Developmental hypomyelination in Wolfram syndrome: New insights from neuroimaging and gene expression analyses

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration

Universal Cellular Automata and Class 4

Wolfram has provided a qualitative classification of cellular automata(CA) rules according to which, there exits a class of CA rules (called Class 4) which exhibit complex pattern formation and long-lived dynamical activity (long transients). These properties of Class 4 CA's has led to the conjecture that Class 4 rules are Universal Turing machines i.e. they are bases for computational universality. We describe an embedding of a ``small'' universal Turing machine due to Minsky, into a cellular automaton rule-table. This produces a collection of $(k=18,r=1)$ cellular automata, all of which are computationally universal. However, we observe that these rules are distributed amongst the various Wolfram classes. More precisely, we show that the identification of the Wolfram class depends crucially on the set of initial conditions used to simulate the given CA. This work, among others, indicates that a description of complex systems and information dynamics may need a new framework for non-equilibrium statistical mechanics.Comment: Latex, 10 pages, 5 figures uuencode

An Essay On Interactive Investigations Of The Zeeman Effect In The Interstellar Medium

The paper presents an interactive module created through the Wolfram Demonstrations Project that visualizes the Zeeman effect for the small magnetic field strengths present in the interstellar medium. The paper provides an overview of spectral lines and a few examples of strong and weak Zeeman splitting before discussing the module in depth. Student discovery is aided with example situations to investigate using the interactive module, which is targeted at the upper undergraduate or early graduate level. This module (http://demonstrations.wolfram.com/TheZeemanEffectInTheInterstellarMedium), which uses free software, can be used in classroom activities or as a means of introducing students to the Wolfram Demonstrations Project as a learning resource.Comment: 6 pages, published in JAES

Symbolic Tensor Calculus -- Functional and Dynamic Approach

In this paper, we briefly discuss the dynamic and functional approach to computer symbolic tensor analysis. The ccgrg package for Wolfram Language/Mathematica is used to illustrate this approach. Some examples of applications are attached

Estimation of the order parameter exponent of critical cellular automata using the enhanced coherent anomaly method.

The stochastic cellular automaton of Rule 18 defined by Wolfram [Rev. Mod. Phys. 55 601 (1983)] has been investigated by the enhanced coherent anomaly method. Reliable estimate was found for the $\beta$ critical exponent, based on moderate sized ($n \le 7$) clusters.Comment: 6 pages, RevTeX file, figure available from [email protected]