Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Euforea treatment algorithm for allergic rhinitis

Non peer reviewe

Fuzzy and Quantitative Model-based Control-systems for Robotic Manipulators

Generally fuzzy control systems use simple controllers with a few inputs and one output. Here more complex control systems, based explicitly on a model of the controlled process and primarily developed in the frame of quantitative control, are adapted to fuzzy control. Three model-based control schemes are proposed for position control of a robotic manipulator. The feasibility of such control systems and the ability of their quantitative and fuzzy implementations to cope with disturbances, parameter variations and unmodelled dynamics, are evaluated and compared by simulation analysis. The extension of the model-based control paradigm to fuzzy control pinpoints a concept unknown in the usual fuzzy controllers, i.e. intrinsically fuzzy variables that may be a source of problems in fuzzy feedback loops

Practical design of nonlinear fuzzy controllers with stability analysis for regulating processes with unknown mathematical models - Comment

It is shown in this note that the fuzzy controller with (locally) linear control rules used in Ying (1994) cannot be linearized around the origin, and therefore local stability of closed-loop systems including this type of fuzzy controller cannot be analyzed by means of the Lyapunov's first method. Besides, it is proved that, with another choice of inference law, the fuzzy controller with (locally) linear control rules can be linearized in a neighbourhood of the origin. Copyright (C) 1996 Elsevier Science Ltd

A guide for the building of daylight scale models

Scale models are frequently used to evaluate daylighting performances of buildings. In order to get accurate results, there are several rules to respect for building these scale models. Some of these rules are universal and others depend on the measurement and observation devices, the type of sky under which the study is carried out and the objectives of the study. This paper, based on the authors experience and on a literature review, presents rules to respect when building a mock-up for daylighting studies. These rules are illustrated by project examples that were tested under the Belgian artificial skies (Single-patch sky and sun simulator, Mirror box and Mechanical sun)