146 research outputs found

    Pain-relief learning in flies, rats, and man: basic research and applied perspectives

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    Memories relating to a painful, negative event are adaptive and can be stored for a lifetime to support preemptive avoidance, escape, or attack behavior. However, under unfavorable circumstances such memories can become overwhelmingly powerful. They may trigger excessively negative psychological states and uncontrollable avoidance of locations, objects, or social interactions. It is therefore obvious that any process to counteract such effects will be of value. In this context, we stress from a basic-research perspective that painful, negative events are "Janus-faced" in the sense that there are actually two aspects about them that are worth remembering: What made them happen and what made them cease. We review published findings from fruit flies, rats, and man showing that both aspects, respectively related to the onset and the offset of the negative event, induce distinct and oppositely valenced memories: Stimuli experienced before an electric shock acquire negative valence as they signal upcoming punishment, whereas stimuli experienced after an electric shock acquire positive valence because of their association with the relieving cessation of pain. We discuss how memories for such punishment-and relief-learning are organized, how this organization fits into the threat-imminence model of defensive behavior, and what perspectives these considerations offer for applied psychology in the context of trauma, panic, and nonsuicidal self-injury

    Energy absorption and mechanical performance of functionally graded soft–hard lattice structures

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    Today, the rational combination of materials and design has enabled the development of bio-inspired lattice structures with unprecedented properties to mimic biological features. The present study aims to investigate the mechanical performance and energy absorption capacity of such sophisticated hybrid soft–hard structures with gradient lattices. The structures are designed based on the diversity of materials and graded size of the unit cells. By changing the unit cell size and arrangement, five different graded lattice structures with various relative densities made of soft and hard materials are numerically investigated. The simulations are implemented using ANSYS finite element modeling (FEM) (2020 R1, 2020, ANSYS Inc., Canonsburg, PA, USA) considering elastic-plastic and the hardening behavior of the materials and geometrical non-linearity. The numerical results are validated against experimental data on three-dimensional (3D)-printed lattices revealing the high accuracy of the FEM. Then, by combination of the dissimilar soft and hard polymeric materials in a homogenous hexagonal lattice structure, two dual-material mechanical lattice statures are designed, and their mechanical performance and energy absorption are studied. The results reveal that not only gradual changes in the unit cell size provide more energy absorption and improve mechanical performance, but also the rational combination of soft and hard materials make the lattice structure with the maximum energy absorption and stiffness, in comparison to those structures with a single material, interesting for multi-functional applications

    Constitutive modeling of multi-stimuli-responsive shape memory polymers with multi-functional capabilities

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    Nowadays, shape memory polymers (SMPs)-based devices are required to be much smarter to produce large shape memory recovery and recovery force with lower working temperatures. They could play a vital role in the advancement of soft robot manipulators, biomedical tools and wearable devices where the working temperatures is a key challenge and must be around the body temperature, or in sustainable smart systems with low energy consumption. The aim of this paper is to introduce thermo-electro-magneto-responsive fibrous SMPs (TEMFSMPs) as a new class of SMPs with highly enhanced shape recovery and recovery force and reduced working temperature. A three-dimensional constitutive model is developed to simulate thermo-electro-magneto-visco-hyperelastic behaviors of SMPs under large deformation for the first time. Constitutive relations are derived by adopting an electro-magneto-visco-hyperelasticity theory and implementing it in a thermo-mechanical cycle of SMPs. To improve the strength of thermo-electro-magneto-responsive SMPs, a bunch of fibers is also embedded into the SMP matrix. Then, the proposed model for thermo-electro-magneto-responsive fibrous shape memory polymers (TEMFSMPs) under uniaxial tension and complex loading regimes such as simultaneous torsion and extension are solved semi-analytically. In addition, the thermo-mechanical response through the proposed model is validated via available SMP experimental tests. Numerical results reveal that electro-magnetic features can significantly enhance shape memory recovery and recovery force of TEMFSMPs and lower their working temperatures. It is found that the electro-magnetic field, the orientation, and stiffness of fibers can effectively be set to tune the shape memory effect and bio-applicability of TEMFSMPs with highly enhanced stress/strain recovery and reduced working temperature

    Event Timing in Associative Learning: From Biochemical Reaction Dynamics to Behavioural Observations

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    Associative learning relies on event timing. Fruit flies for example, once trained with an odour that precedes electric shock, subsequently avoid this odour (punishment learning); if, on the other hand the odour follows the shock during training, it is approached later on (relief learning). During training, an odour-induced Ca++ signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca++-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour. In Aplysia, the effect of serotonin on the corresponding adenylate cyclase is bi-directionally modulated by Ca++, depending on the relative timing of the two inputs. Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning. We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems

    The Radish Gene Reveals a Memory Component with Variable Temporal Properties

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    Memory phases, dependent on different neural and molecular mechanisms, strongly influence memory performance. Our understanding, however, of how memory phases interact is far from complete. In Drosophila, aversive olfactory learning is thought to progress from short-term through long-term memory phases. Another memory phase termed anesthesia resistant memory, dependent on the radish gene, influences memory hours after aversive olfactory learning. How does the radish-dependent phase influence memory performance in different tasks? It is found that the radish memory component does not scale with the stability of several memory traces, indicating a specific recruitment of this component to influence different memories, even within minutes of learning

    Ubiquitous robust communications for emergency response using multi-operator heterogeneous networks

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    A number of disasters in various places of the planet have caused an extensive loss of lives, severe damages to properties and the environment, as well as a tremendous shock to the survivors. For relief and mitigation operations, emergency responders are immediately dispatched to the disaster areas. Ubiquitous and robust communications during the emergency response operations are of paramount importance. Nevertheless, various reports have highlighted that after many devastating events, the current technologies used, failed to support the mission critical communications, resulting in further loss of lives. Inefficiencies of the current communications used for emergency response include lack of technology inter-operability between different jurisdictions, and high vulnerability due to their centralized infrastructure. In this article, we propose a flexible network architecture that provides a common networking platform for heterogeneous multi-operator networks, for interoperation in case of emergencies. A wireless mesh network is the main part of the proposed architecture and this provides a back-up network in case of emergencies. We first describe the shortcomings and limitations of the current technologies, and then we address issues related to the applications and functionalities a future emergency response network should support. Furthermore, we describe the necessary requirements for a flexible, secure, robust, and QoS-aware emergency response multi-operator architecture, and then we suggest several schemes that can be adopted by our proposed architecture to meet those requirements. In addition, we suggest several methods for the re-tasking of communication means owned by independent individuals to provide support during emergencies. In order to investigate the feasibility of multimedia transmission over a wireless mesh network, we measured the performance of a video streaming application in a real wireless metropolitan multi-radio mesh network, showing that the mesh network can meet the requirements for high quality video transmissions

    TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis

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    Visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs; LSK CD150+ CD34- CD48- cells) in bone marrow (BM) are quiescent, we found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer. Quiescent LT-HSCs were maintained in infected RAG2 KO mice, but lost following adoptive transfer of IFNγ-sufficient but not IFNγ-deficient CD4+ T cells. Using mixed BM chimeras, we established that IFNγ and TNF signalling pathways converge at the level of CD4+ T cells. Critically, intrinsic TNF signalling is required for the expansion and/or differentiation of pathogenic IFNγ+CD4+ T cells that promote the irreversible loss of BM function. These finding provide new insights into the pathogenic potential of CD4+ T cells that target hematopoietic function in leishmaniasis and perhaps other infectious diseases where TNF expression and BM dysfunction also occur simultaneously

    Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy

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    Summary Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems
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