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Cancer evolution is driven by the acquisition of somatic mutations that provide cells with a beneficial phenotype in a changing microenvironment. However, mutations that give rise to neoantigens, novel cancer–specific peptides that elicit an immune response, are likely to be disadvantageous. Here we show how the clonal structure and immunogenotype of growing tumours is shaped by negative selection in response to neoantigenic mutations. We construct a mathematical model of neoantigen evolution in a growing tumour, and verify the model using genomic sequencing data. The model predicts that, in the absence of active immune escape mechanisms, tumours either evolve clonal neoantigens (antigen– ‘hot’), or have no clonally– expanded neoantigens at all (antigen– ‘cold’), whereas antigen– ‘warm’ tumours (with high frequency subclonal neoantigens) form only following the evolution of immune evasion. Counterintuitively, strong negative selection for neoantigens during tumour formation leads to an increased number of antigen– warm or – hot tumours, as a consequence of selective pressure for immune escape. Further, we show that the clone size distribution under negative selection is effectively– neutral, and moreover, that stronger negative selection paradoxically leads to more neutral– like dynamics. Analysis of antigen clone sizes and immune escape in colorectal cancer exome sequencing data confirms these results. Overall, we provide and verify a mathematical framework to understand the evolutionary dynamics and clonality of neoantigens in human cancers that may inform patient– specific immunotherapy decision– making.

Species interactions and coevolution are integral to ecological communities, but we lack empirical information on when and how these interactions generate and purge genetic diversity. Using genomic time series data from host-virus experiments, we found that coevolution occurs through consecutive selective sweeps in both species, with temporal consistency across replicates. Sweeps were accompanied by phenotypic change (resistance or infectivity increases) and expansions in population size. In the host, population expansion enabled rapid generation of genetic diversity in accordance with neutral processes. Viral molecular evolution was, in contrast, confined to few genes, all putative targets of selection. This study demonstrates that molecular evolution during species interactions is shaped by both eco-evolutionary feedback dynamics and interspecific differences in how genetic diversity is generated and maintained. published

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. (VLID)3420027

Mit der modernen Architektur steigen auch die Herausforderungen an die Tragwerksplaner. Das Streben nach m��glichst weit gespannten Decken mit wenigen tragenden Elementen wird immer gr����er. Die Architekten werden somit immer freier in der Grundrissgestaltung. Das Institut f��r Tragwerksplanung und Ingenieurholzbau (ITI) an der technischen Universit��t Wien entwickelt zu diesem Zweck ein Verbunddeckensystem aus Beton, Holzleichtbeton und Holz. Die drei Schichten werden dabei den unterschiedlichen Materialeigenschaften entsprechend bestm��glich eingesetzt. In dieser Arbeit wird das Langzeittragverhalten des Verbundsystems sowohl mit Bauteilversuchen als auch rechnerisch beschrieben. Als Berechnungsgrundlage findet die finite Elemente Methode ihre Anwendung. Das finite-Elemente Modell wird in Form von Nachrechnungen bisheriger Forschungsergebnisse verifiziert. In Form einer Parameterstudie wird der Einfluss unterschiedlicher Materialeigenschaften, variierender Schichth��hen und der Lage der Verbindungsmittel analysiert. Als ��bergeordnetes Ziel dieser Diplomarbeit werden abschlie��end Kriechzahlen ermittelt, die es erm��glichen das Verbundsystem unter Ber��cksichtigung der Langzeitverformungen zu berechnen. Abschlie��end wird eine Bemessungstafel entwickelt, um mit geringem Aufwand f��r eine bestimmte Belastung und Spannweite den geeigneten Verbundquerschnittsaufbau zu ermitteln., Modern architecture goes hand in hand with increasing challenges for structural engineers. The efforts being made to create ceilings with as wide a span as possible and few load-bearing elements are constantly increasing. As a consequence, architects are receiving ever more freedom in designing floor plans. For this purpose, the Department of Structural Design and Timber Engineering at TU Wien (Vienna University of Technology) is developing a composite slab system consisting of concrete, lightweight wood concrete and wood. The three layers with different characteristics of their materials are used to the best possible effect. In this thesis, the long-term load-bearing behaviour of the composite system is described by means of component testing and via calculations. The finite element method is used as the basis of the calculations. The finite element model is verified by recalculating previous research results. The influence of various characteristics of materials, varying layer height and the position of the connecting devices is analysed in the form of a parameter study. As the superordinate objective of this master-s thesis, creep coefficients are then determined which make it possible to calculate the composite system, taking into account long-term deformation. Finally, a dimensioning table is developed to determine the suitable composite section for specific loads and lengths of span with little effort.

We present a formally verified global optimization framework. Given a semialgebraic or transcendental function $f$ and a compact semialgebraic domain $K$, we use the nonlinear maxplus template approximation algorithm to provide a certified lower bound of $f$ over $K$. This method allows to bound in a modular way some of the constituents of $f$ by suprema of quadratic forms with a well chosen curvature. Thus, we reduce the initial goal to a hierarchy of semialgebraic optimization problems, solved by sums of squares relaxations. Our implementation tool interleaves semialgebraic approximations with sums of squares witnesses to form certificates. It is interfaced with Coq and thus benefits from the trusted arithmetic available inside the proof assistant. This feature is used to produce, from the certificates, both valid underestimators and lower bounds for each approximated constituent. The application range for such a tool is widespread; for instance Hales' proof of Kepler's conjecture yields thousands of multivariate transcendental inequalities. We illustrate the performance of our formal framework on some of these inequalities as well as on examples from the global optimization literature., Comment: 24 pages, 2 figures, 3 tables

We consider the problem of self-tolerance in the frame of a minimalistic model of the idiotypic network. A node of this network represents a population of B-lymphocytes of the same idiotype, which is encoded by a bit string. The links of the network connect nodes with (nearly) complementary strings. The population of a node survives if the number of occupied neighbors is not too small and not too large. There is an influx of lymphocytes with random idiotype from the bone marrow. Previous investigations have shown that this system evolves toward highly organized architectures, where the nodes can be classified into groups according to their statistical properties. The building principles of these architectures can be analytically described and the statistical results of simulations agree very well with results of a modular mean-field theory. In this paper, we present simulation results for the case that one or several nodes, playing the role of self, are permanently occupied. These self nodes influence their linked neighbors, the autoreactive clones, but are themselves not affected by idiotypic interactions. We observe that the group structure of the architecture is very similar to the case without self antigen, but organized such that the neighbors of the self are only weakly occupied, thus providing self-tolerance. We also treat this situation in mean-field theory, which give results in good agreement with data from simulation. The model supports the view that autoreactive clones, which naturally occur also in healthy organisms are controlled by anti-idiotypic interactions, and could be helpful to understand network aspects of autoimmune disorders.

Political-economic classics of different schools agreed that capitalism inherently and inevitably leads to a decline of market principles. Analyzing indicators of liberalization policies for 21 OECD-countries in five economic and social policy fields, we demonstrate that Western industrialized countries are subject to a convergent trend towards market-creating policies. This stands in stark contrast to the theoretical expectations of classical works in the field of political economy. Since the first half of the 1980s at the latest, Western democracies have entered a new phase of economic liberalization. From a methodological perspective, our findings suggest that the methods for the causal analysis of convergent liberalization policies cannot be identical with the methods that have been used for analyzing the development and consolidation of the varieties of capitalism in the postwar era.

National audience; Peut-on être sûr de la vérité d’une preuve ? Cette preuve de la preuve, comment l’obtenir en pratique ? La vérification formelle de démonstration est de plus en plus utilisée par les mathématiciens.

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