Phenotype-Based Screening of Synthetic Cannabinoids in a Dravet Syndrome Zebrafish Model.

Dravet syndrome is a catastrophic epilepsy of childhood, characterized by cognitive impairment, severe seizures, and increased risk for sudden unexplained death in epilepsy (SUDEP). Although refractory to conventional antiepileptic drugs, emerging preclinical and clinical evidence suggests that modulation of the endocannabinoid system could be therapeutic in these patients. Preclinical research on this topic is limited as cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are designated by United States Drug Enforcement Agency (DEA) as illegal substances. In this study, we used a validated zebrafish model of Dravet syndrome, scn1lab homozygous mutants, to screen for anti-seizure activity in a commercially available library containing 370 synthetic cannabinoid (SC) compounds. SCs are intended for experimental use and not restricted by DEA designations. Primary phenotype-based screening was performed using a locomotion-based assay in 96-well plates, and a secondary local field potential recording assay was then used to confirm suppression of electrographic epileptiform events. Identified SCs with anti-seizure activity, in both assays, included five SCs structurally classified as indole-based cannabinoids JWH 018 N-(5-chloropentyl) analog, JWH 018 N-(2-methylbutyl) isomer, 5-fluoro PB-22 5-hydroxyisoquinoline isomer, 5-fluoro ADBICA, and AB-FUBINACA 3-fluorobenzyl isomer. Our approach demonstrates that two-stage phenotype-based screening in a zebrafish model of Dravet syndrome successfully identifies SCs with anti-seizure activity

A Study on Set-Graphs

A \textit{primitive hole} of a graph $G$ is a cycle of length $3$ in $G$. The number of primitive holes in a given graph $G$ is called the primitive hole number of that graph $G$. The primitive degree of a vertex $v$ of a given graph $G$ is the number of primitive holes incident on the vertex $v$. In this paper, we introduce the notion of set-graphs and study the properties and characteristics of set-graphs. We also check the primitive hole number and primitive degree of set-graphs. Interesting introductory results on the nature of order of set-graphs, degree of the vertices corresponding to subsets of equal cardinality, the number of largest complete subgraphs in a set-graph etc. are discussed in this study. A recursive formula to determine the primitive hole number of a set-graph is also derived in this paper.Comment: 11 pages, 1 figure, submitte

Forward scattering in two-beam laser interferometry

A fractional error as large as 25 pm mm(-1) at the zero optical-path difference has been observed in an optical interferometer measuring the displacement of an x-ray interferometer used to determine the lattice parameter of silicon. Detailed investigations have brought to light that the error was caused by light forward-scattered from the beam feeding the interferometer. This paper reports on the impact of forward-scattered light on the accuracy of two-beam optical interferometry applied to length metrology, and supplies a model capable of explaining the observed error

Wavefront errors in a two-beam interferometer

This paper deals with the impact of wavefront errors, due to the optical aberrations of a two-beam interferometer, on the period of the travelling fringe observed by integrating the interference pattern. A Monte Carlo simulation of the interferometer operation showed that the fringe-period estimate is unbiased if evaluated on the basis of the angular spectrum of the beam entering the interferometer, but the wavefront errors increase the uncertainty

Bayesian Probabilities and the Histories Algebra

We attempt a justification of a generalisation of the consistent histories programme using a notion of probability that is valid for all complete sets of history propositions. This consists of introducing Cox's axioms of probability theory and showing that our candidate notion of probability obeys them. We also give a generalisation of Bayes' theorem and comment upon how Bayesianism should be useful for the quantum gravity/cosmology programmes.Comment: 10 pages, accepted by Int. J. Theo. Phys. Feb 200

A New Approach for Analytic Amplitude Calculations

We present a method for symbolic calculation of Feynman amplitudes for processes involving both massless and massive fermions. With this approach fermion strings in a specific amplitude can be easily evaluated and expressed as basic Lorentz scalars. The new approach renders the symbolic calculation of some complicated physical processes more feasible and easier, especially with the assistance of algebra manipulating codes for computer.Comment: LaTex, no figure, to appear in PR