Abstract
Mutations in Parkin and PINK1 cause early-onset familial Parkinson's disease. Parkin is a RING-In-Between-RING E3 ligase that transfers ubiquitin from an E2 enzyme to a substrate in two steps: (i) thioester intermediate formation on Parkin and (ii) acyl transfer to a substrate lysine. The process is triggered by PINK1, which phosphorylates ubiquitin on damaged mitochondria, which in turn recruits and activates Parkin. This leads to the ubiquitination of outer mitochondrial membrane proteins and clearance of the organelle. While the targets of Parkin on mitochondria are known, the factors determining substrate selectivity remain unclear. To investigate this, we examined how Parkin catalyses ubiquitin transfer to substrates. We found that His433 in the RING2 domain contributes to the catalysis of acyl transfer. In cells, the mutation of His433 impairs mitophagy. In vitro ubiquitination assays with isolated mitochondria show that Mfn2 is a kinetically preferred substrate. Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin (pUb) in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via pUb at these sites.

Abstract
As IoT technologies mature, they are increasingly finding their way into more sensitive domains, such as Medical and Industrial IoT, in which safety and cyber-security are paramount. While the number of deployed IoT devices continues to increase annually, they still present severe cyber-security vulnerabilities, turning them into potential targets and entry points to support further attacks. Naturally, as these nodes are compromised, attackers aim at setting up stealthy communication behaviours, to exfiltrate data or to orchestrate nodes of a botnet in a cloaked fashion. Network covert channels are increasingly being used with such malicious intents. The IEEE 802.15.4 is one of the most pervasive protocols in IoT, and a fundamental part of many communication infrastructures. Despite this fact, the possibility of setting up such covert communication techniques on this medium has received very little attention. We aim at analysing the performance and feasibility of such covert-channel implementations upon the IEEE 802.15.4 protocol. This will enable a better understanding of the involved risk and help supporting the development of further cyber-security mechanisms to mitigate this threat.

Abstract

Abstract
The use of virtual reality (VR) for industrial training helps minimize risks and costs by allowing more frequent and varied use of experiential learning activities, leading to active and improved learning. However, creating VR training experiences is costly and time-consuming, requiring software development experts. Additionally, current authoring tools lack integration with existing data and are desktop-oriented, which detach the pedagogic process of creating the immersive experience from experiencing it in a situated context. In this article, we present a novel interactive approach for immersive authoring of VR-based experiential training by the trainers themselves, from inside the virtual environment and without the support of development experts. The design includes identifying interactable elements, such as 3-D models, equipment, tools, settings, and environment. The trainer also specifies by demonstration the actions to be performed by trainees, as a virtual choreography. During course execution, trainees' activities are also registered as virtual choreographies and matched to those specified by the trainer. Thus, trainer and trainee are culturally situated within their area semantics and social discourse, rather than adopting concepts of the VR system for the learning content. We conducted a usability case study with professionals from an international wind energy company, using detailed models of wind turbines and real-world procedures. Trainers set up a training course using the immersive authoring tool, and trainees executed the course. The learning experience and usability were analyzed, and the training was certified by comparing real-world task completion between a user who had undergone virtual training and a user who did not.

Abstract
Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP) is a neurological genetic illness that inflicts severe symptoms after the onset occurs. Age of onset represents the moment a patient starts to experience the symptoms of a disease. An accurate prediction of this event can improve clinical and operational guidelines that define the work of doctors, nurses, and operational staff. In this work, we transform family trees into compact vectors, that is, embeddings, and handle these as input features to predict the age of onset of patients with TTR-FAP. Our purpose is to evaluate how information present in genealogical trees can be transformed and used to improve a regression-based setting for TTR-FAP age of onset prediction. Our results show that by combining manual and graph-embeddings features there is a decrease in the mean prediction error when there is less information regarding a patient's family. With this work, we open the way for future work in representation learning for genealogical data, enabling a more effective exploitation of machine learning approaches.

Abstract
This paper reviewed machine learning algorit hms, particularly deep learning architectures applied to end-of-line testing systems in industrial environment. In industry, data is also produced when any product is being manufactured. All this information registered when manufacturing a specific product can be manipulated and interpreted using Machine Learning algorithms. Therefore, it is possible to draw conclusions from data and infer valuable results that can positively impact the future of the production line. The reviewed papers showed that machine learning algorithms play a crucial role in detecting, isolating, and preventing anomalies, helping operators make decisions, and allowing industries to save resources. © International Journal of Emerging Technology and Advanced Engineering.All right reserved.