OBJECTIVES/SPECIFIC AIMS: Abnormalities in sensorimotor behavior are present in the majority of individuals with ASD and associated with core symptoms. Cortico-cerebellar networks that control sensorimotor behavior have been implicated in ASD, but little is known about their function during sensorimotor actions. The purpose of this functional magnetic resonance imaging (fMRI) study was to examine cortical-cerebellar function during feedback-guided motor behavior in ASD. METHODS/STUDY POPULATION: Individuals with ASD (11-30 years; N = 18) and age-matched controls (N = 15) completed a visuomotor task of feedback-guided precision gripping during fMRI. Participants pressed with their right thumb and forefinger on a force transducer while viewing a green FORCE bar on a screen that moved upwards with increased force toward a fixed white TARGET bar. Individuals were instructed to maintain the FORCE bar at the level of the TARGET bar for 24 seconds. Target force levels were set at 20% and 60% of each participant’s maximum voluntary contraction (MVC). Force variability was characterized as the coefficient of variation (i.e., standard deviation of the force time series / mean force output; CoV). RESULTS/ANTICIPATED RESULTS: Mean force did not differ between groups indicating participants were able to follow task demands. Participants with ASD showed increased force variability (F(1,30) = 5.214, p = 0.03) at both 20% (d = .45) and 60% (d = .77) MVC compared to controls. Compared to controls, individuals with ASD showed decreased activation in left angular gyrus during the visuomotor task compared to rest (AG; maximum t = 4.31). Individuals with ASD also showed greater visuomotor activation compared to controls in ipsilateral ventral M1, extending anteriorly into posterior ventral pre-motor cortex (PMv; maximum t = −4.06, cluster size = 38 voxels). This difference reflected the finding that control participants showed a selective deactivation of ipsilateral M1/PMv during visuomotor behavior, whereas individuals with ASD did not show this pattern. A significant group x force interaction was observed for contralateral Crus I activation (maximum t = −2.42) that was driven by an increase in activity during 60% compared to 20% MVC in control participants, while individuals with ASD showed no change in Crus I activation between force levels. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased force variability in individuals with ASD suggests impaired processing of sensory feedback to guide precision motor behaviors. Individuals with ASD did not show deactivation of right motor cortex during visuomotor behavior relative to rest, suggesting reduced ability to selectively modulate motor cortical output. Reduced activation in left AG may reflect an inability to integrate visual, haptic, and proprioceptive inputs to reactively adjust ongoing motor output. Failure to show force-dependent scaling of Crus I in ASD suggests lateral cerebellar circuits do not adapt sensory prediction and error processes to maintain precision motor output during more demanding conditions. Together, our results demonstrate multiple cortical-cerebellar mechanisms associated with sensorimotor imprecision in ASD.

We investigated the potential for human-mediated range expansion of an exotic beech leaf-mining weevil, Orchestes fagi (Linnaeus) (Coleoptera: Curculionidae: Curculioninae: Rhamphini) (formerly known as Rhynchaenus fagi) on timber or firewood, which for eight to nine months of the year may harbour adults in diapause. In both relatively low-density and high-density populations, adults were found on the base, middle, and upper boles of the primary host, American beech (Fagus grandifolia Ehrhart; Fagaceae), as well as red maple (Acer rubrum Linnaeus; Sapindaceae) and red spruce (Picea rubens Sargent; Pinaceae) in the vicinity. Comparatively few individuals were found on tree branches, or in the moss, duff, or soil collected beneath beech trees. Overwintering adults appeared to favour parts of trees with relatively high bark roughness. Our study suggests that, between the months of July through May, any woody stems near areas having O. fagi outbreaks are likely to harbour adults. Moreover, as all of the trees studied are common sources of timber or firewood, the harvest and transport of wood from these areas may facilitate outbreak spread; this may explain the multiple, distantly distributed populations of O. fagi that have been reported in eastern Nova Scotia, Canada in recent years.

The Kulshan caldera formed at ∼1.15 Ma on the present-day site of Mt. Baker, Washington State, northwest USA and erupted a compositionally zoned (dacite-rhyolite) magma and a correlative eruptive, the Lake Tapps tephra. This tephra has previously been described, but only from the Puget Lowland of NW Washington. Here an occurrence of a Kulshan caldera correlative tephra is described from the Quaternary Palouse loess at the Washtucna site (WA-3). Site WA-3 is located in east-central Washington, ∼340 km southeast of the Kulshan caldera and ∼300 km east-southeast of the Lake Tapps occurrence in the Puget Lowland. Major- and trace element chemistry and location of the deposit at Washtucna within reversed polarity sediments indicates that it is not correlative with the Mesa Falls, Rockland, Bishop Ash, Lava Creek B or Huckleberry Ridge tephras. Instead the Washtucna deposit is related to the Lake Tapps tephra by fractional crystallisation, but is chemically distinct, a consequence of its eruption from a compositionally zoned magma chamber. The correlation of the Washtucna occurrence to the Kulshan caldera-forming eruption indicates that it had an eruptive volume exceeding 100 km3, and that its tephra could provide a valuable early-Pleistocene chronostratigraphic marker in the Pacific Northwest.

The radiocarbon content of whole air provides a theoretically ideal and now observationally proven tracer for recently added fossil-fuel-derived CO2 in the atmosphere (Cff ). Over large industrialized land areas, determination of Cff also constrains the change in CO2 due to uptake and release by the terrestrial biosphere. Here, we review the development of a Δ14CO2 measurement program and its implementation within the US portion of the NOAA Global Monitoring Division's air sampling network. The Δ14CO2 measurement repeatability is evaluated based on surveillance cylinders of whole air and equates to a Cff detection limit of <0.9 ppm from measurement uncertainties alone. We also attempt to quantify additional sources of uncertainty arising from non-fossil terms in the atmospheric 14CO2 budget and from uncertainties in the composition of “background” air against which Cff enhancements occur. As an example of how we apply the measurements, we present estimates of the boundary layer enhancements of Cff and Cbio using observations obtained from vertical airborne sampling profiles off of the northeastern US. We also present an updated time series of measurements from NOAA GMD's Niwot Ridge site at 3475 m asl in Colorado in order to characterize recent Δ14CO2 variability in the well-mixed free troposphere.

Phytase (PHY) improves growth performance, nutrient digestibility and bone structure in pigs; however, little is known about its effects on intestinal nutrient transporter gene expression. In the present study, a 44 d experiment was carried out using forty-eight pigs (11·76 (sem 0·75) kg) assigned to one of three dietary treatment groups to measure growth performance, coefficient of apparent ileal digestibility (CAID), coefficient of apparent total tract nutrient digestibility (CATTD) and intestinal nutrient transporter gene expression. Dietary treatments during the experimental period were as follows: (1) a high-P (HP) diet containing 3·4 g/kg available P and 7·0 g/kg Ca; (2) a low-P (LP) diet containing 1·9 g/kg available P and 5·9 g/kg Ca; (3) a PHY diet containing LP diet ingredients+1000 phytase units (FTU)/kg of PHY. The PHY diet increased the average daily gain (P< 0·05) and final body weight (P< 0·01) and decreased the feed conversion ratio (P< 0·05) compared with the LP diet. Pigs fed the PHY diet had a higher CAID of gross energy compared with those fed the HP and LP diets (P< 0·001). Pigs fed the PHY diet had increased CAID of P (P< 0·01) and CATTD of Ca and P (P< 0·001) compared with those fed the LP diet. The PHY diet increased the gene expression of the peptide transporter 1 (PEPT1/SLC15A1) (P< 0·05) in the ileum compared with the LP diet. The LP diet decreased the gene expression of the sodium–glucose-linked transporter 1 (SGLT1/SLC5A1) and GLUT2/SLC2A2 (P< 0·05) and increased the expression of membrane Ca channel (TRPV6) and calbindin compared with the HP diet (P< 0·001). In conclusion, feeding a diet supplemented with PHY improves growth performance and nutrient digestibility as well as increases the gene expression of the peptide transporter PEPT1.

Impairments in visual motion perception and use of visual motion information to guide behavior have been reported in autism, but the brain alterations underlying these abnormalities are not well characterized. We performed functional magnetic resonance imaging (fMRI) studies to investigate neural correlates of impairments related to visual motion processing. Sixteen high-functioning individuals with autism and 14 age and IQ-matched typically developing individuals completed two fMRI tasks using passive viewing to examine bottom–up responses to visual motion and visual pursuit tracking to assess top–down modulation of visual motion processing during sensorimotor control. The autism group showed greater activation and faster hemodynamic decay in V5 during the passive viewing task and reduced frontal and V5 activation during visual pursuit. The observations of increased V5 activation and its faster decay during passive viewing suggest alterations in local V5 circuitries that may be associated with reduced GABAergic tone and inhibitory modulation. Reduced frontal and V5 activation during active pursuit suggest reduced top–down modulation of sensory processing. These results suggest that both local intrinsic abnormalities in V5 and more widely distributed network level abnormalities are associated with visual motion processing in autism. (JINS, 2014, 20, 113–122)

This study examined whether processing of emotional words impairs cognitive performance in acutely ill patients with pediatric bipolar disorder (PBD), with or without comorbid attention-deficit hyperactivity disorder (ADHD), relative to healthy controls (HC). Forty youths with PBD without ADHD, 20 youths with PBD and ADHD, and 29 HC (mean age = 12.97 ± 3.13) performed a Synonym Matching task, where they decided which of two probe words was the synonym of a target word. The three words presented on each trial all had the same emotional valence, which could be negative, positive, or neutral. Relative to HC both PBD groups exhibited worse accuracy for emotional words relative to neutral ones. This effect was greater with negative words and observed regardless of whether PBD patients had comorbid ADHD. In the PBD group without ADHD, manic symptoms correlated negatively with accuracy for negative words, and positively with reaction time (RT) for all word types. Our findings suggest a greater disruptive effect of emotional valence in both PBD groups relative to HC, reflecting the adverse effect of altered emotion processing on cognitive function in PBD. Future studies including an ADHD group will help clarify how ADHD symptoms may affect emotional interference independently of PBD. (JINS, 2013, 19, 1–12)

Recent studies have suggested that chito-oligosaccharides can have anti-adipogenic properties. The objectives of the present study were to evaluate the anti-adipogenic potential of four different chito-oligosaccharides (molecular weight (MW) < 1000, 1000–3000, 3000–5000 and 5000–10 000 Da) and to identify molecular mechanisms underlying the chito-oligosaccharide-mediated inhibition of adipogenesis. Mouse 3T3-L1 cells were allowed to differentiate in the presence of chito-oligosaccharide. At day 8 post-induction of differentiation, lipid accumulation, free glycerol release and the quantitative expression of adipogenic marker genes were evaluated. Chito-oligosaccharides had concentration- and MW-dependent inhibitory effects on lipid accumulation (P < 0·001 and < 0·05, respectively), as well as a concentration-dependent effect (P < 0·001) on free glycerol release and the expression of adipogenic marker genes. The 5000–10 000 Da chito-oligosaccharide was selected for subsequent molecular studies. A panel of forty-four lipid metabolic pathway-specific genes was analysed by quantitative real-time PCR. Chito-oligosaccharide-mediated inhibition of adipogenesis was associated with the up-regulation of the IL-6 gene at all concentrations of chito-oligosaccharide examined and the PG-endoperoxide synthase 2 (PTGS2) gene at higher concentrations of chito-oligosaccharide. The effect of chito-oligosaccharide on gene expression was validated by measuring IL-6 protein concentrations in the media. Finally, an IL-6 promoter assay was developed to characterise the effect of chito-oligosaccharide on the transcriptional activity of the IL-6 promoter, which was increased in a concentration-dependent manner (P < 0·001). We conclude that IL-6 is a candidate signalling molecule in the chito-oligosaccharide-mediated inhibition of adipogenesis in 3T3-L1 cells.

Polycrystalline silicon (polySi) is widely used in the semiconductor industry as a gate electrode, interconnect material and for various other applications. Small variations in deposition conditions can significantly affect this material's properties, cause errors in metrology control of the film thicknesses and, ultimately, in device performance. In this work polySi was LPCVD deposited in a vertical reactor with multiple gas inlets and a flat temperature distribution. Deposition conditions were controllably changed to create a matrix of wafers. Characterization is done using production dual wavelength, multiple-angle-of-incidence and research grade spectroscopie ellipsometers. PolySi thickness and composition uniformity are analyzed.

This fMRI study investigates the neural bases of cognitive control of emotion processing in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD). Seventeen un-medicated PBD patients, 15 un-medicated ADHD patients, and 14 healthy controls (HC) (mean age = 13.78 ± 2.47) performed an emotional valence Stroop Task, requiring them to match the color of an emotionally valenced word to the color of either of two adjacent circles. Both patient groups responded significantly slower than HC, but there were no group differences in accuracy. A voxel-wise analysis of variance on brain activation revealed a significant interaction of group by word valence [F(2,41) = 4.44; p = .02]. Similar group differences were found for negative and positive words. For negative versus neutral words, both patient groups exhibited greater activation in dorsolateral prefrontal cortex (DLPFC) and parietal cortex relative to HC. The PBD group exhibited greater activation in ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) relative to HC. The ADHD group exhibited decreased VLPFC activation relative to HC and the PBD group. During cognitive control of emotion processing, PBD patients deployed the VLPFC to a greater extent than HC. The ADHD patients showed decreased VLPFC engagement relative to both HC and PBD patients. (JINS, 2010, 16, 106–117.)

Visual motion perception and pursuit eye movement deficits have been reported in autism. However, it is unclear whether these impairments are related to each other or to clinical symptoms of the disorder. High-functioning individuals with autism (41 with and 36 without delayed language acquisition) and 46 control subjects participated in the present study. All three subject groups were matched on chronological age and Full-Scale IQ. The autism group with delayed language acquisition had bilateral impairments on visual motion discrimination tasks, whereas the autism group without delay showed marginal impairments only in the left hemifield. Both autism groups showed difficulty tracking visual targets, but only the autism group without delayed language acquisition showed increased pursuit latencies and a failure to show the typical rightward directional advantage in pursuit. We observed correlations between performance on the visual perception and pursuit tasks in both autism groups. However, pursuit performance was correlated with manual motor skills only in the autism group with delayed language, suggesting that general sensorimotor or motor disturbances are a significant additional factor related to pursuit deficits in this subgroup. These findings suggest that there may be distinct neurocognitive phenotypes in autism associated with patterns of early language development. (JINS, 2008, 14, 980–989.)

Our objective was to assess the potential of carabid beetles (Coleoptera: Carabidae) as effective bioindicators of the effects of forest management at a Canadian national scale. We present a comparison of carabid beetle assemblages reported from large-scale studies across Canada. Based on the initial response following disturbance treatment, we found that carabid assemblages consistently responded to disturbance, but responses of individual species and changes in species composition were nested within the context of regional geography and finer scale differences among forest ecosystems. We also explored the relationship between rare and dominant taxa and species characteristics as they relate to dispersal capacity and use of within-stand habitat features such as coarse woody debris. We found no relationship between life-history characteristics (such as body size, wing morphology, or reported associations with downed wood) and the relative abundance or frequency of occurrence of species. Our results suggest that carabids are better suited to finer scale evaluations of the effects of forest management than to regional or national monitoring programs. We also discuss several knowledge gaps that currently limit the full potential of using carabids as bioindicators.

Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n = 367) and 12-week (n = 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes. (JINS, 2008, 14, 209–221.)Presented in part at the annual International Neuropsychology Society meeting in Portland, OR, February 2007; and the 2007 International Congress for Schizophrenia Research in Colorado Springs, CO.