Cancer cells must overcome anoikis (detachment-induced death) to successfully metastasize. Using proteomic screens, we found that distinct oncoproteins upregulate IL-1 receptor accessory protein (IL1RAP) to suppress anoikis. IL1RAP is directly induced by oncogenic fusions of Ewing sarcoma (EwS), a highly metastatic childhood sarcoma. IL1RAP inactivation triggers anoikis and impedes metastatic dissemination of EwS cells. Mechanistically, IL1RAP binds the cell surface system X c transporter to enhance exogenous cystine uptake, thereby replenishing cysteine and the glutathione antioxidant. Under cystine depletion, IL1RAP induces cystathionine gamma lyase (CTH) to activate the transsulfuration pathway for de novo cysteine synthesis. Therefore IL1RAP maintains cyst(e)ine and glutathione pools which are vital for redox homeostasis and anoikis resistance. IL1RAP is minimally expressed in pediatric and adult normal tissues, and human anti-IL1RAP antibodies induce potent antibody-dependent cellular cytotoxicity of EwS cells. Therefore, we define IL1RAP as a new cell surface target in EwS, which is potentially exploitable for immunotherapy. SIGNIFICANCEHere we identify cell surface protein IL1RAP as a key driver of metastasis in Ewing sarcoma, a highly aggressive childhood sarcoma. Minimal expression in pediatric and adult normal tissues nominates IL1RAP as a promising target for immunotherapy.Research.
Robotics and artificial intelligence (AI) are revolutionizing all spheres of human life. From industrial processes to graphic design, the implementation of automated intelligent systems is changing how industries work. The spread of robots and AI systems has triggered academic institutions to closely examine how these technologies may affect the humanity—this is how the fields of roboethics and AI ethics have been born. The identification of ethical issues for robotics and AI and creation of ethical frameworks were the first steps to creating a regulatory environment for these technologies. In this paper, we focus on regulatory efforts in Europe and North America to create enforceable regulation for AI and robotics. We describe and compare ethical principles, policies, and regulations that have been proposed by government organizations for the design and use of robots and AI. We also discuss proposed international regulation for robotics and AI. This paper tries to highlight the need for a comprehensive, enforceable, and agile policy to ethically regulate technology today and in the future. Through reviewing existing policies, we conclude that the European Unition currently leads the way in defining roboethics and AI ethical principles and implementing them into policy. Our findings suggest that governments in Europe and North America are aware of the ethical risks that robotics and AI pose, and are engaged in policymaking to create regulatory policies for these new technologies.
The COVID-19 pandemic has caused dramatic effects on the healthcare system, businesses, and education. In many countries, businesses were shut down, universities and schools had to cancel in-person classes, and many workers had to work remotely and socially distance in order to prevent the spread of the virus. These measures opened the door for technologies such as robotics and artificial intelligence to play an important role in minimizing the negative effects of such closures. There have been many efforts in the design and development of robotic systems for applications such as disinfection and eldercare. Healthcare education has seen a lot of potential in simulation robots, which offer valuable opportunities for remote learning during the pandemic. However, there are ethical considerations that need to be deliberated in the design and development of such systems. In this paper, we discuss the principles of roboethics and how these can be applied in the new era of COVID-19. We focus on identifying the most relevant ethical principles and apply them to a case study in dentistry education. DenTeach was developed as a portable device that uses sensors and computer simulation to make dental education more efficient. DenTeach makes remote instruction possible by allowing students to learn and practice dental procedures from home. We evaluate DenTeach on the principles of data, common good, and safety, and highlight the importance of roboethics in Canada. The principles identified in this paper can inform researchers and educational institutions considering implementing robots in their curriculum.
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