Synchronization and oscillatory dynamics in heterogeneous mutually inhibited neurons

We study some mechanisms responsible for synchronous oscillations and loss of synchrony at physiologically relevant frequencies (10-200 Hz) in a network of heterogeneous inhibitory neurons. We focus on the factors that determine the level of synchrony and frequency of the network response, as well as the effects of mild heterogeneity on network dynamics. With mild heterogeneity, synchrony is never perfect and is relatively fragile. In addition, the effects of inhibition are more complex in mildly heterogeneous networks than in homogeneous ones. In the former, synchrony is broken in two distinct ways, depending on the ratio of the synaptic decay time to the period of repetitive action potentials ($\tau_s/T$), where $T$ can be determined either from the network or from a single, self-inhibiting neuron. With $\tau_s/T > 2$, corresponding to large applied current, small synaptic strength or large synaptic decay time, the effects of inhibition are largely tonic and heterogeneous neurons spike relatively independently. With $\tau_s/T < 1$, synchrony breaks when faster cells begin to suppress their less excitable neighbors; cells that fire remain nearly synchronous. We show numerically that the behavior of mildly heterogeneous networks can be related to the behavior of single, self-inhibiting cells, which can be studied analytically.Comment: 17 pages, 6 figures, Kluwer.sty. Journal of Compuational Neuroscience (in press). Originally submitted to the neuro-sys archive which was never publicly announced (was 9802001

The Architecture of MEG Simulation and Analysis Software

MEG (Mu to Electron Gamma) is an experiment dedicated to search for the $\mu^+ \rightarrow e^+\gamma$ decay that is strongly suppressed in the Standard Model but predicted in several Super Symmetric extensions of it at an accessible rate. MEG is a small-size experiment ($\approx 50-60$ physicists at any time) with a life span of about 10 years. The limited human resource available, in particular in the core offline group, emphasized the importance of reusing software and exploiting existing expertise. Great care has been devoted to provide a simple system that hides implementation details to the average programmer. That allowed many members of the collaboration to contribute to the development of the software of the experiment with limited programming skill. The offline software is based on two frameworks: {\bf REM} in FORTRAN 77 used for the event generation and detector simulation package {\bf GEM}, based on GEANT 3, and {\bf ROME} in C++ used in the readout simulation {\bf Bartender} and in the reconstruction and analysis program {\bf Analyzer}. Event display in the simulation is based on GEANT 3 graphic libraries and in the reconstruction on ROOT graphic libraries. Data are stored in different formats in various stage of the processing. The frameworks include utilities for input/output, database handling and format conversion transparent to the user.Comment: Presented at the IEEE NSS Knoxville, 2010 Revised according to referee's remarks Accepted by European Physical Journal Plu

Irredundant Triangular Decomposition

Triangular decomposition is a classic, widely used and well-developed way to represent algebraic varieties with many applications. In particular, there exist sharp degree bounds for a single triangular set in terms of intrinsic data of the variety it represents, and powerful randomized algorithms for computing triangular decompositions using Hensel lifting in the zero-dimensional case and for irreducible varieties. However, in the general case, most of the algorithms computing triangular decompositions produce embedded components, which makes it impossible to directly apply the intrinsic degree bounds. This, in turn, is an obstacle for efficiently applying Hensel lifting due to the higher degrees of the output polynomials and the lower probability of success. In this paper, we give an algorithm to compute an irredundant triangular decomposition of an arbitrary algebraic set $W$ defined by a set of polynomials in C[x_1, x_2, ..., x_n]. Using this irredundant triangular decomposition, we were able to give intrinsic degree bounds for the polynomials appearing in the triangular sets and apply Hensel lifting techniques. Our decomposition algorithm is randomized, and we analyze the probability of success

Permutable entire functions and multiply connected wandering domains

Let f and g be permutable transcendental entire functions. We use a recent analysis of the dynamical behaviour in multiply connected wandering domains to make progress on the long standing conjecture that the Julia sets of f and g are equal; in particular, we show that J(f)=J(g) provided that neither f nor g has a simply connected wandering domain in the fast escaping set

A note on isoparametric polynomials

We show that any homogeneous polynomial solution of |\nabla F(x)|^2=m^2|x|^(2m-2), m>1, is either a radially symmetric polynomial F(x)=\pm |x|^m (for even m's) or it is a composition of a Chebychev polynomial and a Cartan-M\"unzner polynomial.Comment: 6 page

Protein Kinase CK2α Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2α Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma

The protein kinase casein kinase 2 (CK2) is a pleiotropic and constitutively active kinase that plays crucial roles in cellular proliferation and survival. Overexpression of CK2, particularly the α catalytic subunit (CK2α, CSNK2A1), has been implicated in a wide variety of cancers and is associated with poorer survival and resistance to both conventional and targeted anticancer therapies. Here, we found that CK2α protein is elevated in melanoma cell lines compared with normal human melanocytes. We then tested the involvement of CK2α in drug resistance to Food and Drug Administration-approved single agent targeted therapies for melanoma. In BRAF mutant melanoma cells, ectopic CK2α decreased sensitivity to vemurafenib (BRAF inhibitor), dabrafenib (BRAF inhibitor), and trametinib (MEK inhibitor) by a mechanism distinct from that of mutant NRAS. Conversely, knockdown of CK2α sensitized cells to inhibitor treatment. CK2α-mediated RAF-MEK kinase inhibitor resistance was tightly linked to its maintenance of ERK phosphorylation. We found that CK2α post-translationally regulates the ERK-specific phosphatase dual specificity phosphatase 6 (DUSP6) in a kinase dependent-manner, decreasing its abundance. However, we unexpectedly showed, by using a kinase-inactive mutant of CK2α, that RAF-MEK inhibitor resistance did not rely on CK2α kinase catalytic function, and both wild-type and kinase-inactive CK2α maintained ERK phosphorylation upon inhibition of BRAF or MEK. That both wild-type and kinase-inactive CK2α bound equally well to the RAF-MEK-ERK scaffold kinase suppressor of Ras 1 (KSR1) suggested that CK2α increases KSR facilitation of ERK phosphorylation. Accordingly, CK2α did not cause resistance to direct inhibition of ERK by the ERK1/2-selective inhibitor SCH772984. Our findings support a kinase-independent scaffolding function of CK2α that promotes resistance to RAF- and MEK-targeted therapies

Permutable entire functions satisfying algebraic differential equations

It is shown that if two transcendental entire functions permute, and if one of them satisfies an algebraic differential equation, then so does the other one.Comment: 5 page

Development of a plasma panel radiation detector: recent progress and key issues

A radiation detector based on plasma display panel technology, which is the principal component of plasma television displays is presented. Plasma Panel Sensor (PPS) technology is a variant of micropattern gas radiation detectors. The PPS is conceived as an array of sealed plasma discharge gas cells which can be used for fast response (O(5ns) per pixel), high spatial resolution detection (pixel pitch can be less than 100 micrometer) of ionizing and minimum ionizing particles. The PPS is assembled from non-reactive, intrinsically radiation-hard materials: glass substrates, metal electrodes and inert gas mixtures. We report on the PPS development program, including simulations and design and the first laboratory studies which demonstrate the usage of plasma display panels in measurements of cosmic ray muons, as well as the expansion of experimental results on the detection of betas from radioactive sources.Comment: presented at IEEE NSS 2011 (Barcelona