The impact of spike timing variability on the signal-encoding performance of neural spiking models

It remains unclear whether the variability of neuronal spike trains in vivo arises due to biological noise sources or represents highly precise encoding of temporally varying synaptic input signals. Determining the variability of spike timing can provide fundamental insights into the nature of strategies used in the brain to represent and transmit information in the form of discrete spike trains. In this study, we employ a signal estimation paradigm to determine how variability in spike timing affects encoding of random time-varying signals. We assess this for two types of spiking models: an integrate-and-fire model with random threshold and a more biophysically realistic stochastic ion channel model. Using the coding fraction and mutual information as information-theoretic measures, we quantify the efficacy of optimal linear decoding of random inputs from the model outputs and study the relationship between efficacy and variability in the output spike train. Our findings suggest that variability does not necessarily hinder signal decoding for the biophysically plausible encoders examined and that the functional role of spiking variability depends intimately on the nature of the encoder and the signal processing task; variability can either enhance or impede decoding performance

Opioid Analgesic Prescribing Practices of Dental Professionals in the United States

The prescription of opioid analgesics by dental professionals is widespread in the United States. Policy makers, government agencies, and professional organizations consider this phenomenon a growing public health concern. This study examined trends in the prescription of opioid analgesics for adults by dental professionals and associated factors in the United States. Data from the Medical Expenditure Panel Survey (1996-2013) were analyzed. Descriptive statistics were calculated separately for each year. Logistic regression analyses were conducted to estimate the overall trend during the period with and without adjusting for dental procedures and personal characteristics. Survey weights were incorporated to handle the sampling design. The prescription of opioid analgesics following dental care increased over time. After adjusting for sociodemographic factors, source of payment, and type of dental procedure, the odds ratio (OR) of prescribing opioid analgesics following a dental visit per each decade difference was 1.28 (95% confidence interval [CI], 1.19–1.38). Surgical, root canal, and implant procedures had the highest rates of opioid prescriptions and the greatest increases in rates over the study period. After adjusting for personal characteristics and type of dental procedure, the OR of receiving a prescription for opioids comparing blacks, Asians, and Hispanics to whites was 1.29 (95% CI, 1.17–1.41), 0.57 (95% CI, 0.47–0.70), and 0.84 (95% CI, 0.75–0.95), respectively. Opioid analgesic prescriptions following dental visits increased over time after adjusting for personal characteristics and type of dental procedure. The odds of receiving a prescription for opioids were higher for certain racial/ethnic minority groups. Knowledge Transfer Statement: This study highlights dental professionals prescribing practices of opioid analgesics by following dental treatments in the United States. With this knowledge, appropriate guidelines, protocols, and policies can be developed and implemented to address any inappropriate prescribing practices of opioid analgesics. In addition, this information could lead to an improvement in the prescribing practices of dental professionals and to evidence-based therapeutic decision making

Trends and Racial/Ethnic Disparities in Antibiotic Prescribing Practices of Dentists in The United States

Objective The aim of this study was to examine trends and racial/ethnic disparities in antibiotic prescribing practices of dentists in the United States. Methods The US Medical Expenditure Panel Survey data for 1996‐2013 was analyzed. Information on patient sociodemographic characteristics, dental visits, receipt of dental procedures, and type of antibiotics prescribed following visits was obtained. Descriptive statistics were calculated separately for each year. Logistic regression analyses were conducted to identify associations during the period with and without adjustment for dental procedures and sociodemographic characteristics. Survey weights were incorporated to handle the sampling design. Results Nationally, the number of antibiotic prescribed at dental visits was estimated to be higher by 842,749 (0.4 percent) at year 2013 compared to the prescription level at 2003 were the population sociodemographic distribution kept at 2013 level. On average, the odds of prescribing antibiotics following dental care increased with each decade of study (OR: 1.10; 95% CI: [1.04, 1.17]) after adjusting for sociodemographic characteristics and receipt of dental procedures. Compared to Whites, Blacks had 21 percent (95% CI: 11%, 31%) higher odds of receiving a prescription for antibiotics from a dentist after adjusting for dental procedure and other sociodemographic characteristics. Conclusions The prescription of antibiotics following dental visits increased over time after adjustment for sociodemographic characteristics and dental procedure. The probability of being prescribed antibiotics by dentists was higher for Blacks compared to Whites

Accuracy of Mesh Based Cosmological Hydrocodes: Tests and Corrections

We perform a variety of tests to determine the numerical resolution of the cosmological TVD eulerian code developed by Ryu et al (1993). Tests include 512^3 and 256^3 simulations of a Pk=k^{-1} spectrum to check for self-similarity and comparison of results with those from higher resolution SPH and grid-based calculations (Frenk et al 1998). We conclude that in regions where density gradients are not produced by shocks the code degrades resolution with a Gaussian smoothing (radius) length of 1.7 cells. At shock caused gradients (for which the code was designed) the smoothing length is 1.1 cells. Finally, for \beta model fit clusters, we can approximately correct numerical resolution by the transformation R^2_{core}\to R^2_{core}-(C\Delta l)^2, where \Delta l is the cell size and C=1.1-1.7. When we use these corrections on our previously published computations for the SCDM and \Lambda CDM models we find luminosity weighted, zero redshift, X-ray cluster core radii of (210\pm 86, 280\pm 67)h^{-1}kpc, respectively, which are marginally consistent with observed (Jones & Forman 1992) values of 50-200h^{-1}kpc. Using the corrected core radii, the COBE normalized SCDM model predicts the number of bright L_x>10^{43}erg/s clusters too high by a factor of \sim 20 and the \Lambda CDM model is consistent with observations.Comment: ApJ in press (1999

Synthesis of a Molecular Charm Bracelet via Click Cyclization and Olefin Metathesis Clipping

We describe the synthesis of a polycatenated cyclic polymer, a structure that resembles a molecular charm bracelet. Ruthenium-catalyzed ring-opening metathesis polymerization of an aminocontaining cyclic olefin monomer in the presence of a chain transfer agent generated an α,ω-diazide functionalized polyamine. Cyclization of the resulting linear polyamine using pseudo-high-dilution coppercatalyzed click cyclization produced a cyclic polymer in 19% yield. The click reaction was then further employed to remove linear contaminants from the cyclic polymer using azide- and alkyne-functionalized scavenging resins, and the purified cyclic polymer product was characterized by gel permeation chromatography, ^1H NMR spectroscopy, and IR spectroscopy. Polymer hydrogenation and conversion to the corresponding polyammonium species enabled coordination and interlocking of diolefin polyether fragments around the cyclic polymer backbone using ruthenium-catalyzed ring-closing olefin metathesis to afford a molecular charm bracelet structure. This charm bracelet complex was characterized by ^1H NMR spectroscopy, and the catenated nature of the small rings was confirmed using two-dimensional diffusion-ordered NMR spectroscopy

Redox-active ferrocene-modified Cowpea mosaic virus nanoparticles

A naturally occurring nanoparticle, the plant virus Cowpea mosaic virus, can be decorated with ferrocene derivatives, of various linker lengths with amine and carboxylategroups, on the external surface using a range of conjugation strategies. The multiple, organometallic, redox-active ferrocene moieties on the outer surface of the virus are electrochemically independent with reduction potentials that span a potential window of 0.16 V that are dependent on the site of modification and the nature of the ferrocene derivative. The number of ferrocenes coupled to each virus ranges from about 100 to 240 depending upon the conjugation site and the linker length and these redox active units can provide multielectron reservoirs

γ Heavy Chain Disease in Man: cDNA Sequence Supports Partial Gene Deletion Model

Human gamma heavy chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig gamma chain unattached to light chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM gamma 3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein has enabled us to study the biogenesis of the abnormal molecule. In vitro translation of isolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of cDNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues of the V region. An extensive internal deletion encompasses the remainder of the V and the entire CHl domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein. The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing

The Evolved Red Stellar Contents of the Sculptor Group Galaxies NGC55, NGC300, and NGC7793

Deep J, H, and K images are used to probe the evolved stellar contents in the central regions of the Sculptor group galaxies NGC55, NGC300, and NGC7793. The brightest stars are massive red supergiants (RSGs) with K ~ 15 - 15.5. The peak RSG brightness is constant to within ~0.5 mag in K, suggesting that NGC55, NGC300, and NGC7793 are at comparable distances. Comparisons with bright RSGs in the Magellanic Clouds indicate that the difference in distance modulus with respect to the LMC is = 7.5. A rich population of asymptotic giant branch (AGB) stars, which isochrones indicate have ages between 0.1 and 10 Gyr, dominates the (K, J-K) color-magnitude diagram (CMD) of each galaxy. The detection of significant numbers of AGB stars with ages near 10 Gyr indicates that the disks of these galaxies contain an underlying old population. The CMDs and luminosity functions reveal significant galaxy-to-galaxy variations in stellar content. Star-forming activity in the central arcmin of NGC300 has been suppressed for the past Gyr with respect to disk fields at larger radii. Nevertheless, comparisons between fields within each galaxy indicate that star-forming activity during intermediate epochs was coherent on spatial scales of a kpc or more. A large cluster of stars, which isochrones suggest has an age near 100 Myr, is seen in one of the NGC55 fields. The luminosity function of the brightest stars in this cluster is flat, as expected if a linear luminosity-core mass relation is present.Comment: 30 pages, including 13 figure

Channel noise in excitable neuronal membranes

Stochastic fluctuations of voltage-gated ion channels generate current and voltage noise in neuronal membranes. This noise may be a critical determinant of the efficacy of information processing within neural systems. Using Monte-Carlo simulations, we carry out a systematic investigation of the relationship between channel kinetics and the resulting membrane voltage noise using a stochastic Markov version of the Mainen-Sejnowski model of dendritic excitability in cortical neurons. Our simulations show that kinetic parameters which lead to an increase in membrane excitability (increasing channel densities, decreasing temperature) also lead to an increase in the magnitude of the sub-threshold voltage noise. Noise also increases as the membrane is depolarized from rest towards threshold. This suggests that channel fluctuations may interfere with a neuron’s ability to function as an integrator of its synaptic inputs and may limit the reliability and precision of neural information processing

Variability and coding efficiency of noisy neural spike encoders

Encoding synaptic inputs as a train of action potentials is a fundamental function of nerve cells. Although spike trains recorded in vivo have been shown to be highly variable, it is unclear whether variability in spike timing represents faithful encoding of temporally varying synaptic inputs or noise inherent in the spike encoding mechanism. It has been reported that spike timing variability is more pronounced for constant, unvarying inputs than for inputs with rich temporal structure. This could have significant implications for the nature of neural coding, particularly if precise timing of spikes and temporal synchrony between neurons is used to represent information in the nervous system. To study the potential functional role of spike timing variability, we estimate the fraction of spike timing variability which conveys information about the input for two types of noisy spike encoders — an integrate and fire model with randomly chosen thresholds and a model of a patch of neuronal membrane containing stochastic Na+ and K+ channels obeying Hodgkin–Huxley kinetics. The quality of signal encoding is assessed by reconstructing the input stimuli from the output spike trains using optimal linear mean square estimation. A comparison of the estimation performance of noisy neuronal models of spike generation enables us to assess the impact of neuronal noise on the efficacy of neural coding. The results for both models suggest that spike timing variability reduces the ability of spike trains to encode rapid time-varying stimuli. Moreover, contrary to expectations based on earlier studies, we find that the noisy spike encoding models encode slowly varying stimuli more effectively than rapidly varying ones