Myasthenia gravis: a pathologic approach

Our immune system protects us from all kinds of pathogens our body faces every day. However, the immune system can also initiate an immune response against our own proteins. This is called autoimmunity. Myasthenia gravis (MG) is a rare autoimmune disease in which patients show severe muscle weakness, due to antibody production against proteins of the neuromuscular junction, which is the connection between nerve and muscle. At this moment, three different forms of myasthenia gravis are identified. Muscle-specific tyrosine kinase (MuSK)-MG is a form of MG in which patients produce antibodies, predominantly immunoglobulin (Ig)G4, against MuSK. This paper is a summary of a B cell immortalization project, in which antibodies produced by MuSK-MG patients are investigated. The aim of this study was to sequence and generate antibodies produced by these patients in vitro to learn more about the pathological mechanism of MuSK-MG. Blood-derived B cells of MuSK-MG patients were immortalized by the Epstein Bar Virus and stimulated to grow and produce antibodies in culture. Genes of these antibodies were amplified and analyzed. These amplification products were cloned in vectors and will be transfected in a human embryonic kidney (HEK)-cell line. This study showed that the B cell immortalization method worked and that MuSK-MG patients predominantly produce IgM antibodies against MuSK. This is very striking as literature states that these patients predominantly produce IgG4 against MuSK. It is suggested that this high production of IgM is due to the absence of the heavy chain isotype switch from IgM to IgG. Moreover, as the pathologic mechanism of MuSK-MG is still unknown, IgM may play an important pathological role

inel method control in 3-D hyberbolic grid generation

A method is presented for the generation of OH type grids about transport type aircraft. The method combines a hyperbolic grid generation scheme with source terms obtained with a panel method in such a way that OH type grids around fairly complex shapes with concavities can be generated easily. The components of the method: a method to generate grids with a panel method and the hyperbolic grid generation scheme, will be described and applications will be shown

Methods and tools supporting urban resilience planning: experiences from Cork, Ireland

To prevent flood disasters, policymakers call for resilient cities which are better able to cope with flood hazards. However, actual adoption of resilience measures in urban planning is still limited, partly because it is not sufficiently clear how and to what extent resilience should and can be enhanced. To develop resilience strategies, information on the current resilience and on the effects of measures should be available. Since cities are complex systems, an assessment of resilience requires the input of different actors. To obtain and combine this input, a comprehensive approach which brings together many actors is required. Furthermore, resilience must be integrated in planning frameworks in order to enhance adoption by city policy makers. Tools which support and structure the contribution of different disciplines and actors will help to obtain information on the current resilience and to develop a shared vision on measures to enhance urban resilience. We illustrate our view with an example on Cork, Ireland

Methods and tools supporting urban resilience planning: experiences from Cork, Ireland

To prevent flood disasters, policymakers call for resilient cities which are better able to cope with flood hazards. However, actual adoption of resilience measures in urban planning is still limited, partly because it is not sufficiently clear how and to what extent resilience should and can be enhanced. To develop resilience strategies, information on the current resilience and on the effects of measures should be available. Since cities are complex systems, an assessment of resilience requires the input of different actors. To obtain and combine this input, a comprehensive approach which brings together many actors is required. Furthermore, resilience must be integrated in planning frameworks in order to enhance adoption by city policy makers. Tools which support and structure the contribution of different disciplines and actors will help to obtain information on the current resilience and to develop a shared vision on measures to enhance urban resilience. We illustrate our view with an example on Cork, Ireland

Towards A Decision Support System For Consequence Analysis Of Flooding On Critical Infrastructure

The flooding of the rivers Danube and Elbe caused: dozens of deaths; damaged bridges, streets, dams, railway lines and houses; outages of electrical power, drinking water supply, fixed and mobile telecommunication, water level gauges and purification plants; and crop shortfall. The analysis of the events and emergency response actions exposed flaws in preparedness and the understanding of emergency responders of the need to protect critical infrastructure. For instance, water level gauges failed, flood models for extreme amounts of water were flawed, emergency call numbers became unreachable and first responders could not communicate. As a consequence, protection and evacuation measures could not be planned properly, and the recovery and restoration process took long. The project Critical Infrastructure Preparedness and Resiliance Research Network develops a decision support system (DSS). Within this decision support critical infrastructure simulators are linked with simulators of external threats for critical infrastructure. Analysis tools supply real-time or near real-time data for consequence analysis for different courses of action. This provides the Emergency Manager with a comprehensive assessment of the behaviour of critical infrastructure under severe perturbations (produced by the loss of one or more elements in one or more Infrastructures). In the study area at the Rhine in the Dutch-German border area different dike rings with different safety levels are present. In case of high water, emergency managers have different options to manage the flood, for instance one dik ring can be flooded to prevent dike breaks further downstream. We show cascading effects of different flooding scenarios on power grids, telecommunications and drinking water infrastructure, logistics and transport

H2 activation using the first 1:1:1 hetero-tri(aryl)borane

The novel 1:1:1 hetero-tri(aryl)borane (pentafluorophenyl){3,5-bis(trifluoromethyl)phenyl}(pentachlorophenyl)borane has been synthesised and structurally characterised. This has been show to act as the Lewis acidic component in FLPs for the heterolytic cleavage of H2 with three Lewis bases

Metal-free hydrogenation catalyzed by an air-stable borane: use of solvent as a frustrated Lewis base

In recent years ‘frustrated Lewis pairs’ (FLPs) have been shown to be effective metal‐free catalysts for the hydrogenation of many unsaturated substrates. Even so, limited functional‐group tolerance restricts the range of solvents in which FLP‐mediated reactions can be performed, with all FLP‐mediated hydrogenations reported to date carried out in non‐donor hydrocarbon or chlorinated solvents. Herein we report that the bulky Lewis acids B(C6Cl5)x(C6F5)3−x (x=0–3) are capable of heterolytic H2 activation in the strong‐donor solvent THF, in the absence of any additional Lewis base. This allows metal‐free catalytic hydrogenations to be performed in donor solvent media under mild conditions; these systems are particularly effective for the hydrogenation of weakly basic substrates, including the first examples of metal‐free catalytic hydrogenation of furan heterocycles. The air‐stability of the most effective borane, B(C6Cl5)(C6F5)2, makes this a practically simple reaction method