Layer dependent neural modulation of a realistic layered-microcircuit model in visual cortex based on bottom-up and top-down signals

The visual attention allocates its resources of information processing to selected sensory inputs for reducing the load of the processing. Here, we carried out the large-scale simulation with the layered-microcircuit model of the visual cortex based on the current knowledge of cortical neurobiology in order to explore the complex interaction between bottom-up visual input and top-down attentional signal. The visual microcircuit model consisted of about 40,000 integrate-and-fire model neurons and represented layers 2/3, 4, 5 and 6 (Tobias C. Potjans, et al., 2009). Two these microcircuits interacted by lateral inhibition through layer 2/3. Top-down attention was applied to layer 2/3 to facilitate the process of visual stimuli. In order to investigate the mechanism of visual processing and attentional effect in the layered-microcircuit model, we simulated a model with a variety of lateral inhibition and compared to physiological results for neural and attentional modulation (Reynolds et al., 1999). Specifically, a model with the lateral inhibition between presynaptic excitatory and postsynaptic inhibitory neurons indicated the layer-dependent modulation due to the presentation of the anti-preferred stimulus, which suppressed the response to the preferred stimulus in output layers such as layers 2/3 and 5. However, attention recovered the response to the preferred stimulus in these layers. These modulations due to the stimuli and attention agreed with the physiology. The general principle of the canonical cortical circuit was the detailed structure of a column, top-down attentional bias to layer 2/3 and the lateral inhibition from presynaptic excitatory to postsynaptic inhibitory neurons through layer 2/3. Our model allowed us to investigate how the bottom-up visual input and the top-down attentional signal may interact with each other in the laminar structure of the column. These results and functions provided important prediction for attention in visual processing

Two-dimensional imaging of edge-localized modes in KSTAR plasmas unperturbed and perturbed by n=1 external magnetic fields

The temporal evolution of edge-localized modes (ELMs) has been studied using a 2-D electron cyclotron emission imaging system in the KSTAR tokamak. The ELMs are observed to evolve in three distinctive stages: the initial linear growth of multiple filamentary structures having a net poloidal rotation, the interim state of regularly spaced saturated filaments, and the final crash through a short transient phase characterized by abrupt changes in the relative amplitudes and distance among filaments. The crash phase, typically consisted of multiple bursts of a single filament, involves a complex dynamics, poloidal elongation of the bursting filament, development of a fingerlike bulge, and fast localized burst through the finger. Substantial alterations of the ELM dynamics, such as mode number, poloidal rotation, and crash time scale, have been observed under external magnetic perturbations with the toroidal mode number n = 1. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3694842]X1125sciescopu

Fear of the Market or Fear of the Competitor? Ambiguity in a Real Options Game

In this paper we study an investment game between two firms with a first--mover advantage, where payoffs are driven by a geometric Brownian motion. At least one of the firms is assumed to be ambiguous over the drift, with maxmin preferences over a strongly rectangular set of priors. We develop a strategy and equilibrium concept allowing for ambiguity and show that equilibria can be preemptive (a firm invests at a point where investment is Pareto dominated by waiting) or sequential (one firm invests as if it were the exogenously appointed leader). Following the standard literature, the worst--case prior for an ambiguous firm in the follower role is obtained by setting the lowest possible trend in the set of priors. However, if an ambiguous firm is the first mover, then the worst--case drift can fluctuate between the lowest and the highest trends. This novel result shows that ``worst--case prior'' in a setting with drift ambiguity does not always equate to ``lowest trend''. As a consequence, preemptive pressure reduces. We show that this results in the possibility of firm value being increasing in the level of ambiguity. If only one firm is ambiguous, then the value of the non--ambiguous firm can be increasing in the level of ambiguity of the ambiguous firm

Electroweak corrections to W-boson pair production at the LHC

Vector-boson pair production ranks among the most important Standard-Model benchmark processes at the LHC, not only in view of on-going Higgs analyses. These processes may also help to gain a deeper understanding of the electroweak interaction in general, and to test the validity of the Standard Model at highest energies. In this work, the first calculation of the full one-loop electroweak corrections to on-shell W-boson pair production at hadron colliders is presented. We discuss the impact of the corrections on the total cross section as well as on relevant differential distributions. We observe that corrections due to photon-induced channels can be amazingly large at energies accessible at the LHC, while radiation of additional massive vector bosons does not influence the results significantly.Comment: 29 pages, 15 figures, 4 tables; some references and comments on \gamma\gamma -> WW added; matches version published in JHE

Motor Competence in Early Childhood Is Positively Associated with Bone Strength in Late Adolescence

The onset of walking in early childhood results in exposure of the lower limb to substantial forces from weight bearing activity that ultimately contribute to adult bone strength. Relationships between gross motor score (GMS), at 18 months and bone outcomes measured at age 17 years were examined in 2327 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Higher GMS indicated greater motor competence in weight-bearing activities. Total hip bone mineral density (BMD) and hip cross-sectional moment of inertia (CSMI) were assessed from dual-energy X-ray absorptiometry (DXA). Bone measures including cortical bone mineral content (BMC), periosteal circumference (PC), cortical thickness (CT), cortical bone area (CBA), cortical BMD (BMDC) and cross-sectional moment of inertia (CSMI) were assessed by peripheral quantitative computed tomography (pQCT) at 50% distal-proximal length. Before adjustment, GMS was associated with hip BMD, CSMI, and tibia BMC, PC, CT, CBA and CSMI (all p  0.25). Strongest associations (standardized regression coefficients with 95% CI) were between GMS and hip BMD (0.086; 95% CI, 0.067 to 0.105) and tibia BMC (0.105; 95% CI, 0.089 to 0.121). With the exception of hip BMD, larger regression coefficients were observed in males (gender interactions all p < 0.05). Adjustment for lean mass resulted in substantial attenuation of regression coefficients, suggesting associations between impaired motor competence and subsequent bone development are partly mediated by alterations in body composition. In conclusion, impaired motor competence in childhood is associated with lower adolescent bone strength, and may represent a risk factor for subsequent osteoporosis

Quantifying habitual levels of physical activity according to impact in older people: accelerometry protocol for the VIBE study

Physical activity (PA) may need to produce high impacts to be osteogenic. The aim of this study was to identify threshold(s) for defining high impact PA for future analyses in the VIBE (Vertical Impact and Bone in the Elderly) study, based on home recordings with triaxial accelerometers. Recordings were obtained from 19 Master Athlete Cohort (MAC; mean 67.6 years) and 15 Hertfordshire Cohort Study (HCS; mean 77.7 years) participants. Data cleaning protocols were developed to exclude artifacts. Accelerations expressed in g units were categorized into three bands selected from the distribution of positive Y-axis peak accelerations. Data were available for 6.6 and 4.4 days from MAC and HCS participants respectively, with approximately 14 hr recording daily. Three-fold more 0.5–1.0g impacts were observed in MAC versus HCS, 20-fold more 1.0–1.5g impacts, and 140-fold more impacts ≥ 1.5g. Our analysis protocol successfully distinguishes PA levels in active and sedentary older individuals

Breech presentation is associated with lower adolescent tibial bone strength

Summary We compared bone outcomes in adolescents with breech and cephalic presentation. Tibia bone mineral content, density, periosteal circumference, and cross-sectional moment of inertia were lower in breech presentation, and females with breech presentation had lower hip CSA. These findings suggest that prenatal loading may exert long-lasting influences on skeletal development. Introduction Breech position during pregnancy is associated with reduced range of fetal movement, and with lower limb joint stresses. Breech presentation at birth is associated with lower neonatal bone mineral content (BMC) and area, but it is unknown whether these associations persist into later life. Methods We examined associations between presentation at onset of labor, and tibia and hip bone outcomes at age 17 years in 1971 participants (1062 females) from a UK prospective birth cohort that recruited > 15,000 pregnant women in 1991–1992. Cortical BMC, cross-sectional area (CSA) and bone mineral density (BMD), periosteal circumference, and cross-sectional moment of inertia (CSMI) were measured by peripheral quantitative computed tomography (pQCT) at 50% tibia length. Total hip BMC, bone area, BMD, and CSMI were measured by dual-energy X-ray absorptiometry (DXA). Results In models adjusted for sex, age, maternal education, smoking, parity, and age, singleton/multiple births, breech presentation (n = 102) was associated with lower tibial cortical BMC (− 0.14SD, 95% CI − 0.29 to 0.00), CSA (− 0.12SD, − 0.26 to 0.02), BMD (− 0.16SD, − 0.31 to − 0.01), periosteal circumference (− 0.14SD, − 0.27 to − 0.01), and CSMI (− 0.11SD, − 0.24 to 0.01). In females only, breech presentation was associated with lower hip CSA (− 0.24SD, − 0.43 to 0.00) but not with other hip outcomes. Additional adjustment for potential mediators (delivery method, birthweight, gestational age, childhood motor competence and adolescent height and body composition) did not substantially affect associations with either tibia or hip outcomes. Conclusions These findings suggest that prenatal skeletal loading may exert long-lasting influences on skeletal size and strength but require replication

Subregional statistical shape modelling identifies lesser trochanter size as a possible risk factor for radiographic hip osteoarthritis, a cross-sectional analysis from the Osteoporotic Fractures in Men Study

BGF was a National Institute of Health Research academic clinical fellow whilst undertaking part of this research and is now a Medical Research Council clinical research fellow supported by grant MR/S021280/1. FRS was supported by a Medical Research Council UK grant MR/L010399/1 at the time of this study. This study used the SSM cohort funded by Versus Arthritis UK project grant ref 20244. The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: R01 AR052000, K24 AR048841, U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Partial support for this work was provided by the Southwest Research Institute internal research project R9541 and NIAMS research grant AR052013. All authors have made significant contributions to the conception and design of this study, the acquisition of data, its analysis and interpretation. All authors helped draft the article before approving the final version of this manuscript. Dr B Faber ([email protected]) takes responsibility for the integrity of the work in its entirety.Peer reviewedPublisher PD

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state