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Jelle Matthijnssens - One of the best experts on this subject based on the ideXlab platform.
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A robust human norovirus Replication Model in zebrafish larvae
PLoS pathogens, 2019Co-Authors: Jana Van Dycke, Nádia Conceição-neto, Jan Willem Maes, Myra Hosmillo, Arno Cuvry, Ian Goodfellow, Tatiane De Araujo Nogueira, Erik Verbeken, Jelle MatthijnssensAbstract:Human noroviruses (HuNoVs) are the most common cause of foodborne illness, with a societal cost of $60 billion and 219,000 deaths/year. The lack of robust small animal Models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; Replication peaks at day 2 post infection and is detectable for at least 6 days. The virus (HuNoV GII.4) could be passaged from larva to larva two consecutive times. HuNoV is detected in cells of the hematopoietic lineage and the intestine, supporting the notion of a dual tropism. Antiviral treatment reduces HuNoV Replication by >2 log10, showing that this Model is suited for antiviral studies. Zebrafish larvae constitute a simple and robust Replication Model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.
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a robust human norovirus Replication Model in zebrafish larvae
bioRxiv, 2019Co-Authors: Jana Van Dycke, Jan Willem Maes, Myra Hosmillo, Arno Cuvry, Ian Goodfellow, Erik Verbeken, Jelle Matthijnssens, Nadia Conceicaoneto, Tatiane C Nogueira, Peter De WitteAbstract:Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in ∼219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal Models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; Replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV Replication by >2 log10, showing that this Model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV Replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust Replication Model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.
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A robust human norovirus Replication Model in zebrafish larvae: Supplementary data file
2019Co-Authors: Jana Van Dycke, Nádia Conceição-neto, Jan Willem Maes, Myra Hosmillo, Arno Cuvry, Ian Goodfellow, Tatiane De Araujo Nogueira, Erik Verbeken, Jelle MatthijnssensAbstract:Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in ∼219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal Models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; Replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV Replication by >2 log10, showing that this Model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV Replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust Replication Model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.
Kenneth P Birman - One of the best experts on this subject based on the ideXlab platform.
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a history of the virtual synchrony Replication Model
Replication, 2010Co-Authors: Kenneth P BirmanAbstract:In this chapter, we discuss a widely used fault-tolerant data Replication Model called virtual synchrony. The Model responds to two kinds of needs. First, there is the practical question of how best to embed Replication into distributed systems. Virtual synchrony defines dynamic process groups that have self-managed membership. Applications can join or leave groups at will: a process group is almost like a replicated variable that lives in the network. The second need relates to performance. Although state machine Replication is relatively easy to understand, protocols that implement state machine Replication in the standard manner are too slow to be useful in demanding settings, and are hard to deploy in very large data centers of the sort seen in today's cloud-computing environments. Virtual synchrony implementations, in contrast, are able to deliver updates at the same data rates (and with the same low latencies) as IP multicast: the fast (but unreliable) Internet multicast protocol, often supported directly by hardware. The trick that makes it possible to achieve these very high levels of performance is to hide overheads by piggybacking extra information on regular messages that carry updates. The virtual synchrony Replication Model has been very widely adopted, and was used in everything from air traffic control and stock market systems to data center management platforms marketed by companies like IBM and Microsoft. Moreover, in recent years, state machine protocols such as those used in support of Paxos have begun to include elements of the virtual synchrony Model, such as self-managed and very dynamic membership. Our exploration of the Model takes the form of a history. We start by exploring the background, and then follow evolution of the Model over time.
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Replication - A history of the virtual synchrony Replication Model
Lecture Notes in Computer Science, 2010Co-Authors: Kenneth P BirmanAbstract:In this chapter, we discuss a widely used fault-tolerant data Replication Model called virtual synchrony. The Model responds to two kinds of needs. First, there is the practical question of how best to embed Replication into distributed systems. Virtual synchrony defines dynamic process groups that have self-managed membership. Applications can join or leave groups at will: a process group is almost like a replicated variable that lives in the network. The second need relates to performance. Although state machine Replication is relatively easy to understand, protocols that implement state machine Replication in the standard manner are too slow to be useful in demanding settings, and are hard to deploy in very large data centers of the sort seen in today's cloud-computing environments. Virtual synchrony implementations, in contrast, are able to deliver updates at the same data rates (and with the same low latencies) as IP multicast: the fast (but unreliable) Internet multicast protocol, often supported directly by hardware. The trick that makes it possible to achieve these very high levels of performance is to hide overheads by piggybacking extra information on regular messages that carry updates. The virtual synchrony Replication Model has been very widely adopted, and was used in everything from air traffic control and stock market systems to data center management platforms marketed by companies like IBM and Microsoft. Moreover, in recent years, state machine protocols such as those used in support of Paxos have begun to include elements of the virtual synchrony Model, such as self-managed and very dynamic membership. Our exploration of the Model takes the form of a history. We start by exploring the background, and then follow evolution of the Model over time.
Claudio Altafini - One of the best experts on this subject based on the ideXlab platform.
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Investigating the Conformational Stability of Prion Strains through a Kinetic Replication Model
PLoS computational biology, 2009Co-Authors: Mattia Zampieri, Giuseppe Legname, Claudio AltafiniAbstract:Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrPSc structural properties and molecular mechanisms determine prion Replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical Model, how the structural stability of different aggregated forms can influence the kinetics of prion Replication. The Model-based results suggest that prion strains with different conformational stability undergoing in vivo Replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the Model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils' mean length) and is coherent with all experimental observations concerning strain-specific behavior.
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ECC - Prion kinetic Replication Models and strain-dependent stability (to denaturation)
2009 European Control Conference (ECC), 2009Co-Authors: Mattia Zampieri, Giuseppe Legname, Claudio AltafiniAbstract:Prion proteins are known to misfold into a range of different aggregated forms (strains), showing different phenotypic and pathological states, although little is known on which structural properties and molecular mechanisms determine prion Replication, desease progression and strain phenotype. The aim of this work is to establish a relationship between the kinetic properties of a prion Replication Model and the conformational stability of prion aggregated forms. At a qualitative level, the Model structure suggests a direct relationship between the stability and the mean size of the fibrils population. In order to explain this relationship, we propose that different prion strains undergoing Replication are characterizable by means of different rates of breakage. What we argue is consistent with what has been also observed for yeast prion Replication.
Jana Van Dycke - One of the best experts on this subject based on the ideXlab platform.
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A robust human norovirus Replication Model in zebrafish larvae
PLoS pathogens, 2019Co-Authors: Jana Van Dycke, Nádia Conceição-neto, Jan Willem Maes, Myra Hosmillo, Arno Cuvry, Ian Goodfellow, Tatiane De Araujo Nogueira, Erik Verbeken, Jelle MatthijnssensAbstract:Human noroviruses (HuNoVs) are the most common cause of foodborne illness, with a societal cost of $60 billion and 219,000 deaths/year. The lack of robust small animal Models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; Replication peaks at day 2 post infection and is detectable for at least 6 days. The virus (HuNoV GII.4) could be passaged from larva to larva two consecutive times. HuNoV is detected in cells of the hematopoietic lineage and the intestine, supporting the notion of a dual tropism. Antiviral treatment reduces HuNoV Replication by >2 log10, showing that this Model is suited for antiviral studies. Zebrafish larvae constitute a simple and robust Replication Model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.
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a robust human norovirus Replication Model in zebrafish larvae
bioRxiv, 2019Co-Authors: Jana Van Dycke, Jan Willem Maes, Myra Hosmillo, Arno Cuvry, Ian Goodfellow, Erik Verbeken, Jelle Matthijnssens, Nadia Conceicaoneto, Tatiane C Nogueira, Peter De WitteAbstract:Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in ∼219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal Models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; Replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV Replication by >2 log10, showing that this Model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV Replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust Replication Model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.
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A robust human norovirus Replication Model in zebrafish larvae: Supplementary data file
2019Co-Authors: Jana Van Dycke, Nádia Conceição-neto, Jan Willem Maes, Myra Hosmillo, Arno Cuvry, Ian Goodfellow, Tatiane De Araujo Nogueira, Erik Verbeken, Jelle MatthijnssensAbstract:Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in ∼219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal Models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; Replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV Replication by >2 log10, showing that this Model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV Replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust Replication Model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.
Juan Pavón - One of the best experts on this subject based on the ideXlab platform.
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Active Replication of software components
Lecture Notes in Computer Science, 2003Co-Authors: Juan Pavón, Luis M. PefiaAbstract:This paper considers active Replication of distributed objects over CORBA and Java RMI. It describes a Replication Model and tools whose main purpose is the simplification of the design and implementation of applications with replicated components that inter-communicate to collaborate on a task or to maintain their consistency with client requests. The starting point of this work is Sensei, a group communications system that supports the Replication of components as groups of objects working under a virtual synchronous Model. It describes the requirements to support the component abstraction, as a key concept to facilitate the development of fault tolerant applications. This Model is compared with the Replication Model defined by OMG for a fault tolerant service in CORBA.
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SEM - Active Replication of software components
Lecture Notes in Computer Science, 2002Co-Authors: Juan Pavón, L. PeñaAbstract:This paper considers active Replication of distributed objects over CORBA and Java RMI. It describes a Replication Model and tools whose main purpose is the simplification of the design and implementation of applications with replicated components that intercommunicate to collaborate on a task or to maintain their consistency with client requests. The starting point of this work is Sensei, a group communications system that supports the Replication of components as groups of objects working under a virtual synchronous Model. It describes the requirements to support the component abstraction, as a key concept to facilitate the development of fault tolerant applications. This Model is compared with the Replication Model defined by OMG for a fault tolerant service in CORBA.