Partition coefficient and molecular flexibility: the concept of lipophilicity space.

The rationale of this study was to investigate molecular flexibility and its influence on physicochemical properties with a view to uncovering additional information on the fuzzy concept of dynamic molecular structure. Indeed, it is now known that computed molecular interaction fields (MIFs) such as molecular electrostatic potentials (MEPs) and lipophilicity potentials (MLPs) are conformation-dependent, as are dipole moments. A database of 125 compounds was used whose conformational space was explored, while conformation-dependent parameters were computed for each non-redundant conformer found in the conformational space of the compounds. These parameters were the virtual log P (log P(MLP), calculated by a MLP approach), the apolar surface area (ASA), polar surface area (PSA), and solvent-accessible surface (SAS). For each compound, the range taken by each parameter (its property space) was divided by the number of rotors taken as an index of flexibility, yielding a parameter termed 'molecular sensitivity'. This parameter was poorly correlated with others (i.e., it contains novel information) and showed the compounds to fall into two broad classes. 'Sensitive' molecules are those whose computed property ranges are markedly sensitive to conformational effects, whereas 'insensitive' (in fact, less sensitive) molecules have property ranges which are comparatively less affected by conformational fluctuations. A pharmacokinetic application is presented.

A fully-automatic caudate nucleus segmentation of brain MRI: application in volumetric analysis of pediatric attention-deficit/hyperactivity disorder

Background Accurate automatic segmentation of the caudate nucleus in magnetic resonance images (MRI) of the brain is of great interest in the analysis of developmental disorders. Segmentation methods based on a single atlas or on multiple atlases have been shown to suitably localize caudate structure. However, the atlas prior information may not represent the structure of interest correctly. It may therefore be useful to introduce a more flexible technique for accurate segmentations. Method We present Cau-dateCut: a new fully-automatic method of segmenting the caudate nucleus in MRI. CaudateCut combines an atlas-based segmentation strategy with the Graph Cut energy-minimization framework. We adapt the Graph Cut model to make it suitable for segmenting small, low-contrast structures, such as the caudate nucleus, by defining new energy function data and boundary potentials. In particular, we exploit information concerning the intensity and geometry, and we add supervised energies based on contextual brain structures. Furthermore, we reinforce boundary detection using a new multi-scale edgeness measure. Results We apply the novel CaudateCut method to the segmentation of the caudate nucleus to a new set of 39 pediatric attention-deficit/hyperactivity disorder (ADHD) patients and 40 control children, as well as to a public database of 18 subjects. We evaluate the quality of the segmentation using several volumetric and voxel by voxel measures. Our results show improved performance in terms of segmentation compared to state-of-the-art approaches, obtaining a mean overlap of 80.75%. Moreover, we present a quantitative volumetric analysis of caudate abnormalities in pediatric ADHD, the results of which show strong correlation with expert manual analysis. Conclusion CaudateCut generates segmentation results that are comparable to gold-standard segmentations and which are reliable in the analysis of differentiating neuroanatomical abnormalities between healthy controls and pediatric ADHD.

The set of undominated imputations and the core: an axiomatic approach

This paper provides an axiomatic framework to compare the D-core (the set of undominatedimputations) and the core of a cooperative game with transferable utility. Theorem1 states that the D-core is the only solution satisfying projection consistency, reasonableness (from above), (*)-antimonotonicity, and modularity. Theorem 2 characterizes the core replacing (*)-antimonotonicity by antimonotonicity. Moreover, these axioms alsocharacterize the core on the domain of convex games, totally balanced games, balancedgames, and superadditive games

All assignment games with the same core have the same nucleolus

There exist coalitional games with transferable utility which have the same core but different nucleoli. We show that this cannot happen in the case of assignment games. Whenever two assignment games have the same core, their nucleoli also coincide. To show this, we prove that the nucleolus of an assignment game coincides with that of its buyer-seller exact representative

On the monotonic core

The monotonic core of a cooperative game with transferable utility (T.U.-game) is the set formed by all its Population Monotonic Allocation Schemes. In this paper we show that this set always coincides with the core of a certain game associated to the initial game.

On the coincidence between the Shimomura's bargaining sets and the core

[cat] En l'article es dona una condició necessària per a que els conjunts de negociació definits per Shimomura (1997) i el nucli d'un joc cooperatiu amb utilitat transferible coincideixin. A tal efecte, s'introdueix el concepte de vectors de màxim pagament. La condició necessària consiteix a verificar que aquests vectors pertanyen al nucli del joc.

Aggregate monotonic stable single-valued solutions for cooperative games

[cat] En aquest treball caracteritzem les solucions puntuals de jocs cooperatius d'utilitat transferible que compleixen selecció del core i monotonia agregada. També mostrem que aquestes dues propietats són compatibles amb la individualitat racional, la propietat del jugador fals i la propietat de simetria. Finalment, caracteritzem les solucions puntuals que compleixen les cinc propietats a l'hora.

Pure sensory neuropathy in patients with primary Sjogren's syndrome: clinical, immunological and electromyographic findings

A pure sensory neuropathy caused by lymphocytic infiltration of the dorsal root ganglia has been reported in a few patients with Sjögren's syndrome. The clinical, immunological, and electromyographic findings of five patients with this type of neuropathy and primary Sjögren's syndrome were reviewed. Typical clinical indications were the presence of a chronic asymmetrical sensory deficit, initial disease in the hands with a predominant loss of the vibratory and joint position senses, and an association with Adie's pupil syndrome or trigeminal sensory neuropathy. The simultaneous impairment of the central and peripheral evoked cortical potentials suggested that there was a lesion of the neuronal cell body. The neuropathy preceded the diagnosis of Sjögren's syndrome in four patients. Four patients were positive for Ro antibodies, but systemic vasculitis or malignancy was not found after a mean follow up of six years. These findings indicate that in patients with a sensory neuropathy the diagnosis of Sjögren's syndrome has to be considered, even if the patient denies the presence of sicca symptoms, and that appropriate tests must be carried out.

Mouse GLUT9: evidences for a urate uniporter.

GLUT9 (SLC2A9) is a newly described urate transporter whose function, characteristics, and localization have just started to be elucidated. Some transport properties of human GLUT9 have been studied in the Xenopus laevis oocyte expression system, but the type of transport (uniport, coupled transport system, stoichiometry ... .) is still largely unknown. We used the same experimental system to characterize in more detail the transport properties of mouse GLUT9, its sensitivity to several uricosuric drugs, and the specificities of two splice variants, mGLUT9a and mGLUT9b. [(14)C]urate uptake measurements show that both splice variants are high-capacity urate transporters and have a K(m) of approximately 650 microM. The well-known uricosuric agents benzbromarone (500 microM) and losartan (1 mM) inhibit GLUT9-mediated urate uptake by 90 and 50%, respectively. Surprisingly, phloretin, a glucose-transporter blocker, inhibits [(14)C]urate uptake by approximately 50% at 1 mM. Electrophysiological measurements suggest that urate transport by mouse GLUT9 is electrogenic and voltage dependent, but independent of the Na(+) and Cl(-) transmembrane gradients. Taken together, our results suggest that GLUT9 works as a urate (anion) uniporter. Finally, we show by RT-PCR performed on RNA from mouse kidney microdissected tubules that GLUT9a is expressed at low levels in proximal tubules, while GLUT9b is specifically expressed in distal convoluted and connecting tubules. Expression of mouse GLUT9 in the kidney differs from that of human GLUT9, which could account for species differences in urate handling.

A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving.

The epithelial Na+ channel (ENaC) belongs to a new class of channel proteins called the ENaC/DEG superfamily involved in epithelial Na+ transport, mechanotransduction, and neurotransmission. The role of ENaC in Na+ homeostasis and in the control of blood pressure has been demonstrated recently by the identification of mutations in ENaC beta and gamma subunits causing hypertension. The function of ENaC in Na+ reabsorption depends critically on its ability to discriminate between Na+ and other ions like K+ or Ca2+. ENaC is virtually impermeant to K+ ions, and the molecular basis for its high ionic selectivity is largely unknown. We have identified a conserved Ser residue in the second transmembrane domain of the ENaC alpha subunit (alphaS589), which when mutated allows larger ions such as K+, Rb+, Cs+, and divalent cations to pass through the channel. The relative ion permeability of each of the alphaS589 mutants is related inversely to the ionic radius of the permeant ion, indicating that alphaS589 mutations increase the molecular cutoff of the channel by modifying the pore geometry at the selectivity filter. Proper geometry of the pore is required to tightly accommodate Na+ and Li+ ions and to exclude larger cations. We provide evidence that ENaC discriminates between cations mainly on the basis of their size and the energy of dehydration.

The role of actions in auditory object discrimination.

Action representations can interact with object recognition processes. For example, so-called mirror neurons respond both when performing an action and when seeing or hearing such actions. Investigations of auditory object processing have largely focused on categorical discrimination, which begins within the initial 100 ms post-stimulus onset and subsequently engages distinct cortical networks. Whether action representations themselves contribute to auditory object recognition and the precise kinds of actions recruiting the auditory-visual mirror neuron system remain poorly understood. We applied electrical neuroimaging analyses to auditory evoked potentials (AEPs) in response to sounds of man-made objects that were further subdivided between sounds conveying a socio-functional context and typically cuing a responsive action by the listener (e.g. a ringing telephone) and those that are not linked to such a context and do not typically elicit responsive actions (e.g. notes on a piano). This distinction was validated psychophysically by a separate cohort of listeners. Beginning approximately 300 ms, responses to such context-related sounds significantly differed from context-free sounds both in the strength and topography of the electric field. This latency is >200 ms subsequent to general categorical discrimination. Additionally, such topographic differences indicate that sounds of different action sub-types engage distinct configurations of intracranial generators. Statistical analysis of source estimations identified differential activity within premotor and inferior (pre)frontal regions (Brodmann's areas (BA) 6, BA8, and BA45/46/47) in response to sounds of actions typically cuing a responsive action. We discuss our results in terms of a spatio-temporal model of auditory object processing and the interplay between semantic and action representations.

Estudio de la reversibilidad de las alteraciones del SN en alcoholicos cronicos abstinentes con potenciales evocados

Se realizó un estudio de seguimiento de un año de duración a un gmpo de 50 pacientes alcohólicos crónicos en régimen de abstinencia completa. Se practicaron tres tipos de potenciales evocados, auditivos de tronco cerebral (PEATC), visuales en la modalidad de pattern (PEVP) y auditivos de latencia larga (LAEPs). Nuestro objetivo fue evaluar la posible reversibilidad de las alteraciones provocadas por el consumo crónico de alcohol en el sistema nervioso. Al mes de abstinencia los alcohólicos presentaron alteraciones en diversos parametros de PES. Al año de abstinencia se mantuvieron alterados P3 y NI-P2 de LAEPs, y 111-V y I-V de PEATC, mientrasse normalizaron PI00 de PEVP y N2 de LAEPs. Durante este primer aiio se produjo una recuperación parcial de las alteraciones funcionales provocadas por el consumo crónico de alcohol, dependiendo el grado de recuperación del sistema neural explorado.

Thermal resonance in signal transmission

We use temperature tuning to control signal propagation in simple one-dimensional arrays of masses connected by hard anharmonic springs and with no local potentials. In our numerical model a sustained signal is applied at one site of a chain immersed in a thermal environment and the signal-to-noise ratio is measured at each oscillator. We show that raising the temperature can lead to enhanced signal propagation along the chain, resulting in thermal resonance effects akin to the resonance observed in arrays of bistable systems.