Molecular Organisation of Tick-Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions

Molecular Organisation of Tick-Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions

Global existence for semilinear reaction-diffusion systems on evolving domains

We present global existence results for solutions of reaction-diffusion systems on evolving domains. Global existence results for a class of reaction-diffusion systems on fixed domains are extended to the same systems posed on spatially linear isotropically evolving domains. The results hold without any assumptions on the sign of the growth rate. The analysis is valid for many systems that commonly arise in the theory of pattern formation. We present numerical results illustrating our theoretical findings.Comment: 24 pages, 3 figure

POOL development status and production experience

The pool of persistent objects for LHC (POOL) project, part of the large Hadron collider (LHC) computing grid (LCG), is now entering its third year of active development. POOL provides the baseline persistency framework for three LHC experiments. It is based on a strict component model, insulating experiment software from a variety of storage technologies. This paper gives a brief overview of the POOL architecture, its main design principles and the experience gained with integration into LHC experiment frameworks. It also presents recent developments in the POOL works areas of relational database abstraction and object storage into relational database management systems (RDBMS) systems

Distributed Computing Grid Experiences in CMS

The CMS experiment is currently developing a computing system capable of serving, processing and archiving the large number of events that will be generated when the CMS detector starts taking data. During 2004 CMS undertook a large scale data challenge to demonstrate the ability of the CMS computing system to cope with a sustained data-taking rate equivalent to 25% of startup rate. Its goals were: to run CMS event reconstruction at CERN for a sustained period at 25 Hz input rate; to distribute the data to several regional centers; and enable data access at those centers for analysis. Grid middleware was utilized to help complete all aspects of the challenge. To continue to provide scalable access from anywhere in the world to the data, CMS is developing a layer of software that uses Grid tools to gain access to data and resources, and that aims to provide physicists with a user friendly interface for submitting their analysis jobs. This paper describes the data challenge experience with Grid infrastructure and the current development of the CMS analysis system

Housing metadata for the common physicist using a relational database

SAM was developed as a data handling system for Run II at Fermilab. SAM is a collection of services, each described by metadata. The metadata are modeled on a relational database, and implemented in ORACLE. SAM, originally deployed in production for the D0 Run II experiment, has now been also deployed at CDF and is being commissioned at MINOS. This illustrates that the metadata decomposition of its services has a broader applicability than just one experiment. A joint working group on metadata with representatives from ATLAS, BaBar, CDF, CMS, D0, and LHCB in cooperation with EGEE has examined this metadata decomposition in the light of general HEP user requirements. Greater understanding of the required services of a performant data handling system has emerged from Run II experience. This experience is being merged with the understanding being developed in the course of LHC experience with data challenges and user case discussions. We describe the SAM schema and the commonalities of function and service support between this schema and proposals for the LHC experiments. We describe the support structure required for SAM schema updates, the use of development, integration, and production instances. We are also looking at the LHC proposals for the evolution of schema using keyword-value pairs that are then transformed into a normalized, performant database schema

BRIE: transcriptome-wide splicing quantication in single cells

Abstract Single-cell RNA-seq (scRNA-seq) provides a comprehensive measurement of stochasticity in transcription, but the limitations of the technology have prevented its application to dissect variability in RNA processing events such as splicing. Here, we present BRIE (Bayesian regression for isoform estimation), a Bayesian hierarchical model that resolves these problems by learning an informative prior distribution from sequence features. We show that BRIE yields reproducible estimates of exon inclusion ratios in single cells and provides an effective tool for differential isoform quantification between scRNA-seq data sets. BRIE, therefore, expands the scope of scRNA-seq experiments to probe the stochasticity of RNA processing