24 research outputs found

    Hover Acoustic Characteristics of the XV-15 with Advanced Technology Blades

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    An experiment has been performed to investigate the far-field hover acoustic characteristics of the XV-15 aircraft with advanced technology blades (ATB). An extensive, high-quality, far-field acoustics data base was obtained for a rotor tip speed range of 645-771 ft/s. A 12-microphone, 500-ft radius semicircular array combined with two aircraft headings provided acoustic data over the full 360-deg azimuth about the aircraft with a resolution of 15 deg. Altitude variations provided data from near in-plane to 45 deg below the rotor tip path plane. Acoustic directivity characteristics in the lower hemisphere are explored through pressure time histories, narrow-band spectra, and contour plots. Directivity patterns were found to vary greatly with azimuth angle, especially in the forward quadrants. Sharp positive pressure pulses typical of blade-vortex interactions were found to propagate aft of the aircraft and were most intense at 45 deg below the rotor plane. Modest overall sound pressure levels were measured near in-plane indicating that thickness noise is not a major problem for this aircraft when operating in the hover mode with ATB. Rotor tip speed reductions reduced the average overall sound pressure level (dB (0.0002 dyne/cm(exp 2)) by nearly 8 dB in-plane, and 12.6 deg below the rotor plane

    Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse

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    Alterations in peripheral and central indices of serotonin (5-hydroxytryptamine, 5-HT) production, storage and signaling have long been associated with autism. The 5-HT transporter gene (HTT, SERT, SLC6A4) has received considerable attention as a potential risk locus for autism-spectrum disorders, as well as disorders with overlapping symptoms, including obsessive-compulsive disorder (OCD). Here, we review our efforts to characterize rare, nonsynonymous polymorphisms in SERT derived from multiplex pedigrees carrying diagnoses of autism and OCD and present the initial stages of our effort to model one of these variants, Gly56Ala, in vivo. We generated a targeting vector to produce the Gly56Ala substitution in the Slc6a4 locus by homologous recombination. Following removal of a neomycin resistance selection cassette, animals exhibiting germline transmission of the Ala56 variant were bred to establish a breeding colony on a 129S6 background, suitable for initial evaluation of biochemical, physiological and behavioral alterations relative to SERT Gly56 (wildtype) animals. SERT Ala56 mice were achieved and exhibit a normal pattern of transmission. The initial growth and gross morphology of these animals is comparable to wildtype littermate controls. The SERT Ala56 variant can be propagated in 129S6 mice without apparent disruption of fertility and growth. We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits

    A Maternal Influence on Reading the Mind in the Eyes Mediated by Executive Function: Differential Parental Influences on Full and Half-Siblings

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    BACKGROUND: Parent-of-origin effects have been found to influence the mammalian brain and cognition and have been specifically implicated in the development of human social cognition and theory of mind. The experimental design in this study was developed to detect parent-of-origin effects on theory of mind, as measured by the 'Reading the mind in the eyes' (Eyes) task. Eyes scores were also entered into a principal components analysis with measures of empathy, social skills and executive function, in order to determine what aspect of theory of mind Eyes is measuring. METHODOLOGY/PRINCIPAL FINDINGS: Maternal and paternal influences on Eyes scores were compared using correlations between pairs of full (70 pairs), maternal (25 pairs) and paternal siblings (15 pairs). Structural equation modelling supported a maternal influence on Eyes scores over the normal range but not low-scoring outliers, and also a sex-specific influence on males acting to decrease male Eyes scores. It was not possible to differentiate between genetic and environmental influences in this particular sample because maternal siblings tended to be raised together while paternal siblings were raised apart. The principal components analysis found Eyes was associated with measures of executive function, principally behavioural inhibition and attention, rather than empathy or social skills. CONCLUSIONS/SIGNIFICANCE: In conclusion, the results suggest a maternal influence on Eye scores in the normal range and a sex-specific influence acting to reduce scores in males. This influence may act via aspects of executive function such as behavioural inhibition and attention. There may be different influences acting to produce the lowest Eyes scores which implies that the heratibility and/or maternal influence on poor theory of mind skills may be qualitatively different to the influence on the normal range

    Gene-environment interactions in antisocial behavior are mediated by early-life 5-HT2A_{\textrm{2A}} receptor activation

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    The ontogeny of antisocial behavior (ASB) is rooted in complex gene-environment (G×E) interactions. The best-characterized of these interplays occurs between: a) low-activity alleles of the gene encoding monoamine oxidase A (MAOA), the main serotonin-degrading enzyme; and b) child maltreatment. The purpose of this study was to develop the first animal model of this G×E interaction, to help understand the neurobiological mechanisms of ASB and identify novel targets for its therapy. Maoa hypomorphic transgenic mice were exposed to an early-life stress regimen consisting of maternal separation and daily intraperitoneal saline injections and were then compared with their wild-type and non-stressed controls for ASB-related neurobehavioral phenotypes. Maoa hypomorphic mice subjected to stress from postnatal day (PND) 1 through 7 – but not during the second postnatal week - developed overt aggression, social deficits and abnormal stress responses from the fourth week onwards. On PND 8, these mice exhibited low resting heart rate - a well-established premorbid sign of ASB – and a significant and selective up-regulation of serotonin 5-HT2A receptors in the prefrontal cortex. Notably, both aggression and neonatal bradycardia were rescued by the 5-HT2 receptor antagonist ketanserin (1–3 mg kg−1, IP), as well as the selective 5-HT2A receptor blocker MDL-100,907 (volinanserin, 0.1–0.3 mg kg−1, IP) throughout the first postnatal week. These findings provide the first evidence of a molecular basis of G×E interactions in ASB and point to early-life 5-HT2A receptor activation as a key mechanism for the ontogeny of this condition

    Gene-environment interactions in antisocial behavior are mediated by early-life 5-HT2A receptor activation

    No full text
    The ontogeny of antisocial behavior (ASB) is rooted in complex gene-environment (G×E) interactions. The best-characterized of these interplays occurs between: a) low-activity alleles of the gene encoding monoamine oxidase A (MAOA), the main serotonin-degrading enzyme; and b) child maltreatment. The purpose of this study was to develop the first animal model of this G×E interaction, to help understand the neurobiological mechanisms of ASB and identify novel targets for its therapy. Maoa hypomorphic transgenic mice were exposed to an early-life stress regimen consisting of maternal separation and daily intraperitoneal saline injections and were then compared with their wild-type and non-stressed controls for ASB-related neurobehavioral phenotypes. Maoa hypomorphic mice subjected to stress from postnatal day (PND) 1 through 7 – but not during the second postnatal week - developed overt aggression, social deficits and abnormal stress responses from the fourth week onwards. On PND 8, these mice exhibited low resting heart rate - a well-established premorbid sign of ASB – and a significant and selective up-regulation of serotonin 5-HT2A receptors in the prefrontal cortex. Notably, both aggression and neonatal bradycardia were rescued by the 5-HT2 receptor antagonist ketanserin (1–3 mg kg−1, IP), as well as the selective 5-HT2A receptor blocker MDL-100,907 (volinanserin, 0.1–0.3 mg kg−1, IP) throughout the first postnatal week. These findings provide the first evidence of a molecular basis of G×E interactions in ASB and point to early-life 5-HT2A receptor activation as a key mechanism for the ontogeny of this condition

    Pragmatic Abilities in Children with Congenital Visual Impairment: An Exploration of Non-literal Language and Advanced Theory of Mind Understanding

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    Contains fulltext : 102796.pdf (publisher's version ) (Closed access)Children with congenital visual impairment have been reported to be delayed in theory of mind development. So far, research focused on first-order theory of mind, and included mainly blind children, whereas the majority of visually impaired children is not totally blind. The present study set out to explore whether children with a broader range of congenital visual impairments have a delay in more advanced theory of mind understanding, in particular second-order theory of mind (i.e. awareness that other people have beliefs about beliefs) and non-literal language (e.g. irony or figure of speech). Twenty-four children with congenital visual impairment and 24 typically developing sighted children aged between 6 and 13 were included. All children were presented with a series of stories involving understanding of theory of mind and non-literal language. When compared with sighted children of similar age and verbal intelligence, performance of children with congenital visual impairment on advanced theory of mind and non-literal stories was alike. The ability to understand the motivations behind non-literal language was associated with age, verbal intelligence and theory of mind skills, but was not associated with visual ability
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