Spinal muscular atrophy (SMA) is a debilitating neuromuscular disease caused by the loss of survival of motor neuron (SMN) protein. Previously, we demonstrated that ISIS 396443, an antisense oligonucleotide (ASO) targeted to the SMN2 pre-mRNA, is a potent inducer ofSMN2 exon 7 inclusion and SMNprotein expression, and improves function and survival of mild and severe SMA mouse models. Here, we d...

1. Introduction I___-This paper describes ISIS-II*, a constraint-directed reasoning system for the scheduling of factory job-shops. ISIS-II takes a heuristic search approach to generating schedules. The key features of ISIS-II's approach is that it can represent and use a variety of different types of constraints to guide the search, and is able to selectively relax conflicting constraints.

Since the Syrian Civil War began in 2011, tens of thousands foreign fighters from different parts world have joined various armed groups Syria and Iraq. There are three main fighters: Firstly, pro-ISIS who associated with jihadist like Islamic State Iraq (ISIS); secondly, pro-regime Shiite affiliated Assad government; finally, anti-ISIS Western fighters, fighting Kurdish Christian against ISIS ...

Using a dataset of over 1.9 million messages posted on Twitter by about 25,000 ISIS members, we explore how ISIS makes use of social media to spread its propaganda and to recruit militants from the Arab world and across the globe. By distinguishing between violence-driven, theological, and sectarian content, we trace the connection between online rhetoric and key events on the ground. To the be...

This document describes extensions to the ISIS (ISIS) protocol to support Multiprotocol Label Switching (MPLS) and Generalized MPLS (GMPLS) Traffic Engineering (TE) for multiple Autonomous Systems (ASes). It defines ISIS-TE extensions for the flooding of TE information about inter-AS links, which can be used to perform interAS TE path computation. No support for flooding information from within...

ISIS 388626, a 2'-methoxyethyl (MOE)-modified antisense oligonucleotide (ASO) that targets human sodium glucose cotransporter 2 (SGLT2) mRNA, is in clinical trials for the management of diabetes. SGLT2 plays a pivotal role in renal glucose reabsorption, and inhibition of SGLT2 is anticipated to reduce hyperglycemia in diabetic subjects by increasing urinary glucose elimination. To selectively i...

The purpose of this study was to determine whether short interspike intervals (ISIs of <20 ms) would occur naturally during voluntary movement and would increase in number with fatigue. Thirty-four triceps brachii motor units from nine subjects were assessed during a fatigue task consisting of fifty extension and fifty flexion elbow movements against a constant-load opposing extension. Nineteen...

BACKGROUND & AIMS ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). METHODS A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with st...

Recent terrorist attacks carried out on behalf of ISIS on American and European soil by lone wolf attackers or sleeper cells remind us of the importance of understanding the dynamics of radicalization mediated by social media communication channels. In this paper, we shed light on the social media activity of a group of twenty-five thousand users whose association with ISIS online radical propa...

One of the most extreme examples of gene dosage sensitivity is the Triplo-lethal locus (Tpl) on the third chromosome of Drosophila melanogaster, which is lethal when present in either one or three copies. Increased dosage of an unlinked locus, Isis, suppresses the triplo-lethal phenotype of Tpl, but not the haplo-lethal phenotype. We have mapped Isis to the X chromosome region 7E3-8A5, and show...