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Summary: Lattice networks are indispensable to study heterogeneous materials such as concrete or rock as well as textiles and woven fabrics. Due to the discrete character of lattices, they quickly become computationally intensive. The QuasiContinuum (QC) Method resolves this challenge by interpolating the displacement of the underlying lattice with a coarser finite element mesh and sampling strategies to accelerate the assembly of the resulting system of governing equations. In lattices with complex heterogeneous microstructures with a high number of randomly shaped inclusions the QC leads to an almost fully‐resolved system due to the many interfaces. In the present study the QC Method is expanded with enrichment strategies from the eXtended Finite Element Method (XFEM) to resolve material interfaces using nonconforming meshes. The goal of this contribution is to bridge this gap and improve the computational efficiency of the method. To this end, four different enrichment strategies are compared in terms of their accuracy and convergence behavior. These include the Heaviside, absolute value, modified absolute value and the corrected XFEM enrichment. It is shown that the Heaviside enrichment is the most accurate and straightforward to implement. A first‐order interaction based summation rule is applied and adapted for the extended QC for elements intersected by a material interface to complement the Heaviside enrichment. The developed methodology is demonstrated by three numerical examples in comparison with the standard QC and the full solution. The extended QC is also able to predict the results with 5% error compared to the full solution, while employing almost one order of magnitude fewer degrees of freedom than the standard QC and even more compared to the fully‐resolved system. [ABSTRACT FROM AUTHOR]

Abstract Background In addition to selection, the process of evolution is accompanied by stochastic effects, such as changing environmental conditions, genetic drift and mutations. Commonly it is believed that without genetic drift, advantageous mutations quickly fixate in a halpoid population due to strong selection and lead to a continuous increase of the average fitness. This conclusion is based on the assumption of constant fitness. However, for frequency dependent fitness, where the fitness of an individual depends on the interactions with other individuals in the population, this does not hold. Results We propose a mathematical model that allows to understand the consequences of random frequency dependent mutations on the dynamics of an infinite large population. The frequencies of different types change according to the replicator equations and the fitness of a mutant is random and frequency dependent. To capture the interactions of different types, we employ a payoff matrix of variable size and thus are able to accommodate an arbitrary number of mutations. We assume that at most one mutant type arises at a time. The payoff entries to describe the mutant type are random variables obeying a probability distribution which is related to the fitness of the parent type. Conclusions We show that a random mutant can decrease the average fitness under frequency dependent selection, based on analytical results for two types and simulations for n types. Interestingly, in the case of at most two types the probabilities to increase or decrease the average fitness are independent of the concrete probability density function. Instead, they only depend on the probability that the payoff entries of the mutant are larger than the payoff entries of the parent type.

Cement-steel interfacial strength is an important measure for estimating the robustness and hydraulic sealing ability of wells. In this paper, laboratory experiments were performed in which small steel pipes (10 mm in diameter) were cemented in place within a Portland cement slurry under application of constant electrical potential difference between the pipes. The objective was to investigate whether there might be an observable difference between push-out strengths obtained with the pipes of different polarity (anode vs. cathode vs. reference nonpolarized pipe). The duration of the potential application and the magnitude of the potential difference were varied between the tests. The experiments demonstrated that at the higher potential difference (4 V), the duration of potential application had a noticeable effect on interfacial bonding. Application of 4 V for 24 h resulted in loss of bonding at cement-cathode interface, which could be attributed to massive water transportation to the cathode region by small radii cations. At the lower applied potential difference (1 V), there is an improvement in push-out strength at anode at short duration of potential application. This could be due to pore filling by precipitation of expansive minerals in pores and cement particles migration toward anode. The effect of potential on push-out strength in a hardened cement suggests that low potential difference applied for a short period of time might improve cement-steel interfacial strength. [ABSTRACT FROM AUTHOR]

A generic cut elimination theorem is proved showing that cut elimination property holds for all theories having a so-called pre-model. In deduction modulo a theory is formed with a set of axioms and congruences for which normalization holds.

Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth that accounts for somatic mutations, selection, drift and spatial constraints, to simulate multi-region sequencing data derived from spatial sampling of a neoplasm. We show that the spatial structure of a solid cancer has a major impact on the detection of clonal selection and genetic drift from both bulk and single-cell sequencing data. Our results indicate that spatial constrains can introduce significant sampling biases when performing multi-region bulk sampling and that such bias becomes a major confounding factor for the measurement of the evolutionary dynamics of human tumours. We also propose a statistical inference framework that incorporates spatial effects within a growing tumour and so represents a further step forwards in the inference evolutionary dynamics from genomic data. Our analysis shows that measuring cancer evolution using next-generation sequencing while accounting for the numerous confounding factors remains challenging. However, mechanistic model-based approaches have the potential to capture the sources of noise and better interpret the data. [ABSTRACT FROM AUTHOR]

A 'dually open' free movement system has evolved in the European Union (EU), granting EU citizens the right to free movement within the Union as well as cross-border welfare rights. Some scholarly literature and public debates have characterised the system as corrosive to the nationally organised welfare state, which will become a 'magnet' for the European poor. This paper examines how the German and Danish welfare states have responded to the 'dual open' system and its outcomes in terms of EU citizens' take-up rate of non-contributory benefits between 2007 and 2015. We show that the domestic responses were mostly restrictive and that outcomes remained rather stable. Our findings do not support the welfare magnet thesis but instead identify a tendency to a bifurcated social protection system for EU citizens in Germany. [ABSTRACT FROM AUTHOR]

Recent jurisprudence of the European Court of Justice (ECJ) marks a striking shift towards a more restrictive interpretation of EU citizens’ rights. The Court's turnaround is not only highly relevant for practical debates about ‘Social Europe’ or ‘welfare migration’, but also enlightening from a more general, theoretical viewpoint. Several recent studies on the ECJ have argued that the Court is largely constrained by member state governments’ threats of legislative override and non-compliance. We show that an additional mechanism is necessary to explain the Court's turnaround on citizenship. While the ECJ extended EU citizens’ rights even against strong opposition by member state governments, its recent shift reflects changes in the broader political context, i.e., the politicization of free movement in the European Union (EU). The article theorises Court responsiveness to politicization and demonstrates empirically, how the Court's jurisprudence corresponds with changing public debates about EU citizenship. [ABSTRACT FROM AUTHOR]

The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10−9/bp/division in small intestine to 1.6 × 10−7/bp/division in skin. [ABSTRACT FROM AUTHOR]

Trade-offs play an important role in evolution. Without trade-offs, evolution would maximize fitness of all traits leading to a "master of all traits". The shape of trade-offs has been shown to determine evolutionary trajectories and is often assumed to be static and independent of the actual evolutionary process. Here we propose that coevolution leads to a dynamical trade-off. We test this hypothesis in a microbial predator-prey system and show that the bacterial growth-defense trade-off changes from concave to convex, i.e., defense is effective and cheap initially, but gets costly when predators coevolve. We further explore the impact of such dynamical trade-offs by a novel mathematical model incorporating de novo mutations for both species. Predator and prey populations diversify rapidly leading to higher prey diversity when the trade-off is concave (cheap). Coevolution results in more convex (costly) trade-offs and lower prey diversity compared to the scenario where only the prey evolves. [ABSTRACT FROM AUTHOR]

It is broadly acknowledged that the Court of Justice of the European Union (CJEU) is an important engine of European integration. Although this role of the Court is well documented and analysed, there still is little research about the domestic effects of CJEU activism. This article contributes to the emerging literature on Europeanization through case law by analysing national responses to the CJEU adjudication on so called Golden Shares, a jurisdiction that limited member states’ influence on privatized companies. It is argued that the domestic reactions to these CJEU decisions were decisively conditioned by the presence of protective fallback options for the member states – and not by mobilization pressure or legal uncertainty costs, the two most important determinants of national responses to CJEU case law that have been identified so far in the literature. [ABSTRACT FROM PUBLISHER]

The Court of Justice of the European Union (CJEU) is famous for playing a central role in promoting the process of European integration. Although the Court has always been criticized for this pro-integrationist role, Member States have never cut back the CJEU's power. Recently, however, the environment for legal integration has changed: the CJEU is dealing more and more with politically sensitive issues; and that in a period when the integration project as such is becoming increasingly contested. Contrary to the expectations of many scholars, this had not led to more resistance against the CJEU's case law or its power. This article approaches this surprising fact by investigating the CJEU's jurisprudence on Golden Shares, which has substantially reduced national competencies in the contentious issue of corporate control. It shows that the persistent acceptance of the CJEU can be explained with the low and manageable short-term costs of legal integration. [ABSTRACT FROM AUTHOR]

Background: It has been frequently argued that tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical structure of tissues with high cell turnover, where a small number of tissue specific stem cells produces a large number of specialized progeny during multiple differentiation steps. Another well known mechanism is the spatial organization of stem cell populations and it is thought that this organization suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations. Results: We argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organization of a cancer suppressing tissue architecture and should be taken into account in arguments for the evolution of such tissues. Conclusion: We show that for systems that are composed of few cells reflecting the typical organization of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special tissue structures that can suppress most types of non-neutral mutations simultaneously. [ABSTRACT FROM AUTHOR]