Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes.

PURPOSE: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level. METHODS: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. RESULTS: Pathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype-genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed. CONCLUSION: This study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes

Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes.

PURPOSE: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level. METHODS: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. RESULTS: Pathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype-genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed. CONCLUSION: This study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes

Cooperative Artefacts - A Framework for Embedding Knowledge in Real World Objects

Abstract. In this position paper we introduce Cooperative Artefacts, physical objects that embed sensing, communication, computation and actuation in physical objects. In contrast to many other approaches, Cooperative Artefacts do not require any external infrastructure but cooperate by sharing knowledge. They are programmable with application rules abstracting from low level system aspects. We present an instance of our framework in connection with a scenario from the chemicals industry in which appropriate storage of chemicals is critical for safety reasons. We conclude this paper by discussing potential future research directions for Smart Object Systems

Constraint-based Distance Estimation in Ad-hoc Wireless Sensor

We propose a lightweight localisation approach for supporting distance and range queries in ad hoc wireless sensor networks. In contrast to most previous localisation approaches we use a distance graph as spatial representation where edges between nodes are labelled with distance constraints. This approach has been carefully designed to satisfy the requirements of a concrete application scenario with respect to the spatial queries that need to be supported, the required accuracy of location information, and the capabilities of the target hardware. We show that this approach satisfies the accuracy requirements of the example application using simulations. We describe the implementation of the algorithms on wireless sensor nodes

Building intelligent environments with smart-its

Smart-Its are self-contained, stick-on computers that attach to everyday objects. These augmented objects become soft media, enabling dynamic digital relationships with users and each other

NETMAN: The design of a collaborative wearable computer system

This paper presents a wearable groupware system designed to enhance the communication and cooperation of highly mobile network technicians. It provides technicians in the field with the capabilities for real-time audio-conferencing, transmission of video images back to the office, and context-sensitive access to a shared notebook. An infrared location-tracking device allows for the automatic retrieval of notebook entries depending on the user’s current location. 1