Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines

Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype–phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance—i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding

Separation – integration – and now …? - An historical perspective on the relationship between German management accounting and financial accounting

German accounting has traditionally followed a dual ledger approach with strictly separated internal cost accounting, as the basis for management information, and external financial accounting focusing on creditor protection and based on the commercial law. However, the increased adoption of integrated accounting system implies a significant change in the relationship between financial and management accounting systems. We use Hegelian dialectic to trace the historical development of German accounting from separated systems towards antithetical propositions of full integration, and the emergence of partial integration as the synthesis of this transformation process. For this reason, our paper provides a comprehensive analysis of the literature on the relationship between financial and management accounting in Germany. On this basis, we elaborate how financial accounting in Germany has been shaped by its economic context and legislation, and how financial accounting – accompanied by institutional pressures – in turn influenced management accounting. We argue that the changing relationship between management and financial accounting in the German context illustrates how current accounting practice is shaped not only by its environment, but also by its historical path. Based on this reasoning, we discuss several avenues for future research

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Untersuchung der Relaxation von Photofrin-generiertem Singulett-Sauerstoff in Lösungen und in vitro

Im Rahmen der Grundlagenforschung zur Photodynamischen Therapie wurde das Relaxationsverhalten von Photofrin-generiertem Singulett-Sauerstoff über seine Lumineszenz bei 1270 nm zeitaufgelöst untersucht, sowohl in Lösungen in Deuteriumoxid, Suspensionen von Phosphatidylcholin in Wasser und Deuteriumoxid und in Suspensionen von HT-29 Tumorzellen in Wasser und Deuteriumoxid. In wäßriger Lösung wurde eine bidirektionale Kopplung des Singulett-Zustands von Sauerstoff an den Triplett-Zustand von Photofrin nachgewiesen und theoretisch beschrieben. Die Messungen wurden ausgeführt mit einem neuartigen, hochempfindlichen Infrarot-Photomultiplier

Status Characteristics and Expectation States: A Priori Model Parameters and Test

The authors theoretically derive f(i) parameter values for use in calculating relative expectations (ep – eo) in the graph model of the theory of status characteristics and expectation states. This WP was published by the authors (1992)

Biomechanics of knee ligaments: injury, healing, and repair

Abstract Knee ligament injuries are common, particularly in sports and sports related activities. Rupture of these ligaments upsets the balance between knee mobility and stability, resulting in abnormal knee kinematics and damage to other tissues in and around the joint that lead to morbidity and pain. During the past three decades, significant advances have been made in characterizing the biomechanical and biochemical properties of knee ligaments as an individual component as well as their contribution to joint function. Further, significant knowledge on the healing process and replacement of ligaments after rupture have helped to evaluate the effectiveness of various treatment procedures. This review paper provides an overview of the current biological and biomechanical knowledge on normal knee ligaments, as well as ligament healing and reconstruction following injury. Further, it deals with new and exciting functional tissue engineering approaches (ex. growth factors, gene transfer and gene therapy, cell therapy, mechanical factors, and the use of scaffolding materials) aimed at improving the healing of ligaments as well as the interface between a replacement graft and bone. In addition, it explores the anatomical, biological and functional perspectives of current reconstruction procedures. Through the utilization of robotics technology and computational modeling, there is a better understanding of the kinematics of the knee and the in situ forces in knee ligaments and replacement grafts. The research summarized here is multidisciplinary and cutting edge that will ultimately help improve the treatment of ligament injuries. The material presented should serve as an inspiration to future investigators.