A Gossip-based optimistic replication for efficient delay-sensitive streaming using an interactive middleware support system

While sharing resources the efficiency is substantially degraded as a result of the scarceness of availability of the requested resources in a multiclient support manner. These resources are often aggravated by many factors like the temporal constraints for availability or node flooding by the requested replicated file chunks. Thus replicated file chunks should be efficiently disseminated in order to enable resource availability on-demand by the mobile users. This work considers a cross layered middleware support system for efficient delay-sensitive streaming by using each device's connectivity and social interactions in a cross layered manner. The collaborative streaming is achieved through the epidemically replicated file chunk policy which uses a transition-based approach of a chained model of an infectious disease with susceptible, infected, recovered and death states. The Gossip-based stateful model enforces the mobile nodes whether to host a file chunk or not or, when no longer a chunk is needed, to purge it. The proposed model is thoroughly evaluated through experimental simulation taking measures for the effective throughput Eff as a function of the packet loss parameter in contrast with the effectiveness of the replication Gossip-based policy.Comment: IEEE Systems Journal 201

Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer's disease.

There are currently no disease-modifying treatments for Alzheimer's disease (AD), and an understanding of preclinical causal biomarkers to help target disease pathogenesis in the earliest phases remains elusive. Here, we investigated whether 19 metabolites previously associated with midlife cognition-a preclinical predictor of AD-translate to later clinical risk, using Mendelian randomization (MR) to tease out AD-specific causal relationships. Summary statistics from the largest genome-wide association studies (GWASs) for AD and metabolites were used to perform bidirectional univariable MR. Bayesian model averaging (BMA) was additionally performed to address high correlation between metabolites and identify metabolite combinations that may be on the AD causal pathway. Univariable MR indicated four extra-large high-density lipoproteins (XL.HDL) on the causal pathway to AD: free cholesterol (XL.HDL.FC: 95% CI = 0.78 to 0.94), total lipids (XL.HDL.L: 95% CI = 0.80 to 0.97), phospholipids (XL.HDL.PL: 95% CI = 0.81 to 0.97), and concentration of XL.HDL particles (95% CI = 0.79 to 0.96), significant at an adjusted P < 0.009. MR-BMA corroborated XL.HDL.FC to be among the top three causal metabolites, in addition to total cholesterol in XL.HDL (XL.HDL.C) and glycoprotein acetyls (GP). Both XL.HDL.C and GP demonstrated suggestive univariable evidence of causality (P < 0.05), and GP successfully replicated within an independent dataset. This study offers insight into the causal relationship between metabolites demonstrating association with midlife cognition and AD. It highlights GP in addition to several XL.HDLs-particularly XL.HDL.FC-as causal candidates warranting further investigation. As AD pathology is thought to develop decades prior to symptom onset, expanding on these findings could inform risk reduction strategies

A Survey on Consensus Mechanisms and Mining Strategy Management in Blockchain Networks

© 2013 IEEE. The past decade has witnessed the rapid evolution in blockchain technologies, which has attracted tremendous interests from both the research communities and industries. The blockchain network was originated from the Internet financial sector as a decentralized, immutable ledger system for transactional data ordering. Nowadays, it is envisioned as a powerful backbone/framework for decentralized data processing and data-driven self-organization in flat, open-access networks. In particular, the plausible characteristics of decentralization, immutability, and self-organization are primarily owing to the unique decentralized consensus mechanisms introduced by blockchain networks. This survey is motivated by the lack of a comprehensive literature review on the development of decentralized consensus mechanisms in blockchain networks. In this paper, we provide a systematic vision of the organization of blockchain networks. By emphasizing the unique characteristics of decentralized consensus in blockchain networks, our in-depth review of the state-of-the-art consensus protocols is focused on both the perspective of distributed consensus system design and the perspective of incentive mechanism design. From a game-theoretic point of view, we also provide a thorough review of the strategy adopted for self-organization by the individual nodes in the blockchain backbone networks. Consequently, we provide a comprehensive survey of the emerging applications of blockchain networks in a broad area of telecommunication. We highlight our special interest in how the consensus mechanisms impact these applications. Finally, we discuss several open issues in the protocol design for blockchain consensus and the related potential research directions

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. Citation: Shaughnessy DT, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. 2014. Mitochondria, energetics, epigenetics, and cellular responses to stress. Environ Health Perspect 122:1271–1278; http://dx.doi.org/10.1289/ehp.140841

Digital Twins for Ports: Derived from Smart City and Supply Chain Twinning Experience

Ports are striving for innovative technological solutions to cope with the ever-increasing growth of transport, while at the same time improving their environmental footprint. An emerging technology that has the potential to substantially increase the efficiency of the multifaceted and interconnected port processes is the digital twin. Although digital twins have been successfully integrated in many industries, there is still a lack of cross-domain understanding of what constitutes a digital twin. Furthermore, the implementation of the digital twin in complex systems such as the port is still in its infancy. This paper attempts to fill this research gap by conducting an extensive cross-domain literature review of what constitutes a digital twin, keeping in mind the extent to which the respective findings can be applied to the port. It turns out that the digital twin of the port is most comparable to complex systems such as smart cities and supply chains, both in terms of its functional relevance as well as in terms of its requirements and characteristics. The conducted literature review, considering the different port processes and port characteristics, results in the identification of three core requirements of a digital port twin, which are described in detail. These include situational awareness, comprehensive data analytics capabilities for intelligent decision making, and the provision of an interface to promote multi-stakeholder governance and collaboration. Finally, specific operational scenarios are proposed on how the port's digital twin can contribute to energy savings by improving the use of port resources, facilities and operations.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

Expanding the Repertoire of Modified Vaccinia Ankara-Based Vaccine Vectors via Genetic Complementation Strategies

nkara (MVA) is a safe, highly attenuated orthopoxvirus that is being developed as a recombinant vaccine vector for immunization against a number of infectious diseases and cancers. However, the expression by MVA vectors of large numbers of poxvirus antigens, which display immunodominance over vectored antigens-of-interest for the priming of T cell responses, and the induction of vector-neutralizing antibodies, which curtail the efficacy of subsequent booster immunizations, remain as significant impediments to the overall utility of such vaccines. Thus, genetic approaches that enable the derivation of MVA vectors that are antigenically less complex may allow for rational improvement of MVA-based vaccines. during infection, and that the processes governing the generation of antiviral antibody responses are more readily saturated by viral antigen than are those that elicit CD8+ T cell responses. deletion, enables the generation of novel replication-defective MVA mutants and expands the repertoire of genetic viral variants that can now be explored as improved vaccine vectors

Enhancing Networks via Virtualized Network Functions

University of Minnesota Ph.D. dissertation. May 2019. Major: Computer Science. Advisor: Zhi-Li Zhang. 1 computer file (PDF); xii, 116 pages.In an era of ubiquitous connectivity, various new applications, network protocols, and online services (e.g., cloud services, distributed machine learning, cryptocurrency) have been constantly creating, underpinning many of our daily activities. Emerging demands for networks have led to growing traffic volume and complexity of modern networks, which heavily rely on a wide spectrum of specialized network functions (e.g., Firewall, Load Balancer) for performance, security, etc. Although (virtual) network functions (VNFs) are widely deployed in networks, they are instantiated in an uncoordinated manner failing to meet growing demands of evolving networks. In this dissertation, we argue that networks equipped with VNFs can be designed in a fashion similar to how computer software is today programmed. By following the blueprint of joint design over VNFs, networks can be made more effective and efficient. We begin by presenting Durga, a system fusing wide area network (WAN) virtualization on gateway with local area network (LAN) virtualization technology. It seamlessly aggregates multiple WAN links into a (virtual) big pipe for better utilizing WAN links and also provides fast fail-over thus minimizing application performance degradation under WAN link failures. Without the support from LAN virtualization technology, existing solutions fail to provide high reliability and performance required by today’s enterprise applications. We then study a newly standardized protocol, Multipath TCP (MPTCP), adopted in Durga, showing the challenge of associating MPTCP subflows in network for the purpose of boosting throughput and enhancing security. Instead of designing a customized solution in every VNF to conquer this common challenge (making VNFs aware of MPTCP), we implement an online service named SAMPO to be readily integrated into VNFs. Following the same principle, we make an attempt to take consensus as a service in software-defined networks. We illustrate new network failure scenarios that are not explicitly handled by existing consensus algorithms such as Raft, thereby severely affecting their correct or efficient operations. Finally, we re-consider VNFs deployed in a network from the perspective of network administrators. A global view of deployed VNFs brings new opportunities for performance optimization over the network, and thus we explore parallelism in service function chains composing a sequence of VNFs that are typically traversed in-order by data flows