Development of a digital phase measuring system with microradian precision for LISA

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Phasemeter core for intersatellite laser heterodyne interferometry: modelling, simulations and experiments

Inter satellite laser interferometry is a central component of future space-borne gravity instruments like LISA, eLISA, NGO and future geodesy missions. The inherently small laser wavelength allows to measure distance variations with extremely high precision by interfering a reference beam with a measurement beam. The readout of such interferometers is often based on tracking phasemeters, able to measure the phase of an incoming beatnote with high precision over a wide range of frequencies. The implementation of such phasemeters is based on all digital phase-locked loops, hosted in FPGAs. Here we present a precise model of an all digital phase locked loop that allows to design such a readout algorithm and we support our analysis by numerical performance measurements and experiments with analog signals.Comment: 17 pages, 6 figures, accepted for publication in CQ

Breadboard model of the LISA phasemeter

An elegant breadboard model of the LISA phasemeter is currently under development by a Danish-German consortium. The breadboard is build in the frame of an ESA technology development activity to demonstrate the feasibility and readiness of the LISA metrology baseline architecture. This article gives an overview about the breadboard design and its components, including the distribution of key functionalities.Comment: 5 pages, 3 figures, published in ASP Conference Series, Vol. 467, 9th LISA Symposium (2012), pp 271-27

Deep phase modulation interferometry

We have developed a method to equip homodyne interferometers with the capability to operate with constant high sensitivity over many fringes for continuous real-time tracking. The method can be considered as an extension of the "J_1...J_4" methods, and its enhancement to deliver very sensitive angular measurements through Differential Wavefront Sensing is straightforward. Beam generation requires a sinusoidal phase modulation of several radians in one interferometer arm. On a stable optical bench, we have demonstrated a long-term sensitivity over thousands of seconds of 0.1 mrad/sqrt[Hz] that correspond to 20 pm/sqrt[Hz] in length, and 10 nrad/sqrt[Hz] in angle at millihertz frequencies

Readout for intersatellite laser interferometry: Measuring low frequency phase fluctuations of HF signals with microradian precision

Precision phase readout of optical beat note signals is one of the core techniques required for intersatellite laser interferometry. Future space based gravitational wave detectors like eLISA require such a readout over a wide range of MHz frequencies, due to orbit induced Doppler shifts, with a precision in the order of $\mu \textrm{rad}/\sqrt{\textrm{Hz}}$ at frequencies between $0.1\,\textrm{mHz}$ and $1\,\textrm{Hz}$. In this paper, we present phase readout systems, so-called phasemeters, that are able to achieve such precisions and we discuss various means that have been employed to reduce noise in the analogue circuit domain and during digitisation. We also discuss the influence of some non-linear noise sources in the analogue domain of such phasemeters. And finally, we present the performance that was achieved during testing of the elegant breadboard model of the LISA phasemeter, that was developed in the scope of an ESA technology development activity.Comment: submitted to Review of Scientific Instruments on April 30th 201

a randomized, placebo-controlled phase II AIO trial with serum biomarker program

Background As a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response. Methods This double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively. Results Overall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70–1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50–1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed. Conclusions Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti- angiogenic RTK inhibitors are warranted. Trial registration This study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland- Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

<p>Abstract</p> <p>Background</p> <p>Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease.</p> <p>Methods</p> <p>The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts.</p> <p>Results</p> <p>Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p < 0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769.</p> <p>Conclusions</p> <p>The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.</p

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Works by Rosy Geiger-Kullmann.

List of Geiger-Kullmann's compositions, with notes on the title, source text, arrangement, time signature, key, and instrumentation of the compositions, as well as short remarks on the physical state and form of the composition text. Also included are also 2 obituaries for Geiger-Kullmann which contain some biographical information.Ruth Geiger-EngelJoachim MartiniComposer, born 1886 in Frankfurt. Wife of Rudolf Geiger, former vice-president of Congregation Habonim. Died 1964 in Monterey (California).The original German-language inventory is available in the folder.Frankfurt am MainProcessed for digitizationRe-integrated clippingsSent for digitizationReturned from digitizationLinked to online manifestationdigitize