CyberLimb: a novel robotic prosthesis concept with shared and intuitive control.

BACKGROUND: Existing assistive technologies attempt to mimic biological functions through advanced mechatronic designs. In some occasions, the information processing demands for such systems require substantial information bandwidth and convoluted control strategies, which make it difficult for the end-user to operate. Instead, a practical and intuitive semi-automated system focused on accomplishing daily tasks may be more suitable for end-user adoption. METHODS: We developed an intelligent prosthesis for the Cybathlon Global Edition 2020. The device was designed in collaboration with the prosthesis user (pilot), addressing her needs for the competition and aiming for functionality. Our design consists of a soft robotic-based two finger gripper controlled by a force-sensing resistor (FSR) headband interface, automatic arm angle dependent wrist flexion and extension, and manual forearm supination and pronation for a shared control system. The gripper is incorporated with FSR sensors to relay haptic information to the pilot based on the output of a neural network model that estimates geometries and objects material. RESULTS: As a student team of the Munich Institute of Robotics and Machine Intelligence, we achieved 12th place overall in the Cybathlon competition in which we competed against state-of-the-art prosthetic devices. Our pilot successfully accomplished two challenging tasks in the competition. During training sessions, the pilot was able to accomplish the remaining competition tasks except for one. Based on observation and feedback from training sessions, we adapted our developments to fit the user's preferences. Usability ratings indicated that the pilot perceived the prosthesis to not be fully ergonomic due to the size and weight of the system, but argued that the prosthesis was intuitive to control to perform the tasks from the Cybathlon competition. CONCLUSIONS: The system provides an intuitive interface to conduct common daily tasks from the arm discipline of the Cybathlon competition. Based on the feedback from our pilot, future improvements include the prosthesis' reduction in size and weight in order to enhance its mobility. Close collaboration with our pilot has allowed us to continue with the prosthesis development. Ultimately, we developed a simple-to-use solution, exemplifying a new paradigm for prosthesis design, to help assist arm amputees with daily activities.

Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1).

BACKGROUND: Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum membrane. SEC61A1 is a target gene of spliced X-box binding protein 1 and strongly induced during plasma cell (PC) differentiation. OBJECTIVE: We identified a novel genetic defect and studied its pathologic mechanism in 11 patients from 2 unrelated families with PADs. METHODS: Whole-exome and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro in different cell lines to assess the effect of SEC61A1 mutations on B-cell differentiation and survival. RESULTS: We investigated 2 families with patients with hypogammaglobulinemia, severe recurrent respiratory tract infections, and normal peripheral B- and T-cell subpopulations. On in vitro stimulation, B cells showed an intrinsic deficiency to develop into PCs. Genetic analysis and targeted sequencing identified novel heterozygous missense (c.254T>A, p.V85D) and nonsense (c.1325G>T, p.E381*) mutations in SEC61A1, segregating with the disease phenotype. SEC61A1-V85D was deficient in cotranslational protein translocation, and it disturbed the cellular calcium homeostasis in HeLa cells. Moreover, SEC61A1-V85D triggered the terminal unfolded protein response in multiple myeloma cell lines. CONCLUSION: We describe a monogenic defect leading to a specific PC deficiency in human subjects, expanding our knowledge about the pathogenesis of antibody deficiencies.

Diurnal patterns of spatial stream temperature variations reveal the need for integrating thermal heterogeneity in riverscape habitat restoration.

Longer durations of warmer weather, altered precipitation, and modified streamflow patterns driven by climate change are expected to impair ecosystem resilience, exposing freshwater ecosystems and their biota to a severe threat worldwide. Understanding the spatio-temporal temperature variations and the processes governing thermal heterogeneity within the riverscape are essential to inform water management and climate adaptation strategies. We combined UAS-based imagery data of aquatic habitats with meteorological, hydraulic, river morphology and water quality data to investigate how key factors influence spatio-temporal stream heterogeneity on a diurnal basis within different thermal regions of a large recently restored Danube floodplain. Diurnal temperature ranges of aquatic habitats were larger than expected and ranged between 14.2 and 28.0 °C (mean = 20.7 °C), with peak median temperatures (26.1 °C) around 16:00 h. The observed temperature differences in timing and amplitude among thermal regions were unexpectedly high and created a mosaic pattern of temperature heterogeneity. For example, cooler groundwater-influenced thermal regions provided several cold water patches (CWP, below 19.0 °C) and potential cold water refuges (CWRs) around 12:00 h, at the time when other habitats were warmer than 21.0 °C, exceeding the ecological threshold (20.0 °C) for key aquatic species. Within the morphological complexity of the restored floodplain, we identified groundwater influence, shading and river morphology as the key processes driving thermal riverscape heterogeneity. Promoting stream thermal refuges will become increasingly relevant under climate change scenarios, and river restoration should consider both measures to physically prevent habitat from excessive warming and measures to improve connectivity that meet the temperature requirements of target species for conservation. This requires restoring mosaics of complex and dynamic temperature riverscapes.

Arm movement adaptation to concurrent pain constraints.

How do humans coordinate their movements in order to avoid pain? This paper investigates a motor task in the presence of concurrent potential pain sources: the arm must be withdrawn to avoid a slap on the hand while avoiding an elbow obstacle with an electrical noxious stimulation. The results show that our subjects learned to control the hand retraction movement in order to avoid the potential pain. Subject-specific motor strategies were used to modify the joint movement coordination to avoid hitting the obstacle with the elbow at the cost of increasing the risk of hand slap. Furthermore, they used a conservative strategy as if assuming an obstacle in 100% of the trials.

U-Limb: A multi-modal, multi-center database on arm motion control in healthy and post-stroke conditions.

BACKGROUND: Shedding light on the neuroscientific mechanisms of human upper limb motor control, in both healthy and disease conditions (e.g., after a stroke), can help to devise effective tools for a quantitative evaluation of the impaired conditions, and to properly inform the rehabilitative process. Furthermore, the design and control of mechatronic devices can also benefit from such neuroscientific outcomes, with important implications for assistive and rehabilitation robotics and advanced human-machine interaction. To reach these goals, we believe that an exhaustive data collection on human behavior is a mandatory step. For this reason, we release U-Limb, a large, multi-modal, multi-center data collection on human upper limb movements, with the aim of fostering trans-disciplinary cross-fertilization. CONTRIBUTION: This collection of signals consists of data from 91 able-bodied and 65 post-stroke participants and is organized at 3 levels: (i) upper limb daily living activities, during which kinematic and physiological signals (electromyography, electro-encephalography, and electrocardiography) were recorded; (ii) force-kinematic behavior during precise manipulation tasks with a haptic device; and (iii) brain activity during hand control using functional magnetic resonance imaging.

Forward and inverse dynamics modeling of human shoulder-arm musculoskeletal system with scapulothoracic constraint.

In this work, we extend the modeling techniques of human shoulder-arm musculoskeletal dynamics by 1) proposing an extended model with 12 joint degrees of freedom and 27 muscles (modeled as 42 musculotendinous actuators) that is capable of most physiologically and anatomically possible movements, 2) proposing a forward dynamics model driven by muscle activation, where the scapulothoracic constraint is formulated as an anatomically consistent force field, and 3) applying the state-of-the-art inverse dynamics solution on this model. We experimentally validate it against electromyograms for 10 activities of daily living. This validated shoulder-arm musculoskeletal model may e.g., serve as a reference plant model in studying human motor control or as part of a human simulator in the future.

Oral administration of the casein kinase 2 inhibitor TBB leads to persistent KCa2.2 channel up-regulation in the epileptic CA1 area and cortex, but lacks anti-seizure efficacy in the pilocarpine epilepsy model.

Temporal lobe epilepsy (TLE) is the most common epileptic syndrome in adults and often presents with seizures that prove intractable with currently available anticonvulsants. Thus, there is still a need for new anti-seizure drugs in this condition. Recently, we found that the casein kinase 2 inhibitor 4,5,6,7-tetrabromotriazole (TBB) prevented the emergence of spontaneous epileptic discharges in an acute in vitro epilepsy model. This prompted us to study the anti-seizure effects of TBB in the pilocarpine model of chronic epilepsy in vivo. To this end, we performed long-term video-EEG monitoring lasting 78-167 days of nine chronically epileptic rats and obtained a baseline seizure rate of 3.3 ± 1.3 per day (baseline of 27-80 days). We found a significant age effect with more pronounced seizure rates in older animals as compared to younger ones. However, the seizure rate increased to 6.3 ± 2.2 per day during the oral TBB administration (treatment period of 21-50 days), and following discontinuation of TBB, this rate remained stable with 5.2 ± 1.4 seizures per day (follow-up of 30-55 days). After completing the video-EEG during the follow-up the hippocampal tissue was prepared and studied for the expression of the Ca2+-activated K+ channel KCa2.2. We found a significant up-regulation of KCa2.2 in the epileptic CA1 region and in the neocortex, but in no other hippocampal subfield. Hence, our findings indicate that oral administration of TBB leads to persistent up-regulation of KCa2.2 in the epileptic CA1 subfield and in the neocortex, but lacks anti-seizure efficacy in the pilocarpine epilepsy model.

Inositol 1,4,5-trisphosphate-mediated sarcoplasmic reticulum-mitochondrial crosstalk influences adenosine triphosphate production via mitochondrial Ca2+ uptake through the mitochondrial ryanodine receptor in cardiac myocytes.

AIMS: Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac myocytes are typically associated with the development of cardiac hypertrophy, arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3 receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to determine whether IP3-induced Ca(2+ )release affects mitochondrial function and determine the underlying mechanisms. METHODS AND RESULTS: We compared the effects of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation, respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP) generation. Both ET-1 and isoproterenol induced an increase in mitochondrial Ca(2+ )(Ca(2 +) m) but only ET-1 led to an increase in ATP concentration. ET-1-induced effects were prevented by cell treatment with the IP3 antagonist 2-aminoethoxydiphenyl borate and absent in myocytes from transgenic mice expressing an IP3 chelating protein (IP3 sponge). Furthermore, ET-1-induced mitochondrial Ca(2+) uptake was insensitive to the mitochondrial Ca(2+ )uniporter inhibitor Ru360, however was attenuated by RyRs type 1 inhibitor dantrolene. Using real-time polymerase chain reaction, we detected the presence of all three isoforms of IP3Rs and RyRs in murine ventricular myocytes with a dominant presence of type 2 isoform for both receptors. CONCLUSIONS: Stimulation of IP3Rs with ET-1 induces Ca(2+ )release from the SR which is tunnelled to mitochondria via mitochondrial RyR leading to stimulation of mitochondrial ATP production.

Telemedicine for safe and extended use of thrombolysis in stroke: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria.

BACKGROUND AND PURPOSE: Systemic thrombolysis represents the only proven therapy for acute ischemic stroke, but safe treatment is reported only in established stroke units. One major goal of the ongoing Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria is to extend the use of tissue plasminogen activator (tPA) treatment in nonurban areas through telemedic support. METHODS: The stroke centers in Munich-Harlaching and in Regensburg established a telestroke network to provide consultations for 12 local hospitals in eastern Bavaria. The telemedic system consists of a digital network that includes a 2-way video conference system and CT/MRI image transfer with a high-speed data transmission up to 2 Mb/s. Each network hospital established specialized stroke wards in which qualified teams treat acute stroke patients. Physicians in these hospitals are able to contact the stroke centers 24 hours per day. RESULTS: A total of 106 systemic thrombolyses were indicated via teleconsultations between February 1, 2003, and April 7, 2004. During the first 12 months, the rate of thrombolyses was 2.1% of all stroke patients. Mean age was 68 years, and median National Institutes of Health Stroke Scale score was 13. Mean delay between onset and hospital admission was 65 minutes, and door-to-needle time was on average 76 minutes, which included 15 minutes for the teleconsultation. Symptomatic hemorrhage occurred in 8.5% of patients, and in-hospital mortality was 10.4%. CONCLUSIONS: The present data suggest that systemic thrombolysis indicated via stroke experts in the setting of teleconsultation exhibits similar complication rates to those reported in the National Institute of Neurological Disorders and Stroke trial. Therefore, tPA treatment is also safe in this context and can be extended to nonurban areas.