Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomimetic Approaches for Separated Regeneration of Sensory and Motor Fibers in Amputee People: Necessary Conditions for Functional Integration of Sensory–Motor Prostheses With the Peripheral Nerves

The regenerative capacity of the peripheral nervous system after an injury is limited, and a complete function is not recovered, mainly due to the loss of nerve tissue after the injury that causes a separation between the nerve ends and to the disorganized and intermingled growth of sensory and motor nerve fibers that cause erroneous reinnervations. Even though the development of biomaterials is a very promising field, today no significant results have been achieved. In this work, we study not only the characteristics that should have the support that will allow the growth of nerve fibers, but also the molecular profile necessary for a specific guidance. To do this, we carried out an exhaustive study of the molecular profile present during the regeneration of the sensory and motor fibers separately, as well as of the effect obtained by the administration and inhibition of different factors involved in the regeneration. In addition, we offer a complete design of the ideal characteristics of a biomaterial, which allows the growth of the sensory and motor neurons in a differentiated way, indicating (1) size and characteristics of the material; (2) necessity to act at the microlevel, on small groups of neurons; (3) combination of molecules and specific substrates; and (4) temporal profile of those molecules expression throughout the regeneration process. The importance of the design we offer is that it respects the complexity and characteristics of the regeneration process; it indicates the appropriate temporal conditions of molecular expression, in order to obtain a synergistic effect; it takes into account the importance of considering the process at the group of neuron level; and it gives an answer to the main limitations in the current studies.
Exploring Human-Robot Trust Through the Investment Game: An Immersive Space Mission Scenario

As robots become more advanced and capable, developing trust is an important factor of human-robot interaction and cooperation. However, as multiple environmental and social factors can influence trust, it is important to develop more elaborate scenarios and methods to measure human-robot trust. A widely used measurement of trust in social science is the investment game. In this study, we propose a scaled-up, immersive, science fiction Human-Robot Interaction (HRI) scenario for intrinsic motivation on human-robot collaboration, built upon the investment game and aimed at adapting the investment game for human-robot trust. For this purpose, we utilise two Neuro-Inspired Companion (NICO) - robots and a projected scenery. We investigate the applicability of our space mission experiment design to measure trust and the impact of non-verbal communication. We observe a correlation of 0.43 (p=0.02)between self-assessed trust and trust measured from the game and a positive impact of non-verbal communication on trust (p=0.0008) and robot perception for anthropomorphism (p=0.007) and animacy (p=0.00002). We conclude that our scenario is an appropriate method to measure trust in human-robot interaction and also to study how non-verbal communication influences a human's trust in robots.
MTD'20: 7th ACM Workshop on Moving Target Defense

The seventh ACM Workshop on Moving Target Defense (MTD) Workshop is held virtually on November 9, 2020, in conjunction with the ACM Conference on Computer and Communications Security (CCS). The main objective of the workshop is to discuss novel randomization, diversification, and dynamism techniques for computer systems and network, new metric and analysis frameworks to assess and quantify the effectiveness of MTD, and discuss challenges and opportunities that such defenses provide. New this year the workshop has incorporated a number of invited papers to capture systematization of knowledge (SoK) from experts in this field that investigate the past ten years of MTD and discuss the way forward. We have constructed an exciting and diverse program of three refereed papers, five invited papers, and two invited keynote talks that will provide the participant with a vibrant and thought-provoking set of ideas and insights.
Finding Cracks in Shields: On the Security of Control Flow Integrity Mechanisms

Control-flow integrity (CFI) is a promising technique to mitigate control-flow hijacking attacks. In the past decade, dozens of CFI mechanisms have been proposed by researchers. Despite the claims made by themselves, the security promises of these mechanisms have not been carefully evaluated, and thus are questionable. In this paper, we present a solution to measure the gap between the practical security and the claimed theoretical security. First, we propose CScan to precisely measure runtime feasible targets of indirect control transfer (ICT) instructions protected by CFI, by enumerating all potential code addresses and testing whether ICTs are allowed to jump to them. Second, we propose CBench as a sanity check for verifying CFI solutions? effectiveness against typical attacks, by exploiting a comprehensive set of vulnerable programs protected by CFI and verifying the recognized feasible targets. We evaluated 12 most recent open-source CFI mechanisms and discovered 10 flaws in most CFI mechanisms or implementations. For some CFIs, their security policies or protected ICT sets do not match what they claimed. Some CFIs even expand the attack surface (e.g. introducing unintended targets). To facilitate a deeper understanding of CFI, we summarize the flaws into 7 common pitfalls which cover the whole lifetime of CFI mechanisms and reveal issues that affect CFI mechanisms in practical security.
Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy

IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.
Biological influences on hydrogen effects in steel in seawater

Conditions conducive to the enhancement of corrosion-fatigue crack growth and hydrogen embrittlement can be generated by the activity of sulfate-reducing bacteria. However, while the presence of bacteria encourages more hydrogen entry into susceptible metals when compared to similar levels of sulfide generated abiotically, corrosion-fatigue crack growth rates are slower in biological environments than the equivalent abiological environment. These results are discussed in light of recent findings on the enhancement and inhibition of surface corrosion by bacterial biofilms.
Split-HaloTag® Imaging Assay for Sophisticated Microscopy of Protein-Protein Interactions in planta

An ever-increasing number of protein complexes participating in metabolic pathways and of multi-protein intracellular networks have been identified in plant cells. Split-GFP based protein-protein interaction assays combine the advantages of in vivo interaction studies in a native environment with additional visualisation of protein complex localisation. However, fluorescence proteins entail several drawbacks for sophisticated microscopy: high photobleaching rate during long-term observations, correlation of fluorescence intensity to expression level or blinking behaviour. With the HaloTag® system these drawbacks can be overcome asthis reporter is able to form covalent irreversible bonds with several synthetic photostable fluorescence ligands,which can be used in variable concentrations for optimal fluorescence intensity. Therefore, we established the new Split-HaloTag® imaging assay to enable sophisticated fluorescence imaging of protein-protein interactions. This is demonstrated using an well-characterised interaction as an example for protein-protein interaction at cellular structures: the molybdenum cofactor biosynthesis complex anchoring to filamentous actin. Additionally, a specific interaction was visualised with advanced subdiffractional polarisation microscopy in a more distinctive manner as example for sophisticated imaging. Therefore, this assay is a promising new tool for continuative 3D-imaging, single molecule tracking and super-resolution microscopy of protein-protein interactions in plant cells.
Use-Dependent Plasticity Enhances Nociceptive and Non-Nociceptive Somatosensory Cortical Responses in Healthy Individuals

Repetitive movements and multisensory integration promote use-dependent plasticity, which has been consistently demonstrated using musical training as a model. Prolonged and repeated execution of motor patterns is also a main risk factor for developing pain syndromes, yet the neural underpinnings that link repetitive movements and use-dependent plasticity to abnormal pain processing in humans are unknown. Employing nociceptive and non-nociceptive electrical stimulation to evoke brain responses, we demonstrate that healthy musicians compared to non-musicians show larger non-nociceptive N140 and nociceptive N200 responses, smaller non-nociceptive P200 responses, and faster reaction times (RTs) to both stimuli. Across participants, larger N140 and N200 amplitudes predicted the RTs, whereas amount of daily practice in musicians predicted RTs, non-nociceptive P200, and nociceptive P300 components. These novel findings indicate that the mechanisms by which repetitive sensorimotor training and multimodal integration promote neural plasticity in multisensory neural structures may also increase stimulus-selectivity to nociceptive cues in healthy individuals.
Reconstructing Genomes of Carbon Monoxide Oxidisers in Volcanic Deposits Including Members of the Class Ktedonobacteria

Microorganisms can potentially colonize volcanic rocks using the chemical energy in reduced gases such as methane, hydrogen (H2) and carbon monoxide (CO). In this study, we analysed soil metagenomes from Chilean volcanic soils, representing three different successional stages with ages of 380, 269 and 63 years, respectively. A total of 19 metagenome-assembled genomes (MAGs) were retrieved from all stages with a higher number observed in the youngest soil (1640: 2 MAGs, 1751: 1 MAG, 1957: 16 MAGs). Genomic similarity indices showed that several MAGs had amino-acid identity (AAI) values >50% to the phyla Actinobacteria, Acidobacteria, Gemmatimonadetes, Proteobacteria and Chloroflexi. Three MAGs from the youngest site (1957) belonged to the class Ktedonobacteria (Chloroflexi). Complete cellular functions of all the MAGs were characterised, including carbon fixation, terpenoid backbone biosynthesis, formate oxidation and CO oxidation. All 19 environmental genomes contained at least one gene encoding a putative carbon monoxide dehydrogenase (CODH). Three MAGs had form I coxL operon (encoding the large subunit CO-dehydrogenase). One of these MAGs (MAG-1957-2.1, Ktedonobacterales) was highly abundant in the youngest soil. MAG-1957-2.1 also contained genes encoding a [NiFe]-hydrogenase and hyp genes encoding accessory enzymes and proteins. Little is known about the Ktedonobacterales through cultivated isolates, but some species can utilize H2 and CO for growth. Our results strongly suggest that the remote volcanic sites in Chile represent a natural habitat for Ktedonobacteria and they may use reduced gases for growth.
Targeting C5aR1 Increases the Therapeutic Window of Radiotherapy

Engaging innate immune pathways is emerging as a productive way of achieving durable anti-tumor responses. However, systemic administration of these therapies can result in toxicity, deemed to be particularly problematic when combined with current standard-of-care cytotoxic treatments such as radiotherapy. Increasing the therapeutic window of radiotherapy may be achieved by using targeted therapies, however, few pre-clinical studies investigate both tumor and normal tissue responses in detail. Here we show that targeting innate immune receptor C5aR1 improves tumor radiation response while reducing radiation-induced normal tissue toxicity, thereby increasing the therapeutic window. The potent and orally active C5aR1 inhibitor, PMX205, increases IL-10 secretion, which attenuates RelA phosphorylation and enhances apoptosis in tumor cells. Importantly, targeting C5aR1 improves tumor radiation response even in the presence of reduced CD8+ T-cell infiltration, suggesting that this is a good target even in tumors displaying features of T-cell deficiency or exclusion. Furthermore, we find that C5aR1 depletion results in decreased small intestinal histologic damage, crypt cell apoptosis and increased survival of mice following irradiation. Using a preclinical murine model allowing the simultaneous assessment of tumor and normal tissue radiation responses, we show that PMX205 treatment reduces histological and functional markers of small-bowel toxicity while affording a positive tumor response. Our data, therefore, suggest that targeting C5aR1 could be a promising approach for increasing the therapeutic window of radiotherapy.
Proximal arm non-use optimises movement when the shoulder is weak: consequences for stroke patients

Most stroke patients do not use their paretic limb whereas they are able to. The Constraint-Induced Movement Therapy (CIMT) is effective to reverse this non-use behaviour in some patients but is inapplicable or unsuccessful on others. Here, we investigate how much non-use could come from shoulder weakness instead of the behavioural conditioning treated by the CIMT. We asked 26 healthy participants to reach a target while holding a dumbbell. We found that 18/26 participants exhibit proximal arm non-use when loaded and that non-use reduces shoulder torque of final posture. We either found that non-use improves accuracy in a high gravity field. Following optimal control policy, we explain how the non-use could be an adaptative solution when the shoulder is weak. Our results show the need to include muscular strength into cost function used to model human movement. The framework presented here suggests that psychological non-use could be treated effectively with CIMT, while physiological non-use, resulting from shoulder weakness, might respond better to anti-gravity muscles strengthening.
New Genes in Drosophila Quickly Evolved Essential Functions in Viability During Development

It is a conventionally held dogma that the genetic basis underling development is conserved in a long evolutionary time scale. Ample experiments based on mutational, biochemical, functional, and complementary knockdown/knockout approaches have revealed the unexpectedly important role of recently evolved new genes in development of Drosophila. The recent progresses in the analyses of gene effects and improvements in the computational identification of new genes, which has led to large sample sizes of new genes, open the door to investigate the evolution of gene essentiality with a phylogenetically high resolution. These advancements also raised interesting issues related to phenotypic effect analyses of genes, particularly of those that recently originated. Here we reported our analyses of these issues, including the dating of gene ages, the interpretation of RNAi data that may confuse false positive/false negative rates, and the potential confounding impact of compensation and developmental effects that were not considered during previous CRISPR knockout experiments. We further analyzed new data from knockdowns of 702 new genes (~66% of total 1,070 Drosophila melanogaster new genes), revealing a similarly high proportion of essential genes from recent evolution, compared to those found in distant ancestors of D. melanogaster. Knockout of a few young genes detected analogous essentiality. Furthermore, our experimentally determined distribution and comparison of knockdown efficiency in different RNAi libraries provided valuable data for general functional analyses of genes. Taken together, these data, along with an improved understanding of the phenotypic effect analyses of new genes, provide further evidence to the conclusion that new genes in Drosophila quickly evolved essential functions in viability during development.
Associative learning in larval and adult Drosophila is impaired by the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine

Across the animal kingdom, dopamine plays a crucial role in conferring reinforcement signals that teach animals about the causal structure of the world. In the fruit fly Drosophila melanogaster, the dopamine system has largely been studied using a rich genetic toolbox. Here, we suggest a complementary pharmacological approach applying the dopamine-synthesis inhibitor 3-Iodo-L-tyrosine (3IY), which causes acute systemic inhibition of dopamine signaling. Using Pavlovian conditioning, across developmental stages (3rd instar larva versus adult), valence domains (reward versus punishment), and types of reinforcement (natural versus optogenetically induced), we find that 3IY feeding specifically impairs associative learning, whereas additional feeding of L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of dopamine, rescues this impairment. This study establishes a simple, quick, and comparably low-cost approach that can be combined with the available genetic tools to manipulate and clarify the functions of the dopaminergic system – in D. melanogaster and other animals.
The highly evolvable nature of the antibiotic efflux protein TolC limits use of phages and bacterial toxins as antibacterial agents

Bacteriophages and bacterial toxins are promising antibacterial agents to treat infections caused by multidrug resistant (MDR) bacteria. In fact, bacteriophages have recently been successfully used to treat life-threatening infections caused by MDR bacteria [1–3]. One potential problem with using these antibacterial agents is the evolution of resistance against them in the long term. Here, we studied the fitness landscape of the Escherichia coli TolC protein, an outer membrane protein that is exploited by a pore forming toxin called colicin E1 and by TLS-phage [4, 5]. By systematically assessing the distribution of fitness effects (DFEs) of ~9,000 single amino acid replacements in TolC using either positive (antibiotics and bile salts) or negative (colicin E1 and TLS-phage) selection pressures, we quantified evolvability of the TolC. We demonstrated that the TolC is highly optimized for the efflux of antibiotics and bile salts. In contrast, under colicin E1 and TLS phage selection, TolC sequence is very sensitive to mutation. Our findings suggest that TolC is a highly evolvable target limiting the potential clinical use of bacteriophages and bacterial toxins.
Perceptual Degradation Affects Stop-Signal Performance in Normal Healthy Adults

During stop-signal task performance, little is known how the quality of visual information of the ‘go’ stimuli may indirectly affect the interplay between the ‘go’ and ‘stop’ processes. In this study, we assessed how perceptual degradation of the visual ‘go’ stimuli affect response inhibition. Twenty-six healthy individuals (mean age 33.34 ± 9.61) completed a modified 12-minute stop-signal task, where ‘V’ and ‘Y’ letters were used as visual ‘go’ stimuli. The stimuli were subjected to four levels of perceptual degradation using Gaussian smoothing, to parametrically manipulate stop difficulty across low, intermediate-1, intermediate-2 and high difficulty conditions. On 33% of trials, the stop-signal (50ms audio tone) followed a ‘go’ stimulus after a stop-signal delay, which was individually adjusted for each participant. As predicted, we found that with increased level of stop difficulty (little perceptual degradation), reaction times on ‘go’ trials and the proportion of successful behavioural inhibitions on ‘stop’ trials (P(i)) decreased in normal healthy adults. Contrary to our predictions, there was no effect of increased stop difficulty on the number of correct responses on ‘go’ trials and reaction times on ‘stop’ trials. Overall, manipulation of the completion time of the ‘go’ process via perceptual degradation has been partially successful, whereby increased stop difficulty differentially affected P(i) and SSRT. These findings have implications for the relationship between the ‘go’ and ‘stop’ processes and the horse-race model, which may be limited in explaining the role of various cortico-basal ganglia loops in modulation of response inhibition. Highlights Manipulation of the completion time of the ‘go’ process is partially successful Perceptual degradation differentially affects stop-signal performance Increased stop difficulty (easy ‘go’) results in lower P(i) Increased stop difficulty (easy ‘go’) has no effect on SSRT Horse-race model does not fully explain basal ganglia involvement in inhibition
Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells

Adaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses only covers ~1000 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 family – D1Rs that are expressed on horizontal cells and some bipolar and ganglion cells- and the D2 family – D2Rs that are expressed on dopaminergic amacrine cells and D4Rs that are primarily expressed on photoreceptors. However, how these receptors change the synaptic properties of the inputs to ganglion cells is not yet clear. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating D1Rs and D4Rs changed the light-evoked and spontaneous excitatory inputs to ON-sustained (ON-s) ganglion cells. We found that both D1R and D4R activation decrease the light-evoked excitatory inputs to ON-s ganglion cells, but that only the sum of activating the two receptors was similar to the effect of light adaptation to a rod-saturating background. The largest effects on spontaneous excitatory activity of both D1R and D4R agonists was on the frequency of events, suggesting that D1Rs and D4Rs are acting upstream of the ganglion cells.