Road2CPS priorities and recommendations for research and innovation in cyber-physical systems

This document summarises the findings of the Road2CPS project, co-financed by the European Commission under the H2020 Research and Innovation Programme, to develop a roadmap and recommendations for strategic action required for future deployment of Cyber-Physical Systems (CPS). The term Cyber-Physical System describes hardware-software systems, which tightly couple the physical world and the virtual world. They are established from networked embedded systems that are connected with the outside world through sensors and actuators and have the capability to collaborate, adapt, and evolve. In the ARTEMIS Strategic Research Agenda 2016, CPS are described as ‘Embedded Intelligent ICT Systems’ that make products smarter, more interconnected, interdependent, collaborative, and autonomous. In the future world of CPS, a huge number of devices connected to the physical world will be able to exchange data with each other, access web services, and interact with people. Moreover, information systems will sense, monitor and even control the physical world via Cyber-Physical Systems and the Internet of Things (HiPEAC Vision 2015). Cyber-Physical Systems find their application in many highly relevant areas to our society: multi-modal transport, health, smart factories, smart grids and smart cities amongst others. The deployment of Cyber-Physical Systems (CPS) is expected to increase substantially over the next decades, holding great potential for novel applications and innovative product development. Digital technologies have already pervaded day-to-day life massively, affecting all kinds of interactions between humans and their environment. However, the inherent complexity of CPSs, as well as the need to meet optimised performance and comply with essential requirements like safety, privacy, security, raises many questions that are currently being explored by the research community. Road2CPS aims at accelerating uptake and implementation of these efforts. The Road2CPS project identifying and analysing the relevant technology fields and related research priorities to fuel the development of trustworthy CPS, as well as the specific technologies, needs and barriers for a successful implementation in different application domains and to derive recommendations for strategic action. The document at hand was established through an interactive, community-based approach, involving over 300 experts from academia, industry and policy making through a series of workshops and consultations. Visions and priorities of recently produced roadmaps in the area of CPS, IoT (Internet of Things), SoS (System-of-Systems) and FoF (Factories of the Future) were discussed, complemented by sharing views and perspectives on CPS implementation in application domains, evolving multi-sided eco-systems as well as business and policy related barriers, enablers and success factors. From the workshops and accompanying activities recommendations for future research and innovation activities were derived and topics and timelines for their implementation proposed. Amongst the technological topics, and related future research priorities ‘integration, interoperability, standards’ ranged highest in all workshops. The topic is connected to digital platforms and reference architectures, which have already become a key priority theme for the EC and their Digitisation Strategy as well as the work on the right standards to help successful implementation of CPSs. Other themes of very high technology/research relevance revealed to be ‘modelling and simulation’, ‘safety and dependability’, ‘security and privacy’, ‘big data and real-time analysis’, ‘ubiquitous autonomy and forecasting’ as well as ‘HMI/human machine awareness’. Next to this, themes emerged including ‘decision making and support’, ‘CPS engineering (requirements, design)’, ‘CPS life-cycle management’, ‘System-of-Systems’, ‘distributed management’, ‘cognitive CPS’, ‘emergence, complexity, adaptability and flexibility’ and work on the foundations of CPS and ‘cross-disciplinary research/CPS Science’

Analysis of single-cell transcriptome data in drosophila

The fly Drosophila is a versatile model organism that has led to fascinating biological discoveries. In the past few years, Drosophila researchers have used single-cell RNA-sequencing (scRNA-seq) to gain insights into the cellular composition, and developmental processes of various tissues and organs. Given the success of single-cell technologies a variety of computational tools and software packages were developed to enable and facilitate the analysis of scRNA-seq data. In this book chapter we want to give guidance on analyzing droplet-based scRNA-seq data from Drosophila. We will initially describe the preprocessing commonly done for Drosophila, point out possible downstream analyses, and finally highlight computational methods developed using Drosophila scRNA-seq data

RNAi screening in glioma stem-like cells identifies PFKFB4 as a key molecule important for cancer cell survival

The concept of cancer stem-like cells (CSCs) has gained considerable attention in various solid tumors including glioblastoma, the most common primary brain tumor. This sub-population of tumor cells has been intensively investigated and their role in therapy resistance as well as tumor recurrence has been demonstrated. In that respect, development of therapeutic strategies that target CSCs (and possibly also the tumor bulk) appears a promising approach in patients suffering from primary brain tumors. In the present study, we utilized RNA interference (RNAi) to screen the complete human kinome and phosphatome (682 and 180 targets, respectively) in order to identify genes and pathways relevant for the survival of brain CSCs and thereby potential therapeutical targets for glioblastoma. We report of 46 putative candidates including known survival-related kinases and phosphatases. Interestingly, a number of genes identified are involved in metabolism, especially glycolysis, such as PDK1 and PKM2 and, most prominently PFKFB4. In vitro studies confirmed an essential role of PFKFB4 in the maintenance of brain CSCs. Furthermore, high PFKFB4 expression was associated with shorter survival of primary glioblastoma patients. Our findings support the importance of the glycolytic pathway in the maintenance of malignant glioma cells and brain CSCs and imply tumor metabolism as a promising therapeutic target in glioblastoma

Enhanced SARS-CoV-2 entry via UPR-dependent AMPK-related kinase NUAK2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remodels the endoplasmic reticulum (ER) to form replication organelles, leading to ER stress and unfolded protein response (UPR). However, the role of specific UPR pathways in infection remains unclear. Here, we found that SARS-CoV-2 infection causes marginal activation of signaling sensor IRE1α leading to its phosphorylation, clustering in the form of dense ER-membrane rearrangements with embedded membrane openings, and XBP1 splicing. By investigating the factors regulated by IRE1α-XBP1 during SARS-CoV-2 infection, we identified stress-activated kinase NUAK2 as a novel host-dependency factor for SARS-CoV-2, HCoV-229E, and MERS-CoV entry. Reducing NUAK2 abundance or kinase activity impaired SARS-CoV-2 particle binding and internalization by decreasing cell surface levels of viral receptors and viral trafficking likely by modulating the actin cytoskeleton. IRE1α-dependent NUAK2 levels were elevated in SARS-CoV-2-infected and bystander non-infected cells, promoting viral spread by maintaining ACE2 cell surface levels and facilitating virion binding to bystander cells