A Haystack Heuristic for Autoimmune Disease Biomarker Discovery Using Next-Gen Immune Repertoire Sequencing Data.

Large-scale DNA sequencing of immunological repertoires offers an opportunity for the discovery of novel biomarkers for autoimmune disease. Available bioinformatics techniques however, are not adequately suited for elucidating possible biomarker candidates from within large immunosequencing datasets due to unsatisfactory scalability and sensitivity. Here, we present the Haystack Heuristic, an algorithm customized to computationally extract disease-associated motifs from next-generation-sequenced repertoires by contrasting disease and healthy subjects. This technique employs a local-search graph-theory approach to discover novel motifs in patient data. We apply the Haystack Heuristic to nine million B-cell receptor sequences obtained from nearly 100 individuals in order to elucidate a new motif that is significantly associated with multiple sclerosis. Our results demonstrate the effectiveness of the Haystack Heuristic in computing possible biomarker candidates from high throughput sequencing data and could be generalized to other datasets

Robot in the mirror: toward an embodied computational model of mirror self-recognition

Self-recognition or self-awareness is a capacity attributed typically only to humans and few other species. The definitions of these concepts vary and little is known about the mechanisms behind them. However, there is a Turing test-like benchmark: the mirror self-recognition, which consists in covertly putting a mark on the face of the tested subject, placing her in front of a mirror, and observing the reactions. In this work, first, we provide a mechanistic decomposition, or process model, of what components are required to pass this test. Based on these, we provide suggestions for empirical research. In particular, in our view, the way the infants or animals reach for the mark should be studied in detail. Second, we develop a model to enable the humanoid robot Nao to pass the test. The core of our technical contribution is learning the appearance representation and visual novelty detection by means of learning the generative model of the face with deep auto-encoders and exploiting the prediction error. The mark is identified as a salient region on the face and reaching action is triggered, relying on a previously learned mapping to arm joint angles. The architecture is tested on two robots with a completely different face.Comment: To appear in KI - K\"unstliche Intelligenz - German Journal of Artificial Intelligence - Springe

Towards Safe Landing of Falling Quadruped Robots Using a 3-DoF Morphable Inertial Tail

Falling cat problem is well-known where cats show their super aerial reorientation capability and can land safely. For their robotic counterparts, a similar falling quadruped robot problem, has not been fully addressed, although achieving safe landing as the cats has been increasingly investigated. Unlike imposing the burden on landing control, we approach to safe landing of falling quadruped robots by effective flight phase control. Different from existing work like swinging legs and attaching reaction wheels or simple tails, we propose to deploy a 3-DoF morphable inertial tail on a medium-size quadruped robot. In the flight phase, the tail with its maximum length can self-right the body orientation in 3D effectively; before touch-down, the tail length can be retracted to about 1/4 of its maximum for impressing the tail's side-effect on landing. To enable aerial reorientation for safe landing in the quadruped robots, we design a control architecture, which has been verified in a high-fidelity physics simulation environment with different initial conditions. Experimental results on a customized flight-phase test platform with comparable inertial properties are provided and show the tail's effectiveness on 3D body reorientation and its fast retractability before touch-down. An initial falling quadruped robot experiment is shown, where the robot Unitree A1 with the 3-DoF tail can land safely subject to non-negligible initial body angles.Comment: 7 pages, 8 figures, submit to ICRA202

Model-Free Large-Scale Cloth Spreading With Mobile Manipulation: Initial Feasibility Study

Cloth manipulation is common in domestic and service tasks, and most studies use fixed-base manipulators to manipulate objects whose sizes are relatively small with respect to the manipulators' workspace, such as towels, shirts, and rags. In contrast, manipulation of large-scale cloth, such as bed making and tablecloth spreading, poses additional challenges of reachability and manipulation control. To address them, this paper presents a novel framework to spread large-scale cloth, with a single-arm mobile manipulator that can solve the reachability issue, for an initial feasibility study. On the manipulation control side, without modeling highly deformable cloth, a vision-based manipulation control scheme is applied and based on an online-update Jacobian matrix mapping from selected feature points to the end-effector motion. To coordinate the control of the manipulator and mobile platform, Behavior Trees (BTs) are used because of their modularity. Finally, experiments are conducted, including validation of the model-free manipulation control for cloth spreading in different conditions and the large-scale cloth spreading framework. The experimental results demonstrate the large-scale cloth spreading task feasibility with a single-arm mobile manipulator and the model-free deformation controller.Comment: 6 pages, 6 figures, submit to CASE202

Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling

Chemotherapy for suppressing tumor growth and metastasis tends to induce various effects on other organs. Using AZD7762, an inhibitor of checkpoint kinase (Chk) 1 and 2, the present study examined its effect on mammary tumor cells in addition to bone cells (osteoclasts, osteoblasts and osteocytes), using monolayer cell cultures and three-dimensional (3D) cell spheroids. The results revealed that AZD7762 blocked the proliferation of 4T1.2 mammary tumor cells and suppressed the development of RAW264.7 pre-osteoclast cells by downregulating nuclear factor of activated T cells cytoplasmic 1. AZD7762 also promoted the mineralization of MC3T3 osteoblast-like cells and 3D bio-printed bone constructs of MLO-A5 osteocyte spheroids. While a Chk1 inhibitor, PD407824, suppressed the proliferation of tumor cells and the differentiation of pre-osteoclasts, its effect on gene expression in osteoblasts was markedly different compared with AZD7762. Western blotting indicated that the stimulating effect of AZD7762 on osteoblast development was associated with the inhibition of Chk2 and the downregulation of cellular tumor antigen p53. The results of the present study indicated that in addition to acting as a tumor suppressor, AZD7762 may prevent bone loss by inhibiting osteoclastogenesis and stimulating osteoblast mineralization

Study on the Behaviors of a Conceptual Passive Containment Cooling System

The containment is an ultimate and important barrier to mitigate the consequences after the release of mass and energy during such scenarios as loss of coolant accident (LOCA) or main steam line break (MSLB). In this investigation, a passive containment cooling system (PCCS) concept is proposed for a large dry concrete containment. The system is composed of series of heat exchangers, long connecting pipes with relatively large diameter, valves, and a water tank, which is located at the top of the system and serves as the final heat sink. The performance of the system is numerically studied in detail under different conditions. In addition, the influences of condensation heat transfer conditions and containment environment temperature conditions are also studied on the behaviors of the system. The results reveal that four distinct operating stages could be experienced as follows: startup stage, single phase quasisteady stage, flashing speed-up transient stage, and flashing dominated quasisteady operating stage. Furthermore, the mechanisms of system behaviors are thus analyzed. Moreover, the feasibility of the system is also discussed to meet the design purpose for the containment integrity requirement. Considering the passive feature and the compactness of the system, the proposed PCCS is promising for the advanced integral type reactor

Intrathecal B-cell activation in LGI1 antibody encephalitis.

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies