Mechanisms of High Frequency Stimulation of the Subthalamic Nucleus in Parkinson\u27s Disease: From Local to Distal Effects on the Basal Ganglia Network

No abstract availabl

Microcontact printing process for the patterned growth of individual CNTs

We report an original approach to pattern a substrate with isolated carbon nanotubes. Through the improvement of the microcontact printing technique by the use of a new composite stamp, we were able to produce on flat substrates micrometric features of a catalyst suitable for the localised growth of single-walled carbon nanotubes by catalytic chemical vapour deposition. This catalyst material is for the first time prepared via an original sol–gel process. The growth of straight carbon nanotubes between the patterns was observed and a method to promote the controlled growth of such isolated nanoobjects is thus conceivable

Pallidal origin of GABA release within the substantia nigra pars reticulata during high-frequency stimulation of the subthalamic nucleus

High-frequency stimulation of the subthalamic nucleus (HFS-STN) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the neurochemical basis of its effects remains unknown. We showed previously that 1 h of HFS-STN in normal rats increases extracellular glutamate (Glu) level in the output nuclei of the STN, the globus pallidus (GP), and the substantia nigra pars reticulata (SNr), consistent with an increase in the activity of STN neurons. HFS-STN also increases GABA levels in the SNr, but the origin of this increase is unclear. We investigated the effectiveness of HFS-STN for improving Parkinson's disease symptoms, using intracerebral microdialysis to determine the extracellular Glu and GABA levels of the GP and SNr in response to HFS-STN in anesthetized hemiparkinsonian rats [6-hydroxydopamine lesion of the substantia nigra pars compacta (SNc)]. Basal levels of Glu and GABA in the GP and SNr were significantly higher in hemiparkinsonian than in intact rats. HFS-STN did not affect extracellular Glu level in the SNr of hemiparkinsonian rats but doubled the level of GABA. Ibotenic acid lesion of the GP abolished the increase in GABA levels in the SNr induced by HFS-STN in SNc-lesioned rats. These results provide neurochemical confirmation of the hyperactivity of the STN after dopaminergic denervation and suggest that the therapeutic effects of HFS-STN may result partly from the stimulation of pallidonigral fibers, thereby revealing a potential role for pallidal GABA in the inhibition of basal ganglial output structures during HFS-STN

Weight versus voice : how foreign subsidiaries gain attention from corporate headquarters in emerging markets

The research problem of this project is to investigate if, and how, Birkinshaw and Bouquet‟s model of subsidiary attention seeking by means of weight and voice needs to be modified for MNC subsidiaries operating in emerging markets. The qualitative research technique used for this research was the multiple-case study method. Key findings are that weight is moderated by institutional environments and voice by national culture in emerging markets. Recommendations are made to assist managers of subsidiaries in increasing weight and voice in emerging markets in order to gain more attention from Corporate Headquarters. CopyrightDissertation (MBA)--University of Pretoria, 2010.Gordon Institute of Business Science (GIBS)unrestricte

Does MPTP intoxication in mice induce metabolite changes in the nucleus accumbens? A 1H nuclear MRS study: A severe DA denervation in VTA induces metabolite changes in the NAc

International audienceUsing in vivo 1H NMR spectroscopy in a mouse model of Parkinson's disease, we previously showed that glutamate concentrations in the dorsal striatum were highest after dopamine denervation associated with an increase in gamma-aminobutyric acid (GABA) and (Gln) glutamine levels. The aim of this study was to determine whether the changes previously observed in the motor part of the striatum were reproduced in a ventral part of the striatum, the nucleus accumbens (NAc). This study was carried out on controls and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. In vivo spectra were acquired for a voxel (8 L) in the dorsal striatum, and in the NAc (1.56 L). NMR acquisitions were first performed 10 days after the last MPTP injection in a basal condition [after saline intraperitoneal (i.p.) injection] and then in the same animal the week after basal NMR acquisitions, after acute levodopa administration (200 mg kg1, i.p.). Immunohistochemistry was used to determine the levels of (Glu) glutamate, glutamine synthetase (GS) and glutamic acid decarboxylase (GAD) isoform 67 in these two structures. The Glu, Gln and GABA concentrations obtained in the basal state were higher in the NAc of MPTP-intoxicated mice which have the higher dopamine denervation in the ventral tegmental area (VTA) and in the dorsal striatum. Levodopa decreased the levels of these metabolites in MPTP-intoxicated mice to levels similar to those in controls. In parallel, immunohistochemical staining showed that glutamate, GS and GAD67 immunoreactivity increased in the dorsal striatum of MPTP-intoxicated mice and in the NAc for animals with a severe dopamine denervation in VTA. These findings strongly supported a hyperactivity of the glutamatergic cortico-striatal pathway and changes in glial activity when the dopaminergic denervation in the VTA and substantia nigra pars compacta (SNc) was severe. Copyright (c) 2012 John Wiley & Sons, Ltd

Alignment and nano-connections of isolated carbon nanotubes

We report a new approach for the alignment and the electrical nano-connection of isolated carbon nanotubes (CNTs). Through a novel combination of proven technics, we have been able to align isolated carbon nanotubes and selectively contact those CNTs by high resolution electron beam lithography (HREBL). Resistance versus temperature (R(T)) experiments have been carried out to determine the reliability of the metal–CNTs interface and to probe the electronic conductance of the CNT

Probing the electronic properties of individual carbon nanotube in 35 T pulsed magnetic field

After optimization of the alignment and the nano-contact processes of isolated single wall and double-walls carbon nanotube, we investigate the high magnetic field effects on the electronic transport properties of an individual metallic CNT. We develop pioneer multi-probes magneto-transport experiments under a 35 T pulsed field which reveal an unexpected oscillatory behavior of RðHÞ inconsistent with existing theories

Freshness and Reactivity Analysis in Globally Asynchronous Locally Time-Triggered Systems

International audienceCritical embedded systems are often designed as a set of real-time tasks, running on shared computing modules, and communicating through networks. Because of their critical nature, such systems have to meet timing properties. To help the designers to prove the correctness of their system, the real-time systems community has developed numerous approaches for analyzing the worst case times either on the processors (e.g. worst case execution time of a task) or on the networks (e.g. worst case traversal time of a message). However, there is a growing need to consider the complete system and to be able to determine end-to-end properties. Such properties apply to a functional chain which describes the behavior of a sequence of functions, not necessarily hosted on a shared module, from an input until the production of an output. This paper explores two end-to-end properties: freshness and reactivity, and presents an analysis method based on Mixed Integer Linear Programming (MILP). This work is supported by the French National Research Agency within the Satrimmap project

A Synchronous Look at the Simulink Standard Library

International audienceHybrid systems modelers like Simulink come with a rich collection of discrete-time and continuous-time blocks. Most blocks are not defined in terms of more elementary ones—and some cannot be—but are instead written in imperative code and explained informally in a reference manual. This raises the question of defining a minimal set of orthogonal programming constructs such that most blocks can be programmed directly and thereby given a specification that is mathematically precise, and whose compiled version performs comparably to handwritten code. In this paper, we show that a fairly large set of blocks of a standard library like the one provided by Simulink can be programmed in a precise, purely functional language using stream equations, hierarchical automata, Ordinary Differential Equations (ODEs), and deterministic synchronous parallel composition. Some blocks cannot be expressed in our setting as they mix discrete-time and continuous-time signals in unprincipled ways that are statically forbidden by the type checker. The experiment is conducted in Zélus, a synchronous language that conservatively extends Lustre with ODEs to program systems that mix discrete-time and continuous-time signals

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

A promising approach to increase the specificity of photosensitisers used in photodynamic therapy has been through conjugation to monoclonal antibodies (MAb) directed against tumour-associated antigens. Many of the conjugations performed to date have relied on the activated ester method, which can lead to impure conjugate preparations and antibody crosslinking. Here, we report the development of photosensitiser–MAb conjugates utilising two porphyrin isothiocyanates. The presence of a single reactive isothiocyanate allowed facile conjugation to MAb FSP 77 and 17.1A directed against internalising antigens, and MAb 35A7 that binds to a non-internalising antigen. The photosensitiser–MAb conjugates substituted with 1–3 mol of photosensitiser were characterised in vitro. No appreciable loss of immunoreactivity was observed and binding specificity was comparable to that of the unconjugated MAb. Substitution with photosensitiser had a minimal effect on antibody biodistribution in vivo for the majority of the conjugates, although a decreased serum half-life was observed using a cationic photosensitiser at the higher loading ratios. Tumour-to-normal tissue ratios as high as 33.5 were observed using MAb 35A7 conjugates. The internalising conjugate showed a higher level of phototoxicity as compared with the non-internalising reagent, using a cell line engineered to express both target antigens. These data demonstrate the applicability of the isothiocyanate group for the development of high-quality conjugates, and the use of internalising MAb to significantly increase the photodynamic efficiency of conjugates during photoimmunotherapy