The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the ClC-1 channel

Myotonia congenita (MC) is a skeletal-muscle hyperexcitability disorder caused by loss-of-function mutations in the ClC-1 chloride channel. Mutations are scattered over the entire sequence of the channel protein, with more than 30\ua0mutations located in the poorly characterized cytosolic C-terminal domain. In this study, we characterized, through patch clamp, seven ClC-1 mutations identified in patients affected by MC of various severities and located in the C-terminal region. The p.Val829Met, p.Thr832Ile, p.Val851Met, p.Gly859Val, and p.Leu861Pro mutations reside in the CBS2 domain, while p.Pro883Thr and p.Val947Glu are in the C-terminal peptide. We showed that the functional properties of mutant channels correlated with the clinical phenotypes of affected individuals. In addition, we defined clusters of ClC-1 mutations within CBS2 and C-terminal peptide subdomains that share the same functional defect: mutations between 829 and 835 residues and in residue 883 induced an alteration of voltage dependence, mutations between 851 and 859 residues, and in residue 947 induced a reduction of chloride currents, whereas mutations on 861 residue showed no obvious change in ClC-1 function. This study improves our understanding of the mechanisms underlying MC, sheds light on the role of the C-terminal region in ClC-1 function, and provides information to develop new antimyotonic drugs

GRAB: A Dataset of Whole-Body Human Grasping of Objects

Training computers to understand, model, and synthesize human grasping requires a rich dataset containing complex 3D object shapes, detailed contact information, hand pose and shape, and the 3D body motion over time. While "grasping" is commonly thought of as a single hand stably lifting an object, we capture the motion of the entire body and adopt the generalized notion of "whole-body grasps". Thus, we collect a new dataset, called GRAB (GRasping Actions with Bodies), of whole-body grasps, containing full 3D shape and pose sequences of 10 subjects interacting with 51 everyday objects of varying shape and size. Given MoCap markers, we fit the full 3D body shape and pose, including the articulated face and hands, as well as the 3D object pose. This gives detailed 3D meshes over time, from which we compute contact between the body and object. This is a unique dataset, that goes well beyond existing ones for modeling and understanding how humans grasp and manipulate objects, how their full body is involved, and how interaction varies with the task. We illustrate the practical value of GRAB with an example application; we train GrabNet, a conditional generative network, to predict 3D hand grasps for unseen 3D object shapes. The dataset and code are available for research purposes at https://grab.is.tue.mpg.de.Comment: ECCV 202

An Advanced IBVS-Flatness Approach for Real-Time Quadrotor Navigation: A Full Control Scheme in the Image Plane

This article presents an innovative method for planning and tracking the trajectory in the image plane for the visual control of a quadrotor. The community of researchers working on 2D control widely recognizes this challenge as complex, because a trajectory defined in image space can lead to unpredictable movements of the robot in Cartesian space. While researchers have addressed this problem for mobile robots, quadrotors continue to face significant challenges. To tackle this issue, the adopted approach involves considering the separation of altitude control from the other variables, thus reducing the workspace. Furthermore, the movements of the quadrotor (pitch, roll, and yaw) are interdependent. Consequently, the connection between the inputs and outputs cannot be reversed. The task complexity becomes significant. To address this issue, we propose the following scenario: When the quadrotor is equipped with a downward-facing camera, flying at high altitude is sensible to spot a target. However, to minimize disturbances and conserve energy, the quadrotor needs to descend in altitude. This can result in the target being lost. The solution to this problem is a new methodology based on the principle of differential flatness, allowing the separation of altitude control from the other variables. The system first detects the target at high altitude, then plots a trajectory in the image coordinate system between the acquired image and the desired image. It is crucial to emphasize that this step is performed offline, ensuring that the image processing time does not affect the control frequency. Through the proposed trajectory planning, complying with the constraints of differential flatness, the quadrotor can follow the imposed dynamics. To ensure the tracking of the target while following the generated trajectory, the proposed control law takes the form of an Image Based Visual Servoing (IBVS) scheme. We validated this method using the RVCTOOLS environment in MATLAB. The DJI Phantom 1 quadrotor served as a testbed to evaluate, under real conditions, the effectiveness of the proposed control law. We specifically designed an electronic card to transfer calculated commands to the DJI Phantom 1 control joystick via Bluetooth. This card integrates a PIC18F2520 microcontroller, a DAC8564 digital-to-analogue converter, and an RN42 Bluetooth module. The experimental results demonstrate the effectiveness of this method, ensuring the precise tracking of the target as well as the accurate tracking of the path generated in the image coordinate system

Electron Resonance Decay into a Biological Function: Decrease in Viability of E. coli Transformed by Plasmid DNA Irradiated with 0.5–18 eV Electrons

Transient negative ions (TNIs) are ubiquitous in electron-molecule scattering at low electron impact energies (0–20 eV) and are particularly effective in damaging large biomolecules. Because ionizing radiation generates mostly 0–20 eV electrons, TNIs are expected to play important roles in cell mutagenesis and death during radiotherapeutic cancer treatment, although this hypothesis has never been directly verified. Here, we measure the efficiency of transforming E. coli bacteria by inserting into the cells, pGEM-3ZfL(−) plasmid DNA that confers resistance to the antibiotic ampicillin. Before transformation, plasmids are irradiated with electrons of specific energies between 0.5 and 18 eV. The loss of transformation efficiency plotted as a function of irradiation energy reveals TNIs at 5.5 and 9.5 eV, corresponding to similar states observed in the yields of DNA double strand breaks. We show that TNIs are detectable in the electron-energy dependence of a biological process and can decrease cell viability

The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C‐terminal peptide of the ClC‐1 channel

Myotonia congenita (MC) is a skeletal‐muscle hyperexcitability disorder caused by loss‐of‐function mutations in the ClC‐1 chloride channel. Mutations are scattered over the entire sequence of the channel protein, with more than 30 mutations located in the poorly characterized cytosolic C‐terminal domain. In this study, we characterized, through patch clamp, seven ClC‐1 mutations identified in patients affected by MC of various severities and located in the C‐terminal region. The p.Val829Met, p.Thr832Ile, p.Val851Met, p.Gly859Val, and p.Leu861Pro mutations reside in the CBS2 domain, while p.Pro883Thr and p.Val947Glu are in the C‐terminal peptide. We showed that the functional properties of mutant channels correlated with the clinical phenotypes of affected individuals. In addition, we defined clusters of ClC‐1 mutations within CBS2 and C‐terminal peptide subdomains that share the same functional defect: mutations between 829 and 835 residues and in residue 883 induced an alteration of voltage dependence, mutations between 851 and 859 residues, and in residue 947 induced a reduction of chloride currents, whereas mutations on 861 residue showed no obvious change in ClC‐1 function. This study improves our understanding of the mechanisms underlying MC, sheds light on the role of the C‐terminal region in ClC‐1 function, and provides information to develop new antimyotonic drugs