University of Kiel

About: University of Kiel is a education organization based out in Kiel, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 27816 authors who have published 57114 publications receiving 2061802 citations. The organization is also known as: Christian Albrechts University & Christian-Albrechts-Universität zu Kiel.

Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008

Abstract: Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR- and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008 The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance' The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols

The Solar Orbiter mission. Science overview

Abstract: Aims. Solar Orbiter, the first mission of ESA’s Cosmic Vision 2015–2025 programme and a mission of international collaboration between ESA and NASA, will explore the Sun and heliosphere from close up and out of the ecliptic plane. It was launched on 10 February 2020 04:03 UTC from Cape Canaveral and aims to address key questions of solar and heliospheric physics pertaining to how the Sun creates and controls the Heliosphere, and why solar activity changes with time. To answer these, the mission carries six remote-sensing instruments to observe the Sun and the solar corona, and four in-situ instruments to measure the solar wind, energetic particles, and electromagnetic fields. In this paper, we describe the science objectives of the mission, and how these will be addressed by the joint observations of the instruments onboard.Methods. The paper first summarises the mission-level science objectives, followed by an overview of the spacecraft and payload. We report the observables and performance figures of each instrument, as well as the trajectory design. This is followed by a summary of the science operations concept. The paper concludes with a more detailed description of the science objectives.Results. Solar Orbiter will combine in-situ measurements in the heliosphere with high-resolution remote-sensing observations of the Sun to address fundamental questions of solar and heliospheric physics. The performance of the Solar Orbiter payload meets the requirements derived from the mission’s science objectives. Its science return will be augmented further by coordinated observations with other space missions and ground-based observatories.

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Abstract: Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).

Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis

Abstract: Mathematical modeling is required for understanding the complex behavior of large signal transduction networks. Previous attempts to model signal transduction pathways were often limited to small systems or based on qualitative data only. Here, we developed a mathematical modeling framework for understanding the complex signaling behavior of CD95(APO-1/Fas)-mediated apoptosis. Defects in the regulation of apoptosis result in serious diseases such as cancer, autoimmunity, and neurodegeneration. During the last decade many of the molecular mechanisms of apoptosis signaling have been examined and elucidated. A systemic understanding of apoptosis is, however, still missing. To address the complexity of apoptotic signaling we subdivided this system into subsystems of different information qualities. A new approach for sensitivity analysis within the mathematical model was key for the identification of critical system parameters and two essential system properties: modularity and robustness. Our model describes the regulation of apoptosis on a systems level and resolves the important question of a threshold mechanism for the regulation of apoptosis.