103 research outputs found
Multi-label affordance mapping from egocentric vision
Accurate affordance detection and segmentation with pixel precision is an
important piece in many complex systems based on interactions, such as robots
and assitive devices. We present a new approach to affordance perception which
enables accurate multi-label segmentation. Our approach can be used to
automatically extract grounded affordances from first person videos of
interactions using a 3D map of the environment providing pixel level precision
for the affordance location. We use this method to build the largest and most
complete dataset on affordances based on the EPIC-Kitchen dataset, EPIC-Aff,
which provides interaction-grounded, multi-label, metric and spatial affordance
annotations. Then, we propose a new approach to affordance segmentation based
on multi-label detection which enables multiple affordances to co-exists in the
same space, for example if they are associated with the same object. We present
several strategies of multi-label detection using several segmentation
architectures. The experimental results highlight the importance of the
multi-label detection. Finally, we show how our metric representation can be
exploited for build a map of interaction hotspots in spatial action-centric
zones and use that representation to perform a task-oriented navigation.Comment: International Conference on Computer Vision (ICCV) 202
Robust Fusion for Bayesian Semantic Mapping
The integration of semantic information in a map allows robots to understand
better their environment and make high-level decisions. In the last few years,
neural networks have shown enormous progress in their perception capabilities.
However, when fusing multiple observations from a neural network in a semantic
map, its inherent overconfidence with unknown data gives too much weight to the
outliers and decreases the robustness of the resulting map. In this work, we
propose a novel robust fusion method to combine multiple Bayesian semantic
predictions. Our method uses the uncertainty estimation provided by a Bayesian
neural network to calibrate the way in which the measurements are fused. This
is done by regularizing the observations to mitigate the problem of
overconfident outlier predictions and using the epistemic uncertainty to weigh
their influence in the fusion, resulting in a different formulation of the
probability distributions. We validate our robust fusion strategy by performing
experiments on photo-realistic simulated environments and real scenes. In both
cases, we use a network trained on different data to expose the model to
varying data distributions. The results show that considering the model's
uncertainty and regularizing the probability distribution of the observations
distribution results in a better semantic segmentation performance and more
robustness to outliers, compared with other methods.Comment: 7 pages, 7 figures, under review at IEEE IROS 202
RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients
Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). ROR gamma t, the key Thelperl7 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and gamma delta-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular ROR gamma t(+)T-be(lo)PLZF(-) iNKT and gamma delta-hi T cell subsets in healthy peripheral blood. ROR gamma t(+) iNKT and gamma delta-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and gamma delta-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, ROR gamma t inhibition blocked gamma delta 17 and iNKT17 cell function while selectively sparing IL-22(+) subsets. Overall, our findings highlight a unique diversity of human ROR gamma t(+) T cells and underscore the potential of ROR gamma t antagonism to modulate aberrant type 17 responses
Structural studies unravel the active conformation of apo RORγt nuclear receptor and a common inverse agonism of two diverse classes of RORγt inhibitors
The nuclear receptor retinoid acid receptor-related orphan receptor γt (RORγt) is a master regulator of the Th17/IL-17 pathway that plays crucial roles in the pathogenesis of autoimmunity. RORγt has recently emerged as a highly promising target for treatment of a number of autoimmune diseases. Through high-throughput screening, we previously identified several classes of inverse agonists for RORγt. Here, we report the crystal structures for the ligand-binding domain of RORγt in both apo and ligand-bound states. We show that apo RORγt adopts an active conformation capable of recruiting coactivator peptides and present a detailed analysis of the structural determinants that stabilize helix 12 (H12) of RORγt in the active state in the absence of a ligand. The structures of ligand-bound RORγt reveal that binding of the inverse agonists disrupts critical interactions that stabilize H12. This destabilizing effect is supported by ab initio calculations and experimentally by a normalized crystallographic B-factor analysis. Of note, the H12 destabilization in the active state shifts the conformational equilibrium of RORγt toward an inactive state, which underlies the molecular mechanism of action for the inverse agonists reported here. Our findings highlight that nuclear receptor structure and function are dictated by a dynamic conformational equilibrium and that subtle changes in ligand structures can shift this equilibrium in opposite directions, leading to a functional switch from agonists to inverse agonists
An RORγt oral inhibitor modulates IL-17 responses in peripheral blood and intestinal mucosa of Crohn's disease patients
Background and Aims: Despite the negative results of blocking IL-17 in Crohn's disease (CD) patients, selective modulation of Th17-dependent responses warrants further study. Inhibition of retinoic acid-related orphan receptor gamma (RORγt), the master regulator of the Th17 signature, is currently being explored in inflammatory diseases. Our aim was to determine the effect of a novel oral RORγt antagonist (BI119) in human CD and on an experimental model of intestinal inflammation. Methods: 51 CD patients and 11 healthy subjects were included. The effects of BI119 were tested on microbial-stimulated peripheral blood mononuclear cells (PBMCs), intestinal crypts and biopsies from CD patients. The ability of BI119 to prevent colitis in vivo was assessed in the CD4+CD45RBhigh T cell transfer model. Results: In bacterial antigen-stimulated PBMCs from CD patients, BI119 inhibits Th17-related genes and proteins, while upregulating Treg and preserving Th1 and Th2 signatures. Intestinal crypts cultured with supernatants from BI119-treated commensal-specific CD4+ T cells showed decreased expression of CXCL1, CXCL8 and CCL20. BI119 significantly reduced IL17 and IL26 transcription in colonic and ileal CD biopsies and did not affect IL22. BI119 has a more profound effect in ileal CD with additional significant downregulation of IL23R, CSF2, CXCL1, CXCL8, and S100A8, and upregulation of DEFA5. BI119 significantly prevented development of clinical, macroscopic and molecular markers of colitis in the T-cell transfer model. Conclusions: BI119 modulated CD-relevant Th17 signatures, including downregulation of IL23R while preserving mucosa-associated IL-22 responses, and abrogated experimental colitis. Our results provide support to the use of RORγt antagonists as a novel therapy to CD treatment
Maternal uniparental disomy 14 and mosaic trisomy 14 in a Chinese boy with moderate to severe intellectual disability
Frecuencia de translocaciones cromosómicas balanceadas en linfocitos de sobrevivientes a enfermedad de hodgkin tratados con quimioterapia mopp /\ua0tesis que para obtener el grado de Doctorado en Ciencias Biológicas, presenta Consuelo Salas Labadia ; asesor Sara Frias Vázquez
. 82 páginas :\ua0ilustraciones. Doctorado en Ciencias Biológicas\ua0UNAM, Facultad de Medicina,\ua0201
NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization
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