The costs of crossing paths and switching tasks between audition and vision.

Switching from one functional or cognitive operation to another is thought to rely on executive/control processes. The efficacy of these processes may depend on the extent of overlap between neural circuitry mediating the different tasks; more effective task preparation (and by extension smaller switch costs) is achieved when this overlap is small. We investigated the performance costs associated with switching tasks and/or switching sensory modalities. Participants discriminated either the identity or spatial location of objects that were presented either visually or acoustically. Switch costs between tasks were significantly smaller when the sensory modality of the task switched versus when it repeated. This was the case irrespective of whether the pre-trial cue informed participants only of the upcoming task, but not sensory modality (Experiment 1) or whether the pre-trial cue was informative about both the upcoming task and sensory modality (Experiment 2). In addition, in both experiments switch costs between the senses were positively correlated when the sensory modality of the task repeated across trials and not when it switched. The collective evidence supports the independence of control processes mediating task switching and modality switching and also the hypothesis that switch costs reflect competitive interference between neural circuits.

Presentació del dossier Jornades sobre Metodologia de Recerca

L'impuls de l'activitat investigadora caracteritza actualment la major part de les polítiques educatives, i és una realitat inquestionable que augmenta les exigències institucionals relatives a la producció científica en un panorama cada vegada més internacionalitzat. El saber es difon mitjançant circuits cada vegada més ramificats i fluids, alhora que s'accedeix a un volum creixent de producció científica amb una facilitat impensable fa una década, pero també és un fet que es posen més en evidéncia els desfasaments entre ambits científics, entre famílies d'una determinada comunitat científica, entre perspectives agresolades i novedoses del coneixement, entre cosmovisions localistes i d'ampli calat, entre tecnologies transferibles i reflexions epistemologiques ... i podríem seguir mencionant una Ilarga sé-rie de contradiccions que impregnen la nostra realitat diaria. En definitiva, si bé és cert que es tracta de popularitzar l'activitat investigadora, també ho és que es multipliquen determinades barreres que amb més o menys subtilesa s'han d'esquivar perqué la investigació i els seus resultats siguin una realitat tangible.

Donor-site morbidity of the sensate extended lateral arm flap.

The free extended lateral arm flap (ELAF) has gained increasing popularity thank to its slimness and versatility, longer neurovascular pedicle, and greater flap size when compared with the original flap design. The aim of this study was to assess the donor-site morbidity associated with this extended procedure. A retrospective study of 25 consecutive patients analyzing postoperative complications using a visual analogue scale questionnaire revealed high patients satisfaction and negligible donor-site morbidity of the ELAF. Scar visibility was the commonest negative outcome. Impaired mobility of the elbow had the highest correlation with patient dissatisfaction. Sensory deficits or paresthetic disorders did not affect patient satisfaction. The extension of the lateral arm flap and positioning over the lateral humeral epicondyle is a safe and well-accepted procedure with minimal donor-site morbidity. To optimize outcomes, a maximal flap width of 6 or 7 cm and intensive postoperative mobilization therapy is advisable.

Prescriptions de protection incendie en Suisse : étude de leur domaine d'application et de leur respect par l'investigation d'incendies

Avant - Propos Le feu et la protection incendie Quel que soit l'usage d'un bâtiment, chaque étape de la construction est soumise à l'application de normes. Certaines, utilisées par les architectes et les ingénieurs, concernent le gros oeuvre ; en simplifiant leur rôle, elles assurent la solidité et la stabilité de l'immeuble. Si celui-ci est ouvert au public, des aménagements particuliers concernant la sécurité des personnes sont imposés. D'autres comme les prescriptions sur les installations électriques intérieures, précisent la manière de construire une alimentation, le type de matériel utilisable en fonction du courant et de la tension, les sécurités destinées à éviter toute détérioration des circuits et tout risque d'électrocution, etc. Enfin, les prescriptions en matière de protection incendie jouent évidemment un rôle préventif et, dans le domaine judiciaire, servent de références pour qualifier une éventuelle infraction ; elles évitent qu'une source de chaleur installée dans un bâtiment - tel qu'un appareil de chauffage ou des plaques de cuisson - ou susceptible d'apparaître consécutivement à l'usure d'un matériau ou à son vieillissement - disparition d'un isolant thermique, défaut d'étanchéité d'un conduit transportant les gaz chauds de combustion, par exemple - ne communiquent une partie de l'énergie calorifique dégagée à un combustible et ne l'enflamme. Le concept de protection incendie implique d'exposer et de développer les principales notions relatives à l'inflammation d'un matériau, à sa combustion ainsi qu'au transport de l'énergie calorifique. Fréquemment, le milieu dans lequel le générateur de chaleur est installé joue un rôle dans la phase d'allumage de l'incendie. Il est évident que les prescriptions de protection incendie s'appliquent à chaque élément de construction et, par conséquent, doivent être respectées par toute personne participant à la réalisation d'un ouvrage : le chauffagiste, l'électricien, l'installateur sanitaire, le constructeur de cuisine, mais également le maçon qui construit la cheminée, le peintre et le décorateur qui posent des revêtements ou des garnitures inflammables, le menuisier qui utilise le bois pour dissimuler des conduites de fumée, etc. Dès lors, tout sinistre, hormis celui qui est perpétré délibérément, ne peut s'expliquer que par : - le non-respect ou le défaut d'application d'une prescription de protection incendie; - une lacune de la norme qui ignore une source d'échauffement et/ou un mode de transfert de l'énergie calorifique. Le but premier de ce travail consiste à : - analyser les sinistres survenus durant les années 1999 à 2005 dans plusieurs cantons suisses qui ont fait l'objet d'une investigation de la part d'un service technique de la police ou d'un expert ; - examiner les éléments retenus pour expliquer la cause de l'incendie à la norme afin de répondre à la question : « l'application d'une ou de plusieurs directives lors de l'installation ou de l'utilisation du générateur d'énergie calorifique aurait-elle évité à ce dernier de communiquer une partie de la chaleur dégagée à un combustible et à l'enflammer ? » Le second objectif visé est d'apporter une solution à la question précédente : - si la norme existe, c'est un défaut d'installation ou d'utilisation de la source de chaleur qui est à l'origine de l'incendie. Il importe donc de connaître la raison pour laquelle la prescription a été ignorée ou appliquée de manière erronée ou lacunaire; - si la norme n'existe pas, ce sont les prescriptions en matière de protection incendie qui doivent être complétées. Le chapitre suivant abordera ces thèmes en proposant divers postulats destinés à évaluer l'efficacité actuelle du concept de protection incendie en Suisse.

Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice

Background: Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG) disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrP(sc)) of the natural cellular prion protein (PrP(c)) encoded by the Prnp gene. Although several roles have been attributed to PrP(c), its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrP(c) studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. Principal Findings: Here we explore the role of PrP(c) expression in neurotransmission and neural excitability using wild-type, Prnp -/- and PrP(c)-overexpressing mice (Tg20 strain). By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp -/- mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp -/- and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABA(A) and AMPA-kainate receptors are co-regulated in both Prnp -/- and Tg20 mice. Conclusions/Significance: Present results demonstrate that PrP(c) is necessary for the proper homeostatic functioning of hippocampal circuits, because of its relationships with GABA(A) and AMPA-Kainate neurotransmission. New PrP(c) functions have recently been described, which point to PrP(c) as a target for putative therapies in Alzheimer's disease. However, our results indicate that a "gain of function" strategy in Alzheimer's disease, or a "loss of function" in prionopathies, may impair PrP(c) function, with devastating effects. In conclusion, we believe that present data should be taken into account in the development of future therapies.

PDMP blocks brefeldin a-induced retrograde membrane transport from Golgi to ER: evidence for involvement of calcium homeostasis and dissociation from sphingolipid metabolism

In this study, we show that an inhibitor of sphingolipid biosynthesis, d,l-threo-1-phenyl-2- decanoylamino-3-morpholino-1-propanol (PDMP), inhibits brefeldin A (BFA)-induced retrograde membrane transport from Golgi to endoplasmic reticulum (ER). If BFA treatment was combined with or preceded by PDMP administration to cells, disappearance of discrete Golgi structures did not occur. However, when BFA was allowed to exert its effect before PDMP addition, PDMP could not ¿rescue¿ the Golgi compartment. Evidence is presented showing that this action of PDMP is indirect, which means that the direct target is not sphingolipid metabolism at the Golgi apparatus. A fluorescent analogue of PDMP, 6-(N-[7-nitro-2,1,3-benzoxadiazol-4-yl]amino)hexanoyl-PDMP (C6-NBD-PDMP), did not localize in the Golgi apparatus. Moreover, the effect of PDMP on membrane flow did not correlate with impaired C6-NBD-sphingomyelin biosynthesis and was not mimicked by exogenous C6-ceramide addition or counteracted by exogenous C6-glucosylceramide addition. On the other hand, the PDMP effect was mimicked by the multidrug resistance protein inhibitor MK571. The effect of PDMP on membrane transport correlated with modulation of calcium homeostasis, which occurred in a similar concentration range. PDMP released calcium from at least two independent calcium stores and blocked calcium influx induced by either extracellular ATP or thapsigargin. Thus, the biological effects of PDMP revealed a relation between three important physiological processes of multidrug resistance, calcium homeostasis, and membrane flow in the ER/ Golgi system.

Diacylglycerol is required for the formation of COPI vesicles in the Golgi-to-ER transport pathway

Diacylglycerol is necessary for trans-Golgi network (TGN) to cell surface transport, but its functional relevance in the early secretory pathway is unclear. Although depletion of diacylglycerol did not affect ER-to-Golgi transport, it led to a redistribution of the KDEL receptor to the Golgi, indicating that Golgi-to-ER transport was perturbed. Electron microscopy revealed an accumulation of COPI-coated membrane profiles close to the Golgi cisternae. Electron tomography showed that the majority of these membrane profiles originate from coated buds, indicating a block in membrane fission. Under these conditions the Golgi-associated pool of ARFGAP1 was reduced, but there was no effect on the binding of coatomer or the membrane fission protein CtBP3/BARS to the Golgi. The addition of 1,2-dioctanoyl-sn-glycerol or the diacylglycerol analogue phorbol 12,13-dibutyrate reversed the effects of endogenous diacylglycerol depletion. Our findings implicate diacylglycerol in the retrograde transport of proteins from Golgi to the ER and suggest that it plays a critical role at a late stage of COPI vesicle formation.

Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

Développement d'un outil de gestion graduée des risques spécifique au cas des nanomatériaux : rapport d'appui scientifique et technique

L' évaluation quantitative des dangers et des expositions aux nanomatériaux se heurte à de nombreuses incertitudes qui ne seront levées qu'à mesure de la progression des connaissances scientifiques de leurs propriétés. L' une des conséquences de ces incertitudes est que les valeurs limites d'exposition professionnelle définies actuellement pour les poussières ne sont pas nécessairement pertinentes aux nanomatériaux. En l'absence de référentiel quantitatif et, à la demande de la DGS pour éclairer les réflexions de l' AFNOR et de l'ISO sur le sujet, une démarche de gestion graduée des risques (control banding) a été élaborée au sein de l' Anses. Ce développement a été réalisé à l'aide d'un groupe d'experts rapporteurs rattaché au Comité d'experts spécialisés évaluation des risques liés aux agents physiques, aux nouvelles technologies et aux grands aménagements. La mise en oeuvre de la démarche de gestion graduée des risques proposée repose sur quatre grandes étapes: 1. Le recueil des informations. Cette étape consiste à réunir les informations disponibles sur les dangers du nanomatériau manufacturé considéré ; ainsi que sur l'exposition potentielle des personnes aux postes de travail (observation sur le terrain, mesures, etc.). 2. L'attribution d'une bande de danger. Le danger potentiel du nanomatériau manufacturé présent, qu'il soit brut où incorporé dans une matrice (liquide ou solide) est évalué dans cette étape. La bande danger attribuée tient compte de la dangerosité du produit bulk ou de sa substance analogue à l'échelle non-nanométrique, de la bio-persistance du matériau (pour les matériaux fibreux), de sa solubilité et de son éventuelle réactivité. 3. Attribution d'une bande d'exposition. La bande d'exposition du nanomatériau manufacturé considéré ou du produit en contenant est définie par le niveau de potentiel d'émission du produit. Elle tient compte de sa forme physique (solide, liquide, poudre aérosol), de sa pulvérulence et de sa volatilité. Le nombre de travailleurs, la fréquence, la durée d'exposition ainsi que la quantité mise en oeuvre ne sont pas pris en compte, contrairement à une évaluation classique des risques chimiques. 4. Obtention d'une bande de maîtrise des risques. Le croisement des bandes de dangers et d'exposition préalablement attribuées permet de défi nir le niveau de maîtrise du risque. Il fait correspondre les moyens techniques et organisationnels à mettre en oeuvre pour maintenir le risque au niveau le plus faible possible. Un plan d'action est ensuite défi ni pour garantir l'effi cacité de la prévention recommandée par le niveau de maîtrise déterminé. Il tient compte des mesures de prévention déjà existantes et les renforce si nécessaire. Si les mesures indiquées par le niveau de maîtrise de risque ne sont pas réalisables, par exemple, pour des raisons techniques ou budgétaires, une évaluation de risque approfondie devra être réalisée par un expert. La gestion graduée des risques est une méthode alternative pour réaliser une évaluation qualitative de risques et mettre en place des moyens de prévention sans recourir à une évaluation quantitative des risques. Son utilisation semble particulièrement adaptée au contexte des nanomatériaux manufacturés, pour lequel les choix de valeurs de référence (Valeurs limites d'exposition en milieu professionnel) et des techniques de mesurage appropriées souffrent d'une grande incertitude. La démarche proposée repose sur des critères simples, accessibles dans la littérature scientifi que ou via les données techniques relatives aux produits utilisés. Pour autant, sa mise en oeuvre requiert des compétences minimales dans les domaines de la prévention des risques chimiques (chimie, toxicologie, etc.), des nanosciences et des nanotechnologies.

Effect of expiratory flow limitation on respiratory mechanical impedance: a model study

Large phasic variations of respiratory mechanical impedance (Zrs) have been observed during induced expiratory flow limitation (EFL) (M. Vassiliou, R. Peslin, C. Saunier, and C. Duvivier. Eur. Respir. J. 9: 779-786, 1996). To clarify the meaning of Zrs during EFL, we have measured from 5 to 30 Hz the input impedance (Zin) of mechanical analogues of the respiratory system, including flow-limiting elements (FLE) made of easily collapsible rubber tubing. The pressures upstream (Pus) and downstream (Pds) from the FLE were controlled and systematically varied. Maximal flow (Vmax) increased linearly with Pus, was close to the value predicted from wave-speed theory, and was obtained for Pus-Pds of 4-6 hPa. The real part of Zin started increasing abruptly with flow (V) >85%Vmax and either further increased or suddenly decreased in the vicinity of V¿max. The imaginary part of Zin decreased markedly and suddenly above 95%Vmax. Similar variations of Zin during EFL were seen with an analogue that mimicked the changes of airway transmural pressure during breathing. After pressure andV measurements upstream and downstream from the FLE were combined, the latter was analyzed in terms of a serial (Zs) and a shunt (Zp) compartment. Zs was consistent with a large resistance and inertance, and Zp with a mainly elastic element having an elastance close to that of the tube walls. We conclude that Zrs data during EFL mainly reflect the properties of the FLE.

Increase of [(18)F]FLT Tumor Uptake In Vivo Mediated by FdUrd: Toward Improving Cell Proliferation Positron Emission Tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D: -glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Residual thermomechanical stresses in thinned-chip assemblies

A new technology for the three-dimensional (3-D) stacking of very thin chips on a substrate is currently under development within the ultrathin chip stacking (UTCS) Esprit Project 24910. In this work, we present the first-level UTCS structure and the analysis of the thermomechanical stresses produced by the manufacturing process. Chips are thinned up to 10 or 15 m. We discuss potentially critical points at the edges of the chips, the suppression of delamination problems of the peripheral dielectric matrix and produce a comparative study of several technological choices for the design of metallic interconnect structures. The purpose of these calculations is to give inputs for the definition of design rules for this technology. We have therefore undertaken a programme that analyzes the influence of sundry design parameters and alternative development options. Numerical analyses are based on the finite element method.

A physical frequency-dependent compact model for RF integrated inductors

A frequency-dependent compact model for inductors in high ohmic substrates, which is based on an energy point-of-view, is developed. This approach enables the description of the most important coupling phenomena that take place inside the device. Magnetically induced losses are quite accurately calculated and coupling between electric and magnetic fields is given by means of a delay constant. The later coupling phenomenon provides a modified procedure for the computation of the fringing capacitance value, when the self-resonance frequency of the inductor is used as a fitting parameter. The model takes into account the width of every metal strip and the pitch between strips. This enables the description of optimized layout inductors. Data from experiments and electromagnetic simulators are presented to test the accuracy of the model.

Continuous phase shift of sinusoidal signals using injection locked oscillators

This work presents an alternative to generate continuous phase shift of sinusoidal signals based on the use of super harmonic injection locked oscillators (ILO). The proposed circuit is a second harmonic ILO with varactor diodes as tuning elements. In the locking state, by changing the varactor bias, a phase shift instead of a frequency shift is observed at the oscillator output. By combining two of these circuits, relative phases up to 90 could be achieved. Two prototypes of the circuit have been implemented and tested, a hybrid version working in the range of 200-300 MHz and a multichip module (MCM) version covering the 900¿1000 MHz band.

BPSK to ASK signal conversion using injection-locked oscillators-Part I: theory

This paper presents a new method and circuit for the conversion of binary phase-shift keying (BPSK) signals into amplitude shift keying signals. The basic principles of the conversion method are the superharmonic injection and locking of oscillator circuits, and interference phenomena. The first one is used to synchronize the oscillators, while the second is used to generate an amplitude interference pattern that reproduces the original phase modulation. When combined with an envelope detector, the proposed converter circuit allows the coherent demodulation of BPSK signals without need of any explicit carrier recovery system. The time response of the converter circuit to phase changes of the input signal, as well as the conversion limits, are discussed in detail.