The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
John Mclauchlan - One of the best experts on this subject based on the ideXlab platform.
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Structural analysis of hepatitis C virus core-E1 Signal peptide and requirements for cleavage of the genotype 3a Signal sequence by Signal peptide peptidase.
Journal of Virology, 2012Co-Authors: Verena Oehler, Ana Filipe, Roland Montserret, Daniel Da Costa, Gaie Brown, François Penin, John MclauchlanAbstract:The maturation of the hepatitis C virus (HCV) core protein requires proteolytic processing by two host proteases: Signal peptidase (SP) and the intramembrane-cleaving protease Signal peptide peptidase (SPP). Previous work on HCV genotype 1a (GT1a) and GT2a has identified crucial residues required for efficient Signal peptide processing by SPP, which in turn has an effect on the production of infectious virus particles. Here we demonstrate that the JFH1 GT2a core-E1 Signal peptide can be adapted to the GT3a sequence without affecting the production of infectious HCV. Through mutagenesis studies, we identified crucial residues required for core-E1 Signal peptide processing, including a GT3a sequence-specific histidine (His) at position 187. In addition, the stable knockdown of intracellular SPP levels in HuH-7 cells significantly affects HCV virus titers, further demonstrating the requirement for SPP for the maturation of core and the production of infectious HCV particles. Finally, our nuclear magnetic resonance (NMR) structural analysis of a synthetic HCV JFH1 GT2a core-E1 Signal peptide provides an essential structural template for a further understanding of core processing as well as the first model for an SPP substrate within its membrane environment. Our findings give deeper insights into the mechanisms of intramembrane-cleaving proteases and the impact on viral infections.
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Maturation of hepatitis C virus core protein by Signal peptide peptidase is required for virus production.
The Journal of biological chemistry, 2008Co-Authors: Paul Targett-adams, Graham Hope, Steeve Boulant, John MclauchlanAbstract:Complete maturation of hepatitis C virus (HCV) core protein requires coordinate cleavage by Signal peptidase and an intramembrane protease, Signal peptide peptidase. We show that reducing the intracellular levels of Signal peptide peptidase lowers the titer of infectious virus released from cells, indicating that it plays an important role in virus production. Proteolysis by the enzyme at a Signal peptide between core and the E1 glycoprotein is needed to permit targeting of core to lipid droplets. From mutagenesis studies, introducing mutations into the core-E1 Signal peptide delayed the appearance of Signal peptide peptidase-processed core until between 48 and 72 h after the beginning of the infectious cycle. Accumulation of mature core at these times coincided with its localization to lipid droplets and a rise in titer of infectious HCV. Therefore, processing of core by Signal peptide peptidase is a critical event in the virus life cycle. To study the stage in virus production that may be blocked by interfering with intramembrane cleavage of core, we examined the distribution of viral RNA in cells harboring the core-E1 Signal peptide mutant. Results revealed that colocalization of core with HCV RNA required processing of the protein by Signal peptide peptidase. Our findings provide new insights into the sequence requirements for proteolysis by Signal peptide peptidase. Moreover, they offer compelling evidence for a function for an intramembrane protease to facilitate the association of core with viral genomes, thereby creating putative sites for assembly of nascent virus particles.
Elena Simona Lohan - One of the best experts on this subject based on the ideXlab platform.
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PLANS - Dual-frequency Signal processing architecture for robust and precise positioning applications
2018 IEEE ION Position Location and Navigation Symposium (PLANS), 2018Co-Authors: Padma Bolla, Elena Simona LohanAbstract:Availability of new GPS civil Signals L2C and L5 along with existed L1C/A Signal and Galileo E1/E5/E6 Signals has increased the potential ways to generate linear combination of Signals to remove ionosphere errors and improve accuracy in carrier integer ambiguity resolution. Conventionally, a linear combination of dual frequency Signals has been used to remove first order ionosphere delays incurred in Signal propagation path which is a major source of range error. Out of the three civil Signals in GPS and Galileo system, L5/E5 Signals have advanced Signal features such as higher received power, faster chip rate and lower carrier frequency than L1/E1 and L2C/E6 Signals. Hence, dual frequency receiver with combination of L1/L5 and E1/E5 Signals is more suitable to remove ionosphere delay and get benefit from L5/E5 Signal characteristics. However, the major limitation of linear combination of Signal observations is an amplification of receiver noise. To get benefit of two frequency Signals, a suitable Signal processing architecture is needed. By taking advantage of GPS L5/Galileo E5 Signal characteristics, a dual frequency Signal processing architecture is proposed with an aim to reduce the ionosphere-free Signal observation noise and to enhance the L1/E1 Signal tracking loop sensitivity. The L1/E1 Signal tracking loop sensitivity can be enhanced by Doppler aiding from L5/E5 Signal tracking loop. The low noise L5/E5 Signal Doppler aid reduces the noise in the L1/E1 Signal tracking loop. Moreover, two frequency Signals tracked with common Doppler estimate will have common observation errors, which will get cancel in linear combination of observations i.e. ionosphere-free, wide-lane etc. Further, code phase observations can be smoothed (Hatch filter) using carrier phase observations. The carrier phase observations are limited by cycle slip. Hence, we have investigated an optimum combination of divergence-free and ionosphere-free pseudorange smoothing using dual-frequency carrier Doppler observations for GPS L1/L5 and Galileo E1/E5 Signals. The cycle slip in carrier phase observations can be neglected in carrier Doppler observations. The proposed Signal processing architecture incorporated in GPS L1/L5 and Galileo E1/E5 dual frequency receiver will ensure robust Signal tracking and minimum pseudorange errors, suitable to a range of high accuracy standalone and code differential positioning applications. The performance of the proposed dual frequency Signal processing architecture is evaluated with GPS L1/L5 Signals collected from Block-IIF satellites.
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ICL-GNSS - Multi-GNSS analysis based on full constellations simulated data
2016 International Conference on Localization and GNSS (ICL-GNSS), 2016Co-Authors: Nunzia Giorgia Ferrara, Jari Nurmi, Elena Simona LohanAbstract:In the near future, satellite navigation will rely on four global constellations. Two Global Navigation Satellite Systems (GNSS), namely GPS and GLONASS, are already in use. In addition, Galileo and BeiDou/Compass systems, with, respectively, 12 and 19 satellites already in orbit, are expected to be fully operational by 2023. However, exhaustive investigations of the joint performance of the four GNSS as well as of the expected intra- and inter-system interferences are still scarce in the literature, due to the incomplete deployment of Galileo and Compass systems and the consequent scarcity of multi constellation data. In our paper, we extract full constellation data at 50000 randomly spread Earth locations of all the four GNSS via a Spectracom GSG-64 simulator. Then, we present a thorough analysis of the Geometric Dilution of Precision (GDOP) and the intra- and inter-system interference in the presence of the four GNSS compared to single GNSS situations. Based on the realistic multi-GNSS data, we verify that a combined utilization of the four systems will significantly improve the satellite visibility and the GDOP. Furthermore, focusing on the E1-L1-B1 band, we notice that the level of intra- and inter-system interference is slightly higher in the equatorial and pole regions and that the interference level to GPS is the highest among all four GNSS. Finally, by investigating the Carrier-to-Noise density ratio (C/N 0 ) degradation for Galileo E1 Signal caused by the presence of the four constellations, we show that it is rather small and it never surpasses 2.3 dB.
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Effect of Narrowband Interference on Galileo E1 Signal Receiver Performance
International Journal of Navigation and Observation, 2011Co-Authors: Jie Zhang, Elena Simona LohanAbstract:Satellite navigation technology is becoming essential for civil application. The high-accuracy navigation service is demanded. However, the satellite Signal may be exposed to the Signal from other systems, which are sharing the same frequency band. This is a potential threat for the performance of navigation devices. The aim of this paper is to present an interference impact assessment in the context of global navigation based on the new modulation Composite Binary Offset Carrier (CBOC) that will be used for Galileo E1 civil Signal. The focus is on the analysis of the Galileo CBOC-modulated Signal robustness against narrowband interference.
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PSATS - Galileo E1 and E5a Link-Level Performances in Single and Multipath Channels
Lecture Notes of the Institute for Computer Sciences Social Informatics and Telecommunications Engineering, 2011Co-Authors: Jie Zhang, Elena Simona LohanAbstract:The emerging global satellites system Galileo has gained much public interest regarding location and positioning services. Two new modulations, Composite Binary Offset Carrier (CBOC) and Alternate Binary Offset Carrier (AltBOC) will be used in the E1 and E5 band in the Galileo Open service (OS), respectively. The AltBOC modulation has the advantage that the E5a and E5b band can be processed independently as traditional BPSK Signal or together, leading to a better tracking performance in terms of noise and multipath mitigation at the cost of a large front-end bandwidth and increased complexity. The theoretical study of the Signal tracking in each band, separately, has been addressed before, but a comparison between the E1 and E5 Signals and validation through the simulation with the realistic channel are still lacking in the current literature. In this paper, the tracking performance between the Galileo E5a Signal and Galileo E1 Signal with different noise level and multipath profiles are compared by using the Simulink-based simulators built within our department at Tampere University of Technology. The simulation results are shown in terms of Root Mean Square Error (RMSE). The probability distribution of code tracking error is also investigated.
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Advanced Multipath Mitigation Techniques for Satellite-Based Positioning Applications
International Journal of Navigation and Observation, 2010Co-Authors: Mohammad Zahidul H. Bhuiyan, Elena Simona LohanAbstract:Multipath remains a dominant source of ranging errors in Global Navigation Satellite Systems (GNSS), such as the Global Positioning System (GPS) or the future European satellite navigation system Galileo. Multipath is generally considered undesirable in the context of GNSS, since the reception of multipath can make significant distortion to the shape of the correlation function used for time delay estimation. However, some wireless communications techniques exploit multipath in order to provide Signal diversity though in GNSS, the major challenge is to effectively mitigate the multipath, since we are interested only in the satellite-receiver transit time offset of the Line-Of-Sight (LOS) Signal for the receiver's position estimate. Therefore, the multipath problem has been approached from several directions in order to mitigate the impact of multipath on navigation receivers, including the development of novel Signal processing techniques. In this paper, we propose a maximum likelihood-based technique, namely, the Reduced Search Space Maximum Likelihood (RSSML) delay estimator, which is capable of mitigating the multipath effects reasonably well at the expense of increased complexity. The proposed RSSML attempts to compensate the multipath error contribution by performing a nonlinear curve fit on the input correlation function, which finds a perfect match from a set of ideal reference correlation functions with certain amplitude(s), phase(s), and delay(s) of the multipath Signal. It also incorporates a threshold-based peak detection method, which eventually reduces the code-delay search space significantly. However, the downfall of RSSML is the memory requirement which it uses to store the reference correlation functions. The multipath performance of other delay-tracking methods previously studied for Binary Phase Shift Keying-(BPSK-) and Sine Binary Offset Carrier- (SinBOC-) modulated Signals is also analyzed in closed loop model with the new Composite BOC (CBOC) modulation chosen for Galileo E1 Signal. The simulation results show that the RSSML achieves the best multipath mitigation performance in a uniformly distributed two-to-four paths Rayleigh fading channel model for all three modulated Signals.
Paul Targett-adams - One of the best experts on this subject based on the ideXlab platform.
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Maturation of hepatitis C virus core protein by Signal peptide peptidase is required for virus production.
The Journal of biological chemistry, 2008Co-Authors: Paul Targett-adams, Graham Hope, Steeve Boulant, John MclauchlanAbstract:Complete maturation of hepatitis C virus (HCV) core protein requires coordinate cleavage by Signal peptidase and an intramembrane protease, Signal peptide peptidase. We show that reducing the intracellular levels of Signal peptide peptidase lowers the titer of infectious virus released from cells, indicating that it plays an important role in virus production. Proteolysis by the enzyme at a Signal peptide between core and the E1 glycoprotein is needed to permit targeting of core to lipid droplets. From mutagenesis studies, introducing mutations into the core-E1 Signal peptide delayed the appearance of Signal peptide peptidase-processed core until between 48 and 72 h after the beginning of the infectious cycle. Accumulation of mature core at these times coincided with its localization to lipid droplets and a rise in titer of infectious HCV. Therefore, processing of core by Signal peptide peptidase is a critical event in the virus life cycle. To study the stage in virus production that may be blocked by interfering with intramembrane cleavage of core, we examined the distribution of viral RNA in cells harboring the core-E1 Signal peptide mutant. Results revealed that colocalization of core with HCV RNA required processing of the protein by Signal peptide peptidase. Our findings provide new insights into the sequence requirements for proteolysis by Signal peptide peptidase. Moreover, they offer compelling evidence for a function for an intramembrane protease to facilitate the association of core with viral genomes, thereby creating putative sites for assembly of nascent virus particles.
Verena Oehler - One of the best experts on this subject based on the ideXlab platform.
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Structural analysis of hepatitis C virus core-E1 Signal peptide and requirements for cleavage of the genotype 3a Signal sequence by Signal peptide peptidase.
Journal of Virology, 2012Co-Authors: Verena Oehler, Ana Filipe, Roland Montserret, Daniel Da Costa, Gaie Brown, François Penin, John MclauchlanAbstract:The maturation of the hepatitis C virus (HCV) core protein requires proteolytic processing by two host proteases: Signal peptidase (SP) and the intramembrane-cleaving protease Signal peptide peptidase (SPP). Previous work on HCV genotype 1a (GT1a) and GT2a has identified crucial residues required for efficient Signal peptide processing by SPP, which in turn has an effect on the production of infectious virus particles. Here we demonstrate that the JFH1 GT2a core-E1 Signal peptide can be adapted to the GT3a sequence without affecting the production of infectious HCV. Through mutagenesis studies, we identified crucial residues required for core-E1 Signal peptide processing, including a GT3a sequence-specific histidine (His) at position 187. In addition, the stable knockdown of intracellular SPP levels in HuH-7 cells significantly affects HCV virus titers, further demonstrating the requirement for SPP for the maturation of core and the production of infectious HCV particles. Finally, our nuclear magnetic resonance (NMR) structural analysis of a synthetic HCV JFH1 GT2a core-E1 Signal peptide provides an essential structural template for a further understanding of core processing as well as the first model for an SPP substrate within its membrane environment. Our findings give deeper insights into the mechanisms of intramembrane-cleaving proteases and the impact on viral infections.
Graham Hope - One of the best experts on this subject based on the ideXlab platform.
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Maturation of hepatitis C virus core protein by Signal peptide peptidase is required for virus production.
The Journal of biological chemistry, 2008Co-Authors: Paul Targett-adams, Graham Hope, Steeve Boulant, John MclauchlanAbstract:Complete maturation of hepatitis C virus (HCV) core protein requires coordinate cleavage by Signal peptidase and an intramembrane protease, Signal peptide peptidase. We show that reducing the intracellular levels of Signal peptide peptidase lowers the titer of infectious virus released from cells, indicating that it plays an important role in virus production. Proteolysis by the enzyme at a Signal peptide between core and the E1 glycoprotein is needed to permit targeting of core to lipid droplets. From mutagenesis studies, introducing mutations into the core-E1 Signal peptide delayed the appearance of Signal peptide peptidase-processed core until between 48 and 72 h after the beginning of the infectious cycle. Accumulation of mature core at these times coincided with its localization to lipid droplets and a rise in titer of infectious HCV. Therefore, processing of core by Signal peptide peptidase is a critical event in the virus life cycle. To study the stage in virus production that may be blocked by interfering with intramembrane cleavage of core, we examined the distribution of viral RNA in cells harboring the core-E1 Signal peptide mutant. Results revealed that colocalization of core with HCV RNA required processing of the protein by Signal peptide peptidase. Our findings provide new insights into the sequence requirements for proteolysis by Signal peptide peptidase. Moreover, they offer compelling evidence for a function for an intramembrane protease to facilitate the association of core with viral genomes, thereby creating putative sites for assembly of nascent virus particles.
