Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs

Xenotransplantation using genetically modified pig organs could solve the donor organ shortage problem. Two inactivated genes that make humans unique from pigs are GGTA1 and CMAH, the products of which produce the carbohydrate epitopes, aGal and Neu5Gc that attract preformed human antibody. When the GGTA1 and CMAH genes were deleted in pigs, human antibody binding was reduced in preliminary analysis. We analyzed the binding of human IgM and IgG from 121 healthy human serum samples for binding to GGTA1 KO and GGTA1/CMAH KO peripheral blood mononuclear cells (PBMCs). We analyzed a sub population for reactivity toward genetically modified pig PBMCs as compared to chimpanzee and human PBMCs. Deletion of the GGTA1 and CMAH genes in pigs improved the crossmatch results beyond those observed with chimpanzees. Sorting the 121 human samples tested against the GGTA1/CMAH KO pig PBMCs did not reveal a distinguishing feature such as blood group, age or gender. Modification of genes to make pig carbohydrates more similar to humans has improved the crossmatch with human serum significantly

Silencing porcine CMAH and GGTA1 genes significantly reduces xenogeneic consumption of human platelets by porcine livers

BACKGROUND: A profound thrombocytopenia limits hepatic xenotransplantation in the pig-to-primate model. Porcine livers also have shown the ability to phagocytose human platelets in the absence of immune-mediated injury. Recently, inactivation of the porcine ASGR1 gene has been shown to decrease this phenomenon. Inactivating GGTA1 and CMAH genes has reduced the antibody-mediated barrier to xenotransplantation; herein, we describe the effect that these modifications have on xenogeneic consumption of human platelets in the absence of immune-mediated graft injury. METHODS: Wild type (WT), ASGR1, GGTA1, and GGTA1CMAH knockout pigs were compared for their xenogeneic hepatic consumption of human platelets. An in vitro assay was established to measure the association of human platelets with liver sinusoidal endothelial cells (LSECs) by immunohistochemistry. Perfusion models were used to measure human platelet uptake in livers from WT, ASGR1, GGTA1, and GGTA1 CMAH pigs. RESULTS: GGTA1, CMAH LSECs exhibited reduced levels of human platelet binding in vitro when compared with GGTA1 and WT LSECs. In a continuous perfusion model, GGTA1 CMAH livers consumed fewer human platelets than GGTA1 and WT livers. GGTA1 CMAH livers also consumed fewer human platelets than ASGR1 livers in a single-pass model. CONCLUSIONS: Silencing the porcine carbohydrate genes necessary to avoid antibody-mediated rejection in a pig-to-human model also reduces the xenogeneic consumption of human platelets by the porcine liver. The combination of these genetic modifications may be an effective strategy to limit the thrombocytopenia associated with pig-to-human hepatic xenotransplantation

A computational approach to implicit entities and events in text and discourse

In this paper we will focus on the notion of “implicit” or lexically unexpressed linguistic elements that are nonetheless necessary for a complete semantic interpretation of a text. We refer to “entities” and “events” because the recovery of the implicit material may affect all the modules of a system for semantic processing, from the grammatically guided components to the inferential and reasoning ones. Reference to the system GETARUNS offers one possible implementation of the algorithms and procedures needed to cope with the problem and enables us to deal with all the spectrum of phenomena. The paper will address at first the following three types of “implicit” entities and events: – the grammatical ones, as suggested by a linguistic theories like LFG or similar generative theories; – the semantic ones suggested in the FrameNet project, i.e. CNI, DNI, INI; – the pragmatic ones: here we will present a theory and an implementation for the recovery of implicit entities and events of (non-) standard implicatures. In particular we will show how the use of commonsense knowledge may fruitfully contribute to find relevant implied meanings. Last Implicit Entity only touched on, though for lack of space, is the Subject of Point of View, which is computed by Semantic Informational Structure and contributes the intended entity from whose point of view a given subjective statement is expressed

Reduced human platelet uptake by pig livers deficient in the asialoglycoprotein receptor 1 protein

BACKGROUND: The lethal thrombocytopenia that accompanies liver xenotransplantation is a barrier to clinical application. Human platelets are bound by the asialoglycoprotein receptor (ASGR) on pig sinusoidal endothelial cells and phagocytosed. Inactivation of the ASGR1 gene in donor pigs may prevent xenotransplantation-induced thrombocytopenia. METHODS: Transcription activator-like effector nucleases (TALENs) were targeted to the ASGR1 gene in pig liver-derived cells. ASGR1 deficient pig cells were used for somatic cell nuclear transfer (SCNT). ASGR1 knock out (ASGR1-/-) fetal fibroblasts were used to produce healthy ASGR1 knock out piglets. Human platelet uptake was measured in ASGR1+/+ and ASGR1-/- livers. RESULTS: Targeted disruption of the ASGR1 gene with TALENs eliminated expression of the receptor. ASGR1-/- livers phagocytosed fewer human platelets than domestic porcine livers during perfusion. CONCLUSIONS: The use of TALENs in liver-derived cells followed by SCNT enabled the production of healthy homozygous ASGR1 knock out pigs. Livers from ASGR1-/- pigs exhibit decreased human platelet uptake. Deletion of the ASGR1 gene is a viable strategy to diminish platelet destruction in pig-to-human xenotransplantation

A Pilot Study with a Novel Setup for Collaborative Play of the Humanoid Robot KASPAR with children with autism

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article describes a pilot study in which a novel experimental setup, involving an autonomous humanoid robot, KASPAR, participating in a collaborative, dyadic video game, was implemented and tested with children with autism, all of whom had impairments in playing socially and communicating with others. The children alternated between playing the collaborative video game with a neurotypical adult and playing the same game with the humanoid robot, being exposed to each condition twice. The equipment and experimental setup were designed to observe whether the children would engage in more collaborative behaviours while playing the video game and interacting with the adult than performing the same activities with the humanoid robot. The article describes the development of the experimental setup and its first evaluation in a small-scale exploratory pilot study. The purpose of the study was to gain experience with the operational limits of the robot as well as the dyadic video game, to determine what changes should be made to the systems, and to gain experience with analyzing the data from this study in order to conduct a more extensive evaluation in the future. Based on our observations of the childrens’ experiences in playing the cooperative game, we determined that while the children enjoyed both playing the game and interacting with the robot, the game should be made simpler to play as well as more explicitly collaborative in its mechanics. Also, the robot should be more explicit in its speech as well as more structured in its interactions. Results show that the children found the activity to be more entertaining, appeared more engaged in playing, and displayed better collaborative behaviours with their partners (For the purposes of this article, ‘partner’ refers to the human/robotic agent which interacts with the children with autism. We are not using the term’s other meanings that refer to specific relationships or emotional involvement between two individuals.) in the second sessions of playing with human adults than during their first sessions. One way of explaining these findings is that the children’s intermediary play session with the humanoid robot impacted their subsequent play session with the human adult. However, another longer and more thorough study would have to be conducted in order to better re-interpret these findings. Furthermore, although the children with autism were more interested in and entertained by the robotic partner, the children showed more examples of collaborative play and cooperation while playing with the human adult.Peer reviewe

Music-aided affective interaction between human and service robot

This study proposes a music-aided framework for affective interaction of service robots with humans. The framework consists of three systems, respectively, for perception, memory, and expression on the basis of the human brain mechanism. We propose a novel approach to identify human emotions in the perception system. The conventional approaches use speech and facial expressions as representative bimodal indicators for emotion recognition. But, our approach uses the mood of music as a supplementary indicator to more correctly determine emotions along with speech and facial expressions. For multimodal emotion recognition, we propose an effective decision criterion using records of bimodal recognition results relevant to the musical mood. The memory and expression systems also utilize musical data to provide natural and affective reactions to human emotions. For evaluation of our approach, we simulated the proposed human-robot interaction with a service robot, iRobiQ. Our perception system exhibited superior performance over the conventional approach, and most human participants noted favorable reactions toward the music-aided affective interaction.open0

Multimodal Detection of Engagement in Groups of Children Using Rank Learning

In collaborative play, children exhibit different levels of engagement. Some children are engaged with other children while some play alone. In this study, we investigated multimodal detection of individual levels of engagement using a ranking method and non-verbal features: turn-taking and body movement. Firstly, we automatically extracted turn-taking and body movement features in naturalistic and challenging settings. Secondly, we used an ordinal annotation scheme and employed a ranking method considering the great heterogeneity and temporal dynamics of engagement that exist in interactions. We showed that levels of engagement can be characterised by relative levels between children. In particular, a ranking method, Ranking SVM, outperformed a conventional method, SVM classification. While either turn-taking or body movement features alone did not achieve promising results, combining the two features yielded significant error reduction, showing their complementary power