Adaptive circular deconvolution by model selection under unknown error distribution

We consider a circular deconvolution problem, in which the density $f$ of a circular random variable $X$ must be estimated nonparametrically based on an i.i.d. sample from a noisy observation $Y$ of $X$. The additive measurement error is supposed to be independent of $X$. The objective of this work was to construct a fully data-driven estimation procedure when the error density $\varphi$ is unknown. We assume that in addition to the i.i.d. sample from $Y$, we have at our disposal an additional i.i.d. sample drawn independently from the error distribution. We first develop a minimax theory in terms of both sample sizes. We propose an orthogonal series estimator attaining the minimax rates but requiring optimal choice of a dimension parameter depending on certain characteristics of $f$ and $\varphi$, which are not known in practice. The main issue addressed in this work is the adaptive choice of this dimension parameter using a model selection approach. In a first step, we develop a penalized minimum contrast estimator assuming that the error density is known. We show that this partially adaptive estimator can attain the lower risk bound up to a constant in both sample sizes $n$ and $m$. Finally, by randomizing the penalty and the collection of models, we modify the estimator such that it no longer requires any previous knowledge of the error distribution. Even when dispensing with any hypotheses on $\varphi$, this fully data-driven estimator still preserves minimax optimality in almost the same cases as the partially adaptive estimator. We illustrate our results by computing minimal rates under classical smoothness assumptions.Comment: Published in at http://dx.doi.org/10.3150/12-BEJ422 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Adaptive Gaussian inverse regression with partially unknown operator

This work deals with the ill-posed inverse problem of reconstructing a function $f$ given implicitly as the solution of $g = Af$, where $A$ is a compact linear operator with unknown singular values and known eigenfunctions. We observe the function $g$ and the singular values of the operator subject to Gaussian white noise with respective noise levels $\varepsilon$ and $\sigma$. We develop a minimax theory in terms of both noise levels and propose an orthogonal series estimator attaining the minimax rates. This estimator requires the optimal choice of a dimension parameter depending on certain characteristics of $f$ and $A$. This work addresses the fully data-driven choice of the dimension parameter combining model selection with Lepski's method. We show that the fully data-driven estimator preserves minimax optimality over a wide range of classes for $f$ and $A$ and noise levels $\varepsilon$ and $\sigma$. The results are illustrated considering Sobolev spaces and mildly and severely ill-posed inverse problems

Transnational Ashkenaz: Yiddish culture after the Holocaust

After the Holocaust’s near complete destruction of European Yiddish cultural centres, the Yiddish language was largely viewed as a remnant of the past, tragically eradicated in its prime. This article reveals that, on the contrary, for two and a half decades following the Holocaust Yiddish culture was in dynamic flux. Yiddish writers and cultural organisations maintained a staggering level of activity in fostering publications and performances, collecting archival and historical materials, and launching young literary talents. This article provides a cultural historical map of a Yiddish transnational network that derived its unity from the common purpose of commemorating and bearing witness to the destruction of the Jewish heartland in Central and Eastern Europe.&nbsp

IST Austria Thesis

Directed cell migration is a hallmark feature, present in almost all multi-cellular organisms. Despite its importance, basic questions regarding force transduction or directional sensing are still heavily investigated. Directed migration of cells guided by immobilized guidance cues - haptotaxis - occurs in key-processes, such as embryonic development and immunity (Middleton et al., 1997; Nguyen et al., 2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues comprise adhesive ligands, such as collagen and fibronectin (Barczyk et al., 2009), or chemokines - the main guidance cues for migratory leukocytes (Middleton et al., 1997; Weber et al., 2013). While adhesive ligands serve as attachment sites guiding cell migration (Carter, 1965), chemokines instruct haptotactic migration by inducing adhesion to adhesive ligands and directional guidance (Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis of the cellular response to immobilized guidance cues requires in vitro assays that foster cell migration, offer accurate control of the immobilized cues on a subcellular scale and in the ideal case closely reproduce in vivo conditions. The exploration of haptotactic cell migration through design and employment of such assays represents the main focus of this work. Dendritic cells (DCs) are leukocytes, which after encountering danger signals such as pathogens in peripheral organs instruct naïve T-cells and consequently the adaptive immune response in the lymph node (Mellman and Steinman, 2001). To reach the lymph node from the periphery, DCs follow haptotactic gradients of the chemokine CCL21 towards lymphatic vessels (Weber et al., 2013). Questions about how DCs interpret haptotactic CCL21 gradients have not yet been addressed. The main reason for this is the lack of an assay that offers diverse haptotactic environments, hence allowing the study of DC migration as a response to different signals of immobilized guidance cue. In this work, we developed an in vitro assay that enables us to quantitatively assess DC haptotaxis, by combining precisely controllable chemokine photo-patterning with physically confining migration conditions. With this tool at hand, we studied the influence of CCL21 gradient properties and concentration on DC haptotaxis. We found that haptotactic gradient sensing depends on the absolute CCL21 concentration in combination with the local steepness of the gradient. Our analysis suggests that the directionality of migrating DCs is governed by the signal-to-noise ratio of CCL21 binding to its receptor CCR7. Moreover, the haptotactic CCL21 gradient formed in vivo provides an optimal shape for DCs to recognize haptotactic guidance cue. By reconstitution of the CCL21 gradient in vitro we were also able to study the influence of CCR7 signal termination on DC haptotaxis. To this end, we used DCs lacking the G-protein coupled receptor kinase GRK6, which is responsible for CCL21 induced CCR7 receptor phosphorylation and desensitization (Zidar et al., 2009). We found that CCR7 desensitization by GRK6 is crucial for maintenance of haptotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. In the context of the organism, immobilized haptotactic guidance cues often coincide and compete with soluble chemotactic guidance cues. During wound healing, fibroblasts are exposed and influenced by adhesive cues and soluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly, migrating DCs are exposed to both, soluble chemokines (CCL19 and truncated CCL21) inducing chemotactic behavior as well as the immobilized CCL21. To quantitatively assess these complex coinciding immobilized and soluble guidance cues, we implemented our chemokine photo-patterning technique in a microfluidic system allowing for chemotactic gradient generation. To validate the assay, we observed DC migration in competing CCL19/CCL21 environments. Adhesiveness guided haptotaxis has been studied intensively over the last century. However, quantitative studies leading to conceptual models are largely missing, again due to the lack of a precisely controllable in vitro assay. A requirement for such an in vitro assay is that it must prevent any uncontrolled cell adhesion. This can be accomplished by stable passivation of the surface. In addition, controlled adhesion must be sustainable, quantifiable and dose dependent in order to create homogenous gradients. Therefore, we developed a novel covalent photo-patterning technique satisfying all these needs. In combination with a sustainable poly-vinyl alcohol (PVA) surface coating we were able to generate gradients of adhesive cue to direct cell migration. This approach allowed us to characterize the haptotactic migratory behavior of zebrafish keratocytes in vitro. Furthermore, defined patterns of adhesive cue allowed us to control for cell shape and growth on a subcellular scale

Characterization of recombinant Modified Vaccinia virus Ankara delivering Zika virus nonstructural proteins NS2B and NS3pro

Zika virus (ZIKV) was largely ignored for many years after it was first isolated in 1947. Unexpectedly, in 2007 ZIKV caused outbreaks in the Federate States of Micronesia, and from there spread throughout the South Pacific and to Latin America. These outbreaks were associated with neurological diseases and congenital birth disorders, which resulted in the World Health Organization (WHO) declaring the ZIKV outbreak as a “Public Health Emergency of International Concern” in 2016. To date, there are no vaccines or therapeutic agents against ZIKV licensed. As ZIKV shares similarities in immunodominant epitopes of its structural proteins with other related flaviviruses, infections with these pathogens can result in a cross-reactive antibody response. These non-neutralizing immunoglobulins can lead to increased viral replication and disease severity through the phenomenon of antibody-dependent enhancement (ADE). Moreover, flavivirus-vaccines based on structural proteins can also exacerbate the course of infection through this pathomechanism. Consequently, a new strategy to design a vaccine that avoids eliciting ADE could potentially be achieved by targeting the nonstructural proteins of ZIKV. This approach is suggested to mitigate the risk of ADE by inducing a balanced humoral and cellular immune response. However, the role of nonstructural proteins in the immune response against flaviviruses is still poorly understood. Modified vaccinia virus Ankara (MVA), a highly attenuated and replication deficient vaccinia virus with an exceptional safety profile, represents one of the most advanced recombinant viral vector platforms for the development of new vaccines against infectious diseases. This study aims to providing new approaches for a better understanding of the involvement of the cellular immune response in protection against ZIKV and thus to improve future flavivirus vaccine design. To accomplish this goal, we evaluated the safety, immunogenicity, and protective capacity of recombinant MVA-vaccine candidates expressing the ZIKV nonstructural proteins ZIKV-NS2B and ZIKV-NS3pro (MVA-NS2B and MVA-NS3pro)