No abstract

Charcot‐Marie‐Tooth disease type 1A (CMT1A), the most frequent form of GAIT, is caused by a 1.5 Mb duplication on the short arm of chromosome 17. Patients with CMT1A typically have slowed nerve conduction velocities (NCVs), reduced compound motor and sensory nerve action potentials (CMAPs and SNAPs), distal weakness, sensory loss and decreased reflexes. In order to understand further the molecular pathogenesis of CMT1A, as well as to determine which features correlate with neurological dysfunction and might thus be amenable to treatment, we evaluated the clinical and electrophysiological phenotype in 42 patients with CMT1A. In these patients, muscle weakness, CMAP amplitudes and regeneration, motor unit number estimates correlated with clinical disability, while motor NCV did not. In addition, loss of joint position sense and reduction in SNAP amplitudes also correlated with clinical disability, while sensory NCV did not. Taken together, these data strongly support the hypothesis that neurological dysfunction and clinical disability in CMT1A are caused by loss or damage to large calibre motor and sensory axons. Therapeutic approaches to ameliorate disability in CMT1A, as in amyotrophic lateral sclerosis and other neurodegenerative diseases, should thus be directed towards preventing axonal degeneration and/or promoting axonal regeneration.

Physics is the interplay of energy and matter. Energy, in the form of light, interacting with matter, principally in the solid state, underpins this topical review. The subject is developed carefully and methodically, beginning with basic definitions pertaining to terahertz detectors and terahertz radiation, then proceeding systematically to delineate characteristics of terahertz photons and terahertz detectors in more detail. In-between, the intimate connection linking terahertz sensors and terahertz sources is highlighted-an important aspect unfortunately often overlooked or ignored when terahertz detectors are discussed in isolation. At the centre of this topical review are the various physical mechanisms by which electromagnetic radiation of terahertz frequencies interacts with matter. The logic is to present first the underlying physical principles of detection before presenting the practical implementation in a specific device, rather than the other way around. A taxonomy of terahertz detectors is then proposed based on the underlying physical principles of detection. Following on from this classification, stateof-the-art terahertz detectors are surveyed and appraised; this overview constitutes the longest section of the review. Key detector parameters which inform applications are then presented and tabulated. Finally, the present state-of-the-art is anchored within the wider scientific context of historical developments and future prospects.

Advances in solid-state device design now allow the spectrum of transmitted electrons in thermionic and thermoelectric devices to be engineered in ways that were not previously possible. Here we show that the shape of the electron energy spectrum in these devices has a significant impact on their performance. We distinguish between traditional thermionic devices where electron momentum is filtered in the direction of transport only and a second type, in which the electron filtering occurs according to total electron momentum. Such "total momentum filtered" thermionic devices could potentially be implemented in, for example, quantum dot superlattices. It is shown that whilst total momentum filtered thermionic devices may achieve an efficiency equal to the Carnot value, traditional thermionic devices are limited to an efficiency below this. Our second main result is that the electronic efficiency of a device is not only improved by reducing the width of the transmission filter as has previously been shown, but also strongly depends on whether the transmission probability rises sharply from zero to full transmission. The benefit of increasing efficiency through a sharply rising transmission probability is that it can be achieved without sacrificing device power, in contrast to the use of a narrow transmission filter which can greatly reduce power. We show that devices that have a sharply rising transmission probability significantly outperform those that do not and that such transmission probabilities may be achieved with practical single and multibarrier devices. We discuss how the shape of the electron energy spectrum will also have an effect on the electronic efficiency of thermoelectric devices due to mathematical equivalences in the ballistic and diffusive formalisms. Finally, we present an experimental measure that might be used to provide an indication of the nature of the electron energy spectrum and the electronic efficiency of a ballistic device.