Design Space Exploration and Resource Management of Multi/Many-Core Systems

The increasing demand of processing a higher number of applications and related data on computing platforms has resulted in reliance on multi-/many-core chips as they facilitate parallel processing. However, there is a desire for these platforms to be energy-efficient and reliable, and they need to perform secure computations for the interest of the whole community. This book provides perspectives on the aforementioned aspects from leading researchers in terms of state-of-the-art contributions and upcoming trends

New Insights into the Mechanisms Underlying NEDD8 Structural and Functional Specificities

Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins are small polypeptides that are conjugated to substrates affecting their activity and stability. Cells encode “receptors” containing Ub-/Ubl-binding domains that interpret and translate each modification into appropriate cellular responses. Among the different Ubls, NEDD8, which is the ubiquitin’s closest relative, retains many of the structural determinants that enable ubiquitin the ability to target proteins to degradation. Nevertheless, the direct involvement of NEDD8 conjugation to proteasome recruitment has been proved only in a few cases. To date, well-defined major NEDD8 substrates are primarily members of the cullin family, and cullin neddylation does not appear to mark these proteins for degradation. Various studies have demonstrated that selectivity between ubiquitin and NEDD8 is guaranteed by small but substantial differences. Nevertheless, several issues still need to be addressed, mainly concerning which interaction surfaces mediate NEDD8 function and what domains recognize them. Recently, two novel domains identified in KHNYN and N4BP1 proteins have shed new light on this research area. Here, I discuss some recent reports that contributed to shed light on the mechanisms underlining the discrimination between ubiquitin and NEDD8. Understanding the details of these molecular mechanisms represents a prominent facet for the identification of new therapeutic targets

Recent Developments on Mobile Ad-Hoc Networks and Vehicular Ad-Hoc Networks

This book presents collective works published in the recent Special Issue (SI) entitled "Recent Developments on Mobile Ad-Hoc Networks and Vehicular Ad-Hoc Networks”. These works expose the readership to the latest solutions and techniques for MANETs and VANETs. They cover interesting topics such as power-aware optimization solutions for MANETs, data dissemination in VANETs, adaptive multi-hop broadcast schemes for VANETs, multi-metric routing protocols for VANETs, and incentive mechanisms to encourage the distribution of information in VANETs. The book demonstrates pioneering work in these fields, investigates novel solutions and methods, and discusses future trends in these field

On Improving Generalization of CNN-Based Image Classification with Delineation Maps Using the CORF Push-Pull Inhibition Operator

Deployed image classification pipelines are typically dependent on the images captured in real-world environments. This means that images might be affected by different sources of perturbations (e.g. sensor noise in low-light environments). The main challenge arises by the fact that image quality directly impacts the reliability and consistency of classification tasks. This challenge has, hence, attracted wide interest within the computer vision communities. We propose a transformation step that attempts to enhance the generalization ability of CNN models in the presence of unseen noise in the test set. Concretely, the delineation maps of given images are determined using the CORF push-pull inhibition operator. Such an operation transforms an input image into a space that is more robust to noise before being processed by a CNN. We evaluated our approach on the Fashion MNIST data set with an AlexNet model. It turned out that the proposed CORF-augmented pipeline achieved comparable results on noise-free images to those of a conventional AlexNet classification model without CORF delineation maps, but it consistently achieved significantly superior performance on test images perturbed with different levels of Gaussian and uniform noise

Profiling Large-scale Live Video Streaming and Distributed Applications

PhDToday, distributed applications run at data centre and Internet scales, from intensive data analysis, such as MapReduce; to the dynamic demands of a worldwide audience, such as YouTube. The network is essential to these applications at both scales. To provide adequate support, we must understand the full requirements of the applications, which are revealed by the workloads. In this thesis, we study distributed system applications at different scales to enrich this understanding. Large-scale Internet applications have been studied for years, such as social networking service (SNS), video on demand (VoD), and content delivery networks (CDN). An emerging type of video broadcasting on the Internet featuring crowdsourced live video streaming has garnered attention allowing platforms such as Twitch to attract over 1 million concurrent users globally. To better understand Twitch, we collected real-time popularity data combined with metadata about the contents and found the broadcasters rather than the content drives its popularity. Unlike YouTube and Netflix where content can be cached, video streaming on Twitch is generated instantly and needs to be delivered to users immediately to enable real-time interaction. Thus, we performed a large-scale measurement of Twitchs content location revealing the global footprint of its infrastructure as well as discovering the dynamic stream hosting and client redirection strategies that helped Twitch serve millions of users at scale. We next consider applications that run inside the data centre. Distributed computing applications heavily rely on the network due to data transmission needs and the scheduling of resources and tasks. One successful application, called Hadoop, has been widely deployed for Big Data processing. However, little work has been devoted to understanding its network. We found the Hadoop behaviour is limited by hardware resources and processing jobs presented. Thus, after characterising the Hadoop traffic on our testbed with a set of benchmark jobs, we built a simulator to reproduce Hadoops job traffic With the simulator, users can investigate the connections between Hadoop traffic and network performance without additional hardware cost. Different network components can be added to investigate the performance, such as network topologies, queue policies, and transport layer protocols. In this thesis, we extended the knowledge of networking by investigated two widelyused applications in the data centre and at Internet scale. We (i)studied the most popular live video streaming platform Twitch as a new type of Internet-scale distributed application revealing that broadcaster factors drive the popularity of such platform, and we (ii)discovered the footprint of Twitch streaming infrastructure and the dynamic stream hosting and client redirection strategies to provide an in-depth example of video streaming delivery occurring at the Internet scale, also we (iii)investigated the traffic generated by a distributed application by characterising the traffic of Hadoop under various parameters, (iv)with such knowledge, we built a simulation tool so users can efficiently investigate the performance of different network components under distributed applicationQueen Mary University of Londo

PROTEOMIC APPROACHES TO IDENTIFY UNIQUE AND SHARED SUBSTRATES AMONG KINASE FAMILY MEMBERS

Protein phosphorylation is a reversible post-translational modification that is a critical component of almost all signaling pathways. Kinases regulate substrate proteins through phosphorylation, and nearly all proteins are phosphorylated to some extent. Crucially, breakdown in phosphorylation signaling is an underlying factor in many diseases, including cancer. Understanding how phosphorylation signaling mediates cellular pathways is crucial for understanding cell biology and human disease. Targeted protein degradation (TPD) is a strategy to rapidly deplete a protein of interest (POI) and is applicable to any gene that is amenable to CRISPR-Cas9 editing. One TPD approach is the auxin-inducible degron (AID) system, which relies on the expression of an AID fusion protein and the F-box protein Tir1. Addition of auxin drives binding of the AID-POI and Tir1, resulting in rapid ubiquitination and degradation. Recently, we demonstrated that this approach can be used to study kinase-substrate relationships in a manner analogous to small-molecule inhibition using the kinase Plk1 as a proof-of-concept. Based on the results of this study, we applied AID-Tir1 protein degradation to interrogate kinase-substrate relationships for the Polo-like kinase (Plk), p21-activated kinase (PAK), and Aurora kinase families. Additionally, we made significant improvements to the CRISPR-Cas9 workflow and improved efficiency of AID-Tir1 cell line generation for kinases of interest. Targeted degradation of PAK1 revealed low PAK1 activity in HEK293 cells. Follow-up experiments showed that, while many phosphorylation sites are regulated by the group 1 PAKs, PAK1 does not regulate these pathways alone and likely has overlapping functions with the closely related kinase, PAK2. We applied AID-Tir1 to Aurora B and observed high correlation between Aurora B degradation and inhibition by the Aurora B inhibitor AZD1152, demonstrating that protein degradation is a selective approach to identify direct Aurora B substrates. We identified an uncharacterized truncated Aurora B isoform that is sufficient for Aurora B signaling in the absence of full-length Aurora B. Finally, we used fluorescent reporter proteins and Fluorescence Activated Cell Sorting (FACS) to greatly improve the efficiency of AID-Tir1 cell line generation for kinases of interest. These improvements make strides towards widespread implementation of targeted degradation as a tool to study kinase-substrate relationships

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

This work was supported by the National Institute of General Medical Sciences [GM131919].In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.PostprintPeer reviewe