Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors have been identified that drive the degeneration of motor neurons in ALS, increase susceptibility to the disease or influence the rate of its progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, the induction of stress at the endoplasmic reticulum and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through liquid-liquid phase separation. Extraordinary progress in understanding the biology of ALS provides new reasons for optimism that meaningful therapies will be identified.

Decoding ALS: from genes to mechanism

Population-based study からみた神経予後不良因子の検討

Dynamic analysis of flexible manipulators, a literature review

The GGGGCC (G4C2) repeat expansion in a noncoding region of C9orf72 is the most common cause of sporadic and familial forms of amyotrophic lateral sclerosis and frontotemporal dementia. The basis for pathogenesis is unknown. To elucidate the consequences of G4C2 repeat expansion in a tractable genetic system, we generated transgenic fly lines expressing 8, 28 or 58 G4C2-repeat-containing transcripts that do not have a translation start site (AUG) but contain an open-reading frame for green fluorescent protein to detect repeat-associated non-AUG (RAN) translation. We show that these transgenic animals display dosage-dependent, repeat-length-dependent degeneration in neuronal tissues and RAN translation of dipeptide repeat (DPR) proteins, as observed in patients with C9orf72-related disease. This model was used in a large-scale, unbiased genetic screen, ultimately leading to the identification of 18 genetic modifiers that encode components of the nuclear pore complex (NPC), as well as the machinery that coordinates the export of nuclear RNA and the import of nuclear proteins. Consistent with these results, we found morphological abnormalities in the architecture of the nuclear envelope in cells expressing expanded G4C2 repeats in vitro and in vivo. Moreover, we identified a substantial defect in RNA export resulting in retention of RNA in the nuclei of Drosophila cells expressing expanded G4C2 repeats and also in mammalian cells, including aged induced pluripotent stem-cell-derived neurons from patients with C9orf72-related disease. These studies show that a primary consequence of G4C2 repeat expansion is the compromise of nucleocytoplasmic transport through the nuclear pore, revealing a novel mechanism of neurodegeneration.

GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport

A review of mechanical drilling for composite laminates

A human-in-the-loop experiment was conducted at the NASA Ames and Langley Research Centers, investigating the En Route Free Maneuvering component of a future air traffic management concept termed Distributed Air/Ground Traffic Management (DAG-TM) NASA Langley test subject pilots used the Autonomous Operations Planner (AOP) airborne toolset to detect and resolve traffic conflicts, interacting with subject pilots and air traffic controllers at NASA Ames Experimental results are presented, focusing on conflict resolution maneuver choices, AOP resolution guidance acceptability, and performance metrics Based on these results, suggestions are made to further improve the AOP interface and functionality

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Pilot Preference, Compliance, and Performance With an Airborne Conflict Management Toolset

This paper describes an Electro-Hydraulics Laboratory (EH Lab) at the University of Missouri - Rolla (UMR), which was recently established with a gift from Caterpillar Inc. The goal of this laboratory is to provide students the opportunity for hands-on experience with signal processing, dynamic modeling, and real-time control of industrial-grade electro-hydraulic systems. Unlike most comparable educational laboratories, nearly all of the components used in this laboratory were originally intended for industrial use, yielding a much more real-world experience for students. The laboratory utilizes the xPC Target software for rapid prototyping and execution of real-time data acquisition and control systems using Simulink. Several laboratories, as well as a course project, that utilize the EH Lab are presented.Copyright © 2006 by ASME

Development of a Novel Electro-Hydraulic Laboratory

Ethnobotany of India, Volume 1: Eastern Ghats and Deccan

The Concepts of Handedness, Asymmetry, Chirality, Spirality, and Helicity

A game theoretic based scheme is considered in this study for multidisciplinary design optimization under uncertain conditions. The methodology developed is illustrated by considering the example of an internal combustion (IC) engine. Various game protocols are used to model the optimization process and the results obtained are compared with each other. A genetic algorithm (GA) is used as an optimization and constraining tool. Convergence, constraint handling and processing time are considered to evaluate the efficacy of the methodology developed.Copyright © 2004 by ASME

Karthik Krishnamurthy

Papers

Pilot Preference, Compliance, and Performance With an Airborne Conflict Management Toolset

Development of a Novel Electro-Hydraulic Laboratory

Ethnobotany of India, Volume 1: Eastern Ghats and Deccan

The Concepts of Handedness, Asymmetry, Chirality, Spirality, and Helicity

A Game Theoretic Based Scheme for Multidisciplinary Optimization with Uncertainty