1,677 research outputs found
Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition in Staphylococcus aureus
No full textSufficient access to transition metals such as iron is essential for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogen Staphylococcus aureus uses the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane of S. aureus possesses special compartments (functional membrane microdomains [FMMs]) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.German Center of Infection Research
Deutsche Forschungsgemeinschaft
Fortuene Program University Hospital Tuebingen
Spanish Ministry of Science
Deutsche Forschungsgemeinschaft
Grant reference number
TTU 08.708_00
EXC 2124 - 390838134
2507-0-0
PID2020-115699GB-100
398967434 -TRR261
Author
Simon Heilbronner
Simon Heilbronner
Simon Heilbronner
Daniel Lopez
Simon HeilbronnerPeer reviewe
Two-dimensional N = (2, 2) super Yang-Mills theory on the lattice
No full textSupersymmetry is one of the possible scenarios for physics beyond the standard model. By introducing a symmetry between bosons and fermions, it might be able to solve several theoretical problems while providing dark matter candidates. As all supersymmetric extensions of the standard model are based on strongly coupled gauge theories, we need non-perturbative methods, to fully investigate them. In this thesis we use lattice calculations, to investigate the two-dimensional N = (2, 2) super Yang-Mills theory, which we derive by a dimensional reduction of the four-dimensional N = 1 super Yang-Mills theory. Unfortunately our lattice formulation breaks supersymmetry explicitly. Thus we devote the first part of the thesis to present the lattice theory and analyze it thoroughly. First we have to discretize Majorana fermions, which leads to a real but not necessarily positive fermion determinant. Second, the classical potential of the scalar fields posses flat directions. Both problems could thwart our lattice simulations. Fortunately, as we demonstrate, both of them are absent in our simulations. At last, we show that the lattice theory posses only one relevant operator, the scalar mass, whose value in the continuum limit is known. The second part of the thesis is devoted to the numerical results. Introducing an additional fine-tuning of the fermion mass, we can reduce the influence of supersymmetry violating terms. Calculating lattice Ward identities, we show the restoration of supersymmetry in the chiral and continuum limit. Finally we calculate the lowlying bound states and extrapolate their masses to the continuum limit. We find two super-multiplets, as predicted from low energy effective theories. The first is the Farrar-Gabadadze-Schwetz super-multiplet which decouples from the theory. The second is the Veneziano-Yankielowicz super-multiplet which becomes massless in the chiral limit. We are further able to estimate the masses of the excited mesons of the latter. They are of the same size as the mass of the gluino-glueball.Supersymmetry ist ein mögliches Konzept, das Physik jenseits des Standardmodells beschreiben könnte. Durch die Einführung einer Symmetrie zwischen Bosonen und Fermionen werden einige theoretische Probleme gelöst und Kandidaten für die Dunkle Materie eingeführt. Da alle supersymmetrischen Erweiterungen des Standardmodells auf stark gekoppelten Eichtheorien beruhen, benötigen wir nichtperturbative Methoden, um sie vollständig zu untersuchen. In dieser Doktorarbeit nutzen wir Gitterrechnungen um die zweidimensionale N = (2, 2) superymmetrische Yang-Mills Theorie zu untersuchen. Wir erhalten dieses Model durch eine dimensionale Reduktion der vierdimensionalen N = 1 supersymmetrischen Yang-Mills Theorie. Unglücklicherweise bricht unser Gitterformalismus die Supersymmetry explizit. Daher nutzen wir den ersten Teil der Doktorarbeit, um unsere Gittertheorie vorzustellen und sorgfältig zu untersuchen. Zuerst müssen wir Majorana Fermionen diskretisieren. Dies führt zu einer reellen aber nicht notwendigerweise positiven Fermionendeterminante. Weiterhin besitzt das klassische Potential der Skalarfelder flache Richtungen. Beide Probleme könnten unsere Simulation unmöglich machen. Glücklicherweise
können wir zeigen, dass beide in unserer Simulation abwesend sind. Zum Schluß zeigen wir, dass die Gittertheorie nur einen relevanten Operator, die skalare Masse, besitzt, deren Wert für den Kontinuumslimes bekannt ist. Im zweiten Teil der Doktorarbeit präsentieren wir die numerischen Resultate. Durch die Einführung und Feinabstimmung eines zusätzlichen Parameters, die Fermionenmasse, können wir den Einfluss von Operatoren, die Supersymmetrie brechen, reduzieren. Durch die Berechnung von Gitterwardidentitäten können wir die Wiederherstellung der Supersymmetrie im chiralen und Kontinuumslimes zeigen. Zum Schluß
bestimmen wir das Spektrum der leichten Bindungszustände. Wir finden zwei Supermultiplets. Das Erste ist das Farrar-Gabadadze-Schwetz Supermultiplet, welches von der Theorie entkoppelt. Das Zweite ist das Veneziano-Yankielowicz Supermultiplet, welches im chiralen Limes masselos ist. Zusätzlich können wir auch die Massen der angeregten Zustände für das Letztere bestimmen. Sie sind von der gleichen Größenordnung wie die Masse des Gluino-Glueballs
What can ecosystems learn? Expanding evolutionary ecology with learning theory
No full textBackground: The structure and organisation of ecological interactions within an ecosystem is modified by the evolution and coevolution of the individual species it contains. Understanding how historical conditions have shaped this architecture is vital for understanding system responses to change at scales from the microbial upwards. However, in the absence of a group selection process, the collective behaviours and ecosystem functions exhibited by the whole community cannot be organised or adapted in a Darwinian sense. A long-standing open question thus persists: Are there alternative organising principles that enable us to understand and predict how the coevolution of the component species creates and maintains complex collective behaviours exhibited by the ecosystem as a whole?Results: Here we answer this question by incorporating principles from connectionist learning, a previously unrelated discipline already using well-developed theories on how emergent behaviours arise in simple networks. Specifically, we show conditions where natural selection on ecological interactions is functionally equivalent to a simple type of connectionist learning, ‘unsupervised learning’, well-known in neural-network models of cognitive systems to produce many non-trivial collective behaviours. Accordingly, we find that a community can self-organise in a well-defined and non-trivial sense without selection at the community level; its organisation can be conditioned by past experience in the same sense as connectionist learning models habituate to stimuli. This conditioning drives the community to form a distributed ecological memory of multiple past states, causing the community to: a) converge to these states from any random initial composition; b) accurately restore historical compositions from small fragments; c) recover a state composition following disturbance; and d) to correctly classify ambiguous initial compositions according to their similarity to learned compositions. We examine how the formation of alternative stable states alters the community’s response to changing environmental forcing, and we identify conditions under which the ecosystem exhibits hysteresis with potential for catastrophic regime shifts.Conclusions: This work highlights the potential of connectionist theory to expand our understanding of evo-eco dynamics and collective ecological behaviours. Within this framework we find that, despite not being a Darwinian unit, ecological communities can behave like connectionist learning systems, creating internal conditions that habituate to past environmental conditions and actively recalling those conditions.Theoretical ecology, Communityassembly, Network structures, Ecological memory, Associative learning, Regime shifts, Community matrix*Correspondence
False hopes why America's quest for perfect health is a recipe for failure
No full textAuthor Daniel Callahan discusses what he thinks is the cause of the health care crisis in the United States, and gives an alternative solution to the problem
Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions
No full textThe mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions
Correction: Corrigendum: Leukocyte integrin Mac-1 regulates thrombosis via interaction with platelet GPIbα
No full textNature Communications 8: Article number:15559 (2017); Published 30 May 2017; Updated 4 July 2017 The original version of this Article contained an error in the email address of the corresponding author Daniel I. Simon. The correct email is [email protected]. The error has been corrected in the HTML and PDF versions of the article.</jats:p
Remnants and Revenants: politics and violence in the work of Agamben and Derrida
No full textThis is the peer reviewed version of the following article: Frazer, Elizabeth, and Kimberly Hutchings. "Remnants and revenants: politics and violence in the work of Agamben and Derrida." The British Journal of Politics & International Relations 13.2 (2011): 127-144, which has been published in final form at http://dx.doi.org/10.1111/j.1467-856X.2010.00428.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Jacques Derrida and Giorgio Agamben both consider the question of whether there can be politics without violence, offering contrasting responses. In the case of Agamben, the remnant (that which remains) is disruptive and destabilising of present institutions; in the case of Derrida the revenant, the spectre, promises a future that is open. This reading of the two theories suggests that Derrida's response to the question of politics and violence is more persuasive than Agamben's. But the abstraction of his argument, like the tensions and contradictions in Agamben's, means that we are not hereby furnished with the resources to think politically about violence
Inclusive Fitness Theory: is it still relevant in discussions of altruism?
No full textFor nearly 50 years, Inclusive Fitness Theory has provided researchers an avenue to understand altruistic interactions among individuals in a colony. It has recently come under fire by prominent academics suggesting it is unsatisfactory in describing altruism. This thesis aims to provide a history of inclusive fitness theory and dissect the arguments against the theory and in favor of it. Using scientific research articles from such publications as Nature and Science, I have collected information on the history of Inclusive Fitness Theory and the development of the theory over time. Furthermore, this thesis will also delve into the methods of testing Inclusive Fitness Theory as well as fields that have arisen due to the theory. Ultimately, using arguments made by opponents and proponents to the theory, conclusions will be drawn about the validity of the theory. While the arguments against the theory seem sound, they ultimately fail to provide alternative insights into the development of altruism in colonies, and moreover these arguments are successfully refuted by leaders in the field.M.S.Includes bibliographical referencesIncludes vitaby Daniel Wasim Awar
War palimpsests: the Latin intertext in Claude Simon
No full textO romance de Claude Simon dialoga com muitos textos por meio de diversos procedimentos de composição, em especial devido à intertextualidade explícita em muitos casos. Ligado ao contexto estético do nouveau roman, o novo romance francês, o autor lida em sua escrita com aspectos linguísticos peculiares, dentre eles a perspectiva temporal, que evidenciam seu caráter literário. Evidencia-se, por consequência, para o crítico, a necessidade de entender como os diversos princípios de organização do texto se articulam em favor de sua unidade, feita de fragmentos que se colam e se deformam conforme as demandas do escritor, constituindo-se, assim, uma espécie de palimpsesto. O intertexto latino, ou seja, as relações entre um texto e a literatura romana antiga, tem papel fundamental na construção do texto simoniano, o que interfere também em nossa leitura de outros elementos que interagem com ele. Um dos romances em que se expõe com clareza esse fator intertextual na literatura de Simon é La Bataille de Pharsale (1969), nossa opção para objeto de estudo, dada à acentuação dos problemas postos pela presença da cultura clássica na obra por relações e transformações. Nesse romance, a guerra é um dos principais pontos de encontro derivados das relações entre antigos e modernos exercidas pela escrita, de modo que os outros aspectos composicionais do texto, como o tempo e a enunciação, parecem estabelecer uma interferência recíproca com o intertexto. Levando em conta esses fatores, nossa análise buscou se pautar na necessidade de reavaliar o percurso crítico feito sobre a obra do autor sob uma visão comparatista e multidisciplinar a fim de fornecer conclusões relevantes sobre nosso objeto. A partir desse estudo, fornecemos possibilidades de leitura do romance com base nessa discussão, bem como novas perspectivas para a compreensão da obra de Claude Simon e do romance moderno em relação à tradição clássica.The novel of Claude Simon dialogues with many texts through various composition procedures, especially due to the explicit intertextuality in many cases. In the aesthetic context of the nouveau roman, the French \"new novel\", the author deals in his writing with peculiar linguistic aspects, including the time perspective, which demonstrate its literary character. Thus, there is a clear need to the critics to understand how the various text organizational principles articulate among themselves in favor of a unit, made of fragments that stick and deform according to the demands of the writer, being thus a kind of palimpsest. The Latin intertext, the relationship between a text and the ancient Roman literature, plays a key role in the creation of the Simonian text, which also interferes in our reading of other elements that interact with it. One of the novels which sets out clearly that intertextual factor in Simon\'s literature is La Bataille de Pharsale (1969), our option for object of study, given the rise of problems posed by the presence of classical culture in the work by relations and transformations. In this novel, the war is one of the main points derived from the relations between ancient and modern in writing, so that other compositional aspects of the text, as time and enunciation, seem to establish a reciprocal interference with the intertext. Taking into account these factors, our analysis had the aim of reassessing the critical path on the author\'s work in a comparative and multidisciplinary approach to provide relevant conclusions about our object. From this study, we provide reading possibilities for the novel based on our discussion, as well as new perspectives for the understanding of Claude Simon\'s work and the modern novel in relation to the classical tradition
Refactoring = Substitution + Rewriting: Towards Generic, Language-Independent Refactorings
No full textEelco Visser’s work has always encouraged stepping back from the particular to look at the underlying, conceptual problems.
In that spirit we present an approach to describing refactorings that abstracts away from particular refactorings to classes of similar transformations, and presents an implementation of these that works by substitution and subsequent rewriting.
Substitution is language-independent under this approach, while the rewrites embody language-specific aspects. Intriguingly, it also goes back to work on API migration by Huiqing Li and the first author, and sets refactoring in that general context
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