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

A survey of assistive technologies and applications for blind users on mobile platforms: a review and foundation for research

This paper summarizes recent developments in audio and tactile feedback based assistive technologies targeting the blind community. Current technology allows applications to be efficiently distributed and run on mobile and handheld devices, even in cases where computational requirements are significant. As a result, electronic travel aids, navigational assistance modules, text-to-speech applications, as well as virtual audio displays which combine audio with haptic channels are becoming integrated into standard mobile devices. This trend, combined with the appearance of increasingly user- friendly interfaces and modes of interaction has opened a variety of new perspectives for the rehabilitation and training of users with visual impairments. The goal of this paper is to provide an overview of these developments based on recent advances in basic research and application development. Using this overview as a foundation, an agenda is outlined for future research in mobile interaction design with respect to users with special needs, as well as ultimately in relation to sensor-bridging applications in genera

Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

<p>Abstract</p> <p>Background</p> <p>Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold.</p> <p>Methods</p> <p>The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects.</p> <p>Results</p> <p>Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs.</p> <p>Conclusions</p> <p>To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes.</p

Repeated Training with Augmentative Vibrotactile Feedback Increases Object Manipulation Performance

Most users of prosthetic hands must rely on visual feedback alone, which requires visual attention and cognitive resources. Providing haptic feedback of variables relevant to manipulation, such as contact force, may thus improve the usability of prosthetic hands for tasks of daily living. Vibrotactile stimulation was explored as a feedback modality in ten unimpaired participants across eight sessions in a two-week period. Participants used their right index finger to perform a virtual object manipulation task with both visual and augmentative vibrotactile feedback related to force. Through repeated training, participants were able to learn to use the vibrotactile feedback to significantly improve object manipulation. Removal of vibrotactile feedback in session 8 significantly reduced task performance. These results suggest that vibrotactile feedback paired with training may enhance the manipulation ability of prosthetic hand users without the need for more invasive strategies

A brain-computer interface with vibrotactile biofeedback for haptic information

<p>Abstract</p> <p>Background</p> <p>It has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only <it>vibrotactile feedback</it>, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.</p> <p>Methods</p> <p>A Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.</p> <p>Results and Conclusion</p> <p>Subjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.</p

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

<p>Abstract</p> <p>Background</p> <p>Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.</p> <p>Methods</p> <p>A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by <it>ex vivo </it>SPECT. IS and MO were evaluated by <it>ex vivo </it>MRI.</p> <p>Results</p> <p>No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.</p> <p>Conclusion</p> <p>Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.</p

Boron isotopes in foraminifera : systematics, biomineralisation, and CO2 reconstruction

Funding: Fellowship from University of St Andrews, $100 (pending) from Richard Zeebe, UK NERC grants NE/N003861/1 and NE/N011716/1.The boron isotope composition of foraminifera provides a powerful tracer for CO2 change over geological time. This proxy is based on the equilibrium of boron and its isotopes in seawater, which is a function of pH. However while the chemical principles underlying this proxy are well understood, its reliability has previously been questioned, due to the difficulty of boron isotope (δ11B) analysis on foraminferal samples and questions regarding calibrations between δ11B and pH. This chapter reviews the current state of the δ11B-pH proxy in foraminfera, including the pioneering studies that established this proxy’s potential, and the recent work that has improved understanding of boron isotope systematics in foraminifera and applied this tracer to the geological record. The theoretical background of the δ11B-pH proxy is introduced, including an accurate formulation of the boron isotope mass balance equations. Sample preparation and analysis procedures are then reviewed, with discussion of sample cleaning, the potential influence of diagenesis, and the strengths and weaknesses of boron purification by column chromatography versus microsublimation, and analysis by NTIMS versus MC-ICPMS. The systematics of boron isotopes in foraminifera are discussed in detail, including results from benthic and planktic taxa, and models of boron incorporation, fractionation, and biomineralisation. Benthic taxa from the deep ocean have δ11B within error of borate ion at seawater pH. This is most easily explained by simple incorporation of borate ion at the pH of seawater. Planktic foraminifera have δ11B close to borate ion, but with minor offsets. These may be driven by physiological influences on the foraminiferal microenvironment; a novel explanation is also suggested for the reduced δ11B-pH sensitivities observed in culture, based on variable calcification rates. Biomineralisation influences on boron isotopes are then explored, addressing the apparently contradictory observations that foraminifera manipulate pH during chamber formation yet their δ11B appears to record the pH of ambient seawater. Potential solutions include the influences of magnesium-removal and carbon concentration, and the possibility that pH elevation is most pronounced during initial chamber formation under favourable environmental conditions. The steps required to reconstruct pH and pCO2 from δ11B are then reviewed, including the influence of seawater chemistry on boron equilibrium, the evolution of seawater δ11B, and the influence of second carbonate system parameters on δ11B-based reconstructions of pCO2. Applications of foraminiferal δ11B to the geological record are highlighted, including studies that trace CO2 storage and release during recent ice ages, and reconstructions of pCO2 over the Cenozoic. Relevant computer codes and data associated with this article are made available online.Publisher PDFPeer reviewe

Single-lens mass measurement in the high-magnification microlensing event Gaia 19bld located in the Galactic disc

CONTEXT: Microlensing provides a unique opportunity to detect non-luminous objects. In the rare cases that the Einstein radius θ_{E} and microlensing parallax π_{E} can be measured, it is possible to determine the mass of the lens. With technological advances in both ground- and space-based observatories, astrometric and interferometric measurements are becoming viable, which can lead to the more routine determination of θ_{E} and, if the microlensing parallax is also measured, the mass of the lens. AIMS: We present the photometric analysis of Gaia19bld, a high-magnification (A ≈ 60) microlensing event located in the southern Galactic plane, which exhibited finite source and microlensing parallax effects. Due to a prompt detection by the Gaia satellite and the very high brightness of I = 9.05 mag at the peak, it was possible to collect a complete and unique set of multi-channel follow-up observations, which allowed us to determine all parameters vital for the characterisation of the lens and the source in the microlensing event. METHODS: Gaia19bld was discovered by the Gaia satellite and was subsequently intensively followed up with a network of ground-based observatories and the Spitzer Space Telescope. We collected multiple high-resolution spectra with Very Large Telescope (VLT)/X-shooter to characterise the source star. The event was also observed with VLT Interferometer (VLTI)/PIONIER during the peak. Here we focus on the photometric observations and model the light curve composed of data from Gaia, Spitzer, and multiple optical, ground-based observatories. We find the best-fitting solution with parallax and finite source effects. We derived the limit on the luminosity of the lens based on the blended light model and spectroscopic distance. RESULTS: We compute the mass of the lens to be 1.13 ± 0.03 M_{⊙} and derive its distance to be 5.52_{−0.64}^{+0.35} kpc. The lens is likely a main sequence star, however its true nature has yet to be verified by future high-resolution observations. Our results are consistent with interferometric measurements of the angular Einstein radius, emphasising that interferometry can be a new channel for determining the masses of objects that would otherwise remain undetectable, including stellar-mass black holes

Single-lens mass measurement in the high-magnification microlensing event Gaia19bld located in the Galactic disc

This work was supported from the Polish NCN grants: Preludium No. 2017/25/N/ST9/01253, Harmonia No. 2018/30/M/ST9/00311, MNiSW grant DIR/WK/2018/12, Daina No. 2017/27/L/ST9/03221, and by the Research Council of Lithuania, grant No. S-LL-19-2. The OGLE project has received funding from the NCN grant MAESTRO 2014/14/A/ST9/00121 to AU. We acknowledge the European Commission’s H2020 OPTICON grant No. 730890. YT acknowledges the support of DFG priority program SPP 1992 “Exploring the Diversity of Extrasolar Planets” (WA 1047/11-1). EB and RS gratefully acknowledge support from NASA grant 80NSSC19K0291. Work by AG was supported by JPL grant 1500811. Work by JCY was supported by JPL grant 1571564. SJF thanks Telescope Live for access to their telescope network. NN acknowledges the support of Data Science Research Center, Chiang Mai University. FOE acknowledges the support from the FONDECYT grant nr. 1201223. MK acknowledges the support from the NCN grant No. 2017/27/B/ST9/02727.Context. Microlensing provides a unique opportunity to detect non-luminous objects. In the rare cases that the Einstein radius θE and microlensing parallax πE can be measured, it is possible to determine the mass of the lens. With technological advances in both ground- and space-based observatories, astrometric and interferometric measurements are becoming viable, which can lead to the more routine determination of θE and, if the microlensing parallax is also measured, the mass of the lens.  Aims. We present the photometric analysis of Gaia19bld, a high-magnification (A approximate to 60) microlensing event located in the southern Galactic plane, which exhibited finite source and microlensing parallax effects. Due to a prompt detection by the Gaia satellite and the very high brightness of I = 9.05 mag at the peak, it was possible to collect a complete and unique set of multi-channel follow-up observations, which allowed us to determine all parameters vital for the characterisation of the lens and the source in the microlensing event.  Methods. Gaia19bld was discovered by the Gaia satellite and was subsequently intensively followed up with a network of ground-based observatories and the Spitzer Space Telescope. We collected multiple high-resolution spectra with Very Large Telescope (VLT)/X-shooter to characterise the source star. The event was also observed with VLT Interferometer (VLTI)/PIONIER during the peak. Here we focus on the photometric observations and model the light curve composed of data from Gaia, Spitzer, and multiple optical, ground-based observatories. We find the best-fitting solution with parallax and finite source effects. We derived the limit on the luminosity of the lens based on the blended light model and spectroscopic distance.  Results. We compute the mass of the lens to be 1.13 ± 0.03 M⊙ and derive its distance to be 5.52-0.64+0.35 kpc. The lens is likely a main sequence star, however its true nature has yet to be verified by future high-resolution observations. Our results are consistent with interferometric measurements of the angular Einstein radius, emphasising that interferometry can be a new channel for determining the masses of objects that would otherwise remain undetectable, including stellar-mass black holes.Publisher PDFPeer reviewe