilia, and particle transport was strongly dependent on the ciliary positions. Although the maximum wall shear rate was also influenced by ciliary position, the mean wall shear rate at the perinodal wall increased monotonically with the number of cilia. We also investigated the membrane tension of immotile cilia, which is relevant to the regulation of mechanotransduction. The results indicated that tension of about 0.1 mu Nm(-1) was exerted at the base even when the fluid shear rate was applied at about 0.1 s(-1). The area of high tension was also localized at the upstream side, and negative tension appeared at the downstream side. Such localization may be useful to sense the flow direction at the periphery, as time-averaged anticlockwise circulation was induced in the node by rotation of a few cilia. Our numerical results support the mechanosensing hypothesis, and we expect that our study will stimulate further experimental investigations of mechanotransduction in the near future.
Local observations indicate that climate change and shifting disturbance regimes are causing permafrost degradation. However, the occurrence and distribution of permafrost region disturbances (PRDs) remain poorly resolved across the Arctic and Subarctic. Here we quantify the abundance and distribution of three primary PRDs using time-series analysis of 30-m resolution Landsat imagery from 1999 to 2014. Our dataset spans four continental-scale transects in North America and Eurasia, covering similar to 10% of the permafrost region. Lake area loss (-1.45%) dominated the study domain with enhanced losses occurring at the boundary between discontinuous and continuous permafrost regions. Fires were the most extensive PRD across boreal regions (6.59%), but in tundra regions (0.63%) limited to Alaska. Retrogressive thaw slumps were abundant but highly localized (< 10(-5)%). Our analysis synergizes the global-scale importance of PRDs. The findings highlight the need to include PRDs in next-generation land surface models to project the permafrost carbon feedback.
We consider a distributed learning approach in supervised learning for a large class of spectral regularization methods in an reproducing kernel Hilbert space (RKHS) framework. The data set of size n is partitioned into m = O (n(alpha)), alpha < 1/2, disjoint subsamples. On each subsample, some spectral regularization method (belonging to a large class, including in particular Kernel Ridge Regression, L-2-boosting and spectral cut-off) is applied. The regression function f is then estimated via simple averaging, leading to a substantial reduction in computation time. We show that minimax optimal rates of convergence are preserved if m grows sufficiently slowly (corresponding to an upper bound for alpha) as n -> infinity, depending on the smoothness assumptions on f and the intrinsic dimensionality. In spirit, the analysis relies on a classical bias/stochastic error analysis.
Background and objective Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort (R) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Methods Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort (R) or 20 mg of Infacort (R)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Results Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline (cort),15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing < 20 kg. Conclusions Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing < 20 kg.
Frühe mathematische Bildung
(2018)
Im vorliegenden Beitrag werden aktuelle Forschungstrends im Bereich der frühen mathematischen Bildung im Kontext jüngst formulierter Zieldimensionen für die frühe mathematische Bildung (siehe Benz et al., 2017) dargestellt. Es wird auf spielbasierte Fördermaßnahmen, Kompetenzen im Bereich „Raum und Form“, den Einfluss sprachlicher Parameter auf die Entwicklung mathematischer Kompetenzen sowie auf mathematikbezogene Kompetenzen frühpädagogischer Fachkräfte eingegangen. Darüber hinaus werden die Ergebnisse einer aktuellen Feldstudie zur Förderung früher mathematischer Kompetenzen (siehe Dillon, Kannan, Dean, Spelke & Duflo, 2017) vorgestellt. Abschließend wird die Entwicklung und Implementierung anschlussfähiger Bildungskonzepte als eine der zentralen Herausforderungen zukünftiger Forschungs- und Bildungsbemühungen diskutiert
We prove finiteness and diameter bounds for graphs having a positive Ricci-curvature bound in the Bakry–Émery sense. Our first result using only curvature and maximal vertex degree is sharp in the case of hypercubes. The second result depends on an additional dimension bound, but is independent of the vertex degree. In particular, the second result is the first Bonnet–Myers type theorem for unbounded graph Laplacians. Moreover, our results improve diameter bounds from Fathi and Shu (Bernoulli 24(1):672–698, 2018) and Horn et al. (J für die reine und angewandte Mathematik (Crelle’s J), 2017, https://doi.org/10.1515/crelle-2017-0038) and solve a conjecture from Cushing et al. (Bakry–Émery curvature functions of graphs, 2016).
The simultaneous detection of energy, momentum and temporal information in electron spectroscopy is the key aspect to enhance the detection efficiency in order to broaden the range of scientific applications. Employing a novel 60 degrees wide angle acceptance lens system, based on an additional accelerating electron optical element, leads to a significant enhancement in transmission over the previously employed 30 degrees electron lenses. Due to the performance gain, optimized capabilities for time resolved electron spectroscopy and other high transmission applications with pulsed ionizing radiation have been obtained. The energy resolution and transmission have been determined experimentally utilizing BESSY II as a photon source. Four different and complementary lens modes have been characterized. (C) 2017 The Authors. Published by Elsevier B.V.