Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously

Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from two α-subunits, and one each of the β-, δ-, and ϵ- subunits. To form functional channels, the subunits must assemble with one another in a precise stoichiometry and arrangement. Despite being different, the four subunits share a common ancestor that is presumed to have formed homopentamers. The extent to which the properties of the modern-day receptor result from its subunit complexity is unknown. Here we show that a reconstructed ancestral muscle-type β-subunit can form homopentameric ion channels. These homopentamers open spontaneously and display single-channel hallmarks of muscle type acetylcholine receptor activity. Our findings demonstrate that signature features of muscle-type acetylcholine receptor function are independent of agonist, and do not necessitate the complex heteropentameric architecture of the modern-day receptor.

Peak Space Motion Artifact Cancellation Applied to Textile Electrode Waist Electrocardiograms Recording During Outdoors Walking and Jogging

Background: Obtaining reliable rate heart estimates from waist based electrocardiograms (ECGs) poses a very challenging problem due to the presence of extreme motion artifacts. The literature reveals few, if any, attempts to apply motion artifact cancellation methods to waist based ECGs. This paper describes a new methodology for ameliorating the effects of motion artifacts in ECGs by specifically targeting ECG peaks for elimination that are determined to be correlated with accelerometer peaks. This peak space cancellation was applied to real world waist based ECGs. Algorithm Summary: The methodology includes successive applications of a previously described pattern-based heart beat detection scheme (Temporal Pattern Search, or TEPS) that can also detect patterns in other types of peak sequences. In the first application, TEPS is applied to accelerometer signals recorded contemporaneously with ECG signals to identify high-quality accelerometer peak sequences (SA) indicative of quasi-periodic motion likely to impair identification of peaks in a corresponding ECG signal. The process then performs ECG peak detection and locates the closest in time ECG peak to each peak in an SA. The differences in time between ECG and SA peaks are clustered. If the number of elements in a cluster of peaks in an SA exceeds a threshold, the ECG peaks in that cluster are removed from further processing. After this peak removal process, further QRS detection proceeds according to TEPS. Experiment: The above procedure was applied to data from real world experiments involving four sessions of walking and jogging on a dirt road for approximately 20-25 minutes. A compression shirt with textile electrodes served as the ground truth recording. A textile electrode based chest strap was worn around the waist to generate a single channel signal upon which to test peak space cancellation/TEPS. Results: Both walking and jogging heart rates were generally well tracked. In the four recordings, the percentage of 5 second segments within 10 beats/minute of reference was 96%, 99%, 92% and 96%. The percentage of segments within 5 beats/minute of reference was 86%, 90%, 82% and 78%. There was very good agreement between the RR intervals associated with the reference and waist recordings. For acceptable quality segments, the root mean square sum of successive RR interval differences (RMSSD) was calculated for both the reference and waist recordings. Next, the difference between waist and reference RMSSDs was calculated (∆RMSSD). The mean ∆RMSSD (over acceptable segments) was 4.6 m, 5.2 ms, 5.2 ms and 6.6 ms for the four recordings. Conclusion: Given that only one waist ECG channel was available, and that the strap used for the waist recording was not tailored for that purpose, the proposed methodology shows promise for waist based sinus rhythm QRS detection.

Range and Accuracy Improvement of Artillery Rocket Using Fixed Canards Trajectory Correction Fuze

This paper presents a two-phase guidance and control algorithm to extend the range and improve the impact point accuracy of a 122-mm rocket using a fixed canards trajectory correction fuze. The guidance algorithm consists of a unique glide and correction phase of the rocket trajectory that is activated after the flight’s apex. The glide phase operates in an open-loop configuration where guidance commands are generated to increase the range of the rocket. In contrast, the correction phase operates in a closed-loop configuration where the Impact Point Prediction method based on Modified Projectile Linear Theory is used as a feedback channel to correct the range and drift errors. The proposed fixed canards trajectory correction fuze has a simple and reliable single channel roll-orientation control configuration. The rocket trajectory model consists of a 7-DOF non-linear dynamic model of a dual-spin rocket configuration with a fixed canards correction fuze mounted at the nose. A Monte Carlo simulation of the rocket’s inertial and launch point perturbations show that the fixed canards fuze with the proposed guidance algorithm can double the range of the rocket without changing the rocket motor thrust-time curve. At the same time, the rocket’s accuracy can also be improved beyond the results of an unguided rocket.

Enhanced long-term potentiation and impaired learning in mice lacking alternative exon 33 of CaV1.2 calcium channel

The CACNA1C (calcium voltage-gated channel subunit alpha 1 C) gene that encodes the CaV1.2 channel is a prominent risk gene for neuropsychiatric and neurodegenerative disorders with cognitive and social impairments like schizophrenia, bipolar disorders, depression and autistic spectrum disorders (ASD). We have shown previously that mice with exon 33 deleted from CaV1.2 channel (CaV1.2-exon 33−/−) displayed increased CaV1.2 current density and single channel open probability in cardiomyocytes, and were prone to develop arrhythmia. As Ca2+ entry through CaV1.2 channels activates gene transcription in response to synaptic activity, we were intrigued to explore the possible role of Cav1.2Δ33 channels in synaptic plasticity and behaviour. Homozygous deletion of alternative exon 33 resulted in enhanced long-term potentiation (LTP), and lack of long- term depression (LTD), which did not correlate with enhanced learning. Exon 33 deletion also led to a decrease in social dominance, sociability and social novelty. Our findings shed light on the effect of gain-of-function of CaV1.2Δ33 signalling on synaptic plasticity and behaviour and provides evidence for a link between CaV1.2 and distinct cognitive and social behaviours associated with phenotypic features of psychiatric disorders like schizophrenia, bipolar disorder and ASD.

Rolling Bearing Fault Diagnosis Based on Component Screening Vector Local Characteristic-Scale Decomposition

The fault vibration signal of a bearing has nonstationary and nonlinear characteristics and can be regarded as the combination of multiple amplitude- and frequency-modulation components. The envelope of a single component contains the fault characteristics of a bearing. Local characteristic-scale decomposition (LCD) can decompose the vibration signal into a series of multiple intrinsic scale components. Some components can clearly reflect the running state of a bearing, and fault diagnosis is conducted according to the envelope spectrum. However, the conventional LCD takes a single-channel signal as the research object, which cannot fully reflect the characteristic information of the rotor, and the analysis results based on different channel signals of the same section will be inconsistent. To solve this problem, based on full vector spectrum technology, the homologous dual-channel information is fused. A vector LCD method based on cross-correlation coefficient component selection is given, and a simulation analysis is completed. The effectiveness of the proposed method is verified by simulated signals and experimental signals of a bearing, which provides a method for bearing feature extraction and fault diagnosis.