Impact of intrinsic biophysical diversity on the activity of spiking neurons

We study the effect of intrinsic heterogeneity on the activity of a population of leaky integrate-and-fire neurons. By rescaling the dynamical equation, we derive mathematical relations between multiple neuronal parameters and a fluctuating input noise. To this end, common input to heterogeneous neurons is conceived as an identical noise with neuron-specific mean and variance. As a consequence, the neuronal output rates can differ considerably, and their relative spike timing becomes desynchronized. This theory can quantitatively explain some recent experimental findings.Comment: 4 pages, 5 figure

Finding Galaxy Clusters using Voronoi Tessellations

We present an objective and automated procedure for detecting clusters of galaxies in imaging galaxy surveys. Our Voronoi Galaxy Cluster Finder (VGCF) uses galaxy positions and magnitudes to find clusters and determine their main features: size, richness and contrast above the background. The VGCF uses the Voronoi tessellation to evaluate the local density and to identify clusters as significative density fluctuations above the background. The significance threshold needs to be set by the user, but experimenting with different choices is very easy since it does not require a whole new run of the algorithm. The VGCF is non-parametric and does not smooth the data. As a consequence, clusters are identified irrispective of their shape and their identification is only slightly affected by border effects and by holes in the galaxy distribution on the sky. The algorithm is fast, and automatically assigns members to structures.Comment: 11 pages, 11 figures. It uses aa.cls (included). Accepted by A&

A Functional Approach to Deconvolve Dynamic Neuroimaging Data.

Positron emission tomography (PET) is an imaging technique which can be used to investigate chemical changes in human biological processes such as cancer development or neurochemical reactions. Most dynamic PET scans are currently analyzed based on the assumption that linear first-order kinetics can be used to adequately describe the system under observation. However, there has recently been strong evidence that this is not the case. To provide an analysis of PET data which is free from this compartmental assumption, we propose a nonparametric deconvolution and analysis model for dynamic PET data based on functional principal component analysis. This yields flexibility in the possible deconvolved functions while still performing well when a linear compartmental model setup is the true data generating mechanism. As the deconvolution needs to be performed on only a relative small number of basis functions rather than voxel by voxel in the entire three-dimensional volume, the methodology is both robust to typical brain imaging noise levels while also being computationally efficient. The new methodology is investigated through simulations in both one-dimensional functions and 2D images and also applied to a neuroimaging study whose goal is the quantification of opioid receptor concentration in the brain.The research of Ci-Ren Jiang is supported in part by NSC 101-2118-M-001-013-MY2 (Taiwan); the research of Jane-Ling Wang is supported by NSF grants, DMS-09-06813 and DMS-12-28369. JA is supported by EPSRC grant EP/K021672/2. The authors would like to thank SAMSI and the NDA programme where some of this research was carried out.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1080/01621459.2015.106024

Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall And Brent REvisited) Study.

Aims/hypothesis: South Asian individuals have an increased risk of diabetes compared with Europeans that is unexplained by obesity and traditional or established metabolic measures. Circulating amino acids (AAs) may provide additional explanatory insights. In a unique cohort of European and South Asian men, we compared cross-sectional associations between AAs, metabolic and obesity traits, and longitudinal associations with incident diabetes. / Methods: Nuclear magnetic spectroscopy was used to measure the baseline (1988–1991) levels of nine AAs in serum samples from a British population-based cohort of 1,279 European and 1,007 South Asian non-diabetic men aged 40–69 years. Follow-up was complete for 19 years in 801 European and 643 South Asian participants. / Results: The serum concentrations of isoleucine, phenylalanine, tyrosine and alanine were significantly higher in South Asian men, while cross-sectional correlations of AAs with glycaemia and insulin resistance were similar in the two ethnic groups. However, most AAs were less strongly correlated with measures of obesity in the South Asian participants. Diabetes developed in 227 (35%) South Asian and 113 (14%) European men. Stronger adverse associations were observed between branched chain and aromatic AAs and incident diabetes in South Asian men. Tyrosine was a particularly strong predictor of incident diabetes in South Asian individuals, even after adjustment for metabolic risk factors, including obesity and insulin resistance (adjusted OR for a 1 SD increment, 1.47, 95% CI 1.17,1.85, p = 0.001) compared with Europeans (OR 1.10, 0.87, 1.39, p = 0.4; p = 0.045 for ethnicity × tyrosine interaction). / Conclusions/interpretation: Branched chain and aromatic AAs, particularly tyrosine, may be a focus for identifying novel aetiological mechanisms and potential treatment targets for diabetes in South Asian populations and may contribute to their excess risk of diabetes

An Electrocorticographic Brain Interface in an Individual with Tetraplegia

Brain-computer interface (BCI) technology aims to help individuals with disability to control assistive devices and reanimate paralyzed limbs. Our study investigated the feasibility of an electrocorticography (ECoG)-based BCI system in an individual with tetraplegia caused by C4 level spinal cord injury. ECoG signals were recorded with a high-density 32-electrode grid over the hand and arm area of the left sensorimotor cortex. The participant was able to voluntarily activate his sensorimotor cortex using attempted movements, with distinct cortical activity patterns for different segments of the upper limb. Using only brain activity, the participant achieved robust control of 3D cursor movement. The ECoG grid was explanted 28 days post-implantation with no adverse effect. This study demonstrates that ECoG signals recorded from the sensorimotor cortex can be used for real-time device control in paralyzed individuals

Embedded large eddy simulation of transitional flow over NACA0012 aerofoil

An accurate computation of near-field unsteady turbulent flow around aerofoil is of outstanding importance for aerofoil trailing edge noise source prediction, which is a representative of main contributor to airframe noise and fan noise in modern commercial aircraft. In this study, an embedded large eddy simulation (ELES) is fully implemented in a separation-induced transitional flow over NACA0012 aerofoil at a moderate Reynolds number. It aims to evaluate the performance of the ELES method in aerodynamics simulation for wall-bounded aerospace flow in terms of accuracy, computational cost and complexity of implementation. Some good practice is presented including the special treatments at RANS-LES interface to provide more realistic turbulence generation in LES inflow. A comprehensive validation of the ELES results is performed by comparing with the experimental data and the wall-resolved large eddy simulation results. It is concluded that the ELES method could provide sufficient accuracy in the transitional flow simulations around aerofoil. It is proved to be a promising alternative to the pure LES for industrial flow applications involving wall boundary layer due to its significant computational efficiency

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms