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Advances in archaeomagnetic dating in Britain: New data, new approaches and a new calibration curve(2017-09)Archaeomagnetic dating offers a valuable chronological tool for archaeological investigations, particularly for dating fired material. The method depends on the establishment of a dated record of secular variation of the Earth's magnetic field and this paper presents new and updated archaeomagnetic directional data from the UK and geomagnetic secular variation curves arising from them. The data are taken from publications from the 1950's to the present day; 422 dated entries derived from existing archaeo and geomagnetic databases are re-evaluated and 487 new directions added, resulting in 909 entries with corresponding dates, the largest collection of dated archaeomagnetic directions from a single country. An approach to improving the largest source of uncertainty, the independent dating, is proposed and applied to the British Iron Age, resulting in 145 directions from currently available databases being updated with revised ages and/or uncertainties, and a large scale reassessment of age assignments prior to inclusion into the Magnetic Moments of the Past and GEOMAGIA50 databases. From the significantly improved dataset a new archaeomagnetic dating curve for the UK is derived through the development of a temporally continuous geomagnetic field model, and is compared with previous UK archaeomagnetic dating curves and global field models. The new model, ARCH-UK.1 allows model predictions for any location in the UK with associated uncertainties. It is shown to improve precision and accuracy in archaeomagnetic dating, and to provide new insight into past geomagnetic field changes.
A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations(2017-11-01)Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in rats have indicated that arrhythmias arose as a result of augmentation of the late Na+ current. The purpose of the present study was to examine the basis for CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs) more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes as well as from human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S mutant form of ether-a-go-go–related gene (ERG; Kv11.1). We also monitored the formation of peroxynitrite (ONOO−) in HEK293 cells fluorimetrically. CO—applied as the CO-releasing molecule, CORM-2—prolonged the APs and induced early afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild-type, but not C723S mutant, Kv11.1 K+ currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also raised ONOO− levels, an effect that was reversed by the ONOO− scavenger, FeTPPS [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes via the ONOO−-mediated inhibition of Kv11.1 K+ channels.
Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats(2018-03-12)We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9Hz. Action potential waveforms recorded at 1Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na+-channel blocker (5μM) ranolazine or the intracellular Ca2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller inMCTmyocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.
Going Along to get Along: Victimization inc.(2016)It has long been recognized that "when bad men combine, the good must associate; else they will fall, one by one, an unpitied sacrifice in a contemptible struggle" (Burke 1770, p. 146). In order words, all that is needed for evil to triumph is for good people to do nothing. Edmond Burke made the peril of inaction and dissociation in the midst of wrongdoing clear. When the need to act against victimisation arises, resistance is essential, and should not befall a brave few, for as Burke contended, there is safety in numbers. Despite Burke's advice, social psychological research (most notably by Latané and Darley 1970; Milgam 1974; Zimbardo, Banks and Jaffe 1973) has demonstrated the unreliability of unsolicited prosocial intervention into even the most glaring atrocities. Simply put, the numbers needed to ensure safety may not be there. While the reasons for inaction are both complex and manifold, they invariably point to a lack of supererogation and fiduciary responsibility. People look on rather than intervene either because they do not consider the fate of others their responsibility or business (Zimbardo 2007). Hence, are those who witness rather than contest victimisation innocent bystanders or accomplices? The answer has particular consequences for employees made victims of unscrupulous corporate supervisors, leaders, managers, and, most notably, their followers. This paper examines the moral question that inaction against victimisation in the corporate realm raises.
Understanding images in biological and computer vision(2018-06-15)This issue of Interface Focus is a collection of papers arising out of a Royal Society Discussion meeting entitled ‘Understanding images in biological and computer vision’ held at Carlton Terrace on the 19th and 20th February, 2018. There is a strong tradition of inter-disciplinarity in the study of visual perception and visual cognition. Many of the great natural scientists including Newton , Young  and Maxwell (see ) were intrigued by the relationship between light, surfaces and perceived colour considering both physical and perceptual processes. Brewster  invented both the lenticular stereoscope and the binocular camera but also studied the perception of shape-from-shading. More recently, Marr's  description of visual perception as an information processing problem led to great advances in our understanding of both biological and computer vision: both the computer vision and biological vision communities have a Marr medal. The recent successes of deep neural networks in classifying the images that we see and the fMRI images that reveal the activity in our brains during the act of seeing are both intriguing. The links between machine vision systems and biology may at sometimes be weak but the similarity of some of the operations is nonetheless striking . This two-day meeting brought together researchers from the fields of biological and computer vision, robotics, neuroscience, computer science and psychology to discuss the most recent developments in the field. The meeting was divided into four themes: vision for action, visual appearance, vision for recognition and machine learning.