Cosmic Calibration: Constraints from the Matter Power Spectrum and the Cosmic Microwave Background

Several cosmological measurements have attained significant levels of maturity and accuracy over the last decade. Continuing this trend, future observations promise measurements of the statistics of the cosmic mass distribution at an accuracy level of one percent out to spatial scales with k~10 h/Mpc and even smaller, entering highly nonlinear regimes of gravitational instability. In order to interpret these observations and extract useful cosmological information from them, such as the equation of state of dark energy, very costly high precision, multi-physics simulations must be performed. We have recently implemented a new statistical framework with the aim of obtaining accurate parameter constraints from combining observations with a limited number of simulations. The key idea is the replacement of the full simulator by a fast emulator with controlled error bounds. In this paper, we provide a detailed description of the methodology and extend the framework to include joint analysis of cosmic microwave background and large scale structure measurements. Our framework is especially well-suited for upcoming large scale structure probes of dark energy such as baryon acoustic oscillations and, especially, weak lensing, where percent level accuracy on nonlinear scales is needed.Comment: 15 pages, 14 figure

The Obliteration of Truth by Management: Badiou, St. Paul and the Question of Economic Managerialism in Education

This paper considers the questions that Badiou’s theory of the subject poses to cultures of economic managerialism within education. His argument that radical change is possible, for people and the situations they inhabit, provides a stark challenge to the stifling nature of much current educational climate. In 'Saint Paul: The Foundation of Universalism', Badiou describes the current universalism of capitalism, monetary homogeneity and the rule of the count. Badiou argues that the politics of identity are all too easily subsumed by the prerogatives of the marketplace and unable to present, therefore, a critique of the status quo. These processes are, he argues, without the potential for truth. What are the implications of Badiou’s claim that education is the arranging of ‘the forms of knowledge in such a way that truth may come to pierce a hole in them’ (Badiou, 2005, p. 9)? In this paper, I argue that Badiou’s theory opens up space for a kind of thinking about education that resists its colonisation by cultures of management and marketisation and leads educationalists to consider the emancipatory potential of education in a new light

Constraining the initial state granularity with bulk observables in Au+Au collisions at sNN=200\sqrt{s_{\rm NN}}=200 GeV

In this paper we conduct a systematic study of the granularity of the initial state of hot and dense QCD matter produced in ultra-relativistic heavy-ion collisions and its influence on bulk observables like particle yields, $m_T$ spectra and elliptic flow. For our investigation we use a hybrid transport model, based on (3+1)d hydrodynamics and a microscopic Boltzmann transport approach. The initial conditions are generated by a non-equilibrium hadronic transport approach and the size of their fluctuations can be adjusted by defining a Gaussian smoothing parameter $\sigma$. The dependence of the hydrodynamic evolution on the choices of $\sigma$ and $t_{start}$ is explored by means of a Gaussian emulator. To generate particle yields and elliptic flow that are compatible with experimental data the initial state parameters are constrained to be $\sigma=1$ fm and $t_{\rm start}=0.5$ fm. In addition, the influence of changes in the equation of state is studied and the results of our event-by-event calculations are compared to a calculation with averaged initial conditions. We conclude that even though the initial state parameters can be constrained by yields and elliptic flow, the granularity needs to be constrained by other correlation and fluctuation observables.Comment: 14 pages, 8 figures, updated references, version to appear in J. Phys.

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether <it>in situ </it>carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression.</p> <p>Methods</p> <p>Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression.</p> <p>Results</p> <p>Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP.</p> <p>Conclusion</p> <p>TMAs are not suitable for IHC analysis of <it>in situ </it>aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. <it>In situ </it>aromatase expression in tumor cells is associated with ER expression and may thus point towards good prognosis. Aromatase expression in cancer cells is not predictive of response to endocrine therapy, indicating that <it>in situ </it>estrogen synthesis may not be the major source of intratumoral estrogen. However, aromatase expression in combination with high PR expression may select letrozole treated patients with longer TTP.</p> <p>Trial registration</p> <p>Sub-study of trial P025 for advanced breast cancer.</p

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants

Salicylic acid (SA) is a plant immune signal produced upon pathogen challenge to induce systemic acquired resistance (SAR). It is the only major plant hormone for which the receptor has not been firmly identified. SAR in Arabidopsis requires the transcription cofactor NPR1 (nonexpresser of PR genes 1), whose degradation serves as a molecular switch for SAR. Here we show that NPR1 paralogues, NPR3 and NPR4, are SA receptors that bind SA with different affinities and function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the npr3 npr4 mutant accumulates higher levels of NPR1 and is insensitive to SAR induction. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge

Psychoanalytic sociology and the traumas of history: Alexander Mitscherlich between the disciplines

This article examines the way aspects of recent history were excluded in key studies emerging from psychoanalytic social psychology of the mid-twentieth century. It draws on work by Erikson, Marcuse and Fromm, but focuses in particular on Alexander Mitscherlich. Mitscherlich, a social psychologist associated with the later Frankfurt school, was also the most important psychoanalytic figure in postwar Germany. This makes his work significant for tracing ways in which historical experience of the war and Nazism was filtered out of psychosocial narratives in this period, in favour of more structural analyses of the dynamics of social authority. Mitscherlich?s 1967 work The Inability to Mourn, co-authored with Margarete Mitscherlich, is often cited as the point at which the ?missing? historical experience flooded back into psychoanalytic accounts of society. I argue that this landmark publication doesn?t hail the shift towards the psychoanalysis of historical experience with which it is often associated. These more sociological writers of the mid-century were writing before the impact of several trends occurring in the 1980s-90s which decisively shifted psychoanalytic attention away from the investigation of social authority and towards a focus on historical trauma. Ultimately this is also a narrative about the transformations which occur when psychoanalysis moves across disciplines

A modular analysis of the Auxin signalling network

Auxin is essential for plant development from embryogenesis onwards. Auxin acts in large part through regulation of transcription. The proteins acting in the signalling pathway regulating transcription downstream of auxin have been identified as well as the interactions between these proteins, thus identifying the topology of this network implicating 54 Auxin Response Factor (ARF) and Aux/IAA (IAA) transcriptional regulators. Here, we study the auxin signalling pathway by means of mathematical modeling at the single cell level. We proceed analytically, by considering the role played by five functional modules into which the auxin pathway can be decomposed: the sequestration of ARF by IAA, the transcriptional repression by IAA, the dimer formation amongst ARFs and IAAs, the feedback loop on IAA and the auxin induced degradation of IAA proteins. Focusing on these modules allows assessing their function within the dynamics of auxin signalling. One key outcome of this analysis is that there are both specific and overlapping functions between all the major modules of the signaling pathway. This suggests a combinatorial function of the modules in optimizing the speed and amplitude of auxin-induced transcription. Our work allows identifying potential functions for homo- and hetero-dimerization of transcriptional regulators, with ARF:IAA, IAA:IAA and ARF:ARF dimerization respectively controlling the amplitude, speed and sensitivity of the response and a synergistic effect of the interaction of IAA with transcriptional repressors on these characteristics of the signaling pathway. Finally, we also suggest experiments which might allow disentangling the structure of the auxin signaling pathway and analysing further its function in plants