Controlling swimming and crawling in a fish robot using a central pattern generator

Online trajectory generation for robots with multiple degrees of freedom is still a difficult and unsolved problem, in particular for non-steady state locomotion, that is, when the robot has to move in a complex environment with continuous variations of the speed, direction, and type of locomotor behavior. In this article we address the problem of controlling the non-steady state swimming and crawling of a novel fish robot. For this, we have designed a control architecture based on a central pattern generator (CPG) implemented as a system of coupled nonlinear oscillators. The CPG, like its biological counterpart, can produce coordinated patterns of rhythmic activity while being modulated by simple control parameters. To test our controller, we designed BoxyBot, a simple fish robot with three actuated fins capable of swimming in water and crawling on firm ground. Using the CPG model, the robot is capable of performing and switching between a variety of different locomotor behaviors such as swimming forwards, swimming backwards, turning, rolling, moving upwards/downwards, and crawling. These behaviors are triggered and modulated by sensory input provided by light, water, and touch sensors. Results are presented demonstrating the agility of the robot and interesting properties of a CPG-based control approach such as stability of the rhythmic patterns due to limit cycle behavior, and the production of smooth trajectories despite abrupt changes of control parameters. The robot is currently used in a temporary 20-month long exhibition at the EPFL. We present the hardware setup that was designed for the exhibition, and the type of interactions with the control system that allow visitors to influence the behavior of the robot. The exhibition is useful to test the robustness of the robot for long term use, and to demonstrate the suitability of the CPG-based approach for interactive control with a human in the loop. This article is an extended version of an article presented at BioRob2006 the first IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronic

Controlling swimming and crawling in a fish robot using a central pattern generator

Online trajectory generation for robots with multiple degrees of freedom is still a difficult and unsolved problem, in particular for non-steady state locomotion, that is, when the robot has to move in a complex environment with continuous variations of the speed, direction, and type of locomotor behavior. In this article we address the problem of controlling the non-steady state swimming and crawling of a novel fish robot. For this, we have designed a control architecture based on a central pattern generator (CPG) implemented as a system of coupled nonlinear oscillators. The CPG, like its biological counterpart, can produce coordinated patterns of rhythmic activity while being modulated by simple control parameters. To test our controller, we designed BoxyBot, a simple fish robot with three actuated fins capable of swimming in water and crawling on firm ground. Using the CPG model, the robot is capable of performing and switching between a variety of different locomotor behaviors such as swimming forwards, swimming backwards, turning, rolling, moving upwards/downwards, and crawling. These behaviors are triggered and modulated by sensory input provided by light, water, and touch sensors. Results are presented demonstrating the agility of the robot and interesting properties of a CPG-based control approach such as stability of the rhythmic patterns due to limit cycle behavior, and the production of smooth trajectories despite abrupt changes of control parameters. The robot is currently used in a temporary 20-month long exhibition at the EPFL. We present the hardware setup that was designed for the exhibition, and the type of interactions with the control system that allow visitors to influence the behavior of the robot. The exhibition is useful to test the robustness of the robot for long term use, and to demonstrate the suitability of the CPG-based approach for interactive control with a human in the loop. This article is an extended version of an article presented at BioRob2006 the first IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal deathResearch in context

Summary: Background: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. Methods: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. Findings: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. Interpretation: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. Funding: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)

Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO

The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting

High rate of hypomorphic variants as the cause of inherited ataxia and related diseases: study of a cohort of 366 families

International audiencePurpose: Diagnosis of inherited ataxia and related diseases represents a real challenge given the tremendous heterogeneity and clinical overlap of the various causes. We evaluated the efficacy of molecular diagnosis of these diseases by sequencing a large cohort of undiagnosed families.Methods: We analyzed 366 unrelated consecutive patients with undiagnosed ataxia or related disorders by clinical exome-capture sequencing. In silico analysis was performed with an in-house pipeline that combines variant ranking and copy-number variant (CNV) searches. Variants were interpreted according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines.Results: We established the molecular diagnosis in 46% of the cases. We identified 35 mildly affected patients with causative variants in genes that are classically associated with severe presentations. These cases were explained by the occurrence of hypomorphic variants, but also rarely suspected mechanisms such as C-terminal truncations and translation reinitiation.Conclusion: A significant fraction of the clinical heterogeneity and phenotypic overlap is explained by hypomorphic variants that are difficult to identify and not readily predicted. The hypomorphic C-terminal truncation and translation reinitiation mechanisms that we identified may only apply to few genes, as it relies on specific domain organization and alterations. We identified PEX10 and FASTKD2 as candidates for translation reinitiation accounting for mild disease presentation