Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis

Successful therapy with anti-CD20 monoclonal antibodies (mAbs) has reinforced the key role of B cells in the immunopathology of multiple sclerosis (MS). This study aimed to determine the effects of a novel class of anti-CD20 mAbs on vascular and extravascular central nervous system (CNS)-infiltrating B cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male hCD20xhIgR3 mice and wild-type C57BL/6 (B6) mice were immunized with human myelin oligodendrocyte glycoprotein (MOG)_1–125 to induce EAE. While hCD20xhIgR3 mice were injected intravenously with an anti-human CD20 mAb (5 mg/kg) (rituximab (a type I anti-CD20 mAb) or obinutuzumab (a type II anti-CD20 mAb), B6 mice received the anti-mouse CD20 antibody 18B12. Neither mAb affected clinical disease or serum antibody levels. Obinutuzumab and rituximab had an impact on splenic and CNS-infiltrated B cells with slightly differential depletion efficacy. Additionally, obinutuzumab had beneficial effects on spinal cord myelination. B cell depletion rates in the 18B12/B6 model were comparable with those observed in obinutuzumab-treated hCD20xhIgR3 mice. Our results demonstrate the usefulness of anti-CD20 mAbs for the modulation of B cell-driven peripheral immune response and CNS pathology, with type II antibodies potentially being superior to type I in the depletion of tissue-infiltrating B cells.     

On-the-fly verification and optimization of DTA-properties for large Markov chains

We consider continuous-time Markov chains (CTMC) with very large or infinite state spaces which are, for instance, used to model biological processes or to evaluate the performance of computer and communication networks. We propose a numerical integration algorithm to approximate the probability that a process conforms to a specification that belongs to a subclass of deterministic timed automata (DTAs). We combat the state space explosion problem by using a dynamic state space that contains only the most relevant states. In this way we avoid an explicit construction of the state-transition graph of the composition of the DTA and the CTMC. We also show how to maximize the probability of acceptance of the DTA for parametric CTMCs and substantiate the usefulness of our approach with experimental results from biological case studies.     

Water-soluble SG1-based alkoxyamines: A breakthrough in controlled/living free-radical polymerization in aqueous dispersed media

This feature article describes the application of nitroxide-mediated controlled/living free-radical polymerization in aqueous dispersed systems such as miniemulsion and emulsion polymerizations. It mainly focuses on the acyclic nitroxide SG1 with derived alkoxyamines and aims to show how the recent development of new water-soluble species has allowed a true emulsion polymerization process to be successfully implemented and block copolymers to be created directly in latex particles.     

Treatment of posttraumatic stress disorder by trained lay counselors in an African refugee settlement: A randomized controlled trial.

Traumatic stress due to conflict and war causes major mental health problems in many resource-poor countries. The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder (PTSD) in a refugee settlement. In a randomized controlled dissemination trial in Uganda with 277 Rwandan and Somalian refugees who were diagnosed with PTSD the authors investigated the effectiveness of psychotherapy administered by lay counselors. Strictly manualized narrative exposure therapy (NET) was compared with more flexible trauma counseling (TC) and a no-treatment monitoring group (MG). Fewer participants (4%) dropped out of NET treatment than TC (21%). Both active treatment groups were statistically and clinically superior to MG on PTSD symptoms and physical health but did not differ from each other. At follow-up, a PTSD diagnosis could not be established anymore in 70% of NET and 65% TC participants, whereas only 37% in MG did not meet PTSD criteria anymore. Short-term psychotherapy carried out by lay counselors with limited training can be effective to treat war-related PTSD in a refugee settlement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modelling of Biochemical Reactions by Stochastic Automata Networks

This paper presents a stochastic modelling framework based on stochastic automata networks (SANs) for the analysis of complex biochemical reaction networks. Our approach takes into account the discrete character of quantities of components (i.e. the individual populations of the involved chemical species) and the inherent probabilistic nature of microscopic molecular collisions. Moreover, as for process calculi that have recently been applied to systems in biology, the SAN approach has the advantage of a modular design process being adequate for abstraction purposes. The associated composition operator leads to an elegant and compact representation of the underlying continuous-time Markov chain in form of a Kronecker product. SANs have been extensively used in performance analysis of computer systems and a large variety of numerical and simulative analysis algorithms exist. We illustrate that describing a biochemical reaction network by means of a SAN offers promising opportunities to get insight into the quantitative behaviour of systems in biology while taking advantage of the benefits of a compositional modelling approach.