A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem.

Potassium channels catalyse the permeation of K+ ions across cellular membranes and are identified by a common structural motif, a highly conserved signature sequence of eight amino acids in the P domain of each channel's pore-forming alpha-subunit. Here we describe a novel K+ channel (TOK1) from Saccharomyces cerevisiae that contains two P domains within one continuous polypeptide. Xenopus laevis oocytes expressing the channel exhibit a unique, outwardly rectifying, K(+)-selective current. The channel is permeable to outward flow of ions at membrane potentials above the K+ equilibrium potential; its conduction-voltage relationship is thus sensitive to extracellular K+ ion concentration. In excised membrane patches, external divalent cations block the channel in a voltage-dependent manner, and their removal in this configuration allows inward channel current. These attributes are similar to those described for inwardly rectifying K+ channels, but in the opposite direction, a previously unrecognized channel behaviour. Our results identify a new class of K+ channel which is distinctive in both its primary structure and functional properties. Structural homologues of the channel are present in the genome of Caenorhabditis elegans

Hypervelocity dust particle impacts observed by the Giotto Magnetometer and Plasma Experiments

We report thirteen very short events in the magnetic field of the inner magnetic pile‐up region of comet Halley observed by the Giotto magnetometer experiment together with simultaneous plasma data obtained by the Johnstone plasma analyzer and the ion mass spectrometer experiments. The events are due to dust impacts in the milligram range on the spacecraft at the relative velocity between the cemetery dust and the spacecraft of 68 km/sec. They are generally consistent with dust impact events derived from spacecraft attitude perturbations by the Giotto camera [Curdt and Keller, private communication]. Their characteristic shape generally involves a sudden decrease in magnetic field magnitude, a subsequent overshoot beyond initial field values and an asymptotic approach to the initial field somewhat reminiscent of the magnetic field signature after the AMPTE releases in the solar wind. These observations give a new way of analyzing ultra‐fast dust particles incident on a spacecraft

Day-night asymmetries of low-energy electrons in Saturn's inner magnetosphere

We examine the day-night asymmetry of near-equatorial low energy (12-100 eV) electron fluxes measured by Cassini from July 1, 2004 through April 1, 2010. This energy range is also known to be associated with interchange injections. The electrons are separated into field-aligned (0 degrees to 20 degrees and 160 degrees to 180 degrees) pitch angles and trapped (70 degrees to 110 degrees) pitch angles. There is a stronger day-night asymmetry for the trapped than the field-aligned electrons, but both show enhanced energy fluxes on the nightside relative to the dayside. The dayside electron fluxes decrease sharply at an L-shell of 8, while the nightside electrons exhibit a slow decline in to L = 5. Our finding, along with previous research of high energy electrons, shows that this asymmetry is energy independent. This suggests that interchange injections are stronger, and therefore penetrate deeper into the magnetosphere, on the nightside

Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types.

Cancer cell lines are a cornerstone of cancer research but previous studies have shown that not all cell lines are equal in their ability to model primary tumors. Here we present a comprehensive pan-cancer analysis utilizing transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 tumor types. We perform correlation analysis and gene set enrichment analysis to understand the differences between cell lines and primary tumors. Additionally, we classify cell lines into tumor subtypes in 9 tumor types. We present our pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 is transcriptionally unrepresentative of primary pancreatic adenocarcinomas. Lastly, we propose a new cell line panel, the TCGA-110-CL, for pan-cancer studies. This study provides a resource to help researchers select more representative cell line models

Ion pickup observed at comet 67P with the Rosetta Plasma Consortium (RPC) particle sensors: similarities with previous observations and AMPTE releases, and effects of increasing activity

Rosetta’s unique trajectory is allowing exciting measurements of the development of cometary activity between ~3.6 and 1.2 AU for the first time. For a few months following Rosetta’s arrival at comet 67P in August 2014, data from the Rosetta Plasma Consortium (RPC) particle instruments (the Ion and Electron Spectrometer (IES) and the Ion Composition Analyser (ICA)), have shown that the low activity cometary environment was initially dominated by the solar wind. This was expected in the early stages of the mission. In addition to the solar wind and related He+ populations, a low energy pickup ion population is seen intermittently in the early phase of the mission near the comet. The population is very time dependent, but at times reaches higher energy approaching the solar wind energy. During these intervals, ICA data indicate that the composition is mainly water group ions. The rising energy signatures of these ions observed at times indicate that they are in the early phases of the pickup process, initially accelerated by the electric field (‘early phase pickup’). Here, we compare these exciting pickup ion measurements with Giotto measurements at the relatively weak (compared to Halley) comet Grigg-Skjellerup, where early phase pickup was seen including non-gyrotropic cometary ions, and with the AMPTE lithium and barium releases. Our results reveal some striking similarities with the AMPTE releases, particularly the rising energy signature related to early pickup, and a momentum balance between the pickup ions and the deflected solar wind. There is also evidence for momentum transfer between the pickup ions and the solar wind, with less velocity change seen in the solar wind alpha particles compared to the protons; this was also observed in an AMPTE lithium release. We discuss the effects of increasing activity observed between 3.6 to 1.8 AU, including the increasing dominance and energisation of pickup ions, increasing ionospheric effects and the decreasing effect of the solar wind

Magnetic signatures of plasma-depleted flux tubes in the Saturnian inner magnetosphere

Initial Cassini observations have revealed evidence for interchanging magnetic flux tubes in the inner Saturnian magnetosphere. Some of the reported flux tubes differ remarkably by their magnetic signatures, having a depressed or enhanced magnetic pressure relative to their surroundings. The ones with stronger fields have been interpreted previously as either outward moving mass-loaded or inward moving plasma-depleted flux tubes based on magnetometer observations only. We use detailed multi-instrumental observations of small and large density depletions in the inner Saturnian magnetosphere from Cassini Rev. A orbit that enable us to discriminate amongst the two previous and opposite interpretations. Our analysis undoubtedly confirms the similar nature of both types of reported interchanging magnetic flux tubes, which are plasma-depleted, whatever their magnetic signatures are. Their different magnetic signature is clearly an effect associated with latitude. These Saturnian plasma-depleted flux tubes ultimately may play a similar role as the Jovian ones

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Quantum Phase Transition in a Resonant Level Coupled to Interacting Leads

An interacting one-dimensional electron system, the Luttinger liquid, is distinct from the "conventional" Fermi liquids formed by interacting electrons in two and three dimensions. Some of its most spectacular properties are revealed in the process of electron tunneling: as a function of the applied bias or temperature the tunneling current demonstrates a non-trivial power-law suppression. Here, we create a system which emulates tunneling in a Luttinger liquid, by controlling the interaction of the tunneling electron with its environment. We further replace a single tunneling barrier with a double-barrier resonant level structure and investigate resonant tunneling between Luttinger liquids. For the first time, we observe perfect transparency of the resonant level embedded in the interacting environment, while the width of the resonance tends to zero. We argue that this unique behavior results from many-body physics of interacting electrons and signals the presence of a quantum phase transition (QPT). In our samples many parameters, including the interaction strength, can be precisely controlled; thus, we have created an attractive model system for studying quantum critical phenomena in general. Our work therefore has broadly reaching implications for understanding QPTs in more complex systems, such as cold atoms and strongly correlated bulk materials.Comment: 11 pages total (main text + supplementary

Recognizing Speech in a Novel Accent: The Motor Theory of Speech Perception Reframed

The motor theory of speech perception holds that we perceive the speech of another in terms of a motor representation of that speech. However, when we have learned to recognize a foreign accent, it seems plausible that recognition of a word rarely involves reconstruction of the speech gestures of the speaker rather than the listener. To better assess the motor theory and this observation, we proceed in three stages. Part 1 places the motor theory of speech perception in a larger framework based on our earlier models of the adaptive formation of mirror neurons for grasping, and for viewing extensions of that mirror system as part of a larger system for neuro-linguistic processing, augmented by the present consideration of recognizing speech in a novel accent. Part 2 then offers a novel computational model of how a listener comes to understand the speech of someone speaking the listener's native language with a foreign accent. The core tenet of the model is that the listener uses hypotheses about the word the speaker is currently uttering to update probabilities linking the sound produced by the speaker to phonemes in the native language repertoire of the listener. This, on average, improves the recognition of later words. This model is neutral regarding the nature of the representations it uses (motor vs. auditory). It serve as a reference point for the discussion in Part 3, which proposes a dual-stream neuro-linguistic architecture to revisits claims for and against the motor theory of speech perception and the relevance of mirror neurons, and extracts some implications for the reframing of the motor theory