Subtraction of test mass angular noise in the LISA Technology Package interferometer

We present recent sensitivity measurements of the LISA Technology Package interferometer with articulated mirrors as test masses, actuated by piezo-electric transducers. The required longitudinal displacement resolution of 9 pm/sqrt[Hz] above 3 mHz has been demonstrated with an angular noise that corresponds to the expected in on-orbit operation. The excess noise contribution of this test mass jitter onto the sensitive displacement readout was completely subtracted by fitting the angular interferometric data streams to the longitudinal displacement measurement. Thus, this cross-coupling constitutes no limitation to the required performance of the LISA Technology Package interferometry.Comment: Applied Physics B - Lasers and Optics (2008

Unraveling the In Vivo Protein Corona

Understanding the behavior of nanoparticles upon contact with a physiological environment is of urgent need in order to improve their properties for a successful therapeutic application. Most commonly, the interaction of nanoparticles with plasma proteins are studied under in vitro conditions. However, this has been shown to not reflect the complex situation after in vivo administration. Therefore, here we focused on the investigation of magnetic nanoparticles with blood proteins under in vivo conditions. Importantly, we observed a radically different proteome in vivo in comparison to the in vitro situation underlining the significance of in vivo protein corona studies. Next to this, we found that the in vivo corona profile does not significantly change over time. To mimic the in vivo situation, we established an approach, which we termed “ex vivo” as it uses whole blood freshly prepared from an animal. Overall, we present a comprehensive analysis focusing on the interaction between nanoparticles and blood proteins under in vivo conditions and how to mimic this situation with our ex vivo approach. This knowledge is needed to characterize the true biological identity of nanoparticles

Learning from Sustainability-Oriented Innovation

This chapter argues that insights from the realm of sustainability-oriented innovation can provide useful answers to the question of why Small and Medium-Sized Enterprises (SMEs) would (or should) become interested in implementing responsible innovation practices. It is based on the assumption that “responsible innovation” and “sustainability-oriented innovation” are different approaches aimed at orienting innovation towards increased positive impacts on social and natural environments. Motivations and influences for pursuing sustainability-oriented inno-vation have been studied in the past, and can provide insights into reasons for pursu-ing the implementation of responsible innovation practices

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition

Acceleration disturbances and requirements for ASTROD I

ASTRODynamical Space Test of Relativity using Optical Devices I (ASTROD I) mainly aims at testing relativistic gravity and measuring the solar-system parameters with high precision, by carrying out laser ranging between a spacecraft in a solar orbit and ground stations. In order to achieve these goals, the magnitude of the total acceleration disturbance of the proof mass has to be less than 10−13 m s−2 Hz−1/2 at 0.1 m Hz. In this paper, we give a preliminary overview of the sources and magnitude of acceleration disturbances that could arise in the ASTROD I proof mass. Based on the estimates of the acceleration disturbances and by assuming a simple controlloop model, we infer requirements for ASTROD I. Our estimates show that most of the requirements for ASTROD I can be relaxed in comparison with Laser Interferometer Space Antenna (LISA).Comment: 19 pages, two figures, accepted for publication by Class. Quantum Grav. (at press

State space modelling and data analysis exercises in LISA Pathfinder

LISA Pathfinder is a mission planned by the European Space Agency to test the key technologies that will allow the detection of gravitational waves in space. The instrument on-board, the LISA Technology package, will undergo an exhaustive campaign of calibrations and noise characterisation campaigns in order to fully describe the noise model. Data analysis plays an important role in the mission and for that reason the data analysis team has been developing a toolbox which contains all the functionalities required during operations. In this contribution we give an overview of recent activities, focusing on the improvements in the modelling of the instrument and in the data analysis campaigns performed both with real and simulated data.Comment: Plenary talk presented at the 9th International LISA Symposium, 21-25 May 2012, Pari

Targeted delivery of an ADP-ribosylating bacterial toxin into cancer cells

The actin cytoskeleton is an attractive target for bacterial toxins. The ADP-ribosyltransferase TccC3 from the insect bacterial pathogen Photorhabdus luminescence modifies actin to force its aggregation. We intended to transport the catalytic part of this toxin preferentially into cancer cells using a toxin transporter (Protective antigen, PA) which was redirected to Epidermal Growth Factor Receptors (EGFR) or to human EGF receptors 2 (HER2), which are overexpressed in several cancer cells. Protective antigen of anthrax toxin forms a pore through which the two catalytic parts (lethal factor and edema factor) or other proteins can be transported into mammalian cells. Here, we used PA as a double mutant (N682A, D683A; mPA) which cannot bind to the two natural anthrax receptors. Each mutated monomer is fused either to EGF or to an affibody directed against the human EGF receptor 2 (HER2). We established a cellular model system composed of two cell lines representing HER2 overexpressing esophageal adenocarcinomas (EACs) and EGFR overexpressing esophageal squamous cell carcinomas (ESCCs). We studied the specificity and efficiency of the re-directed anthrax pore for transport of TccC3 toxin and established Photorhabdus luminescence TccC3 as a toxin suitable for the development of a targeted toxin selectively killing cancer cells