Computing with the Integrate and Fire Neuron: Weber's Law, Multiplication and Phase Detection

The integrate and fire model (Stein, 1967) provides an analytically tractable formalism of neuronal firing rate in terms of a neuron's membrane time constant, threshold and refractory period. Integrate and fire (IAF) neurons have mainly been used to model physiologically realistic spike trains but little application of the IAF model appears to have been made in an explicitly computational context. In this paper we show that the transfer function of an IAF neuron provides, over a wide parameter range, a compressive nonlinearity sufficiently close to that of the logarithm so that IAF neurons can be used to multiply neural signals by mere addition of their outputs. Thus, although the IAF transfer function is not explicitly logarithmic, its compressive parameter regime supports a simple, single neuron model for multiplication. A simulation of the IAF multiplier shows that under a wide choice of parameters, the IAF neuron can multiply its inputs to within a 5% relative error. We also show that an IAF neuron under a different, yet biologically reasonable, parameter regime can have a quasi-linear transfer function, acting as an adder or a gain node. We then show an application in which the compressive transfer function of the IAF model provides a simple mechanism for phase-detection: multiplication of 40Hz phasic inputs followed by low-pass filtering yields an output that is a quasi-linear function of the relative phase of the inputs. This is a neural version of the heterodyne phase detection principle. Finally, we briefly discuss the precision and dynamic range of an IAF multiplier that is restricted to reasonable firing rates (in the range of 10-300 Hz) and reasonable computation time (in the range of 25-200 milliseconds).National Institute of Mental Health (5R01MH45969-04); Office of Naval Research (N00014-95-1-0409

Selecton 2007: advanced models for detecting positive and purifying selection using a Bayesian inference approach

Biologically significant sites in a protein may be identified by contrasting the rates of synonymous (Ks) and non-synonymous (Ka) substitutions. This enables the inference of site-specific positive Darwinian selection and purifying selection. We present here Selecton version 2.2 (http://selecton.bioinfo.tau.ac.il), a web server which automatically calculates the ratio between Ka and Ks (ω) at each site of the protein. This ratio is graphically displayed on each site using a color-coding scheme, indicating either positive selection, purifying selection or lack of selection. Selecton implements an assembly of different evolutionary models, which allow for statistical testing of the hypothesis that a protein has undergone positive selection. Specifically, the recently developed mechanistic-empirical model is introduced, which takes into account the physicochemical properties of amino acids. Advanced options were introduced to allow maximal fine tuning of the server to the user's specific needs, including calculation of statistical support of the ω values, an advanced graphic display of the protein's 3-dimensional structure, use of different genetic codes and inputting of a pre-built phylogenetic tree. Selecton version 2.2 is an effective, user-friendly and freely available web server which implements up-to-date methods for computing site-specific selection forces, and the visualization of these forces on the protein's sequence and structure

The Alternative Choice of Constitutive Exons throughout Evolution

Alternative cassette exons are known to originate from two processes exonization of intronic sequences and exon shuffling. Herein, we suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other. Examination of these exons suggests that the common ancestors were constitutively spliced. We show that relaxation of the 59 splice site during evolution is one of the molecular mechanisms by which exons shift from constitutive to alternative splicing. This shift is associated with the fixation of exonic splicing regulatory sequences (ESRs) that are essential for exon definition and control the inclusion level only after the transition to alternative splicing. The effect of each ESR on splicing and the combinatorial effects between two ESRs are conserved from fish to human. Our results uncover an evolutionary pathway that increases transcriptome diversity by shifting exons from constitutive to alternative splicin

FastML: a web server for probabilistic reconstruction of ancestral sequences

Ancestral sequence reconstruction is essential to a variety of evolutionary studies. Here, we present the FastML web server, a user-friendly tool for the reconstruction of ancestral sequences. FastML implements various novel features that differentiate it from existing tools: (i) FastML uses an indel-coding method, in which each gap, possibly spanning multiples sites, is coded as binary data. FastML then reconstructs ancestral indel states assuming a continuous time Markov process. FastML provides the most likely ancestral sequences, integrating both indels and characters; (ii) FastML accounts for uncertainty in ancestral states: it provides not only the posterior probabilities for each character and indel at each sequence position, but also a sample of ancestral sequences from this posterior distribution, and a list of the k-most likely ancestral sequences; (iii) FastML implements a large array of evolutionary models, which makes it generic and applicable for nucleotide, protein and codon sequences; and (iv) a graphical representation of the results is provided, including, for example, a graphical logo of the inferred ancestral sequences. The utility of FastML is demonstrated by reconstructing ancestral sequences of the Env protein from various HIV-1 subtypes. FastML is freely available for all academic users and is available online at http://fastml.tau.ac.i

Complete genome sequence of an Israeli isolate of Xanthomonas hortorum pv. pelargonii strain 305 and novel type III effectors identified in Xanthomonas

Xanthomonas hortorum pv. pelargonii is the causative agent of bacterial blight in geranium ornamental plants, the most threatening bacterial disease of this plant worldwide. Xanthomonas fragariae is the causative agent of angular leaf spot in strawberries, where it poses a significant threat to the strawberry industry. Both pathogens rely on the type III secretion system and the translocation of effector proteins into the plant cells for their pathogenicity. Effectidor is a freely available web server we have previously developed for the prediction of type III effectors in bacterial genomes. Following a complete genome sequencing and assembly of an Israeli isolate of Xanthomonas hortorum pv. pelargonii - strain 305, we used Effectidor to predict effector encoding genes both in this newly sequenced genome, and in X. fragariae strain Fap21, and validated its predictions experimentally. Four and two genes in X. hortorum and X. fragariae, respectively, contained an active translocation signal that allowed the translocation of the reporter AvrBs2 that induced the hypersensitive response in pepper leaves, and are thus considered validated novel effectors. These newly validated effectors are XopBB, XopBC, XopBD, XopBE, XopBF, and XopBG

Studies of the Electrochemical Behavior of LiNi0.80Co0.15Al0.05O2 Electrodes Coated with LiAlO2

In this paper, we studied the influence of LiAlO2 coatings of 0.5, 1 and 2 nm thickness prepared by Atomic Layer Deposition onto LiNi0.8Co0.15Al0.05O2 electrodes, on their electrochemical behavior at 30 and 60 degrees C. It was demonstrated that upon cycling, 2 nm LiAlO2 coated electrodes displayed similar to 3 times lower capacity fading and lower voltage hysteresis comparing to bare electrodes. We established a correlation among the thickness of the LiAlO2 coating and parameters of the self-discharge processes at 30 and 60 degrees C. Significant results on the elevated temperature cycling and aging of bare and LiAlO2 coated electrodes at 4.3 V were obtained and analyzed for the first time. By analyzing of X-ray diffraction patterns of bare and 2 nm coated LiNi0.8Co0.15Al0.05O2 electrodes after cycling, we concluded that cycled materials preserved their original structure described by R-3m space group and no additional phases were detected. (c) The Author(s) 2017. Published by ECS. All rights reserved.Peer reviewe