Dynamic simulation of human motion

In order to study the mechanisms behind the human motion and its disorders, and to comprehend how do neuromuscular impairments affect the human movements, it is crucial to know the human musculoskeletal system. This knowledge is also essential to effectively model and analyse the musculoskeletal system, and to classify the human movement. With this work we conducted preliminary studies over a musculoskeletal model in motion, and performed a comparative analysis in gait between two models: one with a non-pathological gait and another with a disordered gait

Learning hybrid locomotion skills—Learn to exploit residual actions and modulate model-based gait control

This work has developed a hybrid framework that combines machine learning and control approaches for legged robots to achieve new capabilities of balancing against external perturbations. The framework embeds a kernel which is a model-based, full parametric closed-loop and analytical controller as the gait pattern generator. On top of that, a neural network with symmetric partial data augmentation learns to automatically adjust the parameters for the gait kernel, and also generate compensatory actions for all joints, thus significantly augmenting the stability under unexpected perturbations. Seven Neural Network policies with different configurations were optimized to validate the effectiveness and the combined use of the modulation of the kernel parameters and the compensation for the arms and legs using residual actions. The results validated that modulating kernel parameters alongside the residual actions have improved the stability significantly. Furthermore, The performance of the proposed framework was evaluated across a set of challenging simulated scenarios, and demonstrated considerable improvements compared to the baseline in recovering from large external forces (up to 118%). Besides, regarding measurement noise and model inaccuracies, the robustness of the proposed framework has been assessed through simulations, which demonstrated the robustness in the presence of these uncertainties. Furthermore, the trained policies were validated across a set of unseen scenarios and showed the generalization to dynamic walking

Towards general cooperative game playing

Attempts to develop generic approaches to game playing have been around for several years in the field of Artificial Intelligence. However, games that involve explicit cooperation among otherwise competitive players cooperative negotiation games have not been addressed by current approaches. Yet, such games provide a much richer set of features, related with social aspects of interactions, which make them appealing for envisioning real-world applications. This work proposes a generic agent architecture Alpha to tackle cooperative negotiation games, combining elements such as search strategies, negotiation, opponent modeling and trust management. The architecture is then validated in the context of two different games that fall in this category Diplomacy and Werewolves. Alpha agents are tested in several scenarios, against other state-of-the-art agents. Besides highlighting the promising performance of the agents, the role of each architectural component in each game is assessed. (c) Springer International Publishing AG, part of Springer Nature 2018

Gliders2d: Source Code Base for RoboCup 2D Soccer Simulation League

We describe Gliders2d, a base code release for Gliders, a soccer simulation team which won the RoboCup Soccer 2D Simulation League in 2016. We trace six evolutionary steps, each of which is encapsulated in a sequential change of the released code, from v1.1 to v1.6, starting from agent2d-3.1.1 (set as the baseline v1.0). These changes improve performance by adjusting the agents' stamina management, their pressing behaviour and the action-selection mechanism, as well as their positional choice in both attack and defense, and enabling riskier passes. The resultant behaviour, which is sufficiently generic to be applicable to physical robot teams, increases the players' mobility and achieves a better control of the field. The last presented version, Gliders2d-v1.6, approaches the strength of Gliders2013, and outperforms agent2d-3.1.1 by four goals per game on average. The sequential improvements demonstrate how the methodology of human-based evolutionary computation can markedly boost the overall performance with even a small number of controlled steps.Comment: 12 pages, 1 figure, Gliders2d code releas

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

ESR1 amplification is rare in breast cancer and is associated with high grade and high proliferation: a multiplex ligation-dependent probe amplification study

Background: Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα can be caused by estrogen receptor 1 (ESR1) gene amplification and was originally reported to be a frequent event associated with a significantly longer survival for ER-positive women treated with adjuvant tamoxifen monotherapy, which was however questioned by subsequent studies

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Cytochemical techniques and energy-filtering transmission electron microscopy applied to the study of parasitic protozoa

The study of parasitic protozoa plays a major role in cell biology, biochemistry and molecular biology. Numerous cytochemical techniques have been developed in order to unequivocally identify the nature of subcellular compartments. Enzyme and immuno-cytochemistry allow the detection of, respectively, enzymatic activity products and antigens in particular sites within the cell. Energy-filtering transmission electron microscopy permits the detection of specific elements within such compartments. These approaches are particularly useful for studies employing antimicrobial agents where cellular compartments may be destroyed or remarkably altered and thus hardly identified by standard methods of observation. In this regard cytochemical and spectroscopic techniques provide valuable data allowing the determination of the mechanisms of action of such compounds