Auditory motion affects visual biological motion processing.

The processing of biological motion is a critical, everyday task performed with remarkable efficiency by human sensory systems. Interest in this ability has focused to a large extent on biological motion processing in the visual modality (see, for example, Cutting, J. E., Moore, C., & Morrison, R. (1988). Masking the motions of human gait. Perception and Psychophysics, 44(4), 339-347). In naturalistic settings, however, it is often the case that biological motion is defined by input to more than one sensory modality. For this reason, here in a series of experiments we investigate behavioural correlates of multisensory, in particular audiovisual, integration in the processing of biological motion cues. More specifically, using a new psychophysical paradigm we investigate the effect of suprathreshold auditory motion on perceptions of visually defined biological motion. Unlike data from previous studies investigating audiovisual integration in linear motion processing [Meyer, G. F. & Wuerger, S. M. (2001). Cross-modal integration of auditory and visual motion signals. Neuroreport, 12(11), 2557-2560; Wuerger, S. M., Hofbauer, M., & Meyer, G. F. (2003). The integration of auditory and motion signals at threshold. Perception and Psychophysics, 65(8), 1188-1196; Alais, D. & Burr, D. (2004). No direction-specific bimodal facilitation for audiovisual motion detection. Cognitive Brain Research, 19, 185-194], we report the existence of direction-selective effects: relative to control (stationary) auditory conditions, auditory motion in the same direction as the visually defined biological motion target increased its detectability, whereas auditory motion in the opposite direction had the inverse effect. Our data suggest these effects do not arise through general shifts in visuo-spatial attention, but instead are a consequence of motion-sensitive, direction-tuned integration mechanisms that are, if not unique to biological visual motion, at least not common to all types of visual motion. Based on these data and evidence from neurophysiological and neuroimaging studies we discuss the neural mechanisms likely to underlie this effect.

Organizing principles across the senses

ABSTRACT This thesis is composed of two main parts. The first addressed the question of whether the auditory and somatosensory systems, like their visual counterpart, comprise parallel functional pathways for processing identity and spatial attributes (so-called `what' and `where' pathways, respectively). The second part examined the independence of control processes mediating task switching across 'what' and `where' pathways in the auditory and visual modalities. Concerning the first part, electrical neuroimaging of event-related potentials identified the spatio-temporal mechanisms subserving auditory (see Appendix, Study n°1) and vibrotactile (see Appendix, Study n°2) processing during two types of blocks of trials. `What' blocks varied stimuli in their frequency independently of their location.. `Where' blocks varied the same stimuli in their location independently of their frequency. Concerning the second part (see Appendix, Study n°3), a psychophysical task-switching paradigm was used to investigate the hypothesis that the efficacy of control processes depends on the extent of overlap between the neural circuitry mediating the different tasks at hand, such that more effective task preparation (and by extension smaller switch costs) is achieved when the anatomical/functional overlap of this circuitry is small. Performance costs associated with switching tasks and/or switching sensory modalities were measured. Tasks required the analysis of either the identity or spatial location of environmental objects (`what' and `where' tasks, respectively) that were presented either visually or acoustically on any given trial. Pretrial cues informed participants of the upcoming task, but not of the sensory modality. - In the audio-visual domain, the results showed that switch costs between tasks were significantly smaller when the sensory modality of the task switched versus when it repeated. In addition, switch costs between the senses were correlated only when the sensory modality of the task repeated across trials and not when it switched. The collective evidence not only supports the independence of control processes mediating task switching and modality switching, but also the hypothesis that switch costs reflect competitive interterence between neural circuits that in turn can be diminished when these neural circuits are distinct. - In the auditory and somatosensory domains, the findings show that a segregation of location vs. recognition information is observed across sensory systems and that these happen around 100ms for both sensory modalities. - Also, our results show that functionally specialized pathways for audition and somatosensation involve largely overlapping brain regions, i.e. posterior superior and middle temporal cortices and inferior parietal areas. Both these properties (synchrony of differential processing and overlapping brain regions) probably optimize the relationships across sensory modalities. - Therefore, these results may be indicative of a computationally advantageous organization for processing spatial anal identity information.

Parallel imaging with phase scrambling.

PURPOSE: Most existing methods for accelerated parallel imaging in MRI require additional data, which are used to derive information about the sensitivity profile of each radiofrequency (RF) channel. In this work, a method is presented to avoid the acquisition of separate coil calibration data for accelerated Cartesian trajectories. METHODS: Quadratic phase is imparted to the image to spread the signals in k-space (aka phase scrambling). By rewriting the Fourier transform as a convolution operation, a window can be introduced to the convolved chirp function, allowing a low-resolution image to be reconstructed from phase-scrambled data without prominent aliasing. This image (for each RF channel) can be used to derive coil sensitivities to drive existing parallel imaging techniques. As a proof of concept, the quadratic phase was applied by introducing an offset to the x(2) - y(2) shim and the data were reconstructed using adapted versions of the image space-based sensitivity encoding and GeneRalized Autocalibrating Partially Parallel Acquisitions algorithms. RESULTS: The method is demonstrated in a phantom (1 × 2, 1 × 3, and 2 × 2 acceleration) and in vivo (2 × 2 acceleration) using a 3D gradient echo acquisition. CONCLUSION: Phase scrambling can be used to perform parallel imaging acceleration without acquisition of separate coil calibration data, demonstrated here for a 3D-Cartesian trajectory. Further research is required to prove the applicability to other 2D and 3D sampling schemes. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Inherently self-calibrating non-Cartesian parallel imaging.

The use of self-calibrating techniques in parallel magnetic resonance imaging eliminates the need for coil sensitivity calibration scans and avoids potential mismatches between calibration scans and subsequent accelerated acquisitions (e.g., as a result of patient motion). Most examples of self-calibrating Cartesian parallel imaging techniques have required the use of modified k-space trajectories that are densely sampled at the center and more sparsely sampled in the periphery. However, spiral and radial trajectories offer inherent self-calibrating characteristics because of their densely sampled center. At no additional cost in acquisition time and with no modification in scanning protocols, in vivo coil sensitivity maps may be extracted from the densely sampled central region of k-space. This work demonstrates the feasibility of self-calibrated spiral and radial parallel imaging using a previously described iterative non-Cartesian sensitivity encoding algorithm.

Iowa Biodiesel and Ethanol Processing Plants, January 2006

Maps of Iowa's Biodiesel and Ethanol Processing Plants.

Characterization of NALP2 and NALP3 IL-1β processing inflammasomes

Résumé II y a cinq ans, la découverte d'un nouveau domaine, le PYD domaine, lié aux domaines de la mort, a permis la description de la nouvelle famille des NALP protéines. L'analyse structurelle de cette famille de protéines révéla la présence de deux autres domaines, impliqués dans l'oligomerisation, NACHT, et la détection des ligands, Leucine rich repeats ou LRR. Cette architecture protéique est homologue à celle qui est décrite pour les NODs, les Tol1 récepteurs et tes protéines de résistance chez les plantes. Cette homologie suggère une possible implication des NALPs dans la régulation de l'immunité innée. Premièrement, nous avons décrit les composants minimaux qui permettent à l'inflammasomeNALP3 d'activer la caspase pro-inflammatoire, caspase-1. En comparaison à NALP1, NALP3 ne contient pas de FIIND domaine, ni de CARD domaine en C-terminus et n'interagit pas avec caspase-5. Nous avons découvert une protéine très homologue au C-terminus de NALP1, Cardinal, qui se lie au NACHT domaine de NALP2 et NALP3 par l'intermédiaire de son FIIND domaine. Cardinal possède la capacité d'interagir avec caspase-l, mais seul ASC semble être nécessaire à la maturation de la prointerleukine-1β suite à la stimulation de NALP3. Deuxièmement, notre étude s'est concentrée sur la nature du stimulus capable d'induire la formation et l'activation de l'inflammasome-NALP3. Nous avons démontré que l'ajout de muramyl dipeptide (MDP), produit à partir de la digestion enzymatique de peptidoglycaris bactériens, induit à la fois l'expression de la proIL-1β par la voie NOD2 et sa maturation en IL-1β active par la voie NALP3. Bien que le MDP active l'inflammasome-NALP3, il est incapable d'induire la sécrétion de l'IL-1β mature dans la lignée cellulaire THP1, comparé aux monocytes primaires humains. Cette différence pourrait être liée à l'absence, dans les THP1, de la protéine Filamin, qui est proposée d'interagir avec Cardinal. L'implication de NALP3 dans la maturation de l'IL-lb est confirmée suite à la découverte de mutations sur le gène CIAS1/NALP3/cryopyrin associées à trois maladies auto-inflammatoires : le syndrome de Muckle-Wells (MWS), l'urticaire familial au froid (FCU) et le syndrome CINCA/NOMID. Une élévation constitutive de la maturation et de la sécrétion de la proIL-1β en absence de stimulation MDP est détectée dans les macrophages des patients Muckle-Wells. En conclusion, nos études ont démontré que l'inflammasome-NALP3 doit être finement régulé pour éviter une activité incontrôlée qui représente la base moléculaire des symptômes associés aux syndromes auto-inflammatoires liés à NALP3. Summary Five years ago, the description of the NALP family originated from the discovery of a new death-domain fold family, the PYD domain. NALP contains aprotein-protein interaction domain (PYD), an oligomerization domain (NACHT) and a ligand-sensing domain, leucine rich repeats or LRR. This protein architecture shares similarity with receptors involved in immunity, such as NODS, Toll receptors (TLRs) and related plant resistance proteins, and points to an important role of NALPs in defense mechanisms. We first described the minimal complex involved in the pro-inflammatory Interleukin-1beta (IL-1β) cytokine maturation, called the inflammasome, which contains NALP3. In contrast to NALP1, NALP3, like other members of the NALP family, is devoid of C-terminal FIIND and CARD domains and does not interact with the pro-inflammatory caspase-5. Interestingly, a homolog of the C-terminal portion of NALP1 was found in the human genome and was named Cardinal. We found that NALP2 and NALP3 interact with the CARD-containing proteins Cardinal. Cardinal is able to bind to caspase-1 but is not required for IL-1β maturation through NALP3 activation, as demonstrated for the adaptor ASC. Secondly, our study focused on the stimuli involved in the activation of the NALP3 inflammasome. MDP was shown to induce the expression of proIL1β through NOD2 and then the maturation into active IL-1β by activation of the NALP3 inflammasome. However, in the monocytic THP1 cell line, secretion of IL-1β upon MDP stimulation seems to be independent of the inflammasome activation compared to human primary monocytes. This difference might be linked to a Cardinal-interacting protein, filamin. Until now, the role of Cardinal and filamin is still unknown and remains to be elucidated. Finally, mutations in the NALP3/cryopyrin/CIAS1 gene are associated with three autoinflammatory diseases: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. Constitutive, elevated IL-1β maturation and secretion, even in the absence of MDP stimulation, was observed in macrophages from Muckle-Wells patients and confirmed a key role for the NALP3 inflammasome in innate immunity In conclusion, our studies describes the formation of the NALP3 inflammasome and suggests that this complex has to be tightly regulated to avoid an increased deregulated inflammasome activity that is the molecular basis for the symptoms associated with NALP3-dependent autoinflammatory disorders.

The role of awareness, information gathering and processing in school choice

This paper studies the determinants of school choice, focusing on the role of information. Weconsider how parents' search efforts and their capacity to process information (i.e., tocorrectly assess schools) affect the quality of the schools they choose for their children. Usinga novel dataset, we are able to identify parents' awareness of schools in their neighborhoodand measure their capacity to rank the quality of the school with respect to the officialrankings. We find that parents education and wealth are important factors in determiningtheir level of school awareness and information gathering. Moreover, these search effortshave important consequences in terms of the quality of school choice.

Parallel scheduling of multiclass M/M/m queues: Approximate and heavy-traffic optimization of achievable performance

We address the problem of scheduling a multiclass $M/M/m$ queue with Bernoulli feedback on $m$ parallel servers to minimize time-average linear holding costs. We analyze the performance of a heuristic priority-index rule, which extends Klimov's optimal solution to the single-server case: servers select preemptively customers with larger Klimov indices. We present closed-form suboptimality bounds (approximate optimality) for Klimov's rule, which imply that its suboptimality gap is uniformly bounded above with respect to (i) external arrival rates, as long as they stay within system capacity;and (ii) the number of servers. It follows that its relativesuboptimality gap vanishes in a heavy-traffic limit, as external arrival rates approach system capacity (heavy-traffic optimality). We obtain simpler expressions for the special no-feedback case, where the heuristic reduces to the classical $c \mu$ rule. Our analysis is based on comparing the expected cost of Klimov's ruleto the value of a strong linear programming (LP) relaxation of the system's region of achievable performance of mean queue lengths. In order to obtain this relaxation, we derive and exploit a new set ofwork decomposition laws for the parallel-server system. We further report on the results of a computational study on the quality of the $c \mu$ rule for parallel scheduling.

Bilateral dorsal and ventral fiber pathways for the processing of affective prosody identified by probabilistic fiber tracking.

Dorsal and ventral pathways for syntacto-semantic speech processing in the left hemisphere are represented in the dual-stream model of auditory processing. Here we report new findings for the right dorsal and ventral temporo-frontal pathway during processing of affectively intonated speech (i.e. affective prosody) in humans, together with several left hemispheric structural connections, partly resembling those for syntacto-semantic speech processing. We investigated white matter fiber connectivity between regions responding to affective prosody in several subregions of the bilateral superior temporal cortex (secondary and higher-level auditory cortex) and of the inferior frontal cortex (anterior and posterior inferior frontal gyrus). The fiber connectivity was investigated by using probabilistic diffusion tensor based tractography. The results underscore several so far underestimated auditory pathway connections, especially for the processing of affective prosody, such as a right ventral auditory pathway. The results also suggest the existence of a dual-stream processing in the right hemisphere, and a general predominance of the dorsal pathways in both hemispheres underlying the neural processing of affective prosody in an extended temporo-frontal network.

Respiration, metabolic balance, and attention in affective picture processing

The jointly voluntary and involuntary control of respiration, unique among essential physiological processes, the interconnection of breathing with and its influence on the autonomic nervous system, and disease states associated with the interface between psychology and respiration (e.g., anxiety disorders, hyperventilation syndrome, asthma) make the study of the relationship between respiration and emotion both theoretically and clinically of great relevance. However, the respiratory behavior during affective states is not yet completely understood. We studied breathing pattern responses to 13 picture series varying widely in their affective tone in 37 adults (18 men, 19 women, mean age 26). Time and volume parameters were recorded with the LifeShirt system (VivoMetrics Inc., Ventura, California, USA, see image). We also measured end-tidal pCO2 (EtCO2) with a Microcap Handheld Capnograph (Oridion Medical 1987 Ltd., Jerusalem, Israel) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. At the end of each picture series, the participants reported their subjective feeling in the affective dimensions of pleasantness and arousal. Increasing self-rated arousal was associated with increasing minute ventilation but not with decreases in EtCO2, suggesting that ventilatory changes during picture viewing paralleled variations in metabolic activity. EtCO2 correlated with pleasantness, and eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. Like MV, inspiratory drive (i.e., mean inspiratory flow) increased with arousal. This relationship reflected increases in inspiratory volume rather than shortening of the time parameters. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of pleasantness and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal. Finally, end-tidal pCO2 is slightly lower during processing of negative as compared to positive picture contents, which is proposed to enhance sensory perception and reflect a negativity bias in attention.

Three small RNAs jointly ensure secondary metabolism and biocontrol in Pseudomonas fluorescens CHA0.

In many Gram-negative bacteria, the GacS/GacA two-component system positively controls the expression of extracellular products or storage compounds. In the plant-beneficial rhizosphere bacterium Pseudomonas fluorescens CHA0, the GacS/GacA system is essential for the production of antibiotic compounds and hence for biological control of root-pathogenic fungi. The small (119-nt) RNA RsmX discovered in this study, together with RsmY and RsmZ, forms a triad of GacA-dependent small RNAs, which sequester the RNA-binding proteins RsmA and RsmE and thereby antagonize translational repression exerted by these proteins in strain CHA0. This small RNA triad was found to be both necessary and sufficient for posttranscriptional derepression of biocontrol factors and for protection of cucumber from Pythium ultimum. The same three small RNAs also positively regulated swarming motility and the synthesis of a quorum-sensing signal, which is unrelated to N-acyl-homoserine lactones, and which autoinduces the Gac/Rsm cascade. Expression of RsmX and RsmY increased in parallel throughout cell growth, whereas RsmZ was produced during the late growth phase. This differential expression is assumed to facilitate fine tuning of GacS/A-controlled cell population density-dependent regulation in P. fluorescens.

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

A glutathione precursor, N-acetyl-cysteine, modulates mismatch negativity generation in schizophrenia patients

Schizophrenia patients exhibit deficits in low-level processing, including pitch discrimination. This deficiency manifests in auditory evoked potentials (AEPs) as an impaired mismatch negativity (MMN), an electrophysiological response to infrequent target stimuli interspersed among frequent standard stimuli that typically peaks ~100ms post-stimulus onset. NMDA receptor antagonists have been shown to block MMN generation in both animals and humans, and NMDA dysfunction has been linked to the underlying pathophysiology of schizophrenia. A parallel line of evidence indicates that glutathione (GSH) regulation is perturbed in schizophrenia patients at the gene, protein and functional levels (Tosic et al., 2006). This GSH dysregulation leads to NMDA receptors' hypofunction through interaction with their redox site (Steullet et al., 2006). The present study aimed to modulate GSH levels in schizophrenia patients and assessed the effects of such a modulation on MMN generation mechanisms. N-acetyl-cysteine (NAC), a GSH precursor, was administered to schizophrenia patients, using a double-blind cross-over protocol. One group received NAC (2g/day) for 60 days and then placebo for another 60 days, and vice-versa for the second group. AEPs from patients were recorded at the onset of the protocol, at the point of cross-over, and at the end of the study. Participants were instructed to manually respond to target stimuli (2kHz pure tones occurring 20% of the time among 1kHz pure tones). Analyses of AEPs recorded at protocol onset indicated that patients (n=11) were significantly impaired in generating the MMN relative to age-matched controls (n=11). Specifically, the global field power (GFP), an index of AEP magnitude, was measured over the 70- 155ms post-stimulus interval and submitted to an analysis of variance (ANOVA). There was a significant interaction between population and stimulus frequency, indicating impaired MMN generation in patients at protocol onset. Analyses of AEPs recorded during administration of NAC (n=7) versus placebo (n=7) revealed the efficacy of this GSH precursor in modulating MMN generation mechanisms. ANOVA of GFP over the 70- 155ms post-stimulus interval, using stimulus frequency and treatment as within-participants variables, revealed a significant interaction and indicated that NAC can ameliorate MMN generation. We discuss these results in terms of potential therapeutic strategies for schizophrenia.

Prevalence of left ventricular regional dysfunction in arrhythmogenic right ventricular dysplasia: a tagged MRI study.

BACKGROUND: Although arrhythmogenic right ventricular dysplasia (ARVD) predominantly affects the right ventricle (RV), genetic/molecular and histological changes are biventricular. Regional left ventricular (LV) function has not been systematically studied in ARVD. METHODS AND RESULTS: The study population included 21 patients with suspected ARVD who underwent evaluation with MRI including tagging. Eleven healthy volunteers served as control subjects. Peak systolic regional circumferential strain (Ecc, %) was calculated by harmonic phase from tagged MRI based on the 16-segment model. Patients who met ARVD Task Force criteria were classified as definite ARVD, whereas patients with a positive family history who had 1 additional minor criterion and patients without a family history with 1 major or 2 minor criteria were classified as probable ARVD. Of the 21 ARVD subjects, 11 had definite ARVD and 10 had probable ARVD. Compared with control subjects, probable ARVD patients had similar RV ejection fraction (58.9+/-6.2% versus 53.5+/-7.6%, P=0.20), but definite ARVD patients had significantly reduced RV ejection fraction (58.9+/-6.2% versus 45.2+/-6.0%, P=0.001). LV ejection fraction was similar in all 3 groups. Compared with control subjects, peak systolic Ecc was significantly less negative in 6 of 16 (37.5%) segments in definite ARVD and 3 of 16 segments (18.7%) in probable ARVD (all P<0.05). CONCLUSIONS: ARVD is associated with regional LV dysfunction, which appears to parallel degree of RV dysfunction. Further large studies are needed to validate this finding and to better define implications of subclinical segmental LV dysfunction.