Bayesian inverse problems with Gaussian priors

The posterior distribution in a nonparametric inverse problem is shown to contract to the true parameter at a rate that depends on the smoothness of the parameter, and the smoothness and scale of the prior. Correct combinations of these characteristics lead to the minimax rate. The frequentist coverage of credible sets is shown to depend on the combination of prior and true parameter, with smoother priors leading to zero coverage and rougher priors to conservative coverage. In the latter case credible sets are of the correct order of magnitude. The results are numerically illustrated by the problem of recovering a function from observation of a noisy version of its primitive.Comment: Published in at http://dx.doi.org/10.1214/11-AOS920 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Bayesian recovery of the initial condition for the heat equation

We study a Bayesian approach to recovering the initial condition for the heat equation from noisy observations of the solution at a later time. We consider a class of prior distributions indexed by a parameter quantifying "smoothness" and show that the corresponding posterior distributions contract around the true parameter at a rate that depends on the smoothness of the true initial condition and the smoothness and scale of the prior. Correct combinations of these characteristics lead to the optimal minimax rate. One type of priors leads to a rate-adaptive Bayesian procedure. The frequentist coverage of credible sets is shown to depend on the combination of the prior and true parameter as well, with smoother priors leading to zero coverage and rougher priors to (extremely) conservative results. In the latter case credible sets are much larger than frequentist confidence sets, in that the ratio of diameters diverges to infinity. The results are numerically illustrated by a simulated data example.Comment: 17 pages, 4 figures. Published in Comm. Statist. Theory Methods. This version differs from the original in pagination and typographic detail. arXiv admin note: text overlap with arXiv:1103.269

Modulation of ethylene- and heat-controlled hyponastic leaf movement in Arabidopsis thaliana by the plant defence hormones jasmonate and salicylate

Upward leaf movement (hyponastic growth) is adopted by several plant species including Arabidopsis thaliana, as a mechanism to escape adverse growth conditions. Among the signals that trigger hyponastic growth are, the gaseous hormone ethylene, low light intensities, and supra-optimal temperatures (heat). Recent studies indicated that the defence-related phytohormones jasmonic acid (JA) and salicylic acid (SA) synthesized by the plant upon biotic infestation repress low light-induced hyponastic growth. The hyponastic growth response induced by high temperature (heat) treatment and upon application of the gaseous hormone ethylene is highly similar to the response induced by low light. To test if these environmental signals induce hyponastic growth via parallel pathways or converge downstream, we studied here the roles of Methyl-JA (MeJA) and SA on ethylene- and heat-induced hyponastic growth. For this, we used a time-lapse camera setup. Our study includes pharmacological application of MeJA and SA and biological infestation using the JA-inducing caterpillar Pieris rapae as well as mutants lacking JA or SA signalling components. The data demonstrate that MeJA is a positive, and SA, a negative regulator of ethylene-induced hyponastic growth and that both hormones repress the response to heat. Taking previous studies into account, we conclude that SA is the first among many tested components which is repressing hyponastic growth under all tested inductive environmental stimuli. However, since MeJA is a positive regulator of ethylene-induced hyponastic growth and is inhibiting low light- and heat-induced leaf movement, we conclude that defence hormones control hyponastic growth by affecting stimulus-specific signalling pathways

Magnetic-field-induced transition in a quantum dot coupled to a superconductor

The magnetic moment of a quantum dot can be screened by its coupling to a superconducting reservoir, depending on the hierarchy of the superconducting gap and the relevant Kondo scale. This screening-unscreening transition can be driven by electrostatic gating, tunnel coupling, and, as we demonstrate here, a magnetic field. We perform high-resolution spectroscopy of subgap excitations near the screening-unscreening transition of asymmetric superconductor-quantum dot-superconductor (S-QD-S) junctions formed by the electromigration technique. Our measurements reveal a re-entrant phase boundary determined by the competition between Zeeman energy and gap reduction with magnetic field. We further track the evolution of the phase transition with increasing temperature, which is also evinced by thermal replicas of subgap states

Development of a Personalized Tumor Neoantigen Based Vaccine Formulation (FRAME-001) for Use in a Phase II Trial for the Treatment of Advanced Non-Small Cell Lung Cancer

Stage III-IV non-small cell lung cancer (NSCLC) is a devastating disease characterized by a poor prognosis. NSCLC tumors carry genetic mutations, which can lead to the expression of altered protein sequences. Peptides originating from mutated proteins and bound to MHC molecules on the tumor cell surface are referred to as neoantigens, as they are tumor-specific and not expressed in normal cells. Due to their tumor specificity, neoantigens have a strong potential to induce an anti-tumor immune response and have been investigated for development of personalized therapeutic cancer vaccines. The current study describes the development of a clinical grade neoantigen vaccine formulation (FRAME-001) intended as immunotherapy in advanced NSCLC in combination with the immune checkpoint inhibitor pembrolizumab. The detection of aberrant tumor-specific transcripts as well as an algorithm to select immunogenic neoantigen peptides are described. Subsequently, selected neoantigen peptides were synthesized with a high throughput synthesis platform and aseptically formulated under good manufacturing practice (GMP) conditions into four aqueous peptides mixtures that each contained six neoantigen peptides. A validated stability-indicating analytical method was developed in which we considered the personalized nature of the formulation. An extensive stability study performed either at -25 degrees C or -80 degrees C showed that the formulation was stable for up to 32 weeks. The formulation was mixed with the vaccine adjuvant Montanide ISA 51 VG, which yielded the final vaccine emulsion. The stability of the vaccine emulsion was demonstrated using microscopic examination, differential light scattering, and the water-drop test. The presented data show that FRAME-001 is a feasible personalized vaccine formulation for the treatment of stage III-IV NSCLC. The presented data may give guidance in the development of novel personalized therapeutic vaccines since this formulation strategy could be used for any cancer indication

Engineering access to higher education through higher education fairs

Text from van Zanten A., Legavre A. “Engineering access to higher education through higher education fairs”, in Goastellec G., Picard F. (ed.) The Roles of Higher Education and Research in the Fabric of Societies, Leuven, Sense Publishers, 2014 (in press). Transition to higher education is a major social process. This transition has been mostly studied by French sociologists of education and higher education from perspectives focusing predominantly on the role of the socio-economic status, academic profiles and different tracks followed by secondary school students (Merle 1996, Duru-Bellat and Kieffer 2008, Convert 2010), and, to a lesser extent, on the types of secondary schools attended (Duru-Bellat and Mingat 1998, Nakhili 2005) and the local higher education provision (Berthet et al. 2010, Orange 2013). Although these structural determinants play a major role in explaining significant regularities, they provide more powerful explanations for individuals representing the extremes of the different variables considered, leaving room for the influence of other major factors for those students in intermediate situations. In addition, even in the case of students occupying extreme positions, structural perspectives better explain the distribution of students between different higher education tracks than they do between institutions and disciplines. In this chapter, we adopt a perspective that we see as complementary to and interacting with the perspective centred on structural determinants by focusing on the role of the devices that mediate the exchanges between students and higher education institutions, and more specifically on one device: higher education fairs. Our purpose in doing so is not only to document how these various devices frame, in ways that remain largely unexplored by researchers, exchanges between providers and consumers of higher education but also to point out – and further explore in future publications – how these devices, and the specific features of fairs, contribute to the reproduction and transformation of educational inequalities in access to higher education (Benninghoff et al. 2012)

Probing structural relaxation in complex fluids by critical fluctuations

Complex fluids, such as polymer solutions and blends, colloids and gels, are of growing interest in fundamental and applied soft-condensed-matter science. A common feature of all such systems is the presence of a mesoscopic structural length scale intermediate between atomic and macroscopic scales. This mesoscopic structure of complex fluids is often fragile and sensitive to external perturbations. Complex fluids are frequently viscoelastic (showing a combination of viscous and elastic behaviour) with their dynamic response depending on the time and length scales. Recently, non-invasive methods to infer the rheological response of complex fluids have gained popularity through the technique of microrheology, where the diffusion of probe spheres in a viscoelastic fluid is monitored with the aid of light scattering or microscopy. Here we propose an alternative to traditional microrheology that does not require doping of probe particles in the fluid (which can sometimes drastically alter the molecular environment). Instead, our proposed method makes use of the phenomenon of "avoided crossing" between modes associated with the structural relaxation and critical fluctuations that are spontaneously generated in the system.Comment: 4 pages, 4 figure

GATA transcription factors in testicular adrenal rest tumours

Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation