Data-Driven Mathematical Model of Apoptosis Regulation in Memory Plasma Cells

Memory plasma cells constitutively produce copious amounts of antibodies, imposing a critical risk factor for autoimmune disease. We previously found that plasma cell survival requires secreted factors such as APRIL and direct contact to stromal cells, which act in concert to activate NF-κB- and PI3K-dependent signaling pathways to prevent cell death. However, the regulatory properties of the underlying biochemical network are confounded by the complexity of potential interaction and cross-regulation pathways. Here, based on flow-cytometric quantification of key signaling proteins in the presence or absence of the survival signals APRIL and contact to the stromal cell line ST2, we generated a quantitative model of plasma cell survival. Our model emphasizes the non-redundant nature of the two plasma cell survival signals APRIL and stromal cell contact, and highlights a requirement for differential regulation of individual caspases. The modeling approach allowed us to unify distinct data sets and derive a consistent picture of the intertwined signaling and apoptosis pathways regulating plasma cell survival.Leibniz associationLeibniz ScienceCampus Chronic inflammationDeutsche ForschungsgemeinschaftInnovative Medicines InitiativeDr. Rolf M. Schwiete FoundationPeer Reviewe

Magna Carta, the Rule of Law and the Limits on Government

This paper surveys the legal tradition that links Magna Carta with the modern concepts of the rule of law and the limits on government. It documents that the original understanding of the rule of law included substantive commitments to individual freedom and limited government. Then, it attempts at explaining how and why such commitments were lost to a formalist interpretation of the rule of law from 1848 to 1939. The paper concludes by arguing how a revival of the substantive commitments of the rule of law is central in a project of reshaping modern states

Introducción a la filosofía del derecho

Tít. orig:"Vorschule der rechtsphilosophie

Einfuhrung in die Rechts-Wissenschaft

269 hal.; ill.; 22 c

El delincuente por convicción

La presente nota contiene unas breves reflexiones de Gustav Radbruch sobre el tratamiento punitivo de la delincuencia cometida con base en un imperativo moral del autor. El principal argumento es que no cabe la aspiración de reforma ni de retribución sobre el delincuente por convicción, sino tan sólo la custodia o encierro con fines esencialmente asegurativos y de prevención general