Comparison of early cortical networks in efficient and inefficient visual search: an event-related potential study.

Functional magnetic resonance imaging studies have indicated that efficient feature search (FS) and inefficient conjunction search (CS) activate partially distinct frontoparietal cortical networks. However, it remains a matter of debate whether the differences in these networks reflect differences in the early processing during FS and CS. In addition, the relationship between the differences in the networks and spatial shifts of attention also remains unknown. We examined these issues by applying a spatio-temporal analysis method to high-resolution visual event-related potentials (ERPs) and investigated how spatio-temporal activation patterns differ for FS and CS tasks. Within the first 450 msec after stimulus onset, scalp potential distributions (ERP maps) revealed 7 different electric field configurations for each search task. Configuration changes occurred simultaneously in the two tasks, suggesting that contributing processes were not significantly delayed in one task compared to the other. Despite this high spatial and temporal correlation, two ERP maps (120-190 and 250-300 msec) differed between the FS and CS. Lateralized distributions were observed only in the ERP map at 250-300 msec for the FS. This distribution corresponds to that previously described as the N2pc component (a negativity in the time range of the N2 complex over posterior electrodes of the hemisphere contralateral to the target hemifield), which has been associated with the focusing of attention onto potential target items in the search display. Thus, our results indicate that the cortical networks involved in feature and conjunction searching partially differ as early as 120 msec after stimulus onset and that the differences between the networks employed during the early stages of FS and CS are not necessarily caused by spatial attention shifts.

Anticorps antineuronaux: un domaine en plein développement [Anti-neuronal antibodies: a rapidly developing field].

Anti-neuronal antibodies are implicated in various neurological syndromes that are sometimes associated with tumors. Depending on the antigenic target (nuclear, cytoplasmic or extracellular cell-surface or synaptic) the clinical presentation is different. In neurological syndromes associated with antibodies specific for intracellular antigens, the T-cell mediated immunological response predominates as pathogenic effector and the response to treatment is typically poor. In contrast, in syndromes related to antibodies against extracellular targets, the role of the antibodies is pathogenic and the neurological syndrome often responds better to immunomodulatory treatment, associated or not with an anti-tumoral treatment. We review the spectrum of anti-neuronal antibodies and their corresponding clinical and therapeutic characteristics.

Fast docking using the CHARMM force field with EADock DSS.

The prediction of binding modes (BMs) occurring between a small molecule and a target protein of biological interest has become of great importance for drug development. The overwhelming diversity of needs leaves room for docking approaches addressing specific problems. Nowadays, the universe of docking software ranges from fast and user friendly programs to algorithmically flexible and accurate approaches. EADock2 is an example of the latter. Its multiobjective scoring function was designed around the CHARMM22 force field and the FACTS solvation model. However, the major drawback of such a software design lies in its computational cost. EADock dihedral space sampling (DSS) is built on the most efficient features of EADock2, namely its hybrid sampling engine and multiobjective scoring function. Its performance is equivalent to that of EADock2 for drug-like ligands, while the CPU time required has been reduced by several orders of magnitude. This huge improvement was achieved through a combination of several innovative features including an automatic bias of the sampling toward putative binding sites, and a very efficient tree-based DSS algorithm. When the top-scoring prediction is considered, 57% of BMs of a test set of 251 complexes were reproduced within 2 Å RMSD to the crystal structure. Up to 70% were reproduced when considering the five top scoring predictions. The success rate is lower in cross-docking assays but remains comparable with that of the latest version of AutoDock that accounts for the protein flexibility. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011.

A systematic and feasible method for computing nuclear contributions to electrical properties of polyatomic molecules

An analytic method to evaluate nuclear contributions to electrical properties of polyatomic molecules is presented. Such contributions control changes induced by an electric field on equilibrium geometry (nuclear relaxation contribution) and vibrational motion (vibrational contribution) of a molecular system. Expressions to compute the nuclear contributions have been derived from a power series expansion of the potential energy. These contributions to the electrical properties are given in terms of energy derivatives with respect to normal coordinates, electric field intensity or both. Only one calculation of such derivatives at the field-free equilibrium geometry is required. To show the useful efficiency of the analytical evaluation of electrical properties (the so-called AEEP method), results for calculations on water and pyridine at the SCF/TZ2P and the MP2/TZ2P levels of theory are reported. The results obtained are compared with previous theoretical calculations and with experimental values

Decoding decisions in healthy subjects and auditory discrimination in comatose patients through single-trial topographic EEG analyses

Neuroimaging studies analyzing neurophysiological signals are typically based on comparing averages of peri-stimulus epochs across experimental conditions. This approach can however be problematic in the case of high-level cognitive tasks, where response variability across trials is expected to be high and in cases where subjects cannot be considered part of a group. The main goal of this thesis has been to address this issue by developing a novel approach for analyzing electroencephalography (EEG) responses at the single-trial level. This approach takes advantage of the spatial distribution of the electric field on the scalp (topography) and exploits repetitions across trials for quantifying the degree of discrimination between experimental conditions through a classification scheme. In the first part of this thesis, I developed and validated this new method (Tzovara et al., 2012a,b). Its general applicability was demonstrated with three separate datasets, two in the visual modality and one in the auditory. This development allowed then to target two new lines of research, one in basic and one in clinical neuroscience, which represent the second and third part of this thesis respectively. For the second part of this thesis (Tzovara et al., 2012c), I employed the developed method for assessing the timing of exploratory decision-making. Using single-trial topographic EEG activity during presentation of a choice's payoff, I could predict the subjects' subsequent decisions. This prediction was due to a topographic difference which appeared on average at ~516ms after the presentation of payoff and was subject-specific. These results exploit for the first time the temporal correlates of individual subjects' decisions and additionally show that the underlying neural generators start differentiating their responses already ~880ms before the button press. Finally, in the third part of this project, I focused on a clinical study with the goal of assessing the degree of intact neural functions in comatose patients. Auditory EEG responses were assessed through a classical mismatch negativity paradigm, during the very early phase of coma, which is currently under-investigated. By taking advantage of the decoding method developed in the first part of the thesis, I could quantify the degree of auditory discrimination at the single patient level (Tzovara et al., in press). Our results showed for the first time that even patients who do not survive the coma can discriminate sounds at the neural level, during the first hours after coma onset. Importantly, an improvement in auditory discrimination during the first 48hours of coma was predictive of awakening and survival, with 100% positive predictive value. - L'analyse des signaux électrophysiologiques en neuroimagerie se base typiquement sur la comparaison des réponses neurophysiologiques à différentes conditions expérimentales qui sont moyennées après plusieurs répétitions d'une tâche. Pourtant, cette approche peut être problématique dans le cas des fonctions cognitives de haut niveau, où la variabilité des réponses entre les essais peut être très élevéeou dans le cas où des sujets individuels ne peuvent pas être considérés comme partie d'un groupe. Le but principal de cette thèse est d'investiguer cette problématique en développant une nouvelle approche pour l'analyse des réponses d'électroencephalographie (EEG) au niveau de chaque essai. Cette approche se base sur la modélisation de la distribution du champ électrique sur le crâne (topographie) et profite des répétitions parmi les essais afin de quantifier, à l'aide d'un schéma de classification, le degré de discrimination entre des conditions expérimentales. Dans la première partie de cette thèse, j'ai développé et validé cette nouvelle méthode (Tzovara et al., 2012a,b). Son applicabilité générale a été démontrée avec trois ensembles de données, deux dans le domaine visuel et un dans l'auditif. Ce développement a permis de cibler deux nouvelles lignes de recherche, la première dans le domaine des neurosciences cognitives et l'autre dans le domaine des neurosciences cliniques, représentant respectivement la deuxième et troisième partie de ce projet. En particulier, pour la partie cognitive, j'ai appliqué cette méthode pour évaluer l'information temporelle de la prise des décisions (Tzovara et al., 2012c). En se basant sur l'activité topographique de l'EEG au niveau de chaque essai pendant la présentation de la récompense liée à un choix, on a pu prédire les décisions suivantes des sujets (en termes d'exploration/exploitation). Cette prédiction s'appuie sur une différence topographique qui apparaît en moyenne ~516ms après la présentation de la récompense. Ces résultats exploitent pour la première fois, les corrélés temporels des décisions au niveau de chaque sujet séparément et montrent que les générateurs neuronaux de ces décisions commencent à différentier leurs réponses déjà depuis ~880ms avant que les sujets appuient sur le bouton. Finalement, pour la dernière partie de ce projet, je me suis focalisée sur une étude Clinique afin d'évaluer le degré des fonctions neuronales intactes chez les patients comateux. Des réponses EEG auditives ont été examinées avec un paradigme classique de mismatch negativity, pendant la phase précoce du coma qui est actuellement sous-investiguée. En utilisant la méthode de décodage développée dans la première partie de la thèse, j'ai pu quantifier le degré de discrimination auditive au niveau de chaque patient (Tzovara et al., in press). Nos résultats montrent pour la première fois que même des patients comateux qui ne vont pas survivre peuvent discriminer des sons au niveau neuronal, lors de la phase aigue du coma. De plus, une amélioration dans la discrimination auditive pendant les premières 48heures du coma a été observée seulement chez des patients qui se sont réveillés par la suite (100% de valeur prédictive pour un réveil).

Select-divide-and-conquer method for large-scale configuration interaction

A select-divide-and-conquer variational method to approximate configuration interaction (CI) is presented. Given an orthonormal set made up of occupied orbitals (Hartree-Fock or similar) and suitable correlation orbitals (natural or localized orbitals), a large N-electron target space S is split into subspaces S0,S1,S2,...,SR. S0, of dimension d0, contains all configurations K with attributes (energy contributions, etc.) above thresholds T0={T0egy, T0etc.}; the CI coefficients in S0 remain always free to vary. S1 accommodates KS with attributes above T1≤T0. An eigenproblem of dimension d0+d1 for S0+S 1 is solved first, after which the last d1 rows and columns are contracted into a single row and column, thus freezing the last d1 CI coefficients hereinafter. The process is repeated with successive Sj(j≥2) chosen so that corresponding CI matrices fit random access memory (RAM). Davidson's eigensolver is used R times. The final energy eigenvalue (lowest or excited one) is always above the corresponding exact eigenvalue in S. Threshold values {Tj;j=0, 1, 2,...,R} regulate accuracy; for large-dimensional S, high accuracy requires S 0+S1 to be solved outside RAM. From there on, however, usually a few Davidson iterations in RAM are needed for each step, so that Hamiltonian matrix-element evaluation becomes rate determining. One μhartree accuracy is achieved for an eigenproblem of order 24 × 106, involving 1.2 × 1012 nonzero matrix elements, and 8.4×109 Slater determinants

Determination of vibrational polarizabilities and hyperpolarizabilities using field-induced coordinates

An analytical set of field-induced coordinates is defined and is used to show that the vibrational degrees of freedom required to completely describe nuclear relaxation polarizabilities and hyperpolarizabilities is reduced from 3N-6 to a relatively small number. As this number does not depend upon the size of the molecule, the process provides computational advantages. A method is provided to separate anharmonic contributions from harmonic contributions as well as effective mechanical from electrical anharmonicity. The procedures are illustrated by Hartree-Fock calculations, indicating that anharmonicity can be very important

A comparative analysis of two methods for the calculation of electric-field-induced perturbations to molecular vibration

Two common methods of accounting for electric-field-induced perturbations to molecular vibration are analyzed and compared. The first method is based on a perturbation-theoretic treatment and the second on a finite-field treatment. The relationship between the two, which is not immediately apparent, is made by developing an algebraic formalism for the latter. Some of the higher-order terms in this development are documented here for the first time. As well as considering vibrational dipole polarizabilities and hyperpolarizabilities, we also make mention of the vibrational Stark effec

A simplified method of stabilization and hemostasis for minimally invasive coronary artery bypass.

We describe a simple method to achieve both hemostasis and stabilization of the left anterior descending coronary artery during minimally invasive coronary artery bypass grafting. This technique allows the surgeon to perform a precise anastomosis of the left internal mammary artery to the target vessel on a beating heart.

Biological markers of alcohol consumption in alcoholised drivers: Comparison of capillary electrophoresis (CZE CDT) and a direct immunoassay (N Latex CDT) with the traditional method of anion-exchange chromatography-immunoturbidimetry (%CDT TIA).

Objectives: The aim of this study was to compare specificity and sensitivity of different biological markers that can be used in a forensic field to identify potentially dangerous drivers because of their alcohol habits. Methods: We studied 280 Swiss drivers after driving while under the alcohol influence. 33 were excluded for not having CDT N results, 247 were included (218 men (88%) and 29 women (12%). Mean age was 42,4 (SD:12, min: 20 max: 76). The evaluation of the alcohol consumption concerned the month before the CDT test and was considered as such after the interview: Heavy drinkers (>3 drinks per day): 60 (32.7%), < 3 drinks per day and moderate: 127 (51.4%) 114 (46.5%), abstinent: 60 (24.3%) 51 (21%). Alcohol intake was monitored by structured interviews, self-reported drinking habits and the C-Audit questionnaire as well as information provided by their family and general practitioner. Consumption was quantified in terms of standard drinks, which contain approximately 10 grams of pure alcohol (Ref. WHO). Results: comparison between moderate (less or equal to 3 drinks per day) and excessive drinkers (more than 3 drinks) Marker ROC area 95% CI cut-off sensitivity specificity CDT TIA 0.852 0.786-0917 2.6* 0.93 LR+1.43 0.35 LR-0.192 CDT N latex 0.875 0.821-0.930 2.5* 0.66 LR+ 6.93 0.90 LR- 0.369 Asialo+disialo-tf 0.881 0.826-0.936 1.2* 0.78 LR+4.07 0.80 LR-0.268 1.7° 0.66 LR+8.9 0.93 LR-0.360 GGT 0.659 0.580-0.737 85* 0.37 LR+2.14 0.83 LR-0.764 * cut-off point suggested by the manufacturer ° cut-off point suggested by our laboratory Conclusion: With the cut-off point established by the manufacturer, CDT TIA performed poorly in term of specificity. N latex CDT and CZE CDT were better, especially if a 1.7 cut-off is used with CZE

SwissParam: a fast force field generation tool for small organic molecules.

The drug discovery process has been deeply transformed recently by the use of computational ligand-based or structure-based methods, helping the lead compounds identification and optimization, and finally the delivery of new drug candidates more quickly and at lower cost. Structure-based computational methods for drug discovery mainly involve ligand-protein docking and rapid binding free energy estimation, both of which require force field parameterization for many drug candidates. Here, we present a fast force field generation tool, called SwissParam, able to generate, for arbitrary small organic molecule, topologies, and parameters based on the Merck molecular force field, but in a functional form that is compatible with the CHARMM force field. Output files can be used with CHARMM or GROMACS. The topologies and parameters generated by SwissParam are used by the docking software EADock2 and EADock DSS to describe the small molecules to be docked, whereas the protein is described by the CHARMM force field, and allow them to reach success rates ranging from 56 to 78%. We have also developed a rapid binding free energy estimation approach, using SwissParam for ligands and CHARMM22/27 for proteins, which requires only a short minimization to reproduce the experimental binding free energy of 214 ligand-protein complexes involving 62 different proteins, with a standard error of 2.0 kcal mol(-1), and a correlation coefficient of 0.74. Together, these results demonstrate the relevance of using SwissParam topologies and parameters to describe small organic molecules in computer-aided drug design applications, together with a CHARMM22/27 description of the target protein. SwissParam is available free of charge for academic users at www.swissparam.ch.

Does Bt maize cultivation affect the non-target insect community in the agro ecosystem?

ABSTRACT The cultivation of genetically modified crops in Brazil has led to the need to assess the impacts of this technology on non-target species. Under field conditions, the potential effect on insect biodiversity was evaluated by comparing a homogeneous corn field with conventional and transgenic maize, expressing different Bt proteins in seven counties of Minas Gerais, Brazil. The richness pattern of non-target insect species, secondary pests and natural enemies were observed. The results do not support the hypothesis that Bt protein affects insect biodiversity. The richness and diversity data of insects studied were dependent on the location and other factors, such as the use of insecticides, which may be a major factor where they are used.

Dense deformation field estimation for atlas-based segmentation of pathological MR brain images.

Atlas registration is a recognized paradigm for the automatic segmentation of normal MR brain images. Unfortunately, atlas-based segmentation has been of limited use in presence of large space-occupying lesions. In fact, brain deformations induced by such lesions are added to normal anatomical variability and they may dramatically shift and deform anatomically or functionally important brain structures. In this work, we chose to focus on the problem of inter-subject registration of MR images with large tumors, inducing a significant shift of surrounding anatomical structures. First, a brief survey of the existing methods that have been proposed to deal with this problem is presented. This introduces the discussion about the requirements and desirable properties that we consider necessary to be fulfilled by a registration method in this context: To have a dense and smooth deformation field and a model of lesion growth, to model different deformability for some structures, to introduce more prior knowledge, and to use voxel-based features with a similarity measure robust to intensity differences. In a second part of this work, we propose a new approach that overcomes some of the main limitations of the existing techniques while complying with most of the desired requirements above. Our algorithm combines the mathematical framework for computing a variational flow proposed by Hermosillo et al. [G. Hermosillo, C. Chefd'Hotel, O. Faugeras, A variational approach to multi-modal image matching, Tech. Rep., INRIA (February 2001).] with the radial lesion growth pattern presented by Bach et al. [M. Bach Cuadra, C. Pollo, A. Bardera, O. Cuisenaire, J.-G. Villemure, J.-Ph. Thiran, Atlas-based segmentation of pathological MR brain images using a model of lesion growth, IEEE Trans. Med. Imag. 23 (10) (2004) 1301-1314.]. Results on patients with a meningioma are visually assessed and compared to those obtained with the most similar method from the state-of-the-art.

The profiling of false identity documents: a promising method to fight identity fraud

Under the influence of intelligence-led policing models, crime analysis methods have known of important developments in recent years. Applications have been proposed in several fields of forensic science to exploit and manage various types of material evidence in a systematic and more efficient way. However, nothing has been suggested so far in the field of false identity documents.This study seeks to fill this gap by proposing a simple and general method for profiling false identity documents which aims to establish links based on their visual forensic characteristics. A sample of more than 200 false identity documents including French stolen blank passports, counterfeited driving licenses from Iraq and falsified Bulgarian driving licenses was gathered from nine Swiss police departments and integrated into an ad hoc developed database called ProfID. Links detected automatically and systematically through this database were exploited and analyzed to produce strategic and tactical intelligence useful to the fight against identity document fraud.The profiling and intelligence process established for these three types of false identity documents has confirmed its efficiency, more than 30% of documents being linked. Identity document fraud appears as a structured and interregional criminality, against which material and forensic links detected between false identity documents might serve as a tool for investigation.

A noninvasive method for measuring the velocity of diffuse hydrothermal flow by tracking moving refractive index anomalies

Diffuse flow velocimetry (DFV) is introduced as a new, noninvasive, optical technique for measuring the velocity of diffuse hydrothermal flow. The technique uses images of a motionless, random medium (e.g.,rocks) obtained through the lens of a moving refraction index anomaly (e.g., a hot upwelling). The method works in two stages. First, the changes in apparent background deformation are calculated using particle image velocimetry (PIV). The deformation vectors are determined by a cross correlation of pixel intensities across consecutive images. Second, the 2-D velocity field is calculated by cross correlating the deformation vectors between consecutive PIV calculations. The accuracy of the method is tested with laboratory and numerical experiments of a laminar, axisymmetric plume in fluids with both constant and temperaturedependent viscosity. Results show that average RMS errors are ∼5%–7% and are most accurate in regions of pervasive apparent background deformation which is commonly encountered in regions of diffuse hydrothermal flow. The method is applied to a 25 s video sequence of diffuse flow from a small fracture captured during the Bathyluck’09 cruise to the Lucky Strike hydrothermal field (September 2009). The velocities of the ∼10°C–15°C effluent reach ∼5.5 cm/s, in strong agreement with previous measurements of diffuse flow. DFV is found to be most accurate for approximately 2‐D flows where background objects have a small spatial scale, such as sand or gravel