On globally non-trivial almost-commutative manifolds

Within the framework of Connes' noncommutative geometry, we define and study globally non-trivial (or topologically non-trivial) almost-commutative manifolds. In particular, we focus on those almost-commutative manifolds that lead to a description of a (classical) gauge theory on the underlying base manifold. Such an almost-commutative manifold is described in terms of a 'principal module', which we build from a principal fibre bundle and a finite spectral triple. We also define the purely algebraic notion of 'gauge modules', and show that this yields a proper subclass of the principal modules. We describe how a principal module leads to the description of a gauge theory, and we provide two basic yet illustrative examples.Comment: 34 pages, minor revision

Crypto heater:a design fiction

This proposal is to exhibit the work named Crypto Heater which is part of a design fiction [c.f 1,5,8:30] series intended to explore a near future world in which cryptographic currencies such as Bitcoin [6] have become commonplace. This work opens up space for discussion about the activities of the distributed peer-to-peer network of so-called "miners" that ensure the security of the Bitcoin network and regulate the supply of new currency in the Bitcoin economy. The physical part of the work (the heater itself) is set within a fictional near-future reality. In this reality, Bitcoin has become central to our financial service industry, and "mining" in domestic settings is promoted by the government, as a means of heating our homes and to ensure security of the network. A "story world" is constructed using devices such as promotional materials from the UK Government's Ministry of Crypto Currency; technical specifications; customer testimonials; and the heater itself. The main element of the exhibit is a fully working Crypto Heater prototype. This device is (in the fictional world, and the real world) part of the distributed network of Bitcoin miners. Through computation, it converts electrical energy into cryptographic currency. Uniquely Crypto Heater dissipates the heat energy (a by-product of the computational effort required to be a Bitcoin miner) through a standard household radiator. By offsetting the value of the cryptographic currency produced, against the cost of electricity used, the heater provides subsidized domestic heating

Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy

Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the alpha II-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative alpha II-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations