New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

Directory of Open Access Journals (Sweden)

Hugo de Almeida

Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

SPS Injection and Beam Quality for LHC Heavy Ions With 150 ns Kicker Rise Time

CERN Document Server

Goddard, Brennan; Ducimetière, Laurent; Kotzian, Gerd; Uythoven, Jan; Velotti, Francesco

2016-01-01

As part of the LHC Injectors Upgrade project for LHC heavy ions, the SPS injection kicker system rise time needs reduction below its present 225 ns. One technically challenging option under consideration is the addition of fast Pulse Forming Lines in parallel to the existing Pulse Forming Networks for the 12 kicker magnets MKP-S, targeting a system field rise time of 100 ns. An alternative option is to optimise the system to approach the existing individual magnet field rise time (2-98%) of 150 ns. This would still significantly increase the number of colliding bunches in LHC while minimising the cost and effort of the system upgrade. The observed characteristics of the present system are described, compared to the expected system rise time, together with results of simulations and measurements with 175 and 150 ns injection batch spacing. The expected beam quality at injection into LHC is quantified, with the emittance growth and simulated tail population taking into account expected jitter and synchronisatio...

In Silico Screening, Alanine Mutation, and DFT Approaches for Identification of NS2B/NS3 Protease Inhibitors

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R. Balajee

2016-01-01

Full Text Available To identify the ligand that binds to a target protein with high affinity is a nontrivial task in computer-assisted approaches. Antiviral drugs have been identified for NS2B/NS3 protease enzyme on the mechanism to cleave the viral protein using the computational tools. The consequence of the molecular docking, free energy calculations, and simulation protocols explores the better ligand. It provides in-depth structural insights with the catalytic triad of His51, Asp75, Ser135, and Gly133. The MD simulation was employed here to predict the stability of the complex. The alanine mutation has been performed and its stability was monitored by using the molecular dynamics simulation. The minimal RMSD value suggests that the derived complexes are close to equilibrium. The DFT outcome reveals that the HOMO-LUMO gap of Ligand19 is 2.86 kcal/mol. Among the considered ligands, Ligand19 shows the lowest gap and it is suggested that the HOMO of Ligand19 may transfer the electrons to the LUMO in the active regions. The calculated binding energy of Ligand19 using the DFT method is in good agreement with the docking studies. The pharmacological activity of ligand was performed and satisfies Lipinski rule of 5. Moreover, the computational results are compared with the available IC50 values of experimental results.

Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease.

Science.gov (United States)

Qamar, Tahir Ul; Mumtaz, Arooj; Ashfaq, Usman Ali; Azhar, Samia; Fatima, Tabeer; Hassan, Muhammad; Hussain, Syed Sajid; Akram, Waheed; Idrees, Sobia

2014-01-01

Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy.

Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein

Science.gov (United States)

Amelia, F.; Iryani; Sari, P. Y.; Parikesit, A. A.; Bakri, R.; Toepak, E. P.; Tambunan, U. S. F.

2018-04-01

Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.

Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo.

Science.gov (United States)

Yuan, Shuofeng; Chan, Jasper Fuk-Woo; den-Haan, Helena; Chik, Kenn Ka-Heng; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Zheng; Zou, Zijiao; Tee, Kah-Meng; Cai, Jian-Piao; Chan, Kwok-Hung; de la Peña, Jorge; Pérez-Sánchez, Horacio; Cerón-Carrasco, José Pedro; Yuen, Kwok-Yung

2017-09-01

Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir). Molecular docking and molecular dynamics simulations predicted that novobiocin bound to ZIKV NS2B-NS3-protease with high stability. Dexamethasone-immunosuppressed mice with disseminated ZIKV infection and novobiocin treatment had significantly (P < 0.05) higher survival rate (100% vs 0%), lower mean blood and tissue viral loads, and less severe histopathological changes than untreated controls. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of ZIKV. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementation and Evaluation of WLAN 802.11ac for Residential Networks in NS-3

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Andy Bubune Amewuda

2018-01-01

Full Text Available Wi-Fi has been an amazingly successful technology. Its success may be attributed to the fact that, despite the significant advances made in technology over the last decade, it has remained backward compatible. 802.11ac is the latest version of the wireless LAN (WLAN standard that is currently being adopted, and it promises to deliver very high throughput (VHT, operating at the 5 GHz band. In this paper, we report on an implementation of 802.11ac wireless LAN for residential scenario based on the 802.11ax task group scenario document. We evaluate the 802.11ac protocol performance under different operating conditions. Key features such as modulation coding set (MCS, frame aggregation, and multiple-input multiple-output (MIMO were investigated. We also evaluate the average throughput, delay, jitter, optimum range for goodput, and effect of station (STA density per access point (AP in a network. ns-3, an open source network simulator with features supporting 802.11ac, was used to perform the simulation. Results obtained indicate that very high data rates are achievable. The highest data rate, the best mean delay, and mean jitter are possible under combined features of 802.11ac (MIMO and A-MPDU.

Docking, synthesis and bioassay studies of imine derivatives as potential inhibitors for dengue NS2B/ NS3 serine protease

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Neni Frimayanti

2017-11-01

Full Text Available Objective: To search imine derivatives as new active agents against dengue type 2 NS2B/NS3 using molecular docking, since there is no effective vaccine against flaviviral infections. Methods: In this research, molecular docking was performed for a series of imine derivatives and the information obtained from the docking studies was used to explore the binding modes of these imine derivatives with dengue type 2 NS2B/NS3 serine protease. A set of imine were synthesized and bioassay study of the inhibitory activities of these compounds was then performed. Results: The results indicated that MY8 and MY4 have the ability to inhibit DEN2 NS2B/NS3 proteolytic activity. Conclusions: These two compounds were chosen as the reference for the next stage in drug design as new inhibitor agents against NS2B/NS3.

In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4

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Thi Thanh Hanh Nguyen

2013-12-01

Full Text Available The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC50 values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3pro inhibitors were further confirmed as competitive inhibitors with Ki values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3pro active site with inhibition compounds were also identified.

Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J.; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F.; Johnson, Michael E. (UIC); (NWU); (Novalex); (DNSK)

2016-12-26

Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

Energy Technology Data Exchange (ETDEWEB)

D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Lim, Siew Pheng [Novartis Institutes of Tropical Diseases (Singapore); Lefeuvre, Peggy [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Erbel, Paul [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Novartis Institutes of Tropical Diseases (Singapore)

2006-02-01

Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

International Nuclear Information System (INIS)

D’Arcy, Allan; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

2006-01-01

Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained

Supersymmetric non-singular fractional D2-branes and NS-NS 2-branes

International Nuclear Information System (INIS)

Cvetic, M.; Gibbons, G.W.; Lue, H.; Pope, C.N.

2001-01-01

We obtain regular deformed D2-brane solutions with fractional D2-branes arising as wrapped D4-branes. The space transverse to the D2-brane is a complete Ricci-flat 7-manifold of G 2 holonomy, which is asymptotically conical with principal orbits that are topologically CP 3 or the flag manifold SU(3)/(U(1)xU(1)). We obtain the solution by first constructing an L 2 normalisable harmonic 3-form. We also review a previously-obtained regular deformed D2-brane whose transverse space is a different 7-manifold of G 2 holonomy, with principal orbits that are topologically S 3 xS 3 . This describes D2-branes with fractional NS-NS 2-branes coming from the wrapping of 5-branes, which is supported by a non-normalisable harmonic 3-form on the 7-manifold. We prove that both types of solutions are supersymmetric, preserving 1/16 of the maximal supersymmetry and hence that they are dual to N=1 three-dimensional gauge theories. In each case, the spectrum for minimally-coupled scalars is discrete, indicating confinement in the infrared region of the dual gauge theories. We examine resolutions of other branes, and obtain necessary conditions for their regularity. The resolution of many of these seems to lie beyond supergravity. In the process of studying these questions, we construct new explicit examples of complete Ricci-flat metrics

Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

DEFF Research Database (Denmark)

Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

2013-01-01

Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c......LDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...

IP2P K-means: an efficient method for data clustering on sensor networks

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Peyman Mirhadi

2013-03-01

Full Text Available Many wireless sensor network applications require data gathering as the most important parts of their operations. There are increasing demands for innovative methods to improve energy efficiency and to prolong the network lifetime. Clustering is considered as an efficient topology control methods in wireless sensor networks, which can increase network scalability and lifetime. This paper presents a method, IP2P K-means – Improved P2P K-means, which uses efficient leveling in clustering approach, reduces false labeling and restricts the necessary communication among various sensors, which obviously saves more energy. The proposed method is examined in Network Simulator Ver.2 (NS2 and the preliminary results show that the algorithm works effectively and relatively more precisely.

hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

Energy Technology Data Exchange (ETDEWEB)

Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

2014-01-20

The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles

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V.S. Neverov

2017-01-01

Full Text Available XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D diffraction patterns and pair-distribution functions (PDF for amorphous or crystalline nanoparticles (up to ∼107 atoms of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles

Science.gov (United States)

Neverov, V. S.

XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D) diffraction patterns and pair-distribution functions (PDF) for amorphous or crystalline nanoparticles (up to ∼107 atoms) of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

Network Simulation

CERN Document Server

Fujimoto, Richard

2006-01-01

"Network Simulation" presents a detailed introduction to the design, implementation, and use of network simulation tools. Discussion topics include the requirements and issues faced for simulator design and use in wired networks, wireless networks, distributed simulation environments, and fluid model abstractions. Several existing simulations are given as examples, with details regarding design decisions and why those decisions were made. Issues regarding performance and scalability are discussed in detail, describing how one can utilize distributed simulation methods to increase the

Lattice Boltzmann simulation of CO2 reactive transport in network fractured media

Science.gov (United States)

Tian, Zhiwei; Wang, Junye

2017-08-01

Carbon dioxide (CO2) geological sequestration plays an important role in mitigating CO2 emissions for climate change. Understanding interactions of the injected CO2 with network fractures and hydrocarbons is key for optimizing and controlling CO2 geological sequestration and evaluating its risks to ground water. However, there is a well-known, difficult process in simulating the dynamic interaction of fracture-matrix, such as dynamic change of matrix porosity, unsaturated processes in rock matrix, and effect of rock mineral properties. In this paper, we develop an explicit model of the fracture-matrix interactions using multilayer bounce-back treatment as a first attempt to simulate CO2 reactive transport in network fractured media through coupling the Dardis's LBM porous model for a new interface treatment. Two kinds of typical fracture networks in porous media are simulated: straight cross network fractures and interleaving network fractures. The reaction rate and porosity distribution are illustrated and well-matched patterns are found. The species concentration distribution and evolution with time steps are also analyzed and compared with different transport properties. The results demonstrate the capability of this model to investigate the complex processes of CO2 geological injection and reactive transport in network fractured media, such as dynamic change of matrix porosity.

Detergent-resistant membrane association of NS2 and E2 during hepatitis C virus replication.

Science.gov (United States)

Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani; Yi, MinKyung

2015-04-01

Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not targeted to these

Role of nonstructural protein NS2A in flavivirus assembly

NARCIS (Netherlands)

Leung, J.Y.; Pijlman, G.P.; Kondratieva, N.; Hyde, J.; Mackenzie, J.M.; Khromykh, A.A.

2008-01-01

Flavivirus nonstructural (NS) proteins are involved in RNA replication and modulation of the host antiviral response; however, evidence is mounting that some NS proteins also have essential roles in virus assembly. Kunjin virus (KUN) NS2A is a small, hydrophobic, transmembrane protein that is part

Experiment-based thermal micromagnetic simulations of the magnetization reversal for ns-range clocked nanomagnetic logic

Science.gov (United States)

Ziemys, Grazvydas; Breitkreutz-v. Gamm, Stephan; Csaba, Gyorgy; Schmitt-Landsiedel, Doris; Becherer, Markus

2017-05-01

Extensive thermal micromagnetic simulations, based on experimental data and parameters, were performed to investigate the magnetization reversal in Co/Pt nanomagnets with locally reduced perpendicular anisotropy on the nanosecond range. The simulations were supported by experimental data gained on manufactured Co/Pt nanomagnets, as used in nanomagnetic logic. It is known that magnetization reversal is governed by two mechanisms. At pulse lengths longer than 100 ns, thermal activation dominates the magnetization reversal processes and follows the common accepted Arrhenius law. For pulse lengths shorter than 100 ns, the dynamic reversal dominates. With the help of thermal micro-magnetic simulations we found out that the point where the both mechanisms meet is determined by the damping constant α of the multilayer film stack. The optimization of ferromagnetic multilayer film stacks enables higher clocking rates with lower power consumption and, therefore, further improve the performance of pNML.

N/S Co-Doped 3 D Porous Carbon Nanosheet Networks Enhancing Anode Performance of Sodium-Ion Batteries.

Science.gov (United States)

Zou, Lei; Lai, Yanqing; Hu, Hongxing; Wang, Mengran; Zhang, Kai; Zhang, Peng; Fang, Jing; Li, Jie

2017-10-12

A facile and scalable method is realized for the in situ synthesis of N/S co-doped 3 D porous carbon nanosheet networks (NSPCNNs) as anode materials for sodium-ion batteries. During the synthesis, NaCl is used as a template to prepare porous carbon nanosheet networks. In the resultant architecture, the unique 3 D porous architecture ensures a large specific surface area and fast diffusion paths of both electrons and ions. In addition, the import of N/S produces abundant defects, increased interlayer spacings, more active sites, and high electronic conductivity. The obtained products deliver a high specific capacity and excellent long-term cycling performance, specifically, a capacity of 336.2 mA h g -1 at 0.05 A g -1 , remaining as large as 214.9 mA h g -1 after 2000 charge/discharge cycles at 0.5 A g -1 . This material has great prospects for future applications of scalable, low-cost, and environmentally friendly sodium-ion batteries. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simulating Real-Time Aspects of Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Christian Nastasi

2010-01-01

Full Text Available Wireless Sensor Networks (WSNs technology has been mainly used in the applications with low-frequency sampling and little computational complexity. Recently, new classes of WSN-based applications with different characteristics are being considered, including process control, industrial automation and visual surveillance. Such new applications usually involve relatively heavy computations and also present real-time requirements as bounded end-to- end delay and guaranteed Quality of Service. It becomes then necessary to employ proper resource management policies, not only for communication resources but also jointly for computing resources, in the design and development of such WSN-based applications. In this context, simulation can play a critical role, together with analytical models, for validating a system design against the parameters of Quality of Service demanded for. In this paper, we present RTNS, a publicly available free simulation tool which includes Operating System aspects in wireless distributed applications. RTNS extends the well-known NS-2 simulator with models of the CPU, the Real-Time Operating System and the application tasks, to take into account delays due to the computation in addition to the communication. We demonstrate the benefits of RTNS by presenting our simulation study for a complex WSN-based multi-view vision system for real-time event detection.

Mosquito densonucleosis virus non-structural protein NS2 is necessary for a productive infection

International Nuclear Information System (INIS)

Azarkh, Eugene; Robinson, Erin; Hirunkanokpun, Supanee; Afanasiev, Boris; Kittayapong, Pattamaporn; Carlson, Jonathan; Corsini, Joe

2008-01-01

Mosquito densonucleosis viruses synthesize two non-structural proteins, NS1 and NS2. While NS1 has been studied relatively well, little is known about NS2. Antiserum was raised against a peptide near the N-terminus of NS2, and used to conduct Western blot analysis and immuno-fluorescence assays. Western blots revealed a prominent band near the expected size (41 kDa). Immuno-fluorescence studies of mosquito cells transfected with AeDNV indicate that NS2 has a wider distribution pattern than does NS1, and the distribution pattern appears to be a function of time post-infection. Nuclear localization of NS2 requires intact C-terminus but does not require additional viral proteins. Mutations ranging from complete NS2 knock-out to a single missense amino acid substitution in NS2 can significantly reduce viral replication and production of viable progeny

Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

Directory of Open Access Journals (Sweden)

Hung-Yu Sun

Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses.

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Shiryaev, Sergey A; Kozlov, Igor A; Ratnikov, Boris I; Smith, Jeffrey W; Lebl, Michal; Strongin, Alex Y

2007-02-01

Regulated proteolysis of the polyprotein precursor by the NS2B-NS3 protease is required for the propagation of infectious virions. Unless the structural and functional parameters of NS2B-NS3 are precisely determined, an understanding of its functional role and the design of flaviviral inhibitors will be exceedingly difficult. Our objectives were to define the substrate recognition pattern of the NS2B-NS3 protease of West Nile and Dengue virises (WNV and DV respectively). To accomplish our goals, we used an efficient, 96-well plate format, method for the synthesis of 9-mer peptide substrates with the general P4-P3-P2-P1-P1'-P2'-P3'-P4'-Gly structure. The N-terminus and the constant C-terminal Gly of the peptides were tagged with a fluorescent tag and with a biotin tag respectively. The synthesis was followed by the proteolytic cleavage of the synthesized, tagged peptides. Because of the strict requirement for the presence of basic amino acid residues at the P1 and the P2 substrate positions, the analysis of approx. 300 peptide sequences was sufficient for an adequate representation of the cleavage preferences of the WNV and DV proteinases. Our results disclosed the strict substrate specificity of the WNV protease for which the (K/R)(K/R)R/GG amino acid motifs was optimal. The DV protease was less selective and it tolerated well the presence of a number of amino acid residue types at either the P1' or the P2' site, as long as the other position was occupied by a glycine residue. We believe that our data represent a valuable biochemical resource and a solid foundation to support the design of selective substrates and synthetic inhibitors of flaviviral proteinases.

Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.

Science.gov (United States)

Sabet, Salwa; George, Marina A; El-Shorbagy, Haidan M; Bassiony, Heba; Farroh, Khaled Y; Youssef, Tareq; Salaheldin, Taher A

2017-01-01

Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV.

Radiometric calibration of the reflective bands of NS001-Thematic Mapper Simulator (TMS) and modular multispectral radiometers (MMR)

Science.gov (United States)

Markham, Brian L.; Wood, Frank M., Jr.; Ahmad, Suraiya P.

1988-01-01

The NS001 Thematic Mapper Simulator scanner (TMS) and several modular multispectral radiometers (MMRs) are among the primary instruments used in the First ISLSCP (International Satellite Land Surface Climatology Project) Field Experiment (FIFE). The NS001 has a continuously variable gain setting. Calibration of the NS001 data is influenced by drift in the dark current level of up to six counts during a mirror scan at typical gain settings. The MMR instruments are being used in their 1 deg FOV configuration on the helicopter and 15 deg FOV on the ground.

Network Performance Evaluation of Abis Interface over DVB-S2 in the GSM over Satellite Network

Directory of Open Access Journals (Sweden)

S. B. Musabekov

2010-01-01

Full Text Available This paper deals with establishing a GSM link over Satellite. Abis interface, which is defined between Base Transceiver Station (BTS and Base Station Controller (BSC, in a GSM network is considered here to be routed over the Satellite. The satellite link enables a quick and cost-effective GSM link in meagerly populated areas. A different scenario comparison was done to understand the impact of Satellite environment on network availability comparing to terrestrial scenario. We have implemented an Abis interface over DVB S2 in NS2 and evaluated the performance over the high delay and loss satellite channel. Network performance was evaluated with respect to Satellite channel delay and DVB S2 encapsulation efficiency under different amount of user traffic and compared with the terrestrial scenario. The results clearly showed an increased amount of SDCCH and TCH channels required in the case of satellite scenario for the same amount of traffic in comparison to conventional terrestrial scenario. We have optimized the parameters based on the simulation results. Link budget estimation considering DVB-S2 platform was done to find satellite bandwidth and cost requirements for different network setups.

Lyso-myristoyl phosphatidylcholine micelles sustain the activity of Dengue non-structural (NS) protein 3 protease domain fused with the full-length NS2B.

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Huang, Qiwei; Li, Qingxin; Joy, Joma; Chen, Angela Shuyi; Ruiz-Carrillo, David; Hill, Jeffrey; Lescar, Julien; Kang, Congbao

2013-12-01

Dengue virus (DENV), a member of the flavivirus genus, affects 50-100 million people in tropical and sub-tropical regions. The DENV protease domain is located at the N-terminus of the NS3 protease and requires for its enzymatic activity a hydrophilic segment of the NS2B that acts as a cofactor. The protease is an important antiviral drug target because it plays a crucial role in virus replication by cleaving the genome-coded polypeptide into mature functional proteins. Currently, there are no drugs to inhibit DENV protease activity. Most structural and functional studies have been conducted using protein constructs containing the NS3 protease domain connected to a soluble segment of the NS2B membrane protein via a nine-residue linker. For in vitro structural and functional studies, it would be useful to produce a natural form of the DENV protease containing the NS3 protease domain and the full-length NS2B protein. Herein, we describe the expression and purification of a natural form of DENV protease (NS2BFL-NS3pro) containing the full-length NS2B protein and the protease domain of NS3 (NS3pro). The protease was expressed and purified in detergent micelles necessary for its folding. Our results show that this purified protein was active in detergent micelles such as lyso-myristoyl phosphatidylcholine (LMPC). These findings should facilitate further structural and functional studies of the protease and will facilitate drug discovery targeting DENV. Copyright © 2013 Elsevier Inc. All rights reserved.

Remote detection of canopy water stress in coniferous forests using the NS001 Thematic Mapper Simulator and the thermal infrared multispectral scanner

Science.gov (United States)

Pierce, Lars L.; Running, Steven W.; Riggs, George A.

1990-01-01

Water stress was induced in two coniferous forest stands in West Germany by severing tree sapwood. Leaf water potential, Psi(L), measurements indicated that maximum, naturally occurring levels of water stress developed in the stressed plots while control plots exhibited natural diurnal trends. Images of each site were obtained with the Thematic Mapper Simulator (NS001) and the Thermal Infrared Multispectral Scanner (TIMS) 12 to 15 days after stress induction. NS001 bands 2 to 6, NS001 indices combining bands 4 and 6, and NS001 and TIMS thermal bands showed significant radiance differences between stressed and control plots when large differences in Psi(L) and relative water content (RWC) existed during the morning overflights at Munich. However, the NS001 and TIMS sensors could not detect the slightly smaller differences in Psi(L) and RWC during the Munich afternoon and Frankfurt overflights. The results suggest that routine detection of canopy water stress under operational conditions is difficult utilizing current sensor technology.

A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.

Directory of Open Access Journals (Sweden)

Matthew Brecher

2017-05-01

Full Text Available The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and SLC enhancement. We also performed a virtual screen of NCI library compounds to identify allosteric inhibitors, followed by in vitro biochemical screening of the resultant candidates. Only three of these compounds, NSC135618, 260594, and 146771, significantly inhibited the protease of Dengue virus 2 (DENV2 in vitro, with IC50 values of 1.8 μM, 11.4 μM, and 4.8 μM, respectively. Among the three compounds, only NSC135618 significantly suppressed the SLC enhancement triggered by binding of active-site inhibitor in a dose-dependent manner, indicating that it inhibits the conformational change of NS2B. Results from virus titer reduction assays revealed that NSC135618 is a broad spectrum flavivirus protease inhibitor, and can significantly reduce titers of DENV2, Zika virus (ZIKV, West Nile virus (WNV, and Yellow fever virus (YFV on A549 cells in vivo, with EC50 values in low micromolar range. In contrast, the cytotoxicity of NSC135618 is only moderate with CC50 of 48.8 μM on A549 cells. Moreover, NSC135618 inhibited ZIKV in human placental and neural progenitor cells relevant to ZIKV pathogenesis. Results from binding, kinetics, Western blot, mass spectrometry and

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

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Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors

Potential of plant alkaloids as dengue ns3 protease inhibitors: Molecular docking and simulation approach

Directory of Open Access Journals (Sweden)

Muhammad Tahir ul Qamar

2014-08-01

Full Text Available Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6’-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and Tubulosine successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability.

Signal Processing and Neural Network Simulator

Science.gov (United States)

Tebbe, Dennis L.; Billhartz, Thomas J.; Doner, John R.; Kraft, Timothy T.

1995-04-01

The signal processing and neural network simulator (SPANNS) is a digital signal processing simulator with the capability to invoke neural networks into signal processing chains. This is a generic tool which will greatly facilitate the design and simulation of systems with embedded neural networks. The SPANNS is based on the Signal Processing WorkSystemTM (SPWTM), a commercial-off-the-shelf signal processing simulator. SPW provides a block diagram approach to constructing signal processing simulations. Neural network paradigms implemented in the SPANNS include Backpropagation, Kohonen Feature Map, Outstar, Fully Recurrent, Adaptive Resonance Theory 1, 2, & 3, and Brain State in a Box. The SPANNS was developed by integrating SAIC's Industrial Strength Neural Networks (ISNN) Software into SPW.

A framework for visualization of battlefield network behavior

Science.gov (United States)

Perzov, Yury; Yurcik, William

2006-05-01

An extensible network simulation application was developed to study wireless battlefield communications. The application monitors node mobility and depicts broadcast and unicast traffic as expanding rings and directed links. The network simulation was specially designed to support fault injection to show the impact of air strikes on disabling nodes. The application takes standard ns-2 trace files as an input and provides for performance data output in different graphical forms (histograms and x/y plots). Network visualization via animation of simulation output can be saved in AVI format that may serve as a basis for a real-time battlefield awareness system.

2D non-separable linear canonical transform (2D-NS-LCT) based cryptography

Science.gov (United States)

Zhao, Liang; Muniraj, Inbarasan; Healy, John J.; Malallah, Ra'ed; Cui, Xiao-Guang; Ryle, James P.; Sheridan, John T.

2017-05-01

The 2D non-separable linear canonical transform (2D-NS-LCT) can describe a variety of paraxial optical systems. Digital algorithms to numerically evaluate the 2D-NS-LCTs are not only important in modeling the light field propagations but also of interest in various signal processing based applications, for instance optical encryption. Therefore, in this paper, for the first time, a 2D-NS-LCT based optical Double-random- Phase-Encryption (DRPE) system is proposed which offers encrypting information in multiple degrees of freedom. Compared with the traditional systems, i.e. (i) Fourier transform (FT); (ii) Fresnel transform (FST); (iii) Fractional Fourier transform (FRT); and (iv) Linear Canonical transform (LCT), based DRPE systems, the proposed system is more secure and robust as it encrypts the data with more degrees of freedom with an augmented key-space.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

Science.gov (United States)

de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

2013-01-01

Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

Directory of Open Access Journals (Sweden)

Benoît de Chassey

Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

Cooperative Media Streaming Using Adaptive Network Compression

DEFF Research Database (Denmark)

Møller, Janus Heide; Sørensen, Jesper Hemming; Krigslund, Rasmus

2008-01-01

as an adaptive hybrid between LC and MDC. In order to facilitate the use of MDC-CC, a new overlay network approach is proposed, using tree of meshes. A control system for managing description distribution and compression in a small mesh is implemented in the discrete event simulator NS-2. The two traditional...... approaches, MDC and LC, are used as references for the performance evaluation of the proposed scheme. The system is simulated in a heterogeneous network environment, where packet errors are introduced. Moreover, a test is performed at different network loads. Performance gain is shown over both LC and MDC....

Packet Tracer network simulator

CERN Document Server

Jesin, A

2014-01-01

A practical, fast-paced guide that gives you all the information you need to successfully create networks and simulate them using Packet Tracer.Packet Tracer Network Simulator is aimed at students, instructors, and network administrators who wish to use this simulator to learn how to perform networking instead of investing in expensive, specialized hardware. This book assumes that you have a good amount of Cisco networking knowledge, and it will focus more on Packet Tracer rather than networking.

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus.

Science.gov (United States)

Zhu, Shaomei; Li, Tingting; Liu, Bochao; Xu, Yuxia; Sun, Yachun; Wang, Yilin; Wang, Yuanzhan; Shuai, Lifang; Chen, Zixuan; Allain, Jean-Pierre; Li, Chengyao

2016-09-15

A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model for HCV infection

Model-based Compositional Design of Networked Control Systems

Science.gov (United States)

2013-12-01

with event scheduling. In particular, the C++ source code for the ns-2 simulator scheduler is modi - fied to implement the time synchronization mechanism...pump: Security attacks and defenses for a diabetes therapy system. In: 2011 13th IEEE International Conference In e-Health Networking Applications and

On securing wireless sensor network--novel authentication scheme against DOS attacks.

Science.gov (United States)

Raja, K Nirmal; Beno, M Marsaline

2014-10-01

Wireless sensor networks are generally deployed for collecting data from various environments. Several applications specific sensor network cryptography algorithms have been proposed in research. However WSN's has many constrictions, including low computation capability, less memory, limited energy resources, vulnerability to physical capture, which enforce unique security challenges needs to make a lot of improvements. This paper presents a novel security mechanism and algorithm for wireless sensor network security and also an application of this algorithm. The proposed scheme is given to strong authentication against Denial of Service Attacks (DOS). The scheme is simulated using network simulator2 (NS2). Then this scheme is analyzed based on the network packet delivery ratio and found that throughput has improved.

A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

International Nuclear Information System (INIS)

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F.

2016-01-01

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

Energy Technology Data Exchange (ETDEWEB)

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F., E-mail: saeed@southernresearch.org

2016-09-15

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

DESARROLLO DE UN SOFTWARE BASADO EN JAVA CAPAZ DE INTERPRETAR TRAZAS DE ARCHIVOS GENERADOS POR NS-2

Directory of Open Access Journals (Sweden)

Fredy Pachón Barbera

2013-09-01

Full Text Available En la simulación de una red de datos, se trata de evaluar, investigar y/o analizar su comportamiento  en un ambiente real, siempre buscando la optimización los recursos. El análisis de la información es un punto clave para conocer fortalezas y debilidades de la red simulada. El objetivo de este artículo es mostrar el desarrollo de una herramienta de interpretación de trazas generadas por NS-2 basado en el lenguaje de programación Java  y las variables estadísticas que se tuvieron en cuenta para la implementación, con el fin de facilitar el análisis de redes simuladas con la herramienta network simluator. Finalmente se logra la construcción del software, logrando determinar los cálculos de jitter, throughput y bytes enviados por cada nodo, a partir de las trazas generadas por NS-2.

NS19504

DEFF Research Database (Denmark)

Nausch, Bernhard; Rode, Frederik; Jørgensen, Susanne

2014-01-01

channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization......19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µ......M) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels...

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

Optical and EPR spectra of the thionitrosyl complex [Cr(OH2)5(NS)]2+

DEFF Research Database (Denmark)

Døssing, Anders Rørbæk; Dethlefsen, Johannes Wied

2008-01-01

. The optical data indicate that the NS ligand is a weaker p-acceptor than the NO ligand. The EPR parameters of [Cr(OH2)5(NS)]2+ were determined: giso, g¦ and g-: 1.96515, 1.92686(5) and 1.986860(8); Aiso(53Cr), A¦(53Cr) and A-(53Cr): 25.3´10-4, 38´10-4 and 18.5´10-4cm-1; Aiso(14N), A¦(14N) and A-(14N): 6...

A robust fractional-order PID controller design based on active queue management for TCP network

Science.gov (United States)

Hamidian, Hamideh; Beheshti, Mohammad T. H.

2018-01-01

In this paper, a robust fractional-order controller is designed to control the congestion in transmission control protocol (TCP) networks with time-varying parameters. Fractional controllers can increase the stability and robustness. Regardless of advantages of fractional controllers, they are still not common in congestion control in TCP networks. The network parameters are time-varying, so the robust stability is important in congestion controller design. Therefore, we focused on the robust controller design. The fractional PID controller is developed based on active queue management (AQM). D-partition technique is used. The most important property of designed controller is the robustness to the time-varying parameters of the TCP network. The vertex quasi-polynomials of the closed-loop characteristic equation are obtained, and the stability boundaries are calculated for each vertex quasi-polynomial. The intersection of all stability regions is insensitive to network parameter variations, and results in robust stability of TCP/AQM system. NS-2 simulations show that the proposed algorithm provides a stable queue length. Moreover, simulations show smaller oscillations of the queue length and less packet drop probability for FPID compared to PI and PID controllers. We can conclude from NS-2 simulations that the average packet loss probability variations are negligible when the network parameters change.

Enabling parallel simulation of large-scale HPC network systems

International Nuclear Information System (INIS)

Mubarak, Misbah; Carothers, Christopher D.; Ross, Robert B.; Carns, Philip

2016-01-01

Here, with the increasing complexity of today’s high-performance computing (HPC) architectures, simulation has become an indispensable tool for exploring the design space of HPC systems—in particular, networks. In order to make effective design decisions, simulations of these systems must possess the following properties: (1) have high accuracy and fidelity, (2) produce results in a timely manner, and (3) be able to analyze a broad range of network workloads. Most state-of-the-art HPC network simulation frameworks, however, are constrained in one or more of these areas. In this work, we present a simulation framework for modeling two important classes of networks used in today’s IBM and Cray supercomputers: torus and dragonfly networks. We use the Co-Design of Multi-layer Exascale Storage Architecture (CODES) simulation framework to simulate these network topologies at a flit-level detail using the Rensselaer Optimistic Simulation System (ROSS) for parallel discrete-event simulation. Our simulation framework meets all the requirements of a practical network simulation and can assist network designers in design space exploration. First, it uses validated and detailed flit-level network models to provide an accurate and high-fidelity network simulation. Second, instead of relying on serial time-stepped or traditional conservative discrete-event simulations that limit simulation scalability and efficiency, we use the optimistic event-scheduling capability of ROSS to achieve efficient and scalable HPC network simulations on today’s high-performance cluster systems. Third, our models give network designers a choice in simulating a broad range of network workloads, including HPC application workloads using detailed network traces, an ability that is rarely offered in parallel with high-fidelity network simulations

Largenet2: an object-oriented programming library for simulating large adaptive networks.

Science.gov (United States)

Zschaler, Gerd; Gross, Thilo

2013-01-15

The largenet2 C++ library provides an infrastructure for the simulation of large dynamic and adaptive networks with discrete node and link states. The library is released as free software. It is available at http://biond.github.com/largenet2. Largenet2 is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License. gerd@biond.org

Data center network performance evaluation in ns3

DEFF Research Database (Denmark)

Andrus, Bogdan-Mihai; Vegas Olmos, Juan José

2015-01-01

In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3 and subjec......In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3...... and subjecting them to uniformly distributed traffic routed by shortest path algorithms we are able to extract statistics related to average throughput, latency and loss rate that show the decrease in the average throughput per connection is only about 5% for the hypercube compared to 16% for the 3D torus when...

Tetrahedral ↔ octahedral network structure transition in simulated vitreous SiO2

International Nuclear Information System (INIS)

Vo Van Hoang; Nguyen Trung Hai; Hoang Zung

2006-01-01

By using molecular dynamics (MD) simulations we found a transition from a tetrahedral to an octahedral network structure in an amorphous SiO 2 model under compression from 2.20 to 5.35 g/cm 3 . And on heating of a high density amorphous (hda) model of 5.35 g/cm 3 at zero pressure, the structure transforms to a low density amorphous (lda) form. Simulations were done in a model containing 3000 particles under periodic boundary conditions with interatomic potentials which have a weak Coulomb interaction and a Morse type short-range interaction

NCC simulation model. Phase 2: Simulating the operations of the Network Control Center and NCC message manual

Science.gov (United States)

Benjamin, Norman M.; Gill, Tepper; Charles, Mary

1994-01-01

The network control center (NCC) provides scheduling, monitoring, and control of services to the NASA space network. The space network provides tracking and data acquisition services to many low-earth orbiting spacecraft. This report describes the second phase in the development of simulation models for the FCC. Phase one concentrated on the computer systems and interconnecting network.Phase two focuses on the implementation of the network message dialogs and the resources controlled by the NCC. Performance measures were developed along with selected indicators of the NCC's operational effectiveness.The NCC performance indicators were defined in terms of the following: (1) transfer rate, (2) network delay, (3) channel establishment time, (4) line turn around time, (5) availability, (6) reliability, (7) accuracy, (8) maintainability, and (9) security. An NCC internal and external message manual is appended to this report.

NT2 derived neuronal and astrocytic network signalling.

Directory of Open Access Journals (Sweden)

Eric J Hill

Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

Multi-Radio Mobile Device in Role of Hybrid Node Between WiFi and LTE networks

Directory of Open Access Journals (Sweden)

Pavel Masek

2015-05-01

Full Text Available With the ubiquitous wireless network coverage, Machine-Type Communications (MTC is emerging to enable data transfers using devices/sensors without need for human interaction. In this paper we, we introduce a comprehensive simulation scenario for modeling and analysis for heterogeneous MTC. We demonstrate the most expected scenario of MTC communication using the IEEE 802.11 standard for direct communication between sensors and for transmitting data between individual sensor and Machine-Type Communication Gateway (MTCG. The MTCG represents the hybrid node serving as bridge between two heterogeneous networks (WiFi and LTE. Following the idea of hybrid node, two active interfaces must be implemented on this node together with mechanism for handling the incoming traffic (from WiFi network to LTE network. As a simulation tool, the Network Simulator 3 (NS-3 with implemented LTE/EPC Network Simulator (LENA framework was used. The major contribution of this paper therefore lies in the implementation of logic for interconnection of two heterogeneous networks in simulation environment NS-3.

Computational study on the inhibitor binding mode and allosteric regulation mechanism in hepatitis C virus NS3/4A protein.

Directory of Open Access Journals (Sweden)

Weiwei Xue

Full Text Available HCV NS3/4A protein is an attractive therapeutic target responsible for harboring serine protease and RNA helicase activities during the viral replication. Small molecules binding at the interface between the protease and helicase domains can stabilize the closed conformation of the protein and thus block the catalytic function of HCV NS3/4A protein via an allosteric regulation mechanism. But the detailed mechanism remains elusive. Here, we aimed to provide some insight into the inhibitor binding mode and allosteric regulation mechanism of HCV NS3/4A protein by using computational methods. Four simulation systems were investigated. They include: apo state of HCV NS3/4A protein, HCV NS3/4A protein in complex with an allosteric inhibitor and the truncated form of the above two systems. The molecular dynamics simulation results indicate HCV NS3/4A protein in complex with the allosteric inhibitor 4VA adopts a closed conformation (inactive state, while the truncated apo protein adopts an open conformation (active state. Further residue interaction network analysis suggests the communication of the domain-domain interface play an important role in the transition from closed to open conformation of HCV NS3/4A protein. However, the inhibitor stabilizes the closed conformation through interaction with several key residues from both the protease and helicase domains, including His57, Asp79, Asp81, Asp168, Met485, Cys525 and Asp527, which blocks the information communication between the functional domains interface. Finally, a dynamic model about the allosteric regulation and conformational changes of HCV NS3/4A protein was proposed and could provide fundamental insights into the allosteric mechanism of HCV NS3/4A protein function regulation and design of new potent inhibitors.

CAISSON: Interconnect Network Simulator

Science.gov (United States)

Springer, Paul L.

2006-01-01

Cray response to HPCS initiative. Model future petaflop computer interconnect. Parallel discrete event simulation techniques for large scale network simulation. Built on WarpIV engine. Run on laptop and Altix 3000. Can be sized up to 1000 simulated nodes per host node. Good parallel scaling characteristics. Flexible: multiple injectors, arbitration strategies, queue iterators, network topologies.

Splitting Strategy for Simulating Genetic Regulatory Networks

Directory of Open Access Journals (Sweden)

Xiong You

2014-01-01

Full Text Available The splitting approach is developed for the numerical simulation of genetic regulatory networks with a stable steady-state structure. The numerical results of the simulation of a one-gene network, a two-gene network, and a p53-mdm2 network show that the new splitting methods constructed in this paper are remarkably more effective and more suitable for long-term computation with large steps than the traditional general-purpose Runge-Kutta methods. The new methods have no restriction on the choice of stepsize due to their infinitely large stability regions.

Active queue management controller design for TCP communication networks: Variable structure control approach

International Nuclear Information System (INIS)

Chen, C.-K.; Liao, T.-L.; Yan, J.-J.

2009-01-01

On the basis of variable structure control (VSC), an active queue management (AQM) controller is presented for a class of TCP communication networks. In the TCP/IP networks, the packet drop probability is limited between 0 and 1. Therefore, we modeled TCP/AQM as a rate-based non-linear system with a saturated input. The objective of the VSC-based AQM controller is to achieve the desired queue size and to guarantee the asymptotic stability of the closed-loop TCP non-linear system with saturated input. The performance and effectiveness of the proposed control law are then validated for different network scenarios through numerical simulations in both MATLAB and Network Simulator-2 (NS-2). Both sets of simulation results have confirmed that the proposed scheme outperforms other AQM schemes.

Active queue management controller design for TCP communication networks: Variable structure control approach

Energy Technology Data Exchange (ETDEWEB)

Chen, C.-K. [Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan (China); Liao, T.-L. [Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan (China)], E-mail: tlliao@mail.ncku.edu; Yan, J.-J. [Department of Computer and Communication, Shu-Te University, Kaohsiung 824, Taiwan (China)

2009-04-15

On the basis of variable structure control (VSC), an active queue management (AQM) controller is presented for a class of TCP communication networks. In the TCP/IP networks, the packet drop probability is limited between 0 and 1. Therefore, we modeled TCP/AQM as a rate-based non-linear system with a saturated input. The objective of the VSC-based AQM controller is to achieve the desired queue size and to guarantee the asymptotic stability of the closed-loop TCP non-linear system with saturated input. The performance and effectiveness of the proposed control law are then validated for different network scenarios through numerical simulations in both MATLAB and Network Simulator-2 (NS-2). Both sets of simulation results have confirmed that the proposed scheme outperforms other AQM schemes.

Giant magnons under NS-NS and Melvin fields

International Nuclear Information System (INIS)

Huang, W.-H.

2006-01-01

The giant magnon is a rotating spiky string configuration which has the same dispersion relation between the energy and angular momentum as that of a spin magnon. In this paper we investigate the effects of the NS-NS and Melvin fields on the giant magnon. We first analyze the energy and angular momenta of the two-spin spiky D-string moving on the AdS 3 x S 1 with the NS-NS field. Due to the infinite boundary of the AdS spacetime the D-string solution will extend to infinity and it appears the divergences. After adding the counter terms we obtain the dispersion relation of the corresponding giant magnon. The result shows that there will appear a prefactor before the angular momentum, in addition to some corrections in the sine function. We also see that the spiky profile of a rotating D-string plays an important role in mapping it to a spin magnon. We next investigate the energy and angular momentum of the one-spin spiky fundamental string moving on the R x S 2 with the electric or magnetic Melvin field. The dispersion relation of the corresponding deformed giant magnon is also obtained. We discuss some properties of the correction terms and their relations to the spin chain with deformations

Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways

International Nuclear Information System (INIS)

Kim, Kyoung Mi; Kwon, Shi-Nae; Kang, Ju-Il; Lee, Song Hee; Jang, Sung Key; Ahn, Byung-Yoon; Kim, Yoon Ki

2007-01-01

Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway

Message network simulation

OpenAIRE

Shih, Kuo-Tung

1990-01-01

Approved for public release, distribution is unlimited This thesis presents a computer simulation of a multinode data communication network using a virtual network model to determine the effects of various system parameters on overall network performance. Lieutenant Commander, Republic of China (Taiwan) Navy

Process Performances of 2 ns Pulsed Discharge Plasma

Science.gov (United States)

Matsumoto, Takao; Wang, Douyan; Namihira, Takao; Akiyama, Hidenori

2011-08-01

Pulsed discharge plasmas have been used to treat exhaust gases. Since pulse duration and the rise time of applied voltage to the discharge electrode has a strong influence on the energy efficiency of pollutant removal, the development of a short-pulse generator is of paramount importance for practical applications. In this work, it is demonstrated that the non thermal plasma produced by the 2 ns pulsed discharge has a higher energy efficiency than the 5 ns pulsed discharge plasma for NO removal and ozone generation. Typically, the NO removal efficiency was 1.0 mol kW-1 h-1 for 70% NO removal (initial NO concentration = 200 ppm, gas flow = 10 L/min). Meanwhile, the ozone yield was 500 g kW-1 h-1 for 20 g/m3 ozone concentration in the case of oxygen feeding. These energy efficiencies are the highest in the literature.

Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors.

Science.gov (United States)

Saleh, Noha A; Elshemey, Wael M

2017-10-15

Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production.

Science.gov (United States)

Gouklani, H; Beyer, C; Drummer, H; Gowans, E J; Netter, H J; Haqshenas, G

2013-04-01

The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full-length p7 protein of the HCV-A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild-type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV. © 2012 Blackwell Publishing Ltd.

Research of G3-PLC net self-organization processes in the NS-3 modeling framework

Science.gov (United States)

Pospelova, Irina; Chebotayev, Pavel; Klimenko, Aleksey; Myakochin, Yuri; Polyakov, Igor; Shelupanov, Alexander; Zykov, Dmitriy

2017-11-01

When modern infocommunication networks are designed, the combination of several data transfer channels is widely used. It is necessary for the purposes of improvement in quality and robustness of communication. Communication systems based on more than one data transfer channel are named heterogeneous communication systems. For the design of a heterogeneous network, the most optimal solution is the use of mesh technology. Mesh technology ensures message delivery to the destination under conditions of unpredictable interference environment situation in each of two channels. Therewith, one of the high-priority problems is the choice of a routing protocol when the mesh networks are designed. An important design stage for any computer network is modeling. Modeling allows us to design a few different variants of design solutions and also to compute all necessary functional specifications for each of these solutions. As a result, it allows us to reduce costs for the physical realization of a network. In this article the research of dynamic routing in the NS3 simulation modeling framework is presented. The article contains an evaluation of simulation modeling applicability in solving the problem of heterogeneous networks design. Results of modeling may be afterwards used for physical realization of this kind of networks.

Impact of the ceramide subspecies on the nanostructure of stratum corneum lipids using neutron scattering and molecular dynamics simulations. Part I: impact of CER[NS].

Science.gov (United States)

Schmitt, Thomas; Gupta, Rakesh; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Hauß, Thomas; Rai, Beena; Neubert, Reinhard H H

2018-05-30

For this study mixtures based on the ceramides [NS] (NS = non-hydroxy-sphingosine) and [AP] (AP = α-hydroxy-phytosphingosine) in a 2:1 and 1:2 ratio, together with cholesterol and lignoceric acid, were investigated. These mixtures are modelling the uppermost skin layer, the stratum corneum. Neutron diffraction, utilizing specifically deuterated ceramide molecules, was used to obtain a maximum amount of experimental detail. Highly detailed molecular dynamics simulations were used to generate even more information from the experimental data. It was possible to observe a single lamellar phase for both systems. They had a lamellar repeat distance of 5.43 ± 0.05 nm for the [NS]/[AP] 2:1 and a slightly shorter one of 5.34 ± 0.05 nm for the 1:2 system. The structure and water content was uninfluenced by excess humidity. Both the experimental and simulation data indicated slightly tilted ceramides, with their C24 chains overlapping in the lamellar mid-plane. This arrangement is well comparable to systems investigated before. The structure of both systems, except for the differing repeat distance, looks similar at first. However, on a smaller scale there were various distinct differences, demonstrating only low redundancy between the different ceramide species, despite only minor chemical differences. The mainly ceramide [AP] determined 1:2 system has a slightly smaller repeat distance. This is a result of a tighter arrangement of the lipids chain along the bilayer normal and increased overlapping of the long chains in the lamellar middle. For the CER[NS] some novel features could be shown, despite it being the overall most investigated ceramide. These include the low adaptability to changed lateral interactions, leading to an increased chain opening. This effect could explain its low miscibility with other lipids. The investigated model systems allows it to directly compare results from the literature which have used ceramide [NS] to the most recent

Wireless network simulation - Your window on future network performance

NARCIS (Netherlands)

Fledderus, E.

2005-01-01

The paper describes three relevant perspectives on current wireless simulation practices. In order to obtain the key challenges for future network simulations, the characteristics of "beyond 3G" networks are described, including their impact on simulation.

Interfacing Network Simulations and Empirical Data

Science.gov (United States)

2009-05-01

contraceptive innovations in the Cameroon. He found that real-world adoption rates did not follow simulation models when the network relationships were...Analysis of the Coevolution of Adolescents ’ Friendship Networks, Taste in Music, and Alcohol Consumption. Methodology, 2: 48-56. Tichy, N.M., Tushman

Simulating synchronization in neuronal networks

Science.gov (United States)

Fink, Christian G.

2016-06-01

We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.

GNS3 network simulation guide

CERN Document Server

Welsh, Chris

2013-01-01

GNS3 Network Simulation Guide is an easy-to-follow yet comprehensive guide which is written in a tutorial format helping you grasp all the things you need for accomplishing your certification or simulation goal. If you are a networking professional who wants to learn how to simulate networks using GNS3, this book is ideal for you. The introductory examples within the book only require minimal networking knowledge, but as the book progresses onto more advanced topics, users will require knowledge of TCP/IP and routing.

Isotachophoresis of proteins in a networked microfluidic chip: experiment and 2-D simulation.

Science.gov (United States)

Cui, Huanchun; Dutta, Prashanta; Ivory, Cornelius F

2007-04-01

This paper reports both the experimental application and 2-D simulation of ITP of proteins in a networked microfluidic chip. Experiments demonstrate that a mixture of three fluorescent proteins can be concentrated and stacked into adjacent zones of pure protein under a constant voltage of 100 V over a 2 cm long microchannel. Measurements of the isotachophoretic velocity of the moving zones demonstrates that, during ITP under a constant voltage, the zone velocity decreases as more of the channel is occupied by the terminating electrolyte. A 2-D ITP model based on the Nernst-Planck equations illustrates the stacking and separation features of ITP using simulations of three virtual proteins. The self-sharpening behavior of ITP zones dispersed by a T-junction is clearly demonstrated both by experiment and by simulation. Comparison of 2-D simulations of ITP and zone electrophoresis (ZE) confirms that ZE lacks the ability to resharpen protein zones after they pass through a T-junction.

Interference of transcription across H-NS binding sites and repression by H-NS.

Science.gov (United States)

Rangarajan, Aathmaja Anandhi; Schnetz, Karin

2018-05-01

Nucleoid-associated protein H-NS represses transcription by forming extended DNA-H-NS complexes. Repression by H-NS operates mostly at the level of transcription initiation. Less is known about how DNA-H-NS complexes interfere with transcription elongation. In vitro H-NS has been shown to enhance RNA polymerase pausing and to promote Rho-dependent termination, while in vivo inhibition of Rho resulted in a decrease of the genome occupancy by H-NS. Here we show that transcription directed across H-NS binding regions relieves H-NS (and H-NS/StpA) mediated repression of promoters in these regions. Further, we observed a correlation of transcription across the H-NS-bound region and de-repression. The data suggest that the transcribing RNA polymerase is able to remodel the H-NS complex and/or dislodge H-NS from the DNA and thus relieve repression. Such an interference of transcription and H-NS mediated repression may imply that poorly transcribed AT-rich loci are prone to be repressed by H-NS, while efficiently transcribed loci escape repression. © 2018 John Wiley & Sons Ltd.

Stochastic simulation of karst conduit networks

Science.gov (United States)

Pardo-Igúzquiza, Eulogio; Dowd, Peter A.; Xu, Chaoshui; Durán-Valsero, Juan José

2012-01-01

Karst aquifers have very high spatial heterogeneity. Essentially, they comprise a system of pipes (i.e., the network of conduits) superimposed on rock porosity and on a network of stratigraphic surfaces and fractures. This heterogeneity strongly influences the hydraulic behavior of the karst and it must be reproduced in any realistic numerical model of the karst system that is used as input to flow and transport modeling. However, the directly observed karst conduits are only a small part of the complete karst conduit system and knowledge of the complete conduit geometry and topology remains spatially limited and uncertain. Thus, there is a special interest in the stochastic simulation of networks of conduits that can be combined with fracture and rock porosity models to provide a realistic numerical model of the karst system. Furthermore, the simulated model may be of interest per se and other uses could be envisaged. The purpose of this paper is to present an efficient method for conditional and non-conditional stochastic simulation of karst conduit networks. The method comprises two stages: generation of conduit geometry and generation of topology. The approach adopted is a combination of a resampling method for generating conduit geometries from templates and a modified diffusion-limited aggregation method for generating the network topology. The authors show that the 3D karst conduit networks generated by the proposed method are statistically similar to observed karst conduit networks or to a hypothesized network model. The statistical similarity is in the sense of reproducing the tortuosity index of conduits, the fractal dimension of the network, the direction rose of directions, the Z-histogram and Ripley's K-function of the bifurcation points (which differs from a random allocation of those bifurcation points). The proposed method (1) is very flexible, (2) incorporates any experimental data (conditioning information) and (3) can easily be modified when

Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

International Nuclear Information System (INIS)

Asafi, M S; Tekpinar, M; Yildirim, A

2016-01-01

Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated. (paper)

Prioritizing Signaling Information Transmission in Next Generation Networks

Directory of Open Access Journals (Sweden)

Jasmina Baraković

2011-01-01

Full Text Available Next generation transport network is characterized by the use of in-band signaling, where Internet Protocol (IP packets carrying signaling or media information are mixed in transmission. Since transport resources are limited, when any segment of access or core network is congested, IP packets carrying signaling information may be discarded. As a consequence, it may be impossible to implement reachability and quality of service (QoS. Since present approaches are insufficient to completely address this problem, a novel approach is proposed, which is based on prioritizing signaling information transmission. To proof the concept, a simulation study was performed using Network Simulator version 2 (ns-2 and independently developed Session Initiation Protocol (SIP module. The obtained results were statistically processed using Statistical Package for the Social Sciences (SPSS version 15.0. Summarizing our research results, several issues are identified for future work.

Cross-Layer Design Approach for Power Control in Mobile Ad Hoc Networks

Directory of Open Access Journals (Sweden)

A. Sarfaraz Ahmed

2015-03-01

Full Text Available In mobile ad hoc networks, communication among mobile nodes occurs through wireless medium The design of ad hoc network protocol, generally based on a traditional “layered approach”, has been found ineffective to deal with receiving signal strength (RSS-related problems, affecting the physical layer, the network layer and transport layer. This paper proposes a design approach, deviating from the traditional network design, toward enhancing the cross-layer interaction among different layers, namely physical, MAC and network. The Cross-Layer design approach for Power control (CLPC would help to enhance the transmission power by averaging the RSS values and to find an effective route between the source and the destination. This cross-layer design approach was tested by simulation (NS2 simulator and its performance over AODV was found to be better.

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

Directory of Open Access Journals (Sweden)

Sujuan Chen

2017-06-01

Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

Science.gov (United States)

Dong, Hongping; Chang, David C.; Hua, Maggie Ho Chia; Lim, Siew Pheng; Chionh, Yok Hian; Hia, Fabian; Lee, Yie Hou; Kukkaro, Petra; Lok, Shee-Mei; Dedon, Peter C.; Shi, Pei-Yong

2012-01-01

RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2′-O methyltransferase activities that are required for the formation of 5′ type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2′-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2′-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2′-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2′-O-methyladenosine. The 2′-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine) pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2′-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2′-O methylation of internal adenosine of

Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach

Directory of Open Access Journals (Sweden)

Noorsaadah Abd. Rahman

2011-02-01

Full Text Available Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA. The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA with various substituents.

Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen.

Science.gov (United States)

Alves, Rúbens Prince Dos Santos; Pereira, Lennon Ramos; Fabris, Denicar Lina Nascimento; Salvador, Felipe Scassi; Santos, Robert Andreata; Zanotto, Paolo Marinho de Andrade; Romano, Camila Malta; Amorim, Jaime Henrique; Ferreira, Luís Carlos de Souza

2016-06-01

Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein-protein interactions.

Science.gov (United States)

Yates, Christopher M; Sternberg, Michael J E

2013-11-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. © 2013.

Development and application of hepatitis C reporter viruses with genotype 1 to 7 core-nonstructural protein 2 (NS2) expressing fluorescent proteins or luciferase in modified JFH1 NS5A

DEFF Research Database (Denmark)

Gottwein, Judith M; Jensen, Tanja B; Mathiesen, Christian K

2011-01-01

to 2a(J6) tagged with EGFP, DsRed-Express2, mCherry, or Renilla luciferase (RLuc), yielding peak supernatant infectivity titers of 4 to 5 log(10) focus-forming units (FFU)/ml. 2a(J6) with ¿40 or ¿25 was fully viable in Huh7.5 cells. In human liver chimeric mice, 2a(J6)-EGFP¿40 acquired various...... deletions in EGFP, while 2a(J6)¿40 did not show an impaired viability. We further developed panels of JFH1-based genotype 1 to 7 core-NS2 recombinants expressing EGFP- or RLuc-NS5A¿40 fusion proteins. In cell culture, the different EGFP recombinants showed growth characteristics comparable to those...

Identification of human hnRNP C1/C2 as a dengue virus NS1-interacting protein

International Nuclear Information System (INIS)

Noisakran, Sansanee; Sengsai, Suchada; Thongboonkerd, Visith; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Chen, Shui-Tein; Puttikhunt, Chunya

2008-01-01

Dengue virus nonstructural protein 1 (NS1) is a key glycoprotein involved in the production of infectious virus and the pathogenesis of dengue diseases. Very little is known how NS1 interacts with host cellular proteins and functions in dengue virus-infected cells. This study aimed at identifying NS1-interacting host cellular proteins in dengue virus-infected cells by employing co-immunoprecipitation, two-dimensional gel electrophoresis, and mass spectrometry. Using lysates of dengue virus-infected human embryonic kidney cells (HEK 293T), immunoprecipitation with an anti-NS1 monoclonal antibody revealed eight isoforms of dengue virus NS1 and a 40-kDa protein, which was subsequently identified by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) as human heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Further investigation by co-immunoprecipitation and co-localization confirmed the association of hnRNP C1/C2 and dengue virus NS1 proteins in dengue virus-infected cells. Their interaction may have implications in virus replication and/or cellular responses favorable to survival of the virus in host cells

Mapping of Leaf Rust Resistance Genes and Molecular Characterization of the 2NS/2AS Translocation in the Wheat Cultivar Jagger.

Science.gov (United States)

Xue, Shulin; Kolmer, James A; Wang, Shuwen; Yan, Liuling

2018-04-19

Winter wheat cultivar 'Jagger' was recently found to have an alien chromosomal segment 2NS that has Lr37 , a gene conferring resistance against leaf rust caused by Puccinia triticina The objective of this study was to map and characterize the gene(s) for seedling leaf rust resistance in Jagger. The recombinant inbred line (RIL) population of Jagger × '2174' was inoculated with leaf rust pathogen THBJG and BBBDB, and evaluated for infection type (IT) response. A major quantitative trait locus (QTL) for THBJG and BBBDB was coincidently mapped to chromosome arm 2AS, and the QTL accounted for 56.6% - 66.2% of total phenotypic variation in infection type (IT) response to THBJG, and 72.1% - 86.9% to BBBDB. The causal gene for resistance to these rust races was mapped to the 2NS segment in Jagger. The 2NS segment was located in a region of approximately 27.8 Mb starting from the telomere of chromosome arm 2AS, based on the sequences of the A genome in tetraploid wheat. The Lr17a gene on chromosome arm 2AS was delimited to 3.1 Mb in the genomic region, which was orthologous to the 2NS segment. Therefore, the Lr37 gene in the 2NS segment can be pyramided with other effective resistance genes, rather than Lr17a in wheat, to improve resistance to rust diseases. Copyright © 2018, G3: Genes, Genomes, Genetics.

Secure Data Aggregation in Wireless Sensor Network-Fujisaki Okamoto(FO) Authentication Scheme against Sybil Attack.

Science.gov (United States)

Nirmal Raja, K; Maraline Beno, M

2017-07-01

In the wireless sensor network(WSN) security is a major issue. There are several network security schemes proposed in research. In the network, malicious nodes obstruct the performance of the network. The network can be vulnerable by Sybil attack. When a node illicitly assertions multiple identities or claims fake IDs, the WSN grieves from an attack named Sybil attack. This attack threatens wireless sensor network in data aggregation, synchronizing system, routing, fair resource allocation and misbehavior detection. Henceforth, the research is carried out to prevent the Sybil attack and increase the performance of the network. This paper presents the novel security mechanism and Fujisaki Okamoto algorithm and also application of the work. The Fujisaki-Okamoto (FO) algorithm is ID based cryptographic scheme and gives strong authentication against Sybil attack. By using Network simulator2 (NS2) the scheme is simulated. In this proposed scheme broadcasting key, time taken for different key sizes, energy consumption, Packet delivery ratio, Throughput were analyzed.

Bitcoin network simulator data explotation

OpenAIRE

Berini Sarrias, Martí

2015-01-01

This project starts with a brief introduction to the concepts of Bitcoin and blockchain, followed by the description of the di erent known attacks to the Bitcoin network. Once reached this point, the basic structure of the Bitcoin network simulator is presented. The main objective of this project is to help in the security assessment of the Bitcoin network. To accomplish that, we try to identify useful metrics, explain them and implement them in the corresponding simulator modules, aiming to ...

Broadband Fan Noise Prediction System for Turbofan Engines. Volume 2; BFaNS User's Manual and Developer's Guide

Science.gov (United States)

Morin, Bruce L.

2010-01-01

Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the second volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User s Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running BFaNS. It concludes with technical documentation of the BFaNS computer program.

Network Signaling Channel for Improving ZigBee Performance in Dynamic Cluster-Tree Networks

Directory of Open Access Journals (Sweden)

D. Hämäläinen

2008-03-01

Full Text Available ZigBee is one of the most potential standardized technologies for wireless sensor networks (WSNs. Yet, sufficient energy-efficiency for the lowest power WSNs is achieved only in rather static networks. This severely limits the applicability of ZigBee in outdoor and mobile applications, where operation environment is harsh and link failures are common. This paper proposes a network channel beaconing (NCB algorithm for improving ZigBee performance in dynamic cluster-tree networks. NCB reduces the energy consumption of passive scans by dedicating one frequency channel for network beacon transmissions and by energy optimizing their transmission rate. According to an energy analysis, the power consumption of network maintenance operations reduces by 70%–76% in dynamic networks. In static networks, energy overhead is negligible. Moreover, the service time for data routing increases up to 37%. The performance of NCB is validated by ns-2 simulations. NCB can be implemented as an extension on MAC and NWK layers and it is fully compatible with ZigBee.

Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1.

Science.gov (United States)

Ahlstedt, Jonatan; Förnvik, Karolina; Zolfaghari, Shaian; Kwak, Dongoh; Hammarström, Lars G J; Ernfors, Patrik; Salford, Leif G; Redebrandt, Henrietta Nittby

2018-02-02

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro . Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.

Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets.

Science.gov (United States)

Lulu, S Sajitha; Thabitha, A; Vino, S; Priya, A Mohana; Rout, Madhusmita

2016-01-01

Nonstructural proteins of hepatitis C virus had drawn much attention for the scientific fraternity in drug discovery due to its important role in the disease. 3D structure of the protein was predicted using molecular modelling protocol. Docking studies of 10 medicinal plant compounds and three drugs available in the market (control) with NS2 protease were employed by using rigid docking approach of AutoDock 4.2. Among the molecules tested for docking study, naringenin and quercetin revealed minimum binding energy of - 7.97 and - 7.95 kcal/mol with NS2 protease. All the ligands were docked deeply within the binding pocket region of the protein. The docking study results showed that these compounds are potential inhibitors of the target; and also all these docked compounds have good inhibition constant, vdW+Hbond+desolv energy with best RMSD value.

Novel Flexible Transparent Conductive Films with Enhanced Chemical and Electromechanical Sustainability: TiO2 Nanosheet-Ag Nanowire Hybrid.

Science.gov (United States)

Sohn, Hiesang; Kim, Seyun; Shin, Weonho; Lee, Jong Min; Lee, Hyangsook; Yun, Dong-Jin; Moon, Kyoung-Seok; Han, In Taek; Kwak, Chan; Hwang, Seong-Ju

2018-01-24

Flexible transparent conductive films (TCFs) of TiO 2 nanosheet (TiO 2 NS) and silver nanowire (Ag NW) network hybrid were prepared through a simple and scalable solution-based process. The as-formed TiO 2 NS-Ag NW hybrid TCF shows a high optical transmittance (TT: 97% (90.2% including plastic substrate)) and low sheet resistance (R s : 40 Ω/sq). In addition, the TiO 2 NS-Ag NW hybrid TCF exhibits a long-time chemical/aging and electromechanical stability. As for the chemical/aging stability, the hybrid TCF of Ag NW and TiO 2 NS reveals a retained initial conductivity (ΔR s /R s 4000%) or RuO 2 NS-Ag NW hybrid (ΔR s /R s > 200%). As corroborated by the density functional theory simulation, the superb chemical stability of TiO 2 NS-Ag NW hybrid is attributable to the unique role of TiO 2 NS as a barrier, which prevents Ag NW's chemical corrosion via the attenuated adsorption of sulfidation molecules (H 2 S) on TiO 2 NS. With respect to the electromechanical stability, in contrast to Ag NWs (ΔR/R 0 ∼ 152.9%), our hybrid TCF shows a limited increment of fractional resistivity (ΔR/R 0 ∼ 14.4%) after 200 000 cycles of the 1R bending test (strain: 6.7%) owing to mechanically welded Ag NW networks by TiO 2 NS. Overall, our unique hybrid of TiO 2 NS and Ag NW exhibits excellent electrical/optical properties and reliable chemical/electromechanical stabilities.

Boron tolerance in NS wheat lines

Directory of Open Access Journals (Sweden)

Brdar Milka

2006-01-01

Full Text Available Boron is an essential micronutrient for higher plants. Present in excessive amounts boron becomes toxic and can limit plant growth and yield. Suppression of root growth is one of the symptoms of boron toxicity in wheat. This study was undertaken to investigate the response of 10 perspective NS lines of wheat to high concentrations of boron. Analysis of root growth was done on young plants, germinated and grown in the presence of different concentrations of boric acid (0, 50,100 and 150 mg/1. Significant differences occurred between analyzed genotypes and treatments regarding root length. Average suppression of root growth was between 11,6 and 34,2%, for line NS 252/02 are even noted 61,4% longer roots at treatments in relation to the control. Lines with mean suppression of root growth less than 20% (NS 101/02, NS 138/01, NS 53/03 and NS 73/02 may be considered as boron tolerant. Spearmans coefficients showed high level of agreement regarding rang of root length for genotypes treated with 100 and 150 mg H3BO3/l.

50 ns Backup Solution

CERN Document Server

Kain, V; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

2014-01-01

The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed.

50 ns Backup Solution

International Nuclear Information System (INIS)

Kain, V; Arduini, G; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

2014-01-01

The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed

Airport Network Flow Simulator

Science.gov (United States)

1978-10-01

The Airport Network Flow Simulator is a FORTRAN IV simulation of the flow of air traffic in the nation's 600 commercial airports. It calculates for any group of selected airports: (a) the landing and take-off (Type A) delays; and (b) the gate departu...

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms

International Nuclear Information System (INIS)

Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

2011-01-01

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC 50 ) of <1 n, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC 50 =11–120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

Science.gov (United States)

Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

2018-04-27

Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

Energy Technology Data Exchange (ETDEWEB)

Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

2013-11-29

Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

Stochastic Characterization of Communication Network Latency for Wide Area Grid Control Applications.

Energy Technology Data Exchange (ETDEWEB)

Ameme, Dan Selorm Kwami [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Guttromson, Ross [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-10-01

This report characterizes communications network latency under various network topologies and qualities of service (QoS). The characterizations are probabilistic in nature, allowing deeper analysis of stability for Internet Protocol (IP) based feedback control systems used in grid applications. The work involves the use of Raspberry Pi computers as a proxy for a controlled resource, and an ns-3 network simulator on a Linux server to create an experimental platform (testbed) that can be used to model wide-area grid control network communications in smart grid. Modbus protocol is used for information transport, and Routing Information Protocol is used for dynamic route selection within the simulated network.

Stochastic Simulation of Biomolecular Reaction Networks Using the Biomolecular Network Simulator Software

National Research Council Canada - National Science Library

Frazier, John; Chusak, Yaroslav; Foy, Brent

2008-01-01

.... The software uses either exact or approximate stochastic simulation algorithms for generating Monte Carlo trajectories that describe the time evolution of the behavior of biomolecular reaction networks...

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus

Directory of Open Access Journals (Sweden)

Margit Mutso

2018-04-01

Full Text Available Infection by Chikungunya virus (CHIKV of the Old World alphaviruses (family Togaviridae in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP (nsP1, nsp2, nsP3 and nsP4 that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

Development and Characterization of a High Sensitivity Segmented Fast Neutron Spectrometer (FaNS-2).

Science.gov (United States)

Langford, T J; Beise, E J; Breuer, H; Heimbach, C R; Ji, G; Nico, J S

2016-01-01

We present the development of a segmented fast neutron spectrometer (FaNS-2) based upon plastic scintillator and 3 He proportional counters. It was designed to measure both the flux and spectrum of fast neutrons in the energy range of few MeV to 1 GeV. FaNS-2 utilizes capture-gated spectroscopy to identify neutron events and reject backgrounds. Neutrons deposit energy in the plastic scintillator before capturing on a 3 He nucleus in the proportional counters. Segmentation improves neutron energy reconstruction while the large volume of scintillator increases sensitivity to low neutron fluxes. A main goal of its design is to study comparatively low neutron fluxes, such as cosmogenic neutrons at the Earth's surface, in an underground environment, or from low-activity neutron sources. In this paper, we present details of its design and construction as well as its characterization with a calibrated 252 Cf source and monoenergetic neutron fields of 2.5 MeV and 14 MeV. Detected monoenergetic neutron spectra are unfolded using a Singular Value Decomposition method, demonstrating a 5% energy resolution at 14 MeV. Finally, we discuss plans for measuring the surface and underground cosmogenic neutron spectra with FaNS-2.

Exploring the molecular basis of dsRNA recognition by NS1 protein of influenza A virus using molecular dynamics simulation and free energy calculation.

Science.gov (United States)

Pan, Dabo; Sun, Huijun; Shen, Yulin; Liu, Huanxiang; Yao, Xiaojun

2011-12-01

The frequent outbreak of influenza pandemic and the limited available anti-influenza drugs highlight the urgent need for the development of new antiviral drugs. The dsRNA-binding surface of nonstructural protein 1 of influenza A virus (NS1A) is a promising target. The detailed understanding of NS1A-dsRNA interaction will be valuable for structure-based anti-influenza drug discovery. To characterize and explore the key interaction features between dsRNA and NS1A, molecular dynamics simulation combined with MM-GBSA calculations were performed. Based on the MM-GBSA calculations, we find that the intermolecular van der Waals interaction and the nonpolar solvation term provide the main driving force for the binding process. Meanwhile, 17 key residues from NS1A were identified to be responsible for the dsRNA binding. Compared with the wild type NS1A, all the studied mutants S42A, T49A, R38A, R35AR46A have obvious reduced binding free energies with dsRNA reflecting in the reduction of the polar and/or nonpolar interactions. In addition, the structural and energy analysis indicate the mutations have a small effect to the backbone structures but the loss of side chain interactions is responsible for the decrease of the binding affinity. The uncovering of NS1A-dsRNA recognition mechanism will provide some useful insights and new chances for the development of anti-influenza drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

The 2nd reactor core of the NS Otto Hahn

International Nuclear Information System (INIS)

Manthey, H.J.; Kracht, H.

1979-01-01

Details of the design of the 2nd reactor core are given, followed by a brief report summarising the operating experience gained with this 2nd core, as well as by an evaluation of measured data and statements concerning the usefulness of the knowledge gained for the development of future reactor cores. Quite a number of these data have been used to improve the concept and thus the specifications for the fuel elements of the 3rd core of the reactor of the NS Otto Hahn. (orig./HP) [de

The reliability of DIVA test based on M2e peptide exceed those based on HA2 or NS1 peptides

Directory of Open Access Journals (Sweden)

Simson Tarigan

2015-06-01

Full Text Available One of the most important disadvantage of vaccination against avian influenza is that it cannot protect vaccinated birds against infection. When vaccinated poultry are heavily exposed to the virus, prolonged, unrecognised, subclinical infection may persist on the farm. The condition can only be serologically monitored by a DIVA (differentiation of infected from vaccinated animals test, whereas conventional diagnostic tests cannot be used. The DIVA tests based on an antibody response following virus replication is the most appropriate approach. For H5N1 influenza such antibodies includes those to the M2e and NS1 proteins and an epitope on the HA2 subunit (HA_488-516. The purpose of this study was to compare the magnitude of the antibody response in chickens vaccinated and infected with an H5N1 virus strain. For that purpose, sera collected from naïve, vaccinated and infected birds, at 1, 2-3, ≥4 weeks post challenge were used. Antibodies were measured by ELISA using biotinylated synthetic peptides as coating antigens. The peptides used include four NS1 peptides corresponding to different regions of the NS1 protein and HA_488-516and M2e peptides. Peptides were coated onto microtitre plates either directly or via a streptavidin bridge. The results showed that vaccination did not cause antibody conversion to any of the peptides, where as challenged birds developed a high antibody response to M2e but, low response to the NS1 and HA2 peptides. Antibodies to the later peptides were detected only by the streptavidin-peptide ELISA. The ELISA based on NS1 or HA_488-516 peptides, therefore, are not reliable for use as DIVA test in H5N1 avian influenza virus infection

BioNSi: A Discrete Biological Network Simulator Tool.

Science.gov (United States)

Rubinstein, Amir; Bracha, Noga; Rudner, Liat; Zucker, Noga; Sloin, Hadas E; Chor, Benny

2016-08-05

Modeling and simulation of biological networks is an effective and widely used research methodology. The Biological Network Simulator (BioNSi) is a tool for modeling biological networks and simulating their discrete-time dynamics, implemented as a Cytoscape App. BioNSi includes a visual representation of the network that enables researchers to construct, set the parameters, and observe network behavior under various conditions. To construct a network instance in BioNSi, only partial, qualitative biological data suffices. The tool is aimed for use by experimental biologists and requires no prior computational or mathematical expertise. BioNSi is freely available at http://bionsi.wix.com/bionsi , where a complete user guide and a step-by-step manual can also be found.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

Directory of Open Access Journals (Sweden)

Markus M. Knodel

2018-01-01

Full Text Available Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

Science.gov (United States)

Knodel, Markus M; Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; Targett-Adams, Paul; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

Science.gov (United States)

Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-01

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles. PMID:29316722

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

KAUST Repository

Knodel, Markus

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Amino acids 16-275 of minute virus of mice NS1 include a domain that specifically binds (ACCA)2-3-containing DNA.

Science.gov (United States)

Mouw, M; Pintel, D J

1998-11-10

GST-NS1 purified from Escherichia coli and insect cells binds double-strand DNA in an (ACCA)2-3-dependent fashion under similar ionic conditions, independent of the presence of anti-NS1 antisera or exogenously supplied ATP and interacts with single-strand DNA and RNA in a sequence-independent manner. An amino-terminal domain (amino acids 1-275) of NS1 [GST-NS1(1-275)], representing 41% of the full-length NS1 molecule, includes a domain that binds double-strand DNA in a sequence-specific manner at levels comparable to full-length GST-NS1, as well as single-strand DNA and RNA in a sequence-independent manner. The deletion of 15 additional amino-terminal amino acids yielded a molecule [GST-NS1(1-275)] that maintained (ACCA)2-3-specific double-strand DNA binding; however, this molecule was more sensitive to increasing ionic conditions than full-length GST-NS1 and GST-NS1(1-275) and could not be demonstrated to bind single-strand nucleic acids. A quantitative filter binding assay showed that E. coli- and baculovirus-expressed GST-NS1 and E. coli GST-NS1(1-275) specifically bound double-strand DNA with similar equilibrium kinetics [as measured by their apparent equilibrium DNA binding constants (KD)], whereas GST-NS1(16-275) bound 4- to 8-fold less well. Copyright 1998 Academic Press.

Rationalizing meat consumption. The 4Ns.

Science.gov (United States)

Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

2015-08-01

Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simulation and Evaluation of Ethernet Passive Optical Network

Directory of Open Access Journals (Sweden)

Salah A. Jaro Alabady

2013-05-01

Full Text Available      This paper studies simulation and evaluation of Ethernet Passive Optical Network (EPON system, IEEE802.3ah based OPTISM 3.6 simulation program. The simulation program is used in this paper to build a typical ethernet passive optical network, and to evaluate the network performance when using the (1580, 1625 nm wavelength instead of (1310, 1490 nm that used in Optical Line Terminal (OLT and Optical Network Units (ONU's in system architecture of Ethernet passive optical network at different bit rate and different fiber optic length. The results showed enhancement in network performance by increase the number of nodes (subscribers connected to the network, increase the transmission distance, reduces the received power and reduces the Bit Error Rate (BER.   

Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

Science.gov (United States)

Yamanaka, Yuki; Winardhi, Ricksen S; Yamauchi, Erika; Nishiyama, So-Ichiro; Sowa, Yoshiyuki; Yan, Jie; Kawagishi, Ikuro; Ishihama, Akira; Yamamoto, Kaneyoshi

2018-06-15

The bacterial nucleoid-associated protein H-NS is a DNA-binding protein, playing a major role in gene regulation. To regulate transcription, H-NS silences genes, including horizontally acquired foreign genes. Escherichia coli H-NS is 137 residues long and consists of two discrete and independent structural domains: an N-terminal oligomerization domain and a C-terminal DNA-binding domain, joined by a flexible linker. The N-terminal oligomerization domain is composed of two dimerization sites, dimerization sites 1 and 2, which are both required for H-NS oligomerization, but the exact role of dimerization site 2 in gene silencing is unclear. To this end, we constructed a whole set of single amino acid substitution variants spanning residues 2 to 137. Using a well-characterized H-NS target, the slp promoter of the glutamic acid-dependent acid resistance (GAD) cluster promoters, we screened for any variants defective in gene silencing. Focusing on the function of dimerization site 2, we analyzed four variants, I70C/I70A and L75C/L75A, which all could actively bind DNA but are defective in gene silencing. Atomic force microscopy analysis of DNA-H-NS complexes revealed that all of these four variants formed condensed complexes on DNA, whereas WT H-NS formed rigid and extended nucleoprotein filaments, a conformation required for gene silencing. Single-molecule stretching experiments confirmed that the four variants had lost the ability to form stiffened filaments. We conclude that dimerization site 2 of H-NS plays a key role in the formation of rigid H-NS nucleoprotein filament structures required for gene silencing. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Fracture network modeling and GoldSim simulation support

International Nuclear Information System (INIS)

Sugita, Kenichirou; Dershowitz, W.

2005-01-01

During Heisei-16, Golder Associates provided support for JNC Tokai through discrete fracture network data analysis and simulation of the Mizunami Underground Research Laboratory (MIU), participation in Task 6 of the AEspoe Task Force on Modeling of Groundwater Flow and Transport, and development of methodologies for analysis of repository site characterization strategies and safety assessment. MIU support during H-16 involved updating the H-15 FracMan discrete fracture network (DFN) models for the MIU shaft region, and developing improved simulation procedures. Updates to the conceptual model included incorporation of 'Step2' (2004) versions of the deterministic structures, and revision of background fractures to be consistent with conductive structure data from the DH-2 borehole. Golder developed improved simulation procedures for these models through the use of hybrid discrete fracture network (DFN), equivalent porous medium (EPM), and nested DFN/EPM approaches. For each of these models, procedures were documented for the entire modeling process including model implementation, MMP simulation, and shaft grouting simulation. Golder supported JNC participation in Task 6AB, 6D and 6E of the AEspoe Task Force on Modeling of Groundwater Flow and Transport during H-16. For Task 6AB, Golder developed a new technique to evaluate the role of grout in performance assessment time-scale transport. For Task 6D, Golder submitted a report of H-15 simulations to SKB. For Task 6E, Golder carried out safety assessment time-scale simulations at the block scale, using the Laplace Transform Galerkin method. During H-16, Golder supported JNC's Total System Performance Assessment (TSPA) strategy by developing technologies for the analysis of the use site characterization data in safety assessment. This approach will aid in the understanding of the use of site characterization to progressively reduce site characterization uncertainty. (author)

Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

Energy Technology Data Exchange (ETDEWEB)

Kumar, Ambuj [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Purohit, Rituraj, E-mail: riturajpurohit@gmail.com [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

2012-10-15

Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R{sub g}), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

International Nuclear Information System (INIS)

Kumar, Ambuj; Purohit, Rituraj

2012-01-01

Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R g ), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

Programmable multi-node quantum network design and simulation

Science.gov (United States)

Dasari, Venkat R.; Sadlier, Ronald J.; Prout, Ryan; Williams, Brian P.; Humble, Travis S.

2016-05-01

Software-defined networking offers a device-agnostic programmable framework to encode new network functions. Externally centralized control plane intelligence allows programmers to write network applications and to build functional network designs. OpenFlow is a key protocol widely adopted to build programmable networks because of its programmability, flexibility and ability to interconnect heterogeneous network devices. We simulate the functional topology of a multi-node quantum network that uses programmable network principles to manage quantum metadata for protocols such as teleportation, superdense coding, and quantum key distribution. We first show how the OpenFlow protocol can manage the quantum metadata needed to control the quantum channel. We then use numerical simulation to demonstrate robust programmability of a quantum switch via the OpenFlow network controller while executing an application of superdense coding. We describe the software framework implemented to carry out these simulations and we discuss near-term efforts to realize these applications.

MATLAB Simulation of Gradient-Based Neural Network for Online Matrix Inversion

Science.gov (United States)

Zhang, Yunong; Chen, Ke; Ma, Weimu; Li, Xiao-Dong

This paper investigates the simulation of a gradient-based recurrent neural network for online solution of the matrix-inverse problem. Several important techniques are employed as follows to simulate such a neural system. 1) Kronecker product of matrices is introduced to transform a matrix-differential-equation (MDE) to a vector-differential-equation (VDE); i.e., finally, a standard ordinary-differential-equation (ODE) is obtained. 2) MATLAB routine "ode45" is introduced to solve the transformed initial-value ODE problem. 3) In addition to various implementation errors, different kinds of activation functions are simulated to show the characteristics of such a neural network. Simulation results substantiate the theoretical analysis and efficacy of the gradient-based neural network for online constant matrix inversion.

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.

Science.gov (United States)

Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

2011-07-01

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC(50)) of MPLW515L mutations or the TEL-JAK2 fusion gene; IC(50)=11-120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs.

LANES - LOCAL AREA NETWORK EXTENSIBLE SIMULATOR

Science.gov (United States)

Gibson, J.

1994-01-01

The Local Area Network Extensible Simulator (LANES) provides a method for simulating the performance of high speed local area network (LAN) technology. LANES was developed as a design and analysis tool for networking on board the Space Station. The load, network, link and physical layers of a layered network architecture are all modeled. LANES models to different lower-layer protocols, the Fiber Distributed Data Interface (FDDI) and the Star*Bus. The load and network layers are included in the model as a means of introducing upper-layer processing delays associated with message transmission; they do not model any particular protocols. FDDI is an American National Standard and an International Organization for Standardization (ISO) draft standard for a 100 megabit-per-second fiber-optic token ring. Specifications for the LANES model of FDDI are taken from the Draft Proposed American National Standard FDDI Token Ring Media Access Control (MAC), document number X3T9.5/83-16 Rev. 10, February 28, 1986. This is a mature document describing the FDDI media-access-control protocol. Star*Bus, also known as the Fiber Optic Demonstration System, is a protocol for a 100 megabit-per-second fiber-optic star-topology LAN. This protocol, along with a hardware prototype, was developed by Sperry Corporation under contract to NASA Goddard Space Flight Center as a candidate LAN protocol for the Space Station. LANES can be used to analyze performance of a networking system based on either FDDI or Star*Bus under a variety of loading conditions. Delays due to upper-layer processing can easily be nullified, allowing analysis of FDDI or Star*Bus as stand-alone protocols. LANES is a parameter-driven simulation; it provides considerable flexibility in specifying both protocol an run-time parameters. Code has been optimized for fast execution and detailed tracing facilities have been included. LANES was written in FORTRAN 77 for implementation on a DEC VAX under VMS 4.6. It consists of two

Simulations of biopolymer networks under shear

NARCIS (Netherlands)

Huisman, Elisabeth Margaretha

2011-01-01

In this thesis we present a new method to simulate realistic three-dimensional networks of biopolymers under shear. These biopolymer networks are important for the structural functions of cells and tissues. We use the method to analyze these networks under shear, and consider the elastic modulus,

Network Modeling and Simulation A Practical Perspective

CERN Document Server

Guizani, Mohsen; Khan, Bilal

2010-01-01

Network Modeling and Simulation is a practical guide to using modeling and simulation to solve real-life problems. The authors give a comprehensive exposition of the core concepts in modeling and simulation, and then systematically address the many practical considerations faced by developers in modeling complex large-scale systems. The authors provide examples from computer and telecommunication networks and use these to illustrate the process of mapping generic simulation concepts to domain-specific problems in different industries and disciplines. Key features: Provides the tools and strate

Constraints of nonresponding flows based on cross layers in the networks

Science.gov (United States)

Zhou, Zhi-Chao; Xiao, Yang; Wang, Dong

2016-02-01

In the active queue management (AQM) scheme, core routers cannot manage and constrain user datagram protocol (UDP) data flows by the sliding window control mechanism in the transport layer due to the nonresponsive nature of such traffic flows. However, the UDP traffics occupy a large part of the network service nowadays which brings a great challenge to the stability of the more and more complex networks. To solve the uncontrollable problem, this paper proposes a cross layers random early detection (CLRED) scheme, which can control the nonresponding UDP-like flows rate effectively when congestion occurs in the access point (AP). The CLRED makes use of the MAC frame acknowledgement (ACK) transmitting congestion information to the sources nodes and utilizes the back-off windows of the MAC layer throttling data rate. Consequently, the UDP-like flows data rate can be restrained timely by the sources nodes in order to alleviate congestion in the complex networks. The proposed CLRED can constrain the nonresponsive flows availably and make the communication expedite, so that the network can sustain stable. The simulation results of network simulator-2 (NS2) verify the proposed CLRED scheme.

Optimization of speed-up network component values for the 30 Ω resistively terminated prototype kicker magnet

International Nuclear Information System (INIS)

Barnes, M.J.; Wait, G.D.

1993-01-01

Kicker magnets are required for all ring-to-ring transfers in the 5 rings of the proposed KAON factory synchrotron. The kick must rise from 1% to 99% of full strength during the time interval of gaps created in the beam (80 ns to 160 ns) so that the beam can be extracted with minimum losses. In order to achieve the specified rise-time and open-quote flatness close-quote for the kick it is necessary to utilize speed-up networks, comprising a capacitor and a resistor, in the electrical circuit. Speed-up networks may be connected electrically on both the input and output of the kicker magnet. In addition it is advantageous to connect a open-quote speed-up close-quote network on the input of the resistive terminator(s). A sequence which may minimize the number of mathematical simulations required to optimize the values of the 8 possible speed-up components is presented. PE2D has been utilized to determine inductance and capacitance values for the resistive terminator; this data has been used in PSpice transient analyses. Results of the PE2D predictions are also presented. The research has culminated in a predicted kick rise time (1% to 99%) of less than 50 ns for a TRIUMF 10 cell prototype kicker magnet. The proposed improvements are currently being implemented on our prototype kicker system

Simulating Social Networks of Online Communities: Simulation as a Method for Sociability Design

Science.gov (United States)

Ang, Chee Siang; Zaphiris, Panayiotis

We propose the use of social simulations to study and support the design of online communities. In this paper, we developed an Agent-Based Model (ABM) to simulate and study the formation of social networks in a Massively Multiplayer Online Role Playing Game (MMORPG) guild community. We first analyzed the activities and the social network (who-interacts-with-whom) of an existing guild community to identify its interaction patterns and characteristics. Then, based on the empirical results, we derived and formalized the interaction rules, which were implemented in our simulation. Using the simulation, we reproduced the observed social network of the guild community as a means of validation. The simulation was then used to examine how various parameters of the community (e.g. the level of activity, the number of neighbors of each agent, etc) could potentially influence the characteristic of the social networks.

Impact of window decrement rate on TCP performance in an adhoc network

Science.gov (United States)

Suherman; Hutasuhut, Arief T. W.; Badra, Khaldun; Al-Akaidi, Marwan

2017-09-01

Transmission control protocol (TCP) is a reliable transport protocol handling end to end connection in TCP/IP stack. It works well in copper or optical fibre link, but experiences increasing delay in wireless network. Further, TCP experiences multiple retransmissions due to higher collision probability within wireless network. The situation may get worsen in an ad hoc network. This paper examines the impact half window or window reduction rate to the overall TCP performances. The evaluation using NS-2 simulator shows that the smaller the window decrement rate results the smaller end to end delay. Delay is reduced to 17.05% in average when window decrement rate decreases. Average jitter also decreases 4.15%, while packet loss is not affected.

Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

Science.gov (United States)

Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

2013-12-29

Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

The NS1 polypeptide of the murine parvovirus minute virus of mice binds to DNA sequences containing the motif [ACCA]2-3.

Science.gov (United States)

Cotmore, S F; Christensen, J; Nüesch, J P; Tattersall, P

1995-03-01

A DNA fragment containing the minute virus of mice 3' replication origin was specifically coprecipitated in immune complexes containing the virally coded NS1, but not the NS2, polypeptide. Antibodies directed against the amino- or carboxy-terminal regions of NS1 precipitated the NS1-origin complexes, but antibodies directed against NS1 amino acids 284 to 459 blocked complex formation. Using affinity-purified histidine-tagged NS1 preparations, we have shown that the specific protein-DNA interaction is of moderate affinity, being stable in 0.1 M salt but rapidly lost at higher salt concentrations. In contrast, generalized (or nonspecific) DNA binding by NS1 could be demonstrated only in low salt. Addition of ATP or gamma S-ATP enhanced specific DNA binding by wild-type NS1 severalfold, but binding was lost under conditions which favored ATP hydrolysis. NS1 molecules with mutations in a critical lysine residue (amino acid 405) in the consensus ATP-binding site bound to the origin, but this binding could not be enhanced by ATP addition. DNase I protection assays carried out with wild-type NS1 in the presence of gamma S-ATP gave footprints which extended over 43 nucleotides on both DNA strands, from the middle of the origin bubble sequence to a position some 14 bp beyond the nick site. The DNA-binding site for NS1 was mapped to a 22-bp fragment from the middle of the 3' replication origin which contains the sequence ACCAACCA. This conforms to a reiterated motif (ACCA)2-3, which occurs, in more or less degenerate form, at many sites throughout the minute virus of mice genome (J. W. Bodner, Virus Genes 2:167-182, 1989). Insertion of a single copy of the sequence (ACCA)3 was shown to be sufficient to confer NS1 binding on an otherwise unrecognized plasmid fragment. The functions of NS1 in the viral life cycle are reevaluated in the light of this result.

Folding Proteins at 500 ns/hour with Work Queue.

Science.gov (United States)

Abdul-Wahid, Badi'; Yu, Li; Rajan, Dinesh; Feng, Haoyun; Darve, Eric; Thain, Douglas; Izaguirre, Jesús A

2012-10-01

Molecular modeling is a field that traditionally has large computational costs. Until recently, most simulation techniques relied on long trajectories, which inherently have poor scalability. A new class of methods is proposed that requires only a large number of short calculations, and for which minimal communication between computer nodes is required. We considered one of the more accurate variants called Accelerated Weighted Ensemble Dynamics (AWE) and for which distributed computing can be made efficient. We implemented AWE using the Work Queue framework for task management and applied it to an all atom protein model (Fip35 WW domain). We can run with excellent scalability by simultaneously utilizing heterogeneous resources from multiple computing platforms such as clouds (Amazon EC2, Microsoft Azure), dedicated clusters, grids, on multiple architectures (CPU/GPU, 32/64bit), and in a dynamic environment in which processes are regularly added or removed from the pool. This has allowed us to achieve an aggregate sampling rate of over 500 ns/hour. As a comparison, a single process typically achieves 0.1 ns/hour.

Construction of global ab initio potential energy surfaces for the HNS system and quantum dynamics calculations for the S({sup 3}P) + NH(X{sup 3}Σ) → NS(X{sup 2}Π) + H({sup 2}S) and N({sup 4}S) + SH(X{sup 2}Π) → NS(X{sup 2}Π) + H({sup 2}S) reactions

Energy Technology Data Exchange (ETDEWEB)

Sato, Kazuma; Takayanagi, Toshiyuki, E-mail: tako@mail.saitama-u.ac.jp

2014-08-17

Highlights: • Low-lying three potential energy surfaces for the HNS/HSN system are developed. • Quantum scattering calculations are performed for S + NH and N + SH reactions. • NS production mechanisms from S + NH and N + SH reactions are discussed. - Abstract: The lowest three adiabatic potential energy surfaces (1{sup 1}A′, 1{sup 1}A″ and 1{sup 3}A″) of the HNS molecular system have been developed using ab initio MRCI + Q-level electronic structure calculations with a complete-basis-set approach in order to understand the NS production mechanisms from the S({sup 3}P) + NH(X{sup 3}Σ) → NS(X{sup 2}Π) + H({sup 2}S) and N({sup 4}S) + SH(X{sup 2}Π) → NS(X{sup 2}Π) + H({sup 2}S) reactions. The results of time-independent quantum reactive scattering calculations show that the reactions proceed with the contribution of both direct and HNS/HSN complex-forming mechanisms on all the three potential energy surfaces. It is found that the reaction dynamics is not entirely statistical and cannot be described with a simple capture theory despite that the reactions are barrierless with large exoergicity.

Design and simulation of fast pulsed kicker/bumper units for the positron accumulator ring at APS

International Nuclear Information System (INIS)

Wang, Ju; Volk, G.J.

1991-01-01

In the design of fast pulsed kicker/burner units for a positron accumulator ring (PAR) at APS, different pulse forming networks (PFN) are considered and different structures for the magnet are studied and simulated. Three fast pulsed kicker/bumper magnets are required in PAR for the beam injection and/or extraction at 450 MeV. These magnets have the same design because they have identical specifications and are expected to produce identical magnetic fields. Each kicker/bumper magnet is required to generate a magnetic field of 0.06 T with rise-time of 80 ns, a flat-top of 80 ns and a fall-time of 80 ns. This paper describes some design considerations and computer simulation results of different designs

Modifying Cement Hydration with NS@PCE Core-Shell Nanoparticles

Directory of Open Access Journals (Sweden)

Yue Gu

2017-01-01

Full Text Available It is generally accepted that fine particles could accelerate cement hydration process, or, more specifically, this accelerating effect can be attributed to additional surface area introduced by fine particles. In addition to this view, the surface state of fine particles is also an important factor, especially for nanoparticles. In the previous study, a series of nano-SiO2-polycarboxylate superplasticizer core-shell nanoparticles (NS@PCE were synthesized, which have a similar particle size distribution but different surface properties. In this study, the impact of NS@PCE on cement hydration was investigated by heat flow calorimetry, mechanical property measurement, XRD, and SEM. Results show that, among a series of NS@PCE, NS@PCE-2 with a moderate shell-core ratio appeared to be more effective in accelerating cement hydration. As dosage increases, the efficiency of NS@PCE-2 would reach a plateau which is quantified by various characteristic values. Compressive strength results indicate that strength has a linear correlation with cumulative heat release. A hypothesis was proposed to explain the modification effect of NS@PCE, which highlights a balance between initial dispersion and pozzolanic reactivity. This paper provides a new understanding for the surface modification of supplementary cementitious materials and their application and also sheds a new light on nano-SiO2 for optimizing cement-based materials.

Fracture network modeling and GoldSim simulation support

International Nuclear Information System (INIS)

Sugita, Kenichiro; Dershowitz, William

2003-01-01

During Heisei-14, Golder Associates provided support for JNC Tokai through data analysis and simulation of the MIU Underground Rock Laboratory, participation in Task 6 of the Aespoe Task Force on Modelling of Groundwater Flow and Transport, and analysis of repository safety assessment technologies including cell networks for evaluation of the disturbed rock zone (DRZ) and total systems performance assessment (TSPA). MIU Underground Rock Laboratory support during H-14 involved discrete fracture network (DFN) modelling in support of the Multiple Modelling Project (MMP) and the Long Term Pumping Test (LPT). Golder developed updated DFN models for the MIU site, reflecting updated analyses of fracture data. Golder also developed scripts to support JNC simulations of flow and transport pathways within the MMP. Golder supported JNC participation in Task 6 of the Aespoe Task Force on Modelling of Groundwater Flow and Transport during H-14. Task 6A and 6B compared safety assessment (PA) and experimental time scale simulations along a pipe transport pathway. Task 6B2 extended Task 6B simulations from 1-D to 2-D. For Task 6B2, Golder carried out single fracture transport simulations on a wide variety of generic heterogeneous 2D fractures using both experimental and safety assessment boundary conditions. The heterogeneous 2D fractures were implemented according to a variety of in plane heterogeneity patterns. Multiple immobile zones were considered including stagnant zones, infillings, altered wall rock, and intact rock. During H-14, JNC carried out extensive studies of the distributed rock zone (DRZ) surrounding repository tunnels and drifts. Golder supported this activity be evaluating the calculation time necessary for simulating a reference heterogeneous DRZ cell network for a range of computational strategies. To support the development of JNC's total system performance assessment (TSPA) strategy, Golder carried out a review of the US DOE Yucca Mountain Project TSPA. This

Purification, crystallization and X-ray diffraction analysis of the C-terminal protease domain of Venezuelan equine encephalitis virus nsP2

International Nuclear Information System (INIS)

Russo, Andrew T.; Watowich, Stanley J.

2006-01-01

The C-terminal protease domain of Venezuelan equine encephalitis virus (VEEV) nsP2 has been overexpressed in E. coli, purified and successfully crystallized. Native crystals diffract to beyond 2.5 Å resolution and isomorphous heavy-atom derivatives suitable for phase analysis have been identified. The C-terminal region of Venezuelan equine encephalitis virus (VEEV) nsP2 is responsible for proteolytic processing of the VEEV polyprotein replication complex. This action regulates the activity of the replication complex and is essential for viral replication, thus making nsP2 a very attractive target for development of VEEV therapeutics. The 338-amino-acid C-terminal region of VEEV nsP2 has been overexpressed in Escherichia coli, purified and crystallized. Crystals diffract to beyond 2.5 Å resolution and belong to the orthorhombic space group P2 1 2 1 2 1 . Isomorphous heavy-atom derivatives suitable for phase analysis have been obtained and work on building a complete structural model is under way

Purification, crystallization and X-ray diffraction analysis of the C-terminal protease domain of Venezuelan equine encephalitis virus nsP2

Energy Technology Data Exchange (ETDEWEB)

Russo, Andrew T.; Watowich, Stanley J., E-mail: watowich@xray.utmb.edu [Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX (United States)

2006-06-01

The C-terminal protease domain of Venezuelan equine encephalitis virus (VEEV) nsP2 has been overexpressed in E. coli, purified and successfully crystallized. Native crystals diffract to beyond 2.5 Å resolution and isomorphous heavy-atom derivatives suitable for phase analysis have been identified. The C-terminal region of Venezuelan equine encephalitis virus (VEEV) nsP2 is responsible for proteolytic processing of the VEEV polyprotein replication complex. This action regulates the activity of the replication complex and is essential for viral replication, thus making nsP2 a very attractive target for development of VEEV therapeutics. The 338-amino-acid C-terminal region of VEEV nsP2 has been overexpressed in Escherichia coli, purified and crystallized. Crystals diffract to beyond 2.5 Å resolution and belong to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}. Isomorphous heavy-atom derivatives suitable for phase analysis have been obtained and work on building a complete structural model is under way.

Accelerator and feedback control simulation using neural networks

International Nuclear Information System (INIS)

Nguyen, D.; Lee, M.; Sass, R.; Shoaee, H.

1991-05-01

Unlike present constant model feedback system, neural networks can adapt as the dynamics of the process changes with time. Using a process model, the ''Accelerator'' network is first trained to simulate the dynamics of the beam for a given beam line. This ''Accelerator'' network is then used to train a second ''Controller'' network which performs the control function. In simulation, the networks are used to adjust corrector magnetics to control the launch angle and position of the beam to keep it on the desired trajectory when the incoming beam is perturbed. 4 refs., 3 figs

Notes on the Wess-Zumino-Witten-like structure: L{sub ∞} triplet and NS-NS superstring field theory

Energy Technology Data Exchange (ETDEWEB)

Matsunaga, Hiroaki [Institute of Physics, the Czech Academy of Sciences,Na Slovance 2, Prague 8 (Czech Republic); Yukawa Institute for Theoretical Physics, Kyoto University,Kyoto 606-8502 (Japan)

2017-05-17

In the NS-NS sector of superstring field theory, there potentially exist three nilpotent generators of gauge transformations and two constraint equations: it makes the gauge algebra of type II theory somewhat complicated. In this paper, we show that every NS-NS actions have their WZW-like forms, and that a triplet of mutually commutative L{sub ∞} products completely determines the gauge structure of NS-NS superstring field theory via its WZW-like structure. We give detailed analysis about it and present its characteristic properties by focusing on two NS-NS actions proposed by https://www.doi.org/10.1007/JHEP01(2017)022 and https://www.doi.org/10.1007/JHEP08(2014)158.

LHC experience with different bunch spacings in 2011 (25, 50 and 75 ns)

International Nuclear Information System (INIS)

Rumolo, G.; Iadarola, G.; Dominguez, O.; Arduini, G.; Bartosik, H.; Claudet, S.; Esteban-Mueller, J.; Roncarolo, F.; Shaposhnikova, E.; Tavian, L.

2012-01-01

LHC operation in 2011 had a smooth start in March with 75 ns beams and only one month later moved to 50 ns beam, after a successful dedicated scrubbing run. Several observables, such as pressure rise, heat load in the arcs, beam instability, emittance growth and synchronous phase shift, clearly pointed to the presence of an electron cloud inside the machine during the first days of operation with 50 ns beams. The gradual reduction of all these effects, and their eventual disappearance, over the days of the scrubbing run, indicated electron cloud mitigation and allowed physics production to shift to 50 ns beams. Up to the end of the run the quality of the 50 ns beams was increased by regular stages (first lower transverse emittances, then higher intensities), so that these beams could provide steadily improving peak luminosities. Furthermore, five MD sessions with 25 ns beams took place in the period June-October, but the quality of these beams was always deteriorated by severe electron cloud effects. However, a clear improvement was noticed also with the 25 ns runs. An estimation of the present state of conditioning of the machine and the required scrubbing time can be inferred from electron cloud simulations compared with measured data. (authors)

Evaluasi Kinerja IEEE 802.11e HCCA untuk Dukungan QoS pada WLAN Menggunakan NS-2

Directory of Open Access Journals (Sweden)

Amry Daulat Gultom

2014-06-01

Full Text Available Wireless Local Area Network (WLAN digunakan oleh trafik multimedia yang seharusnya memerlukan persyaratan jaringan yang lebih baik terhadap delay, jitter dan packet losses. IEEE 802.11 Task Group E memperkenalkan perbaikan protokol MAC 802.11, yaitu Hybrid Coordination Function (HCF, yang terdiri dari dua mekanisme akses: Enhanced Distributed Channel Access (EDCA dan HCF Controlled Channel Access (HCCA yang memberikan dukungan Kualitas Layanan/Quality of Service (QoS bagi trafik multimedia. Tujuan dari penelitian ini adalah untuk memahami algoritma protokol MAC IEEE 802.11e HCCA pada jaringan WLAN, dan menganalisis kinerja protokol MAC 802.11e HCCA pada aplikasi multimedia dengan menggunakan metode simulasi pada NS-2. Metrik kinerja yang diukur adalah jitter dan throughput-nya. Hasil penelitian ini menunjukkan bahwa protokol MAC HCCA dapat memberikan jaminan QoS dibanding protokol MAC DCF, dimana jitter HCCA lebih stabil dari pada jitter DCF. Begitupula dengan throughput HCCA yang tidak berubah selama trafik berlangsung, tidak seperti pada DCF yang masih mengalami fluktuasi yang besar.

Biological transportation networks: Modeling and simulation

KAUST Repository

Albi, Giacomo

2015-09-15

We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation and angiogenesis) and ion transportation networks (e.g., neural networks) is explained in detail and basic analytical features like the gradient flow structure of the fluid transportation network model and the impact of the model parameters on the geometry and topology of network formation are analyzed. We also present a numerical finite-element based discretization scheme and discuss sample cases of network formation simulations.

Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase.

Science.gov (United States)

Idrus, Syarifuddin; Tambunan, Usman Sumo Friend; Zubaidi, Ahmad Ardilla

2012-01-01

NS5 methyltransferase (Mtase) has a crucial role in the replication of dengue virus. There are two active sites on NS5 Mtase i.e., SAM and RNA-cap binding sites. Inhibition of the NS5 Mtase activity is expected to prevent the propagation of dengue virus. This study was conducted to design cyclic peptide ligands as enzyme inhibitors of dengue virus NS5 Mtase through computational approach. Cyclopentapeptides were designed as ligand of SAM binding site as much as 1635 and 736 cyclopentpeptides were designed as ligand of RNA-cap binding site. Interaction between ligand and NS5 Mtase has been conducted on the Docking simulation. The result shows that cyclopentapeptide CTWYC was the best peptide candidate on SAM binding site, with estimated free binding energy -30.72 kca/mol. Cyclopentapeptide CYEFC was the best peptide on RNA-cap binding site with estimated free binding energy -22.89 kcal/mol. Both peptides did not have tendency toward toxicity properties. So it is expected that both CTWYC and CYEFC ligands could be used as a potential antiviral drug candidates, which can inhibit the SAM and RNA-cap binding sites of dengue virus NS5 Mtase.

Event-based simulation of networks with pulse delayed coupling

Science.gov (United States)

Klinshov, Vladimir; Nekorkin, Vladimir

2017-10-01

Pulse-mediated interactions are common in networks of different nature. Here we develop a general framework for simulation of networks with pulse delayed coupling. We introduce the discrete map governing the dynamics of such networks and describe the computation algorithm for its numerical simulation.

NS Pudarka: A new winter wheat cultivar

Directory of Open Access Journals (Sweden)

Hristov Nikola

2014-01-01

Full Text Available The high-yielding, medium late winter wheat cultivar NS Pudarka was developed by crossing genetic divergent parents: line NMNH-07 and cv. NS 40S and Simonida. In cultivar NS Pudarka genes responsible for high yield potential, very good technological quality, resistance to lodging, low temperature and diseases, were successfully combined. It was registered by Ministry of agriculture, forestry and water management of Serbia Republic in 2013. This cultivar has wide adaptability and stability of yield that enable growing in different environments with optimal agricultural practice. On the base of technological quality this cultivar belongs to the second quality class, A2 farinograph subgroup and second technological group.

A Network Contention Model for the Extreme-scale Simulator

Energy Technology Data Exchange (ETDEWEB)

Engelmann, Christian [ORNL; Naughton III, Thomas J [ORNL

2015-01-01

The Extreme-scale Simulator (xSim) is a performance investigation toolkit for high-performance computing (HPC) hardware/software co-design. It permits running a HPC application with millions of concurrent execution threads, while observing its performance in a simulated extreme-scale system. This paper details a newly developed network modeling feature for xSim, eliminating the shortcomings of the existing network modeling capabilities. The approach takes a different path for implementing network contention and bandwidth capacity modeling using a less synchronous and accurate enough model design. With the new network modeling feature, xSim is able to simulate on-chip and on-node networks with reasonable accuracy and overheads.

Efficient hepatitis c virus genotype 1b core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors

DEFF Research Database (Denmark)

Pham, Long V.; Ramirez Almeida, Santseharay; Carlsen, Thomas H R

2017-01-01

Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants......, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5= untranslated region (5=UTR)-NS2, NS4A, or NS5A regions. Importantly...

Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

Science.gov (United States)

Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

2015-07-01

An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

Numerical simulation of the SLAC X-100 klystron using RKTW2D

International Nuclear Information System (INIS)

Ryne, R.D.; Vlieks, A.E.

1991-05-01

We have performed numerical simulations of the X-100 klystron being developed at Stanford Linear Accelerator Center. The X-100 is being developed as a possible source for the next generation of linear collider, and will be required to produce ∼100 MW of power for a duration of ∼800 ns. Our simulations were performed using the simulation programs RKTW1D and RKTW2D, developed at Lawrence Livermore National Laboratory. The codes were used to investigate the operation of the klystron over a wide range of operating conditions. We will present comparisons of the simulation results with experimental results. 3 refs., 5 figs

Hybrid simulation models of production networks

CERN Document Server

Kouikoglou, Vassilis S

2001-01-01

This book is concerned with a most important area of industrial production, that of analysis and optimization of production lines and networks using discrete-event models and simulation. The book introduces a novel approach that combines analytic models and discrete-event simulation. Unlike conventional piece-by-piece simulation, this method observes a reduced number of events between which the evolution of the system is tracked analytically. Using this hybrid approach, several models are developed for the analysis of production lines and networks. The hybrid approach combines speed and accuracy for exceptional analysis of most practical situations. A number of optimization problems, involving buffer design, workforce planning, and production control, are solved through the use of hybrid models.

Analysis of Time Delay Simulation in Networked Control System

OpenAIRE

Nyan Phyo Aung; Zaw Min Naing; Hla Myo Tun

2016-01-01

The paper presents a PD controller for the Networked Control Systems (NCS) with delay. The major challenges in this networked control system (NCS) are the delay of the data transmission throughout the communication network. The comparative performance analysis is carried out for different delays network medium. In this paper, simulation is carried out on Ac servo motor control system using CAN Bus as communication network medium. The True Time toolbox of MATLAB is used for simulation to analy...

Wurf.it: A Network Coding Reliable Multicast Content Streaming Solution

DEFF Research Database (Denmark)

Hernandez, Nestor; Pihl, Jeppe; Heide, Janus

demonstrator consists of stored simulations with ns-3 in a laptop and a Wurf.it implementation within a WiFi network. For the implementation, a video content from a mobile camera is distributed with low delay using SCORE to a set of heterogenous receivers (e.g. dierent platforms). Use cases of Wurf.it are mild...

Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

Directory of Open Access Journals (Sweden)

Leticia Barboza Rocha

2017-10-01

Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection.

Directory of Open Access Journals (Sweden)

Jincheng Chen

2015-07-01

Full Text Available Dengue virus (DV infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC. IL-6 and TNF-α production by PBMC were reduced when TLR2 and TLR6 were blocked using TLR2 and TLR6 neutralizing antibodies during DV infection. These results suggested that signaling pathways of TLR2 and TLR6 were activated during DV infection and its activation contributed to IL-6 and TNF-α production. DV NS1 protein was found to significantly increase the production of IL-6 and TNF-α when added to PBMC. The amount of IL-6 and TNF-α stimulated by DV NS1 protein was reduced when TLR2 and TLR6 were blocked, suggesting that DV NS1 protein is the viral protein responsible for the activation of TLR2 and TLR6 during DV infection. Secreted alkaline phosphatase (SEAP reporter assay was used to further confirm activation of TLR2 and TLR6 by DV NS1 protein. In addition, DV-infected and DV NS1 protein-treated TLR6-/- mice have higher survivability compared to DV-infected and DV NS1 protein-treated wild-type mice. Hence, activation of TLR6 via DV NS1 protein could potentially play an important role in the immunopathogenesis of DV infection.

Title: Using Alignment and 2D Network Simulations to Study Charge Transport Through Doped ZnO Nanowire Thin Film Electrodes

KAUST Repository

Phadke, Sujay

2011-09-30

Factors affecting charge transport through ZnO nanowire mat films were studied by aligning ZnO nanowires on substrates and coupling experimental measurements with 2D nanowire network simulations. Gallium doped ZnO nanowires were aligned on thermally oxidized silicon wafer by shearing a nanowire dispersion in ethanol. Sheet resistances of nanowire thin films that had current flowing parallel to nanowire alignment direction were compared to thin films that had current flowing perpendicular to nanowire alignment direction. Perpendicular devices showed ∼5 fold greater sheet resistance than parallel devices supporting the hypothesis that aligning nanowires would increase conductivity of ZnO nanowire electrodes. 2-D nanowire network simulations of thin films showed that the device sheet resistance was dominated by inter-wire contact resistance. For a given resistivity of ZnO nanowires, the thin film electrodes would have the lowest possible sheet resistance if the inter-wire contact resistance was one order of magnitude lower than the single nanowire resistance. Simulations suggest that the conductivity of such thin film devices could be further enhanced by using longer nanowires. Solution processed Gallium doped ZnO nanowires are aligned on substrates using an innovative shear coating technique. Nanowire alignment has shown improvement in ZnO nanowire transparent electrode conductivity. 2D network simulations in conjunction with electrical measurements have revealed different regimes of operation of nanowire thin films and provided a guideline for improving electrical performance of nanowire electrodes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HCV NS5A protein containing potential ligands for both Src homology 2 and 3 domains enhances autophosphorylation of Src family kinase Fyn in B cells.

Science.gov (United States)

Nakashima, Kenji; Takeuchi, Kenji; Chihara, Kazuyasu; Horiguchi, Tomoko; Sun, Xuedong; Deng, Lin; Shoji, Ikuo; Hotta, Hak; Sada, Kiyonao

2012-01-01

Hepatitis C virus (HCV) infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A) protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV) implied that NS5A was tyrosine phosphorylated by pervanadate (PV) treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST)-fusion proteins of various Src homology 2 (SH2) domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3) domain. Substitution of Arg(176) to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr(334) was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

HCV NS5A protein containing potential ligands for both Src homology 2 and 3 domains enhances autophosphorylation of Src family kinase Fyn in B cells.

Directory of Open Access Journals (Sweden)

Kenji Nakashima

Full Text Available Hepatitis C virus (HCV infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV implied that NS5A was tyrosine phosphorylated by pervanadate (PV treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST-fusion proteins of various Src homology 2 (SH2 domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3 domain. Substitution of Arg(176 to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr(334 was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

Parvovirus B19 NS1 protein induces cell cycle arrest at G2-phase by activating the ATR-CDC25C-CDK1 pathway.

Directory of Open Access Journals (Sweden)

Peng Xu

2017-03-01

Full Text Available Human parvovirus B19 (B19V infection of primary human erythroid progenitor cells (EPCs arrests infected cells at both late S-phase and G2-phase, which contain 4N DNA. B19V infection induces a DNA damage response (DDR that facilitates viral DNA replication but is dispensable for cell cycle arrest at G2-phase; however, a putative C-terminal transactivation domain (TAD2 within NS1 is responsible for G2-phase arrest. To fully understand the mechanism underlying B19V NS1-induced G2-phase arrest, we established two doxycycline-inducible B19V-permissive UT7/Epo-S1 cell lines that express NS1 or NS1mTAD2, and examined the function of the TAD2 domain during G2-phase arrest. The results confirm that the NS1 TAD2 domain plays a pivotal role in NS1-induced G2-phase arrest. Mechanistically, NS1 transactivated cellular gene expression through the TAD2 domain, which was itself responsible for ATR (ataxia-telangiectasia mutated and Rad3-related activation. Activated ATR phosphorylated CDC25C at serine 216, which in turn inactivated the cyclin B/CDK1 complex without affecting nuclear import of the complex. Importantly, we found that the ATR-CHK1-CDC25C-CDK1 pathway was activated during B19V infection of EPCs, and that ATR activation played an important role in B19V infection-induced G2-phase arrest.

Toward the laboratory identification of the not-so-simple NS2 neutral and anion isomers

Science.gov (United States)

Fortenberry, Ryan C.; Thackston, Russell; Francisco, Joseph S.; Lee, Timothy J.

2017-08-01

The NS2 radical is a simple arrangement of atoms with a complex electronic structure. This molecule was first reported by Hassanzadeh and Andrew's group [J. Am. Chem. Soc. 114, 83 (1992)] through Ar matrix isolation experiments. In the quarter century since this seminal work was published, almost nothing has been reported about nitrogen disulfide even though NS2 is isovalent with the common NO2. The present study aims to shed new insight into possible challenges with the characterization of this radical. No less than three potential energy surfaces all intersect in the C2v region of the SNS radical isomer. A type-C Renner-Teller molecule is present for the linear 2Πu state where the potential energy surface is fully contained within the 2.05 kcal/mol lower energy X ˜ 2A1 state. A C2v, 1 2B1 state is present in this same region, but a double excitation is required to access this state from the X ˜ 2A1 state of SNS. Additionally, a 1 2A' NSS isomer is also present but with notable differences in the geometry from the global minimum. Consequently, the rovibronic spectrum of these NS2 isomers is quite complicated. While the present theory and previous Ar matrix experiments agree well on isotopic shifts, they differ notably for the absolute fundamental vibrational frequency transitions. These differences are likely a combination of matrix shifts and issues associated with the neglect of non-adiabatic coupling in the computations. In either case, it is clear that high-resolution gas phase experimental observations will be complicated to sort. The present computations should aid in their analysis.

A Flexible System for Simulating Aeronautical Telecommunication Network

Science.gov (United States)

Maly, Kurt; Overstreet, C. M.; Andey, R.

1998-01-01

At Old Dominion University, we have built Aeronautical Telecommunication Network (ATN) Simulator with NASA being the fund provider. It provides a means to evaluate the impact of modified router scheduling algorithms on the network efficiency, to perform capacity studies on various network topologies and to monitor and study various aspects of ATN through graphical user interface (GUI). In this paper we describe briefly about the proposed ATN model and our abstraction of this model. Later we describe our simulator architecture highlighting some of the design specifications, scheduling algorithms and user interface. At the end, we have provided the results of performance studies on this simulator.

Multiscale Quantum Mechanics/Molecular Mechanics Simulations with Neural Networks.

Science.gov (United States)

Shen, Lin; Wu, Jingheng; Yang, Weitao

2016-10-11

Molecular dynamics simulation with multiscale quantum mechanics/molecular mechanics (QM/MM) methods is a very powerful tool for understanding the mechanism of chemical and biological processes in solution or enzymes. However, its computational cost can be too high for many biochemical systems because of the large number of ab initio QM calculations. Semiempirical QM/MM simulations have much higher efficiency. Its accuracy can be improved with a correction to reach the ab initio QM/MM level. The computational cost on the ab initio calculation for the correction determines the efficiency. In this paper we developed a neural network method for QM/MM calculation as an extension of the neural-network representation reported by Behler and Parrinello. With this approach, the potential energy of any configuration along the reaction path for a given QM/MM system can be predicted at the ab initio QM/MM level based on the semiempirical QM/MM simulations. We further applied this method to three reactions in water to calculate the free energy changes. The free-energy profile obtained from the semiempirical QM/MM simulation is corrected to the ab initio QM/MM level with the potential energies predicted with the constructed neural network. The results are in excellent accordance with the reference data that are obtained from the ab initio QM/MM molecular dynamics simulation or corrected with direct ab initio QM/MM potential energies. Compared with the correction using direct ab initio QM/MM potential energies, our method shows a speed-up of 1 or 2 orders of magnitude. It demonstrates that the neural network method combined with the semiempirical QM/MM calculation can be an efficient and reliable strategy for chemical reaction simulations.

STEADY-STATE modeling and simulation of pipeline networks for compressible fluids

Directory of Open Access Journals (Sweden)

A.L.H. Costa

1998-12-01

Full Text Available This paper presents a model and an algorithm for the simulation of pipeline networks with compressible fluids. The model can predict pressures, flow rates, temperatures and gas compositions at any point of the network. Any network configuration can be simulated; the existence of cycles is not an obstacle. Numerical results from simulated data on a proposed network are shown for illustration. The potential of the simulator is explored by the analysis of a pressure relief network, using a stochastic procedure for the evaluation of system performance.

Healthcare Supported by Data Mule Networks in Remote Communities of the Amazon Region

OpenAIRE

Coutinho, Mauro Margalho; Efrat, Alon; Johnson, Thienne; Richa, Andrea; Liu, Mengxue

2014-01-01

This paper investigates the feasibility of using boats as data mule nodes, carrying medical ultrasound videos from remote and isolated communities in the Amazon region in Brazil, to the main city of that area. The videos will be used by physicians to perform remote analysis and follow-up routine of prenatal examinations of pregnant women. Two open source simulators (the ONE and NS-2) were used to evaluate the results obtained utilizing a CoDPON (continuous displacement plan oriented network)....

Numerical simulation for gas-liquid two-phase flow in pipe networks

International Nuclear Information System (INIS)

Li Xiaoyan; Kuang Bo; Zhou Guoliang; Xu Jijun

1998-01-01

The complex pipe network characters can not directly presented in single phase flow, gas-liquid two phase flow pressure drop and void rate change model. Apply fluid network theory and computer numerical simulation technology to phase flow pipe networks carried out simulate and compute. Simulate result shows that flow resistance distribution is non-linear in two phase pipe network

Performance Evaluation of Beacon-Enabled Mode for IEEE 802.15.4 Wireless Sensor Network

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M. Udin Harun Al Rasyid

2013-12-01

Full Text Available IEEE 802.15.5 standard support structure of star and peer-to-peer network formation. Strating from these, the cluster tree network can be built as a special case of peer-to-peer network to increse coverage area. In this paper, we provide an performance evaluation of beacon- enabled mode for IEEE 802.15.4 wireless sensor network on star and cluster topology in order to get the maximum result to apply the appropriate topology model as needed. We conduct analysis on each topology model by using the numbers of nodes from 10 nodes to 100 nodes to analyze throughput, delay, energy consumption, and probability success packet by using NS2 simulator. The simulation results show that the throughput and the probability of success packet of cluster topology are higher than that of star topology, and the energy consumption of cluster topology is lesser than that of star topology. However, cluster topology increases the delay more than star topology. Keywords: IEEE 802.15.4, wireless sensor network, beacon-enabled mode, topology, csma/ca

Graphical user interface for wireless sensor networks simulator

Science.gov (United States)

Paczesny, Tomasz; Paczesny, Daniel; Weremczuk, Jerzy

2008-01-01

Wireless Sensor Networks (WSN) are currently very popular area of development. It can be suited in many applications form military through environment monitoring, healthcare, home automation and others. Those networks, when working in dynamic, ad-hoc model, need effective protocols which must differ from common computer networks algorithms. Research on those protocols would be difficult without simulation tool, because real applications often use many nodes and tests on such a big networks take much effort and costs. The paper presents Graphical User Interface (GUI) for simulator which is dedicated for WSN studies, especially in routing and data link protocols evaluation.

Influenza A H3N2 subtype virus NS1 protein targets into the nucleus and binds primarily via its C-terminal NLS2/NoLS to nucleolin and fibrillarin

Science.gov (United States)

2012-01-01

Background Influenza A virus non-structural protein 1 (NS1) is a virulence factor, which is targeted into the cell cytoplasm, nucleus and nucleolus. NS1 is a multi-functional protein that inhibits host cell pre-mRNA processing and counteracts host cell antiviral responses. Previously, we have shown that the NS1 protein of the H3N2 subtype influenza viruses possesses a C-terminal nuclear localization signal (NLS) that also functions as a nucleolar localization signal (NoLS) and targets the protein into the nucleolus. Results Here, we show that the NS1 protein of the human H3N2 virus subtype interacts in vitro primarily via its C-terminal NLS2/NoLS and to a minor extent via its N-terminal NLS1 with the nucleolar proteins, nucleolin and fibrillarin. Using chimeric green fluorescence protein (GFP)-NS1 fusion constructs, we show that the nucleolar retention of the NS1 protein is determined by its C-terminal NLS2/NoLS in vivo. Confocal laser microscopy analysis shows that the NS1 protein colocalizes with nucleolin in nucleoplasm and nucleolus and with B23 and fibrillarin in the nucleolus of influenza A/Udorn/72 virus-infected A549 cells. Since some viral proteins contain NoLSs, it is likely that viruses have evolved specific nucleolar functions. Conclusion NS1 protein of the human H3N2 virus interacts primarily via the C-terminal NLS2/NoLS and to a minor extent via the N-terminal NLS1 with the main nucleolar proteins, nucleolin, B23 and fibrillarin. PMID:22909121

Two unusual hepatitis C virus subtypes, 2j and 2q, in Spain: Identification by nested-PCR and sequencing of a NS5B region.

Science.gov (United States)

Margall, N; March, F; Español, M; Torras, X; Gallego, A; Coll, P

2015-10-01

Many studies have reported the use of the NS5B gene to subtype hepatitis C virus (HCV). Other HCV genes, such as HCV-5' UTR, Core (C) and E1, have also been used. In some studies, NS5B have been used together with 5'-UTR or C genes to improve genotyping results obtained using commercial procedures. Only two studies in Spain have compared molecular techniques versus commercial procedures regarding the efficacy of HCV subtyping. The aim of this study was to determine whether nested PCR and sequencing of a NS5B region was more reliable than commercial procedures to subtype HCV. We analyzed the results of HCV genotyping in [726] serum specimens collected from 2001 to 2013. From 2001 to 2011, we used PCR and INNO-LiPA hybridization or its new version Versant HCV Genotype 2.0 assay (471 samples). From 2012 to 2013, we used nested PCR and sequencing of a NS5B region (255 cases). This method used two pairs of primers to amplify the RNA of the sample converted to DNA by retrotranscription. The amplification product of 270 base pairs was further sequenced. To identify the subtype, the sequences obtained were compared to those in the international database: http://hcv.lanl.gov./content/sequence/, HCV/ToolsOutline.html and Geno2pheno[hcv] http://hcv.bioinf.mpi-inf.mpg.de/index.php. Nested PCR of a NS5B region and sequencing identified all but one subtype (0.4%, 1/255), differentiated all 1a subtypes from 1b subtypes, and characterized all HCV 2-4 subtypes. This approach also distinguished two subtypes, 2j and 2q, that had rarely been detected previously in Spain. However, commercial procedures failed to subtype 12.7% (60/471) of samples and to genotype 0.6% of specimens (3/471). Nested PCR and sequencing of a NS5B region improved the subtyping of HCV in comparison with classical procedures and identified two rare subtypes in Spain: 2j and 2q. However, full length genome sequencing is recommended to confirm HCV 2j and 2q subtypes. Copyright © 2015. Published by Elsevier B.V.

Modified network simulation model with token method of bus access

Directory of Open Access Journals (Sweden)

L.V. Stribulevich

2013-08-01

Full Text Available Purpose. To study the characteristics of the local network with the marker method of access to the bus its modified simulation model was developed. Methodology. Defining characteristics of the network is carried out on the developed simulation model, which is based on the state diagram-layer network station with the mechanism of processing priorities, both in steady state and in the performance of control procedures: the initiation of a logical ring, the entrance and exit of the station network with a logical ring. Findings. A simulation model, on the basis of which can be obtained the dependencies of the application the maximum waiting time in the queue for different classes of access, and the reaction time usable bandwidth on the data rate, the number of network stations, the generation rate applications, the number of frames transmitted per token holding time, frame length was developed. Originality. The technique of network simulation reflecting its work in the steady condition and during the control procedures, the mechanism of priority ranking and handling was proposed. Practical value. Defining network characteristics in the real-time systems on railway transport based on the developed simulation model.

Network simulation of nonstationary ionic transport through liquid junctions

International Nuclear Information System (INIS)

Castilla, J.; Horno, J.

1993-01-01

Nonstationary ionic transport across the liquid junctions has been studied using Network Thermodynamics. A network model for the time-dependent Nernst-Plack-Poisson system of equation is proposed. With this network model and the electrical circuit simulation program PSPICE, the concentrations, charge density, and electrical potentials, at short times, have been simulated for the binary system NaCl/NaCl. (Author) 13 refs

A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

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Mohamed Lamine Hafirassou

2017-12-01

Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

Functional investigation of grass carp reovirus nonstructural protein NS80

Directory of Open Access Journals (Sweden)

Shao Ling

2011-04-01

Full Text Available Abstract Background Grass Carp Reovirus (GCRV, a highly virulent agent of aquatic animals, has an eleven segmented dsRNA genome encased in a multilayered capsid shell, which encodes twelve proteins including seven structural proteins (VP1-VP7, and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16. It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein μNS in the genus of Orthoreovirus. Results As a step to understanding the basis of the part played by NS80 in GCRV replication and particle assembly, we used the yeast two-hybrid (Y2H system to identify NS80 interactions with proteins NS38, VP4, and VP6 as well as NS80 and NS38 self-interactions, while no interactions appeared in the four protein pairs NS38-VP4, NS38-VP6, VP4-VP4, and VP4-VP6. Bioinformatic analyses of NS80 with its corresponding proteins were performed with all currently available homologous protein sequences in ARVs (avian reoviruses and MRVs (mammalian reoviruses to predict further potential functional domains of NS80 that are related to VFLS (viral factory-like structures formation and other roles in viral replication. Two conserved regions spanning from aa (amino acid residues of 388 to 433, and 562 to 580 were discovered in this study. The second conserved region with corresponding conserved residues Tyr565, His569, Cys571, Asn573, and Glu576 located between the two coiled-coils regions (aa ~513-550 and aa ~615-690 in carboxyl-proximal terminus were supposed to be essential to form VFLS, so that aa residues ranging from 513 to 742 of NS80 was inferred to be the smallest region that is necessary for forming VFLS. The function of the first conserved region including Ala395, Gly419, Asp421, Pro422, Leu438, and Leu443 residues is unclear, but one-third of the amino-terminal region might be species specific, dominating interactions with other viral components. Conclusions Our

Meeting the memory challenges of brain-scale network simulation

Directory of Open Access Journals (Sweden)

Susanne eKunkel

2012-01-01

Full Text Available The development of high-performance simulation software is crucial for studying the brain connectome. Using connectome data to generate neurocomputational models requires software capable of coping with models on a variety of scales: from the microscale, investigating plasticity and dynamics of circuits in local networks, to the macroscale, investigating the interactions between distinct brain regions. Prior to any serious dynamical investigation, the first task of network simulations is to check the consistency of data integrated in the connectome and constrain ranges for yet unknown parameters. Thanks to distributed computing techniques, it is possible today to routinely simulate local cortical networks of around 10^5 neurons with up to 10^9 synapses on clusters and multi-processor shared-memory machines. However, brain-scale networks are one or two orders of magnitude larger than such local networks, in terms of numbers of neurons and synapses as well as in terms of computational load. Such networks have been studied in individual studies, but the underlying simulation technologies have neither been described in sufficient detail to be reproducible nor made publicly available. Here, we discover that as the network model sizes approach the regime of meso- and macroscale simulations, memory consumption on individual compute nodes becomes a critical bottleneck. This is especially relevant on modern supercomputers such as the Bluegene/P architecture where the available working memory per CPU core is rather limited. We develop a simple linear model to analyze the memory consumption of the constituent components of a neuronal simulator as a function of network size and the number of cores used. This approach has multiple benefits. The model enables identification of key contributing components to memory saturation and prediction of the effects of potential improvements to code before any implementation takes place.

BioNessie - a grid enabled biochemical networks simulation environment

OpenAIRE

Liu, X.; Jiang, J.; Ajayi, O.; Gu, X.; Gilbert, D.; Sinnott, R.O.

2008-01-01

The simulation of biochemical networks provides insight and understanding about the underlying biochemical processes and pathways used by cells and organisms. BioNessie is a biochemical network simulator which has been developed at the University of Glasgow. This paper describes the simulator and focuses in particular on how it has been extended to benefit from a wide variety of high performance compute resources across the UK through Grid technologies to support larger scale simulations.

The 4p3(2P) ns, nd configurations of Se I

International Nuclear Information System (INIS)

Mazzoni, M.

1989-01-01

The photoabsorption spectrum of Se I has been photographed in the 1100-900 A wavelength region, using a flash-pyrolisys system: About twenty lines were observed, most of them for the first time. With the support of Hartree-Fock calculations they have been identified and assigned to the 4p 4 →4p 3 ns 3 P(n=7-14) and 4p 4 →4p 3 nd 3 D (n=5-17) series, both converging on the limit 4p 3 ( 2 P 3/2 ). (orig.)

A subjective scheduler for subjective dedicated networks

Science.gov (United States)

Suherman; Fakhrizal, Said Reza; Al-Akaidi, Marwan

2017-09-01

Multiple access technique is one of important techniques within medium access layer in TCP/IP protocol stack. Each network technology implements the selected access method. Priority can be implemented in those methods to differentiate services. Some internet networks are dedicated for specific purpose. Education browsing or tutorial video accesses are preferred in a library hotspot, while entertainment and sport contents could be subjects of limitation. Current solution may use IP address filter or access list. This paper proposes subjective properties of users or applications are used for priority determination in multiple access techniques. The NS-2 simulator is employed to evaluate the method. A video surveillance network using WiMAX is chosen as the object. Subjective priority is implemented on WiMAX scheduler based on traffic properties. Three different traffic sources from monitoring video: palace, park, and market are evaluated. The proposed subjective scheduler prioritizes palace monitoring video that results better quality, xx dB than the later monitoring spots.

The structure of a mixed GluR2 ligand-binding core dimer in complex with (S)-glutamate and the antagonist (S)-NS1209

DEFF Research Database (Denmark)

Kasper, Christina; Pickering, Darryl S; Mirza, Osman

2006-01-01

domains has been observed. (S)-NS1209 adopts a novel binding mode, including hydrogen bonding to Tyr450 and Gly451 of D1. Parts of (S)-NS1209 occupy new areas of the GluR2 ligand-binding cleft, and bind near residues that are not conserved among receptor subtypes. The affinities of (RS)-NS1209 at the Glu....... The thermodynamics of binding of the antagonists (S)-NS1209, DNQX and (S)-ATPO to the GluR2 ligand-binding core have been determined by displacement isothermal titration calorimetry. The displacement of (S)-glutamate by all antagonists was shown to be driven by enthalpy....

On a simulation study for reliable and secured smart grid communications

Science.gov (United States)

Mallapuram, Sriharsha; Moulema, Paul; Yu, Wei

2015-05-01

Demand response is one of key smart grid applications that aims to reduce power generation at peak hours and maintain a balance between supply and demand. With the support of communication networks, energy consumers can become active actors in the energy management process by adjusting or rescheduling their electricity usage during peak hours based on utilities pricing incentives. Nonetheless, the integration of communication networks expose the smart grid to cyber-attacks. In this paper, we developed a smart grid simulation test-bed and designed evaluation scenarios. By leveraging the capabilities of Matlab and ns-3 simulation tools, we conducted a simulation study to evaluate the impact of cyber-attacks on demand response application. Our data shows that cyber-attacks could seriously disrupt smart grid operations, thus confirming the need of secure and resilient communication networks for supporting smart grid operations.

A gene network simulator to assess reverse engineering algorithms.

Science.gov (United States)

Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

2009-03-01

In the context of reverse engineering of biological networks, simulators are helpful to test and compare the accuracy of different reverse-engineering approaches in a variety of experimental conditions. A novel gene-network simulator is presented that resembles some of the main features of transcriptional regulatory networks related to topology, interaction among regulators of transcription, and expression dynamics. The simulator generates network topology according to the current knowledge of biological network organization, including scale-free distribution of the connectivity and clustering coefficient independent of the number of nodes in the network. It uses fuzzy logic to represent interactions among the regulators of each gene, integrated with differential equations to generate continuous data, comparable to real data for variety and dynamic complexity. Finally, the simulator accounts for saturation in the response to regulation and transcription activation thresholds and shows robustness to perturbations. It therefore provides a reliable and versatile test bed for reverse engineering algorithms applied to microarray data. Since the simulator describes regulatory interactions and expression dynamics as two distinct, although interconnected aspects of regulation, it can also be used to test reverse engineering approaches that use both microarray and protein-protein interaction data in the process of learning. A first software release is available at http://www.dei.unipd.it/~dicamill/software/netsim as an R programming language package.

NS1 of H7N9 Influenza A Virus Induces NO-Mediated Cellular Senescence in Neuro2a Cells

OpenAIRE

Yinxia Yan; Yongming Du; Huali Zheng; Gefei Wang; Rui Li; Jieling Chen; Kangsheng Li

2017-01-01

Background/Aims: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. Methods: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expres...

Hybrid Network Simulation for the ATLAS Trigger and Data Acquisition (TDAQ) System

CERN Document Server

Bonaventura, Matias Alejandro; The ATLAS collaboration; Castro, Rodrigo Daniel; Foguelman, Daniel Jacob

2015-01-01

The poster shows the ongoing research in the ATLAS TDAQ group in collaboration with the University of Buenos Aires in the area of hybrid data network simulations. he Data Network and Processing Cluster filters data in real-time, achieving a rejection factor in the order of 40000x and has real-time latency constrains. The dataflow between the processing units (TPUs) and Readout System (ROS) presents a “TCP Incast”-type network pathology which TCP cannot handle it efficiently. A credits system is in place which limits rate of queries and reduces latency. This large computer network, and the complex dataflow has been modelled and simulated using a PowerDEVS, a DEVS-based simulator. The simulation has been validated and used to produce what-if scenarios in the real network. Network Simulation with Hybrid Flows: Speedups and accuracy, combined • For intensive network traffic, Discrete Event simulation models (packet-level granularity) soon becomes prohibitive: Too high computing demands. • Fluid Flow simul...

WDM Systems and Networks Modeling, Simulation, Design and Engineering

CERN Document Server

Ellinas, Georgios; Roudas, Ioannis

2012-01-01

WDM Systems and Networks: Modeling, Simulation, Design and Engineering provides readers with the basic skills, concepts, and design techniques used to begin design and engineering of optical communication systems and networks at various layers. The latest semi-analytical system simulation techniques are applied to optical WDM systems and networks, and a review of the various current areas of optical communications is presented. Simulation is mixed with experimental verification and engineering to present the industry as well as state-of-the-art research. This contributed volume is divided into three parts, accommodating different readers interested in various types of networks and applications. The first part of the book presents modeling approaches and simulation tools mainly for the physical layer including transmission effects, devices, subsystems, and systems), whereas the second part features more engineering/design issues for various types of optical systems including ULH, access, and in-building system...

Transforming network simulation data to semantic data for network attack planning

CSIR Research Space (South Africa)

Chan, Ke Fai Peter

2017-03-01

Full Text Available study was performed, using the Common Open Research Emulator (CORE), to generate the necessary network simulation data. The simulation data was analysed, and then transformed into linked data. The result of the transformation is a data file that adheres...

ExoMol molecular line lists - XXVI: spectra of SH and NS

Science.gov (United States)

Yurchenko, Sergei N.; Bond, Wesley; Gorman, Maire N.; Lodi, Lorenzo; McKemmish, Laura K.; Nunn, William; Shah, Rohan; Tennyson, Jonathan

2018-04-01

Line lists for the sulphur-containing molecules SH (the mercapto radical) and NS are computed as part of the ExoMol project. These line lists consider transitions within the X 2Π ground state for 32SH, 33SH, 34SH and 32SD, and 14N32S, 14N33S, 14N34S, 14N36S and 15N32S. Ab initio potential energy (PEC) and spin-orbit coupling (SOC) curves are computed and then improved by fitting to experimentally observed transitions. Fully ab initio dipole moment curves (DMCs) computed at high level of theory are used to produce the final line lists. For SH, our fit gives a root-mean-square (rms) error of 0.03 cm-1 between the observed (vmax = 4, Jmax = 34.5) and calculated transitions wavenumbers; this is extrapolated such that all X 2Π rotational-vibrational-electronic (rovibronic) bound states are considered. For 32SH the resulting line list contains about 81 000 transitions and 2 300 rovibronic states, considering levels up to vmax = 14 and Jmax = 60.5. For NS the refinement used a combination of experimentally determined frequencies and energy levels and led to an rms fitting error of 0.002 cm-1. Each NS calculated line list includes around 2.8 million transitions and 31 000 rovibronic states with a vibrational range up to v = 53 and rotational range to J = 235.5, which covers up to 23 000 cm-1. Both line lists should be complete for temperatures up to 5000 K. Example spectra simulated using this line list are shown and comparisons made to the existing data in the CDMS database. The line lists are available from the CDS (http://cdsarc.u-strasbg.fr) and ExoMol (www.exomol.com) data bases.

System Identification, Prediction, Simulation and Control with Neural Networks

DEFF Research Database (Denmark)

Sørensen, O.

1997-01-01

a Gauss-Newton search direction is applied. 3) Amongst numerous model types, often met in control applications, only the Non-linear ARMAX (NARMAX) model, representing input/output description, is examined. A simulated example confirms that a neural network has the potential to perform excellent System......The intention of this paper is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... study of the networks themselves. With this end in view the following restrictions have been made: 1) Amongst numerous neural network structures, only the Multi Layer Perceptron (a feed-forward network) is applied. 2) Amongst numerous training algorithms, only the Recursive Prediction Error Method using...

Hierarchical Network Design Using Simulated Annealing

DEFF Research Database (Denmark)

Thomadsen, Tommy; Clausen, Jens

2002-01-01

networks are described and a mathematical model is proposed for a two level version of the hierarchical network problem. The problem is to determine which edges should connect nodes, and how demand is routed in the network. The problem is solved heuristically using simulated annealing which as a sub......-algorithm uses a construction algorithm to determine edges and route the demand. Performance for different versions of the algorithm are reported in terms of runtime and quality of the solutions. The algorithm is able to find solutions of reasonable quality in approximately 1 hour for networks with 100 nodes....

Aggregated Representation of Distribution Networks for Large-Scale Transmission Network Simulations

DEFF Research Database (Denmark)

Göksu, Ömer; Altin, Müfit; Sørensen, Poul Ejnar

2014-01-01

As a common practice of large-scale transmission network analysis the distribution networks have been represented as aggregated loads. However, with increasing share of distributed generation, especially wind and solar power, in the distribution networks, it became necessary to include...... the distributed generation within those analysis. In this paper a practical methodology to obtain aggregated behaviour of the distributed generation is proposed. The methodology, which is based on the use of the IEC standard wind turbine models, is applied on a benchmark distribution network via simulations....

Nonstructural protein 2 (nsP2) of Chikungunya virus (CHIKV) enhances protective immunity mediated by a CHIKV envelope protein expressing DNA Vaccine.

Science.gov (United States)

Bao, Huihui; Ramanathan, Aarti A; Kawalakar, Omkar; Sundaram, Senthil G; Tingey, Colleen; Bian, Charoran B; Muruganandam, Nagarajan; Vijayachari, Paluru; Sardesai, Niranjan Y; Weiner, David B; Ugen, Kenneth E; Muthumani, Karuppiah

2013-02-01

Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv+pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.

Binding of influenza A virus NS1 protein to the inter-SH2 domain of p85 suggests a novel mechanism for phosphoinositide 3-kinase activation.

Science.gov (United States)

Hale, Benjamin G; Batty, Ian H; Downes, C Peter; Randall, Richard E

2008-01-18

Influenza A virus NS1 protein stimulates host-cell phosphoinositide 3-kinase (PI3K) signaling by binding to the p85beta regulatory subunit of PI3K. Here, in an attempt to establish a mechanism for this activation, we report further on the functional interaction between NS1 and p85beta. Complex formation was found to be independent of NS1 RNA binding activity and is mediated by the C-terminal effector domain of NS1. Intriguingly, the primary direct binding site for NS1 on p85beta is the inter-SH2 domain, a coiled-coil structure that acts as a scaffold for the p110 catalytic subunit of PI3K. In vitro kinase activity assays, together with protein binding competition studies, reveal that NS1 does not displace p110 from the inter-SH2 domain, and indicate that NS1 can form an active heterotrimeric complex with PI3K. In addition, it was established that residues at the C terminus of the inter-SH2 domain are essential for mediating the interaction between p85beta and NS1. Equivalent residues in p85alpha have previously been implicated in the basal inhibition of p110. However, such p85alpha residues were unable to substitute for those in p85beta with regards NS1 binding. Overall, these data suggest a model by which NS1 activates PI3K catalytic activity by masking a normal regulatory element specific to the p85beta inter-SH2 domain.

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB).

Science.gov (United States)

Wang, Nai-Jyuan; Lee, Chi-Ching; Cheng, Chao-Sheng; Lo, Wei-Cheng; Yang, Ya-Fen; Chen, Ming-Nan; Lyu, Ping-Chiang

2012-01-01

Plant non-specific lipid transfer proteins (nsLTPs) are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database--nsLTPDB--which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB

Directory of Open Access Journals (Sweden)

Wang Nai-Jyuan

2012-01-01

Full Text Available Abstract Background Plant non-specific lipid transfer proteins (nsLTPs are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. Methods In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database -- nsLTPDB -- which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Results Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Conclusions Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

Parallel discrete-event simulation of FCFS stochastic queueing networks

Science.gov (United States)

Nicol, David M.

1988-01-01

Physical systems are inherently parallel. Intuition suggests that simulations of these systems may be amenable to parallel execution. The parallel execution of a discrete-event simulation requires careful synchronization of processes in order to ensure the execution's correctness; this synchronization can degrade performance. Largely negative results were recently reported in a study which used a well-known synchronization method on queueing network simulations. Discussed here is a synchronization method (appointments), which has proven itself to be effective on simulations of FCFS queueing networks. The key concept behind appointments is the provision of lookahead. Lookahead is a prediction on a processor's future behavior, based on an analysis of the processor's simulation state. It is shown how lookahead can be computed for FCFS queueing network simulations, give performance data that demonstrates the method's effectiveness under moderate to heavy loads, and discuss performance tradeoffs between the quality of lookahead, and the cost of computing lookahead.

Real-Time-Simulation of IEEE-5-Bus Network on OPAL-RT-OP4510 Simulator

Science.gov (United States)

Atul Bhandakkar, Anjali; Mathew, Lini, Dr.

2018-03-01

The Real-Time Simulator tools have high computing technologies, improved performance. They are widely used for design and improvement of electrical systems. The advancement of the software tools like MATLAB/SIMULINK with its Real-Time Workshop (RTW) and Real-Time Windows Target (RTWT), real-time simulators are used extensively in many engineering fields, such as industry, education, and research institutions. OPAL-RT-OP4510 is a Real-Time Simulator which is used in both industry and academia. In this paper, the real-time simulation of IEEE-5-Bus network is carried out by means of OPAL-RT-OP4510 with CRO and other hardware. The performance of the network is observed with the introduction of fault at various locations. The waveforms of voltage, current, active and reactive power are observed in the MATLAB simulation environment and on the CRO. Also, Load Flow Analysis (LFA) of IEEE-5-Bus network is computed using MATLAB/Simulink power-gui load flow tool.

Toward Designing a Quantum Key Distribution Network Simulation Model

OpenAIRE

Miralem Mehic; Peppino Fazio; Miroslav Voznak; Erik Chromy

2016-01-01

As research in quantum key distribution network technologies grows larger and more complex, the need for highly accurate and scalable simulation technologies becomes important to assess the practical feasibility and foresee difficulties in the practical implementation of theoretical achievements. In this paper, we described the design of simplified simulation environment of the quantum key distribution network with multiple links and nodes. In such simulation environment, we analyzed several ...

A framework for multi-object tracking over distributed wireless camera networks

Science.gov (United States)

Gau, Victor; Hwang, Jenq-Neng

2010-07-01

In this paper, we propose a unified framework targeting at two important issues in a distributed wireless camera network, i.e., object tracking and network communication, to achieve reliable multi-object tracking over distributed wireless camera networks. In the object tracking part, we propose a fully automated approach for tracking of multiple objects across multiple cameras with overlapping and non-overlapping field of views without initial training. To effectively exchange the tracking information among the distributed cameras, we proposed an idle probability based broadcasting method, iPro, which adaptively adjusts the broadcast probability to improve the broadcast effectiveness in a dense saturated camera network. Experimental results for the multi-object tracking demonstrate the promising performance of our approach on real video sequences for cameras with overlapping and non-overlapping views. The modeling and ns-2 simulation results show that iPro almost approaches the theoretical performance upper bound if cameras are within each other's transmission range. In more general scenarios, e.g., in case of hidden node problems, the simulation results show that iPro significantly outperforms standard IEEE 802.11, especially when the number of competing nodes increases.

Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir.

Directory of Open Access Journals (Sweden)

Kristi L Berger

Full Text Available The resistance profile of anti-hepatitis C virus (HCV agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor, deleobuvir (HCV polymerase non-nucleoside inhibitor, and ribavirin in multiple clinical studies.HCV NS3/4A and NS5B population sequencing (Sanger method was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b. Persistence and time to loss of resistance-associated variants (RAVs was estimated using Kaplan-Meier analysis.Faldaprevir RAVs (NS3 R155 and D168 and deleobuvir RAVs (NS5B 495 and 496 were rare (90%. Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b; some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b. Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months was less than that of GT-1b NS3 D168 (8.5 months and GT-1a R155 RAVs (11.5 months.Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b may reduce response to this deleobuvir-based regimen.

Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

Science.gov (United States)

Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

2017-11-21

Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

Development of neural network simulating power distribution of a BWR fuel bundle

International Nuclear Information System (INIS)

Tanabe, A.; Yamamoto, T.; Shinfuku, K.; Nakamae, T.

1992-01-01

A neural network model is developed to simulate the precise nuclear physics analysis program code for quick scoping survey calculations. The relation between enrichment and local power distribution of BWR fuel bundles was learned using two layers neural network (ENET). A new model is to introduce burnable neutron absorber (Gadolinia), added to several fuel rods to decrease initial reactivity of fresh bundle. The 2nd stages three layers neural network (GNET) is added on the 1st stage network ENET. GNET studies the local distribution difference caused by Gadolinia. Using this method, it becomes possible to survey of the gradients of sigmoid functions and back propagation constants with reasonable time. Using 99 learning patterns of zero burnup, good error convergence curve is obtained after many trials. This neural network model is able to simulate no learned cases fairly as well as the learned cases. Computer time of this neural network model is about 100 times faster than a precise analysis model. (author)

Simulation of Stimuli-Responsive Polymer Networks

Directory of Open Access Journals (Sweden)

Thomas Gruhn

2013-11-01

Full Text Available The structure and material properties of polymer networks can depend sensitively on changes in the environment. There is a great deal of progress in the development of stimuli-responsive hydrogels for applications like sensors, self-repairing materials or actuators. Biocompatible, smart hydrogels can be used for applications, such as controlled drug delivery and release, or for artificial muscles. Numerical studies have been performed on different length scales and levels of details. Macroscopic theories that describe the network systems with the help of continuous fields are suited to study effects like the stimuli-induced deformation of hydrogels on large scales. In this article, we discuss various macroscopic approaches and describe, in more detail, our phase field model, which allows the calculation of the hydrogel dynamics with the help of a free energy that considers physical and chemical impacts. On a mesoscopic level, polymer systems can be modeled with the help of the self-consistent field theory, which includes the interactions, connectivity, and the entropy of the polymer chains, and does not depend on constitutive equations. We present our recent extension of the method that allows the study of the formation of nano domains in reversibly crosslinked block copolymer networks. Molecular simulations of polymer networks allow the investigation of the behavior of specific systems on a microscopic scale. As an example for microscopic modeling of stimuli sensitive polymer networks, we present our Monte Carlo simulations of a filament network system with crosslinkers.

Simulation of lung motions using an artificial neural network

International Nuclear Information System (INIS)

Laurent, R.; Henriet, J.; Sauget, M.; Gschwind, R.; Makovicka, L.; Salomon, M.; Nguyen, F.

2011-01-01

Purpose. A way to improve the accuracy of lung radiotherapy for a patient is to get a better understanding of its lung motion. Indeed, thanks to this knowledge it becomes possible to follow the displacements of the clinical target volume (CTV) induced by the lung breathing. This paper presents a feasibility study of an original method to simulate the positions of points in patient's lung at all breathing phases. Patients and methods. This method, based on an artificial neural network, allowed learning the lung motion on real cases and then to simulate it for new patients for which only the beginning and the end breathing data are known. The neural network learning set is made up of more than 600 points. These points, shared out on three patients and gathered on a specific lung area, were plotted by a MD. Results. - The first results are promising: an average accuracy of 1 mm is obtained for a spatial resolution of 1 x 1 x 2.5 mm 3 . Conclusion. We have demonstrated that it is possible to simulate lung motion with accuracy using an artificial neural network. As future work we plan to improve the accuracy of our method with the addition of new patient data and a coverage of the whole lungs. (authors)

In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model

Directory of Open Access Journals (Sweden)

Katalin Szentpáli-Gavallér

2016-02-01

Full Text Available West Nile virus (WNV strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578/10; Central Europe was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L, NS2A (A30P, NS3 (P249H NS4B (P38G, C102S, E249G. The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA.

Smart vehicle monitoring and assistance using cloud computing in vehicular Ad Hoc networks

Directory of Open Access Journals (Sweden)

Yash Agarwal

2018-03-01

Full Text Available The increasing number of on road vehicles has become a major cause for congestion, accidents and pollution. Intelligent Transportation Systems (ITS might be the key to achieve solutions that help in reducing these problems significantly. The connected vehicular networks stream is a rapidly growing field for research and development of various real-time applications. In this paper, novel techniques have been proposed to serve the speed based lane changing, collision avoidance and time of arrival (TOA based localization in Vehicular Ad Hoc Networks (VANETs. As GPS requires clear line-of-sight for accurate services of positioning and localization applications, we designed a Time of Arrival (ToA based algorithm for areas where strong GPS signals are unavailable. Collision avoidance using automatic braking and camera-based surveillance are a few other applications that we addressed. The feasibility and the viability of the algorithms were demonstrated through simulations in Simulation of Urban Mobility (SUMO and Network Simulator-2 (NS-2. We prototyped a working hardware and tested it on actual vehicles to assess the effectiveness of the proposed system. We designed a mobile app interface for the on-board unit for smart, efficient and remote traffic monitoring. The integrated VANET Cloud Computing architecture acts as the platform for the proposed applications.

Integration of Continuous-Time Dynamics in a Spiking Neural Network Simulator

Directory of Open Access Journals (Sweden)

Jan Hahne

2017-05-01

Full Text Available Contemporary modeling approaches to the dynamics of neural networks include two important classes of models: biologically grounded spiking neuron models and functionally inspired rate-based units. We present a unified simulation framework that supports the combination of the two for multi-scale modeling, enables the quantitative validation of mean-field approaches by spiking network simulations, and provides an increase in reliability by usage of the same simulation code and the same network model specifications for both model classes. While most spiking simulations rely on the communication of discrete events, rate models require time-continuous interactions between neurons. Exploiting the conceptual similarity to the inclusion of gap junctions in spiking network simulations, we arrive at a reference implementation of instantaneous and delayed interactions between rate-based models in a spiking network simulator. The separation of rate dynamics from the general connection and communication infrastructure ensures flexibility of the framework. In addition to the standard implementation we present an iterative approach based on waveform-relaxation techniques to reduce communication and increase performance for large-scale simulations of rate-based models with instantaneous interactions. Finally we demonstrate the broad applicability of the framework by considering various examples from the literature, ranging from random networks to neural-field models. The study provides the prerequisite for interactions between rate-based and spiking models in a joint simulation.

Integration of Continuous-Time Dynamics in a Spiking Neural Network Simulator.

Science.gov (United States)

Hahne, Jan; Dahmen, David; Schuecker, Jannis; Frommer, Andreas; Bolten, Matthias; Helias, Moritz; Diesmann, Markus

2017-01-01

Contemporary modeling approaches to the dynamics of neural networks include two important classes of models: biologically grounded spiking neuron models and functionally inspired rate-based units. We present a unified simulation framework that supports the combination of the two for multi-scale modeling, enables the quantitative validation of mean-field approaches by spiking network simulations, and provides an increase in reliability by usage of the same simulation code and the same network model specifications for both model classes. While most spiking simulations rely on the communication of discrete events, rate models require time-continuous interactions between neurons. Exploiting the conceptual similarity to the inclusion of gap junctions in spiking network simulations, we arrive at a reference implementation of instantaneous and delayed interactions between rate-based models in a spiking network simulator. The separation of rate dynamics from the general connection and communication infrastructure ensures flexibility of the framework. In addition to the standard implementation we present an iterative approach based on waveform-relaxation techniques to reduce communication and increase performance for large-scale simulations of rate-based models with instantaneous interactions. Finally we demonstrate the broad applicability of the framework by considering various examples from the literature, ranging from random networks to neural-field models. The study provides the prerequisite for interactions between rate-based and spiking models in a joint simulation.

ExoMol molecular line lists - XXVI: spectra of SH and NS

Science.gov (United States)

Yurchenko, Sergei N.; Bond, Wesley; Gorman, Maire N.; Lodi, Lorenzo; McKemmish, Laura K.; Nunn, William; Shah, Rohan; Tennyson, Jonathan

2018-07-01

Line lists for the sulphur-containing molecules SH (the mercapto radical) and NS are computed as part of the ExoMol project. These line lists consider transitions within the X2Π ground state for 32SH, 33SH, 34SH,36SH and, 32SD, and 14N32S, 14N33S, 14N34S, 14N36S, and 15N32S. Ab initio potential energy (PEC) and spin-orbit coupling (SOC) curves are computed and then improved by fitting to experimentally observed transitions. Fully ab initio dipole moment curves (DMCs) computed at high level of theory are used to produce the final line lists. For SH, our fit gives a root-mean-square (rms) error of 0.03 cm-1 between the observed (vmax = 4, Jmax = 34.5) and calculated transitions wavenumbers; this is extrapolated such that all X2Π rotational-vibrational-electronic (rovibronic) bound states are considered. For 32SH the resulting line list contains about 81 000 transitions and 2300 rovibronic states, considering levels up to vmax = 14 and Jmax = 60.5. For NS the refinement used a combination of experimentally determined frequencies and energy levels and led to an rms-fitting error of 0.002 cm-1. Each NS-calculated line list includes around 2.8 million transitions and 31 000 rovibronic states with a vibrational range up to v = 53 and rotational range up to J = 235.5, which covers up to 23 000 cm-1. Both line lists should be complete for temperatures up to 5000 K. Example spectra simulated using this line list are shown and comparisons made to the existing data in the CDMS data base. The line lists are available from the CDS (http://cdsarc.u-strasbg.fr) and ExoMol (www.exomol.com) data bases.

NeuroFlow: A General Purpose Spiking Neural Network Simulation Platform using Customizable Processors.

Science.gov (United States)

Cheung, Kit; Schultz, Simon R; Luk, Wayne

2015-01-01

NeuroFlow is a scalable spiking neural network simulation platform for off-the-shelf high performance computing systems using customizable hardware processors such as Field-Programmable Gate Arrays (FPGAs). Unlike multi-core processors and application-specific integrated circuits, the processor architecture of NeuroFlow can be redesigned and reconfigured to suit a particular simulation to deliver optimized performance, such as the degree of parallelism to employ. The compilation process supports using PyNN, a simulator-independent neural network description language, to configure the processor. NeuroFlow supports a number of commonly used current or conductance based neuronal models such as integrate-and-fire and Izhikevich models, and the spike-timing-dependent plasticity (STDP) rule for learning. A 6-FPGA system can simulate a network of up to ~600,000 neurons and can achieve a real-time performance of 400,000 neurons. Using one FPGA, NeuroFlow delivers a speedup of up to 33.6 times the speed of an 8-core processor, or 2.83 times the speed of GPU-based platforms. With high flexibility and throughput, NeuroFlow provides a viable environment for large-scale neural network simulation.

Discovery of Dengue Virus NS4B Inhibitors

Science.gov (United States)

Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

2015-01-01

ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

Ekofisk chalk: core measurements, stochastic reconstruction, network modeling and simulation

Energy Technology Data Exchange (ETDEWEB)

Talukdar, Saifullah

2002-07-01

This dissertation deals with (1) experimental measurements on petrophysical, reservoir engineering and morphological properties of Ekofisk chalk, (2) numerical simulation of core flood experiments to analyze and improve relative permeability data, (3) stochastic reconstruction of chalk samples from limited morphological information, (4) extraction of pore space parameters from the reconstructed samples, development of network model using pore space information, and computation of petrophysical and reservoir engineering properties from network model, and (5) development of 2D and 3D idealized fractured reservoir models and verification of the applicability of several widely used conventional up scaling techniques in fractured reservoir simulation. Experiments have been conducted on eight Ekofisk chalk samples and porosity, absolute permeability, formation factor, and oil-water relative permeability, capillary pressure and resistivity index are measured at laboratory conditions. Mercury porosimetry data and backscatter scanning electron microscope images have also been acquired for the samples. A numerical simulation technique involving history matching of the production profiles is employed to improve the relative permeability curves and to analyze hysteresis of the Ekofisk chalk samples. The technique was found to be a powerful tool to supplement the uncertainties in experimental measurements. Porosity and correlation statistics obtained from backscatter scanning electron microscope images are used to reconstruct microstructures of chalk and particulate media. The reconstruction technique involves a simulated annealing algorithm, which can be constrained by an arbitrary number of morphological parameters. This flexibility of the algorithm is exploited to successfully reconstruct particulate media and chalk samples using more than one correlation functions. A technique based on conditional simulated annealing has been introduced for exact reproduction of vuggy

Teleradiology system analysis using a discrete event-driven block-oriented network simulator

Science.gov (United States)

Stewart, Brent K.; Dwyer, Samuel J., III

1992-07-01

Performance evaluation and trade-off analysis are the central issues in the design of communication networks. Simulation plays an important role in computer-aided design and analysis of communication networks and related systems, allowing testing of numerous architectural configurations and fault scenarios. We are using the Block Oriented Network Simulator (BONeS, Comdisco, Foster City, CA) software package to perform discrete, event- driven Monte Carlo simulations in capacity planning, tradeoff analysis and evaluation of alternate architectures for a high-speed, high-resolution teleradiology project. A queuing network model of the teleradiology system has been devise, simulations executed and results analyzed. The wide area network link uses a switched, dial-up N X 56 kbps inverting multiplexer where the number of digital voice-grade lines (N) can vary from one (DS-0) through 24 (DS-1). The proposed goal of such a system is 200 films (2048 X 2048 X 12-bit) transferred between a remote and local site in an eight hour period with a mean delay time less than five minutes. It is found that: (1) the DS-1 service limit is around 100 films per eight hour period with a mean delay time of 412 +/- 39 seconds, short of the goal stipulated above; (2) compressed video teleconferencing can be run simultaneously with image data transfer over the DS-1 wide area network link without impacting the performance of the described teleradiology system; (3) there is little sense in upgrading to a higher bandwidth WAN link like DS-2 or DS-3 for the current system; and (4) the goal of transmitting 200 films in an eight hour period with a mean delay time less than five minutes can be achieved simply if the laser printer interface is updated from the current DR-11W interface to a much faster SCSI interface.

Fracture Simulation of Highly Crosslinked Polymer Networks: Triglyceride-Based Adhesives

Science.gov (United States)

Lorenz, Christian; Stevens, Mark; Wool, Richard

2003-03-01

The ACRES program at the U. of Delaware has shown that triglyceride oils derived from plants are a favorable alternative to the traditional adhesives. The triglyceride networks are formed from an initial mixture of styrene monomers, free-radical initiators and triglycerides. We have performed simulations to study the effect of physical composition and physical characteristics of the triglyceride network on the strength of triglyceride network. A coarse-grained, bead-spring model of the triglyceride system is used. The average triglyceride consists of 6 beads per chain, the styrenes are represented as a single bead and the initiators are two bead chains. The polymer network is formed using an off-lattice 3D Monte Carlo simulation, in which the initiators activate the styrene and triglyceride reactive sites and then bonds are randomly formed between the styrene and active triglyceride monomers producing a highly crosslinked polymer network. Molecular dynamics simulations of the network under tensile and shear strains were performed to determine the strength as a function of the network composition. The relationship between the network structure and its strength will also be discussed.

Electron paramagnetic resonance of the ns1 centers in crystals

International Nuclear Information System (INIS)

Nistor, S.V.; Ursu, I.

1993-05-01

The results of the EPR studies concerning the paramagnetic centers with ns 1 (N=n>2) outer electronic configuration contained in crystals are reviewed. Such centers, with 2 S 1/2 ground state, are produced by electron trapping at impurities of the IB and IIB group or by hole trapping at impurities of the IIIB and IV group of elements. The production and structural properties of such centers consisting of ns 1 ions (atoms) at various sites in the crystal lattice with different configurations of neighbouring defects are discussed in connection with their EPR characteristics. Tables containing the spin Hamiltonian parameters of all ns 1 centers reported in the literature until the end of year 1992 are given. (author). 146 refs, 14 tabs

EVALUATING AUSTRALIAN FOOTBALL LEAGUE PLAYER CONTRIBUTIONS USING INTERACTIVE NETWORK SIMULATION

Directory of Open Access Journals (Sweden)

Jonathan Sargent

2013-03-01

Full Text Available This paper focuses on the contribution of Australian Football League (AFL players to their team's on-field network by simulating player interactions within a chosen team list and estimating the net effect on final score margin. A Visual Basic computer program was written, firstly, to isolate the effective interactions between players from a particular team in all 2011 season matches and, secondly, to generate a symmetric interaction matrix for each match. Negative binomial distributions were fitted to each player pairing in the Geelong Football Club for the 2011 season, enabling an interactive match simulation model given the 22 chosen players. Dynamic player ratings were calculated from the simulated network using eigenvector centrality, a method that recognises and rewards interactions with more prominent players in the team network. The centrality ratings were recorded after every network simulation and then applied in final score margin predictions so that each player's match contribution-and, hence, an optimal team-could be estimated. The paper ultimately demonstrates that the presence of highly rated players, such as Geelong's Jimmy Bartel, provides the most utility within a simulated team network. It is anticipated that these findings will facilitate optimal AFL team selection and player substitutions, which are key areas of interest to coaches. Network simulations are also attractive for use within betting markets, specifically to provide information on the likelihood of a chosen AFL team list "covering the line".

CIAE 600 kV ns pulse neutron generator

International Nuclear Information System (INIS)

Shen Guanren; Guan Xialing; Chen Hongtao

2001-01-01

The overall composition of CIAE 600 kV ns Pulse Neutron Generator (CPNG) are introduced, and its characteristic, main technological performance and application were also given. CPNG consists of high voltage power supply with highest output voltage 600 kV, direct current 15 mA, stability and ripple ≤0.1%, 2214 mm x 1604 mm x 1504 mm stainless steel high voltage electrode, built in head equipment uniform field accelerating tube, ns pulsed installation, turbomolecular vacuum pump system and drift pipes at 0 degree and 45 degree. Its characteristics are: (1) high current beam; (2) high current beam ns pulsed installation made use of low energy for chopper and high energy for buncher; (3) compactly laid out and simple in structure

Ranking important nodes in complex networks by simulated annealing

International Nuclear Information System (INIS)

Sun Yu; Yao Pei-Yang; Shen Jian; Zhong Yun; Wan Lu-Jun

2017-01-01

In this paper, based on simulated annealing a new method to rank important nodes in complex networks is presented. First, the concept of an importance sequence (IS) to describe the relative importance of nodes in complex networks is defined. Then, a measure used to evaluate the reasonability of an IS is designed. By comparing an IS and the measure of its reasonability to a state of complex networks and the energy of the state, respectively, the method finds the ground state of complex networks by simulated annealing. In other words, the method can construct a most reasonable IS. The results of experiments on real and artificial networks show that this ranking method not only is effective but also can be applied to different kinds of complex networks. (paper)

[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

DEFF Research Database (Denmark)

Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

2014-01-01

-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

FERN - a Java framework for stochastic simulation and evaluation of reaction networks.

Science.gov (United States)

Erhard, Florian; Friedel, Caroline C; Zimmer, Ralf

2008-08-29

Stochastic simulation can be used to illustrate the development of biological systems over time and the stochastic nature of these processes. Currently available programs for stochastic simulation, however, are limited in that they either a) do not provide the most efficient simulation algorithms and are difficult to extend, b) cannot be easily integrated into other applications or c) do not allow to monitor and intervene during the simulation process in an easy and intuitive way. Thus, in order to use stochastic simulation in innovative high-level modeling and analysis approaches more flexible tools are necessary. In this article, we present FERN (Framework for Evaluation of Reaction Networks), a Java framework for the efficient simulation of chemical reaction networks. FERN is subdivided into three layers for network representation, simulation and visualization of the simulation results each of which can be easily extended. It provides efficient and accurate state-of-the-art stochastic simulation algorithms for well-mixed chemical systems and a powerful observer system, which makes it possible to track and control the simulation progress on every level. To illustrate how FERN can be easily integrated into other systems biology applications, plugins to Cytoscape and CellDesigner are included. These plugins make it possible to run simulations and to observe the simulation progress in a reaction network in real-time from within the Cytoscape or CellDesigner environment. FERN addresses shortcomings of currently available stochastic simulation programs in several ways. First, it provides a broad range of efficient and accurate algorithms both for exact and approximate stochastic simulation and a simple interface for extending to new algorithms. FERN's implementations are considerably faster than the C implementations of gillespie2 or the Java implementations of ISBJava. Second, it can be used in a straightforward way both as a stand-alone program and within new

Optimization of blanking process using neural network simulation

International Nuclear Information System (INIS)

Hambli, R.

2005-01-01

The present work describes a methodology using the finite element method and neural network simulation in order to predict the optimum punch-die clearance during sheet metal blanking processes. A damage model is used in order to describe crack initiation and propagation into the sheet. The proposed approach combines predictive finite element and neural network modeling of the leading blanking parameters. Numerical results obtained by finite element computation including damage and fracture modeling were utilized to train the developed simulation environment based on back propagation neural network modeling. The comparative study between the numerical results and the experimental ones shows the good agreement. (author)

Thin film removal mechanisms in ns-laser processing of photovoltaic materials

International Nuclear Information System (INIS)

Bovatsek, J.; Tamhankar, A.; Patel, R.S.; Bulgakova, N.M.; Bonse, J.

2010-01-01

The removal of thin films widely used in photovoltaics (amorphous silicon, tin oxide, zinc oxide, aluminum, and molybdenum) is studied experimentally using multi-kHz Q-switched solid-state lasers at 532 nm and 1064 nm wavelengths. The processing ('scribing') is performed through the film-supporting glass plate at scribing speeds of the order of m/s. The dependence of the film removal threshold on the laser pulse duration (8 ns to 40 ns) is investigated and the results are complemented by a multi-layer thermal model used for numerical simulations of the laser-induced spatio-temporal temperature field within the samples. Possible film removal mechanisms are discussed upon consideration of optical, geometrical, thermal and mechanical properties of the layers.

TopoGen: A Network Topology Generation Architecture with application to automating simulations of Software Defined Networks

CERN Document Server

Laurito, Andres; The ATLAS collaboration

2017-01-01

Simulation is an important tool to validate the performance impact of control decisions in Software Defined Networks (SDN). Yet, the manual modeling of complex topologies that may change often during a design process can be a tedious error-prone task. We present TopoGen, a general purpose architecture and tool for systematic translation and generation of network topologies. TopoGen can be used to generate network simulation models automatically by querying information available at diverse sources, notably SDN controllers. The DEVS modeling and simulation framework facilitates a systematic translation of structured knowledge about a network topology into a formal modular and hierarchical coupling of preexisting or new models of network entities (physical or logical). TopoGen can be flexibly extended with new parsers and generators to grow its scope of applicability. This permits to design arbitrary workflows of topology transformations. We tested TopoGen in a network engineering project for the ATLAS detector ...

TopoGen: A Network Topology Generation Architecture with application to automating simulations of Software Defined Networks

CERN Document Server

Laurito, Andres; The ATLAS collaboration

2018-01-01

Simulation is an important tool to validate the performance impact of control decisions in Software Defined Networks (SDN). Yet, the manual modeling of complex topologies that may change often during a design process can be a tedious error-prone task. We present TopoGen, a general purpose architecture and tool for systematic translation and generation of network topologies. TopoGen can be used to generate network simulation models automatically by querying information available at diverse sources, notably SDN controllers. The DEVS modeling and simulation framework facilitates a systematic translation of structured knowledge about a network topology into a formal modular and hierarchical coupling of preexisting or new models of network entities (physical or logical). TopoGen can be flexibly extended with new parsers and generators to grow its scope of applicability. This permits to design arbitrary workflows of topology transformations. We tested TopoGen in a network engineering project for the ATLAS detector ...

Simulated, Emulated, and Physical Investigative Analysis (SEPIA) of networked systems.

Energy Technology Data Exchange (ETDEWEB)

Burton, David P.; Van Leeuwen, Brian P.; McDonald, Michael James; Onunkwo, Uzoma A.; Tarman, Thomas David; Urias, Vincent E.

2009-09-01

This report describes recent progress made in developing and utilizing hybrid Simulated, Emulated, and Physical Investigative Analysis (SEPIA) environments. Many organizations require advanced tools to analyze their information system's security, reliability, and resilience against cyber attack. Today's security analysis utilize real systems such as computers, network routers and other network equipment, computer emulations (e.g., virtual machines) and simulation models separately to analyze interplay between threats and safeguards. In contrast, this work developed new methods to combine these three approaches to provide integrated hybrid SEPIA environments. Our SEPIA environments enable an analyst to rapidly configure hybrid environments to pass network traffic and perform, from the outside, like real networks. This provides higher fidelity representations of key network nodes while still leveraging the scalability and cost advantages of simulation tools. The result is to rapidly produce large yet relatively low-cost multi-fidelity SEPIA networks of computers and routers that let analysts quickly investigate threats and test protection approaches.

Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3.

Science.gov (United States)

Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu

2017-11-01

The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å 2 intramolecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis -cleavage event. Although this conformation is incompatible with protease trans -cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis -cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different

Prototyping and Simulation of Robot Group Intelligence using Kohonen Networks.

Science.gov (United States)

Wang, Zhijun; Mirdamadi, Reza; Wang, Qing

2016-01-01

Intelligent agents such as robots can form ad hoc networks and replace human being in many dangerous scenarios such as a complicated disaster relief site. This project prototypes and builds a computer simulator to simulate robot kinetics, unsupervised learning using Kohonen networks, as well as group intelligence when an ad hoc network is formed. Each robot is modeled using an object with a simple set of attributes and methods that define its internal states and possible actions it may take under certain circumstances. As the result, simple, reliable, and affordable robots can be deployed to form the network. The simulator simulates a group of robots as an unsupervised learning unit and tests the learning results under scenarios with different complexities. The simulation results show that a group of robots could demonstrate highly collaborative behavior on a complex terrain. This study could potentially provide a software simulation platform for testing individual and group capability of robots before the design process and manufacturing of robots. Therefore, results of the project have the potential to reduce the cost and improve the efficiency of robot design and building.

Characterization of Background Traffic in Hybrid Network Simulation

National Research Council Canada - National Science Library

Lauwens, Ben; Scheers, Bart; Van de Capelle, Antoine

2006-01-01

.... Two approaches are common: discrete event simulation and fluid approximation. A discrete event simulation generates a huge amount of events for a full-blown battlefield communication network resulting in a very long runtime...

Unified Approach to Modeling and Simulation of Space Communication Networks and Systems

Science.gov (United States)

Barritt, Brian; Bhasin, Kul; Eddy, Wesley; Matthews, Seth

2010-01-01

Network simulator software tools are often used to model the behaviors and interactions of applications, protocols, packets, and data links in terrestrial communication networks. Other software tools that model the physics, orbital dynamics, and RF characteristics of space systems have matured to allow for rapid, detailed analysis of space communication links. However, the absence of a unified toolset that integrates the two modeling approaches has encumbered the systems engineers tasked with the design, architecture, and analysis of complex space communication networks and systems. This paper presents the unified approach and describes the motivation, challenges, and our solution - the customization of the network simulator to integrate with astronautical analysis software tools for high-fidelity end-to-end simulation. Keywords space; communication; systems; networking; simulation; modeling; QualNet; STK; integration; space networks

[Simulation of lung motions using an artificial neural network].

Science.gov (United States)

Laurent, R; Henriet, J; Salomon, M; Sauget, M; Nguyen, F; Gschwind, R; Makovicka, L

2011-04-01

A way to improve the accuracy of lung radiotherapy for a patient is to get a better understanding of its lung motion. Indeed, thanks to this knowledge it becomes possible to follow the displacements of the clinical target volume (CTV) induced by the lung breathing. This paper presents a feasibility study of an original method to simulate the positions of points in patient's lung at all breathing phases. This method, based on an artificial neural network, allowed learning the lung motion on real cases and then to simulate it for new patients for which only the beginning and the end breathing data are known. The neural network learning set is made up of more than 600 points. These points, shared out on three patients and gathered on a specific lung area, were plotted by a MD. The first results are promising: an average accuracy of 1mm is obtained for a spatial resolution of 1 × 1 × 2.5mm(3). We have demonstrated that it is possible to simulate lung motion with accuracy using an artificial neural network. As future work we plan to improve the accuracy of our method with the addition of new patient data and a coverage of the whole lungs. Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Predictive functional control for active queue management in congested TCP/IP networks.

Science.gov (United States)

Bigdeli, N; Haeri, M

2009-01-01

Predictive functional control (PFC) as a new active queue management (AQM) method in dynamic TCP networks supporting explicit congestion notification (ECN) is proposed. The ability of the controller in handling system delay along with its simplicity and low computational load makes PFC a privileged AQM method in the high speed networks. Besides, considering the disturbance term (which represents model/process mismatches, external disturbances, and existing noise) in the control formulation adds some level of robustness into the PFC-AQM controller. This is an important and desired property in the control of dynamically-varying computer networks. In this paper, the controller is designed based on a small signal linearized fluid-flow model of the TCP/AQM networks. Then, closed-loop transfer function representation of the system is derived to analyze the robustness with respect to the network and controller parameters. The analytical as well as the packet-level ns-2 simulation results show the out-performance of the developed controller for both queue regulation and resource utilization. Fast response, low queue fluctuations (and consequently low delay jitter), high link utilization, good disturbance rejection, scalability, and low packet marking probability are other features of the developed method with respect to other well-known AQM methods such as RED, PI, and REM which are also simulated for comparison.

Developed hydraulic simulation model for water pipeline networks

Directory of Open Access Journals (Sweden)

A. Ayad

2013-03-01

Full Text Available A numerical method that uses linear graph theory is presented for both steady state, and extended period simulation in a pipe network including its hydraulic components (pumps, valves, junctions, etc.. The developed model is based on the Extended Linear Graph Theory (ELGT technique. This technique is modified to include new network components such as flow control valves and tanks. The technique also expanded for extended period simulation (EPS. A newly modified method for the calculation of updated flows improving the convergence rate is being introduced. Both benchmarks, ad Actual networks are analyzed to check the reliability of the proposed method. The results reveal the finer performance of the proposed method.

Dynamic simulation of a steam generator by neural networks

International Nuclear Information System (INIS)

Masini, R.; Padovani, E.; Ricotti, M.E.; Zio, E.

1999-01-01

Numerical simulation by computers of the dynamic evolution of complex systems and components is a fundamental phase of any modern engineering design activity. This is of particular importance for risk-based design projects which require that the system behavior be analyzed under several and often extreme conditions. The traditional methods of simulation typically entail long, iterative, processes which lead to large simulation times, often exceeding the transients real time. Artificial neural networks (ANNs) may be exploited in this context, their advantages residing mainly in the speed of computation, in the capability of generalizing from few examples, in the robustness to noisy and partially incomplete data and in the capability of performing empirical input-output mapping without complete knowledge of the underlying physics. In this paper we present a novel approach to dynamic simulation by ANNs based on a superposition scheme in which a set of networks are individually trained, each one to respond to a different input forcing function. The dynamic simulation of a steam generator is considered as an example to show the potentialities of this tool and to point out the difficulties and crucial issues which typically arise when attempting to establish an efficient neural network simulator. The structure of the networks system is such to feedback, at each time step, a portion of the past evolution of the transient and this allows a good reproduction of also non-linear dynamic behaviors. A nice characteristic of the approach is that the modularization of the training reduces substantially its burden and gives this neural simulation tool a nice feature of transportability. (orig.)

Exploration of structural stability in deleterious nsSNPs of the XPA gene: A molecular dynamics approach

Directory of Open Access Journals (Sweden)

N NagaSundaram

2011-01-01

Full Text Available Background: Distinguishing the deleterious from the massive number of non-functional nsSNPs that occur within a single genome is a considerable challenge in mutation research. In this approach, we have used the existing in silico methods to explore the mutation-structure-function relationship in the XPA gene. Materials and Methods: We used the Sorting Intolerant From Tolerant (SIFT, Polymorphism Phenotyping (PolyPhen, I-Mutant 2.0, and the Protein Analysis THrough Evolutionary Relationships methods to predict the effects of deleterious nsSNPs on protein function and evaluated the impact of mutation on protein stability by Molecular Dynamics simulations. Results: By comparing the scores of all the four in silico methods, nsSNP with an ID rs104894131 at position C108F was predicted to be highly deleterious. We extended our Molecular dynamics approach to gain insight into the impact of this non-synonymous polymorphism on structural changes that may affect the activity of the XPA gene. Conclusion: Based on the in silico methods score, potential energy, root-mean-square deviation, and root-mean-square fluctuation, we predict that deleterious nsSNP at position C108F would play a significant role in causing disease by the XPA gene. Our approach would present the application of in silico tools in understanding the functional variation from the perspective of structure, evolution, and phenotype.

NET-2 Network Analysis Program

International Nuclear Information System (INIS)

Malmberg, A.F.

1974-01-01

The NET-2 Network Analysis Program is a general purpose digital computer program which solves the nonlinear time domain response and the linearized small signal frequency domain response of an arbitrary network of interconnected components. NET-2 is capable of handling a variety of components and has been applied to problems in several engineering fields, including electronic circuit design and analysis, missile flight simulation, control systems, heat flow, fluid flow, mechanical systems, structural dynamics, digital logic, communications network design, solid state device physics, fluidic systems, and nuclear vulnerability due to blast, thermal, gamma radiation, neutron damage, and EMP effects. Network components may be selected from a repertoire of built-in models or they may be constructed by the user through appropriate combinations of mathematical, empirical, and topological functions. Higher-level components may be defined by subnetworks composed of any combination of user-defined components and built-in models. The program provides a modeling capability to represent and intermix system components on many levels, e.g., from hole and electron spatial charge distributions in solid state devices through discrete and integrated electronic components to functional system blocks. NET-2 is capable of simultaneous computation in both the time and frequency domain, and has statistical and optimization capability. Network topology may be controlled as a function of the network solution. (U.S.)

Simulation of Attacks for Security in Wireless Sensor Network.

Science.gov (United States)

Diaz, Alvaro; Sanchez, Pablo

2016-11-18

The increasing complexity and low-power constraints of current Wireless Sensor Networks (WSN) require efficient methodologies for network simulation and embedded software performance analysis of nodes. In addition, security is also a very important feature that has to be addressed in most WSNs, since they may work with sensitive data and operate in hostile unattended environments. In this paper, a methodology for security analysis of Wireless Sensor Networks is presented. The methodology allows designing attack-aware embedded software/firmware or attack countermeasures to provide security in WSNs. The proposed methodology includes attacker modeling and attack simulation with performance analysis (node's software execution time and power consumption estimation). After an analysis of different WSN attack types, an attacker model is proposed. This model defines three different types of attackers that can emulate most WSN attacks. In addition, this paper presents a virtual platform that is able to model the node hardware, embedded software and basic wireless channel features. This virtual simulation analyzes the embedded software behavior and node power consumption while it takes into account the network deployment and topology. Additionally, this simulator integrates the previously mentioned attacker model. Thus, the impact of attacks on power consumption and software behavior/execution-time can be analyzed. This provides developers with essential information about the effects that one or multiple attacks could have on the network, helping them to develop more secure WSN systems. This WSN attack simulator is an essential element of the attack-aware embedded software development methodology that is also introduced in this work.

Simulation of Attacks for Security in Wireless Sensor Network

Science.gov (United States)

Diaz, Alvaro; Sanchez, Pablo

2016-01-01

The increasing complexity and low-power constraints of current Wireless Sensor Networks (WSN) require efficient methodologies for network simulation and embedded software performance analysis of nodes. In addition, security is also a very important feature that has to be addressed in most WSNs, since they may work with sensitive data and operate in hostile unattended environments. In this paper, a methodology for security analysis of Wireless Sensor Networks is presented. The methodology allows designing attack-aware embedded software/firmware or attack countermeasures to provide security in WSNs. The proposed methodology includes attacker modeling and attack simulation with performance analysis (node’s software execution time and power consumption estimation). After an analysis of different WSN attack types, an attacker model is proposed. This model defines three different types of attackers that can emulate most WSN attacks. In addition, this paper presents a virtual platform that is able to model the node hardware, embedded software and basic wireless channel features. This virtual simulation analyzes the embedded software behavior and node power consumption while it takes into account the network deployment and topology. Additionally, this simulator integrates the previously mentioned attacker model. Thus, the impact of attacks on power consumption and software behavior/execution-time can be analyzed. This provides developers with essential information about the effects that one or multiple attacks could have on the network, helping them to develop more secure WSN systems. This WSN attack simulator is an essential element of the attack-aware embedded software development methodology that is also introduced in this work. PMID:27869710

New NS varieties of six-rowed winter barley

Directory of Open Access Journals (Sweden)

Pržulj Novo

2009-01-01

Full Text Available The paper describes the characteristics of several new NS varieties of winter six-rowed barley released in Serbia between 2004 and 2007. These are Somborac, Ozren, Javor, Novosadski 773, Sremac and Leotar. In the official variety trials in the country, all six of these varieties outyielded the check variety, and the margins were as follows: Somborac - 3.4%, Ozren - 5.0%, Javor - 7.3%, Novosadski 773 - 3.4%, Sremac - 7.4%, and Leotar - 7.2%. Yield levels in absolute terms depended on the variety as well as year. All six-rowed NS varieties headed earlier than the check and had better resistance to lodging than the check has. The test weight of the new varieties was 70.2-73.8 kg/hl and the 1000-grain weight 33.4-50.2 g. The cellulose content was 4.4-4.8%, the fat content 1.4%, and the protein content 13.3-14.6%. The high variability of the new NS varieties of winter six-rowed barley makes it possible to choose the most suitable genotype for each barley-growing area in the country. .

Structural features of NS3 of Dengue virus serotypes 2 and 4 in solution and insight into RNA binding and the inhibitory role of quercetin.

Science.gov (United States)

Pan, Ankita; Saw, Wuan Geok; Subramanian Manimekalai, Malathy Sony; Grüber, Ardina; Joon, Shin; Matsui, Tsutomu; Weiss, Thomas M; Grüber, Gerhard

2017-05-01

Dengue virus (DENV), which has four serotypes (DENV-1 to DENV-4), is the causative agent of the viral infection dengue. DENV nonstructural protein 3 (NS3) comprises a serine protease domain and an RNA helicase domain which has nucleotide triphosphatase activities that are essential for RNA replication and viral assembly. Here, solution X-ray scattering was used to provide insight into the overall structure and flexibility of the entire NS3 and its recombinant helicase and protease domains for Dengue virus serotypes 2 and 4 in solution. The DENV-2 and DENV-4 NS3 forms are elongated and flexible in solution. The importance of the linker residues in flexibility and domain-domain arrangement was shown by the compactness of the individual protease and helicase domains. Swapping of the 174 PPAVP 179 linker stretch of the related Hepatitis C virus (HCV) NS3 into DENV-2 NS3 did not alter the elongated shape of the engineered mutant. Conformational alterations owing to RNA binding are described in the protease domain, which undergoes substantial conformational alterations that are required for the optimal catalysis of bound RNA. Finally, the effects of ATPase inhibitors on the enzymatically active DENV-2 and DENV-4 NS3 and the individual helicases are presented, and insight into the allosteric effect of the inhibitor quercetin is provided.

Optimal Node Placement in Underwater Wireless Sensor Networks

KAUST Repository

Felamban, M.

2013-03-25

Wireless Sensor Networks (WSN) are expected to play a vital role in the exploration and monitoring of underwater areas which are not easily reachable by humans. However, underwater communication via acoustic waves is subject to several performance limitations that are very different from those used for terresstrial networks. In this paper, we investigate node placement for building an initial underwater WSN infrastructure. We formulate this problem as a nonlinear mathematical program with the objective of minimizing the total transmission loss under a given number of sensor nodes and targeted coverage volume. The obtained solution is the location of each node represented via a truncated octahedron to fill out the 3D space. Experiments are conducted to verify the proposed formulation, which is solved using Matlab optimization tool. Simulation is also conducted using an ns-3 simulator, and the simulation results are consistent with the obtained results from mathematical model with less than 10% error.

The design and implementation of a network simulation platform

CSIR Research Space (South Africa)

Von Solms, S

2013-11-01

Full Text Available these events and their effects can enable researchers to identify these threats and find ways to counter them. In this paper we present the design of a network simulation platform which can enable researchers to study dynamic behaviour of networks, network...

Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2.

Science.gov (United States)

McCune, Broc T; Tang, Wei; Lu, Jia; Eaglesham, James B; Thorne, Lucy; Mayer, Anne E; Condiff, Emily; Nice, Timothy J; Goodfellow, Ian; Krezel, Andrzej M; Virgin, Herbert W

2017-07-11

The Norovirus genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail. VAPA was required for the efficiency of a step(s) in the viral replication cycle after entry of viral RNA into the cytoplasm but before the synthesis of viral minus-sense RNA. The interaction of VAPA with viral NS1/2 proteins is conserved between murine and human noroviruses. Murine norovirus NS1/2 directly bound the major sperm protein (MSP) domain of VAPA through its NS1 domain. Mutations within NS1 that disrupted interaction with VAPA inhibited viral replication. Structural analysis revealed that the viral NS1 domain contains a mimic of the phenylalanine-phenylalanine-acidic-tract (FFAT) motif that enables host proteins to bind to the VAPA MSP domain. The NS1/2-FFAT mimic region interacted with the VAPA-MSP domain in a manner similar to that seen with bona fide host FFAT motifs. Amino acids in the FFAT mimic region of the NS1 domain that are important for viral replication are highly conserved across murine norovirus strains. Thus, VAPA interaction with a norovirus protein that functionally mimics host FFAT motifs is important for murine norovirus replication. IMPORTANCE Human noroviruses are a leading cause of gastroenteritis worldwide, but host factors involved in norovirus replication are incompletely understood. Murine noroviruses have been studied to define mechanisms of norovirus replication. Here we defined the importance of the interaction between the hitherto poorly studied NS1/2 norovirus protein and the

Network bursts in cortical neuronal cultures: 'noise - versus pacemaker'- driven neural network simulations

NARCIS (Netherlands)

Gritsun, T.; Stegenga, J.; le Feber, Jakob; Rutten, Wim

2009-01-01

In this paper we address the issue of spontaneous bursting activity in cortical neuronal cultures and explain what might cause this collective behavior using computer simulations of two different neural network models. While the common approach to acivate a passive network is done by introducing

Neural Networks in R Using the Stuttgart Neural Network Simulator: RSNNS

Directory of Open Access Journals (Sweden)

Christopher Bergmeir

2012-01-01

Full Text Available Neural networks are important standard machine learning procedures for classification and regression. We describe the R package RSNNS that provides a convenient interface to the popular Stuttgart Neural Network Simulator SNNS. The main features are (a encapsulation of the relevant SNNS parts in a C++ class, for sequential and parallel usage of different networks, (b accessibility of all of the SNNSalgorithmic functionality from R using a low-level interface, and (c a high-level interface for convenient, R-style usage of many standard neural network procedures. The package also includes functions for visualization and analysis of the models and the training procedures, as well as functions for data input/output from/to the original SNNSfile formats.

Spatial and temporal variations of diffuse CO_{2} degassing at the N-S volcanic rift-zone of Tenerife (Canary Islands, Spain) during 2002-2015 period

Science.gov (United States)

Alonso, Mar; Ingman, Dylan; Alexander, Scott; Barrancos, José; Rodríguez, Fátima; Melián, Gladys; Pérez, Nemesio M.

2016-04-01

Tenerife is the largest of the Canary Islands and, together with Gran Canaria Island, is the only one with a central volcanic complex that started to grow at about 3.5 Ma. Nowadays the central complex is formed by Las Cañadas caldera, a volcanic depression measuring 16×9 km that resulted from multiple vertical collapses and was partially filled by post-caldera volcanic products. Up to 297 mafic monogenetic cones have been recognized on Tenerife, and they represent the most common eruptive activity occurring on the island during the last 1 Ma (Dóniz et al., 2008). Most of the monogenetic cones are aligned following a triple junction-shaped rift system, as result of inflation produced by the concentration of emission vents and dykes in bands at 120o to one another as a result of minimum stress fracturing of the crust by a mantle upwelling. The main structural characteristic of the southern volcanic rift (N-S) of the island is an apparent absence of a distinct ridge, and a fan shaped distribution of monogenetic cones. Four main volcanic successions in the southern volcanic rift zone of Tenerife, temporally separated by longer periods (˜70 - 250 ka) without volcanic activity, have been identified (Kröchert and Buchner, 2008). Since there are currently no visible gas emissions at the N-S rift, diffuse degassing surveys have become an important geochemical tool for the surveillance of this volcanic system. We report here the last results of diffuse CO2 efflux survey at the N-S rift of Tenerife, performed using the accumulation chamber method in the summer period of 2015. The objectives of the surveys were: (i) to constrain the total CO2 output from the studied area and (ii) to evaluate occasional CO2 efflux surveys as a volcanic surveillance tool for the N-S rift of Tenerife. Soil CO2 efflux values ranged from non-detectable up to 31.7 g m-2 d-1. A spatial distribution map, constructed following the sequential Gaussian simulation (sGs) procedure, did not show an

Modelling Altitude Information in Two-Dimensional Traffic Networks for Electric Mobility Simulation

Directory of Open Access Journals (Sweden)

Diogo Santos

2016-06-01

Full Text Available Elevation data is important for electric vehicle simulation. However, traffic simulators are often two-dimensional and do not offer the capability of modelling urban networks taking elevation into account. Specifically, SUMO - Simulation of Urban Mobility, a popular microscopic traffic simulator, relies on networks previously modelled with elevation data as to provide this information during simulations. This work tackles the problem of adding elevation data to urban network models - particularly for the case of the Porto urban network, in Portugal. With this goal in mind, a comparison between different altitude information retrieval approaches is made and a simple tool to annotate network models with altitude data is proposed. The work starts by describing the methodological approach followed during research and development, then describing and analysing its main findings. This description includes an in-depth explanation of the proposed tool. Lastly, this work reviews some related work to the subject.

Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C.

Science.gov (United States)

Costantino, Angela; Spada, Enea; Equestre, Michele; Bruni, Roberto; Tritarelli, Elena; Coppola, Nicola; Sagnelli, Caterina; Sagnelli, Evangelista; Ciccaglione, Anna Rita

2015-11-14

The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.

Efficient Culture Adaptation of Hepatitis C Virus Recombinants with Genotype-Specific Core-NS2 by Using Previously Identified Mutations

DEFF Research Database (Denmark)

Scheel, Troels Kasper Høyer; Gottwein, Judith M; Carlsen, Thomas H R

2011-01-01

Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based...... (HC-TN and DH6), 1b (DH1 and DH5), and 3a (DBN) isolates, using previously identified adaptive mutations. Introduction of mutations from isolates of the same subtype either led to immediate efficient virus production or accelerated culture adaptation. The DH6 and DH5 recombinants without introduced...... mutations did not adapt to culture. Universal adaptive effects of mutations in NS3 (Q1247L, I1312V, K1398Q, R1408W, and Q1496L) and NS5A (V2418L) were investigated for JFH1-based genotype 1 to 5 core-NS2 recombinants; several mutations conferred adaptation to H77C (1a), J4 (1b), S52 (3a), and SA13 (5a...

'BioNessie(G) - a grid enabled biochemical networks simulation environment

OpenAIRE

Liu, X; Jiang, J; Ajayi, O; Gu, X; Gilbert, D; Sinnott, R

2008-01-01

The simulation of biochemical networks provides insight and understanding about the underlying biochemical processes and pathways used by cells and organisms. BioNessie is a biochemical network simulator which has been developed at the University of Glasgow. This paper describes the simulator and focuses in particular on how it has been extended to benefit from a wide variety of high performance compute resources across the UK through Grid technologies to support larger scal...

Evolution of Bacterial Global Modulators: Role of a Novel H-NS Paralogue in the Enteroaggregative Escherichia coli Strain 042.

Science.gov (United States)

Prieto, A; Bernabeu, M; Aznar, S; Ruiz-Cruz, S; Bravo, A; Queiroz, M H; Juárez, A

2018-01-01

Bacterial genomes sometimes contain genes that code for homologues of global regulators, the function of which is unclear. In members of the family Enterobacteriaceae , cells express the global regulator H-NS and its paralogue StpA. In Escherichia coli , out of providing a molecular backup for H-NS, the role of StpA is poorly characterized. The enteroaggregative E. coli strain 042 carries, in addition to the hns and stpA genes, a third gene encoding an hns paralogue ( hns2 ). We present in this paper information about its biological function. Transcriptomic analysis has shown that the H-NS2 protein targets a subset of the genes targeted by H-NS. Genes targeted by H-NS2 correspond mainly with horizontally transferred (HGT) genes and are also targeted by the Hha protein, a fine-tuner of H-NS activity. Compared with H-NS, H-NS2 expression levels are lower. In addition, H-NS2 expression exhibits specific features: it is sensitive to the growth temperature and to the nature of the culture medium. This novel H-NS paralogue is widespread within the Enterobacteriaceae . IMPORTANCE Global regulators such as H-NS play key relevant roles enabling bacterial cells to adapt to a changing environment. H-NS modulates both core and horizontally transferred (HGT) genes, but the mechanism by which H-NS can differentially regulate these genes remains to be elucidated. There are several instances of bacterial cells carrying genes that encode homologues of the global regulators. The question is what the roles of these proteins are. We noticed that the enteroaggregative E. coli strain 042 carries a new hitherto uncharacterized copy of the hns gene. We decided to investigate why this pathogenic E. coli strain requires an extra H-NS paralogue, termed H-NS2. In our work, we show that H-NS2 displays specific expression and regulatory properties. H-NS2 targets a subset of H-NS-specific genes and may help to differentially modulate core and HGT genes by the H-NS cellular pool.

Large-scale simulations of plastic neural networks on neuromorphic hardware

Directory of Open Access Journals (Sweden)

James Courtney Knight

2016-04-01

Full Text Available SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 20000 neurons and 51200000 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models.

Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

Science.gov (United States)

Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

2017-01-01

Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Neural Network Emulation of Reionization Simulations

Science.gov (United States)

Schmit, Claude J.; Pritchard, Jonathan R.

2018-05-01

Next generation radio experiments such as LOFAR, HERA and SKA are expected to probe the Epoch of Reionization and claim a first direct detection of the cosmic 21cm signal within the next decade. One of the major challenges for these experiments will be dealing with enormous incoming data volumes. Machine learning is key to increasing our data analysis efficiency. We consider the use of an artificial neural network to emulate 21cmFAST simulations and use it in a Bayesian parameter inference study. We then compare the network predictions to a direct evaluation of the EoR simulations and analyse the dependence of the results on the training set size. We find that the use of a training set of size 100 samples can recover the error contours of a full scale MCMC analysis which evaluates the model at each step.

Accurate Simulation of 802.11 Indoor Links: A "Bursty" Channel Model Based on Real Measurements

Directory of Open Access Journals (Sweden)

Agüero Ramón

2010-01-01

Full Text Available We propose a novel channel model to be used for simulating indoor wireless propagation environments. An extensive measurement campaign was carried out to assess the performance of different transport protocols over 802.11 links. This enabled us to better adjust our approach, which is based on an autoregressive filter. One of the main advantages of this proposal lies in its ability to reflect the "bursty" behavior which characterizes indoor wireless scenarios, having a great impact on the behavior of upper layer protocols. We compare this channel model, integrated within the Network Simulator (ns-2 platform, with other traditional approaches, showing that it is able to better reflect the real behavior which was empirically assessed.

ADAPTIVE GOSSIP BASED PROTOCOL FOR ENERGY EFFICIENT MOBILE ADHOC NETWORK

Directory of Open Access Journals (Sweden)

S. Rajeswari

2012-03-01

Full Text Available In Gossip Sleep Protocol, network performance is enhanced based on energy resource. But energy conservation is achieved with the reduced throughput. In this paper, it has been proposed a new Protocol for Mobile Ad hoc Network to achieve reliability with energy conservation. Based on the probability (p values, the value of sleep nodes is fixed initially. The probability value can be adaptively adjusted by Remote Activated Switch during the transmission process. The adaptiveness of gossiping probability is determined by the Packet Delivery Ratio. For performance comparison, we have taken Routing overhead, Packet Delivery Ratio, Number of dropped packets and Energy consumption with the increasing number of forwarding nodes. We used UDP based traffic models to analyze the performance of this protocol. We analyzed TCP based traffic models for average end to end delay. We have used the NS-2 simulator.

Extremely Scalable Spiking Neuronal Network Simulation Code: From Laptops to Exascale Computers

Science.gov (United States)

Jordan, Jakob; Ippen, Tammo; Helias, Moritz; Kitayama, Itaru; Sato, Mitsuhisa; Igarashi, Jun; Diesmann, Markus; Kunkel, Susanne

2018-01-01

State-of-the-art software tools for neuronal network simulations scale to the largest computing systems available today and enable investigations of large-scale networks of up to 10 % of the human cortex at a resolution of individual neurons and synapses. Due to an upper limit on the number of incoming connections of a single neuron, network connectivity becomes extremely sparse at this scale. To manage computational costs, simulation software ultimately targeting the brain scale needs to fully exploit this sparsity. Here we present a two-tier connection infrastructure and a framework for directed communication among compute nodes accounting for the sparsity of brain-scale networks. We demonstrate the feasibility of this approach by implementing the technology in the NEST simulation code and we investigate its performance in different scaling scenarios of typical network simulations. Our results show that the new data structures and communication scheme prepare the simulation kernel for post-petascale high-performance computing facilities without sacrificing performance in smaller systems. PMID:29503613

Extremely Scalable Spiking Neuronal Network Simulation Code: From Laptops to Exascale Computers.

Science.gov (United States)

Jordan, Jakob; Ippen, Tammo; Helias, Moritz; Kitayama, Itaru; Sato, Mitsuhisa; Igarashi, Jun; Diesmann, Markus; Kunkel, Susanne

2018-01-01

State-of-the-art software tools for neuronal network simulations scale to the largest computing systems available today and enable investigations of large-scale networks of up to 10 % of the human cortex at a resolution of individual neurons and synapses. Due to an upper limit on the number of incoming connections of a single neuron, network connectivity becomes extremely sparse at this scale. To manage computational costs, simulation software ultimately targeting the brain scale needs to fully exploit this sparsity. Here we present a two-tier connection infrastructure and a framework for directed communication among compute nodes accounting for the sparsity of brain-scale networks. We demonstrate the feasibility of this approach by implementing the technology in the NEST simulation code and we investigate its performance in different scaling scenarios of typical network simulations. Our results show that the new data structures and communication scheme prepare the simulation kernel for post-petascale high-performance computing facilities without sacrificing performance in smaller systems.

Extremely Scalable Spiking Neuronal Network Simulation Code: From Laptops to Exascale Computers

Directory of Open Access Journals (Sweden)

Jakob Jordan

2018-02-01

Full Text Available State-of-the-art software tools for neuronal network simulations scale to the largest computing systems available today and enable investigations of large-scale networks of up to 10 % of the human cortex at a resolution of individual neurons and synapses. Due to an upper limit on the number of incoming connections of a single neuron, network connectivity becomes extremely sparse at this scale. To manage computational costs, simulation software ultimately targeting the brain scale needs to fully exploit this sparsity. Here we present a two-tier connection infrastructure and a framework for directed communication among compute nodes accounting for the sparsity of brain-scale networks. We demonstrate the feasibility of this approach by implementing the technology in the NEST simulation code and we investigate its performance in different scaling scenarios of typical network simulations. Our results show that the new data structures and communication scheme prepare the simulation kernel for post-petascale high-performance computing facilities without sacrificing performance in smaller systems.

Power Aware Simulation Framework for Wireless Sensor Networks and Nodes

Directory of Open Access Journals (Sweden)

Daniel Weber

2008-07-01

Full Text Available The constrained resources of sensor nodes limit analytical techniques and cost-time factors limit test beds to study wireless sensor networks (WSNs. Consequently, simulation becomes an essential tool to evaluate such systems.We present the power aware wireless sensors (PAWiS simulation framework that supports design and simulation of wireless sensor networks and nodes. The framework emphasizes power consumption capturing and hence the identification of inefficiencies in various hardware and software modules of the systems. These modules include all layers of the communication system, the targeted class of application itself, the power supply and energy management, the central processing unit (CPU, and the sensor-actuator interface. The modular design makes it possible to simulate heterogeneous systems. PAWiS is an OMNeT++ based discrete event simulator written in C++. It captures the node internals (modules as well as the node surroundings (network, environment and provides specific features critical to WSNs like capturing power consumption at various levels of granularity, support for mobility, and environmental dynamics as well as the simulation of timing effects. A module library with standardized interfaces and a power analysis tool have been developed to support the design and analysis of simulation models. The performance of the PAWiS simulator is comparable with other simulation environments.

Temporal Gillespie Algorithm: Fast Simulation of Contagion Processes on Time-Varying Networks.

Science.gov (United States)

Vestergaard, Christian L; Génois, Mathieu

2015-10-01

Stochastic simulations are one of the cornerstones of the analysis of dynamical processes on complex networks, and are often the only accessible way to explore their behavior. The development of fast algorithms is paramount to allow large-scale simulations. The Gillespie algorithm can be used for fast simulation of stochastic processes, and variants of it have been applied to simulate dynamical processes on static networks. However, its adaptation to temporal networks remains non-trivial. We here present a temporal Gillespie algorithm that solves this problem. Our method is applicable to general Poisson (constant-rate) processes on temporal networks, stochastically exact, and up to multiple orders of magnitude faster than traditional simulation schemes based on rejection sampling. We also show how it can be extended to simulate non-Markovian processes. The algorithm is easily applicable in practice, and as an illustration we detail how to simulate both Poissonian and non-Markovian models of epidemic spreading. Namely, we provide pseudocode and its implementation in C++ for simulating the paradigmatic Susceptible-Infected-Susceptible and Susceptible-Infected-Recovered models and a Susceptible-Infected-Recovered model with non-constant recovery rates. For empirical networks, the temporal Gillespie algorithm is here typically from 10 to 100 times faster than rejection sampling.

An adaptive clustering approach to dynamic load balancing and energy efficiency in wireless sensor networks

International Nuclear Information System (INIS)

Gherbi, Chirihane; Aliouat, Zibouda; Benmohammed, Mohamed

2016-01-01

Clustering is a well known approach to cope with large nodes density and efficiently conserving energy in Wireless Sensor Networks (WSN). Load balancing is an effective approach for optimizing resources like channel bandwidth, the main objective of this paper is to combine these two valuable approaches in order to significantly improve the main WSN service such as information routing. So, our proposal is a routing protocol in which load traffic is shared among cluster members in order to reduce the dropping probability due to queue overflow at some nodes. To this end, a novel hierarchical approach, called Hierarchical Energy-Balancing Multipath routing protocol for Wireless Sensor Networks (HEBM) is proposed. The HEBM approach aims to fulfill the following purposes: decreasing the overall network energy consumption, balancing the energy dissipation among the sensor nodes and as direct consequence: extending the lifetime of the network. In fact, the cluster-heads are optimally determined and suitably distributed over the area of interest allowing the member nodes reaching them with adequate energy dissipation and appropriate load balancing utilization. In addition, nodes radio are turned off for fixed time duration according to sleeping control rules optimizing so their energy consumption. The performance evaluation of the proposed protocol is carried out through the well-known NS2 simulator and the exhibited results are convincing. Like this, the residual energy of sensor nodes was measured every 20 s throughout the duration of simulation, in order to calculate the total number of alive nodes. Based on the simulation results, we concluded that our proposed HEBM protocol increases the profit of energy, and prolongs the network lifetime duration from 32% to 40% compared to DEEAC reference protocol and from 25% to 28% compared to FEMCHRP protocol. The authors also note that the proposed protocol is 41.7% better than DEEAC with respect to FND (Fist node die), and 25

Random vs. Combinatorial Methods for Discrete Event Simulation of a Grid Computer Network

Science.gov (United States)

Kuhn, D. Richard; Kacker, Raghu; Lei, Yu

2010-01-01

This study compared random and t-way combinatorial inputs of a network simulator, to determine if these two approaches produce significantly different deadlock detection for varying network configurations. Modeling deadlock detection is important for analyzing configuration changes that could inadvertently degrade network operations, or to determine modifications that could be made by attackers to deliberately induce deadlock. Discrete event simulation of a network may be conducted using random generation, of inputs. In this study, we compare random with combinatorial generation of inputs. Combinatorial (or t-way) testing requires every combination of any t parameter values to be covered by at least one test. Combinatorial methods can be highly effective because empirical data suggest that nearly all failures involve the interaction of a small number of parameters (1 to 6). Thus, for example, if all deadlocks involve at most 5-way interactions between n parameters, then exhaustive testing of all n-way interactions adds no additional information that would not be obtained by testing all 5-way interactions. While the maximum degree of interaction between parameters involved in the deadlocks clearly cannot be known in advance, covering all t-way interactions may be more efficient than using random generation of inputs. In this study we tested this hypothesis for t = 2, 3, and 4 for deadlock detection in a network simulation. Achieving the same degree of coverage provided by 4-way tests would have required approximately 3.2 times as many random tests; thus combinatorial methods were more efficient for detecting deadlocks involving a higher degree of interactions. The paper reviews explanations for these results and implications for modeling and simulation.

Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

Energy Technology Data Exchange (ETDEWEB)

Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J. (AbbVie)

2017-02-21

The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP2₁2₁2 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

Science.gov (United States)

Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

2017-07-01

Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir

Computer simulation of randomly cross-linked polymer networks

International Nuclear Information System (INIS)

Williams, Timothy Philip

2002-01-01

In this work, Monte Carlo and Stochastic Dynamics computer simulations of mesoscale model randomly cross-linked networks were undertaken. Task parallel implementations of the lattice Monte Carlo Bond Fluctuation model and Kremer-Grest Stochastic Dynamics bead-spring continuum model were designed and used for this purpose. Lattice and continuum precursor melt systems were prepared and then cross-linked to varying degrees. The resultant networks were used to study structural changes during deformation and relaxation dynamics. The effects of a random network topology featuring a polydisperse distribution of strand lengths and an abundance of pendant chain ends, were qualitatively compared to recent published work. A preliminary investigation into the effects of temperature on the structural and dynamical properties was also undertaken. Structural changes during isotropic swelling and uniaxial deformation, revealed a pronounced non-affine deformation dependant on the degree of cross-linking. Fractal heterogeneities were observed in the swollen model networks and were analysed by considering constituent substructures of varying size. The network connectivity determined the length scales at which the majority of the substructure unfolding process occurred. Simulated stress-strain curves and diffraction patterns for uniaxially deformed swollen networks, were found to be consistent with experimental findings. Analysis of the relaxation dynamics of various network components revealed a dramatic slowdown due to the network connectivity. The cross-link junction spatial fluctuations for networks close to the sol-gel threshold, were observed to be at least comparable with the phantom network prediction. The dangling chain ends were found to display the largest characteristic relaxation time. (author)

FRCA: A Fuzzy Relevance-Based Cluster Head Selection Algorithm for Wireless Mobile Ad-Hoc Sensor Networks

Directory of Open Access Journals (Sweden)

Taegwon Jeong

2011-05-01

Full Text Available Clustering is an important mechanism that efficiently provides information for mobile nodes and improves the processing capacity of routing, bandwidth allocation, and resource management and sharing. Clustering algorithms can be based on such criteria as the battery power of nodes, mobility, network size, distance, speed and direction. Above all, in order to achieve good clustering performance, overhead should be minimized, allowing mobile nodes to join and leave without perturbing the membership of the cluster while preserving current cluster structure as much as possible. This paper proposes a Fuzzy Relevance-based Cluster head selection Algorithm (FRCA to solve problems found in existing wireless mobile ad hoc sensor networks, such as the node distribution found in dynamic properties due to mobility and flat structures and disturbance of the cluster formation. The proposed mechanism uses fuzzy relevance to select the cluster head for clustering in wireless mobile ad hoc sensor networks. In the simulation implemented on the NS-2 simulator, the proposed FRCA is compared with algorithms such as the Cluster-based Routing Protocol (CBRP, the Weighted-based Adaptive Clustering Algorithm (WACA, and the Scenario-based Clustering Algorithm for Mobile ad hoc networks (SCAM. The simulation results showed that the proposed FRCA achieves better performance than that of the other existing mechanisms.

FRCA: a fuzzy relevance-based cluster head selection algorithm for wireless mobile ad-hoc sensor networks.

Science.gov (United States)

Lee, Chongdeuk; Jeong, Taegwon

2011-01-01

Clustering is an important mechanism that efficiently provides information for mobile nodes and improves the processing capacity of routing, bandwidth allocation, and resource management and sharing. Clustering algorithms can be based on such criteria as the battery power of nodes, mobility, network size, distance, speed and direction. Above all, in order to achieve good clustering performance, overhead should be minimized, allowing mobile nodes to join and leave without perturbing the membership of the cluster while preserving current cluster structure as much as possible. This paper proposes a Fuzzy Relevance-based Cluster head selection Algorithm (FRCA) to solve problems found in existing wireless mobile ad hoc sensor networks, such as the node distribution found in dynamic properties due to mobility and flat structures and disturbance of the cluster formation. The proposed mechanism uses fuzzy relevance to select the cluster head for clustering in wireless mobile ad hoc sensor networks. In the simulation implemented on the NS-2 simulator, the proposed FRCA is compared with algorithms such as the Cluster-based Routing Protocol (CBRP), the Weighted-based Adaptive Clustering Algorithm (WACA), and the Scenario-based Clustering Algorithm for Mobile ad hoc networks (SCAM). The simulation results showed that the proposed FRCA achieves better performance than that of the other existing mechanisms.

SELANSI: a toolbox for simulation of stochastic gene regulatory networks.

Science.gov (United States)

Pájaro, Manuel; Otero-Muras, Irene; Vázquez, Carlos; Alonso, Antonio A

2018-03-01

Gene regulation is inherently stochastic. In many applications concerning Systems and Synthetic Biology such as the reverse engineering and the de novo design of genetic circuits, stochastic effects (yet potentially crucial) are often neglected due to the high computational cost of stochastic simulations. With advances in these fields there is an increasing need of tools providing accurate approximations of the stochastic dynamics of gene regulatory networks (GRNs) with reduced computational effort. This work presents SELANSI (SEmi-LAgrangian SImulation of GRNs), a software toolbox for the simulation of stochastic multidimensional gene regulatory networks. SELANSI exploits intrinsic structural properties of gene regulatory networks to accurately approximate the corresponding Chemical Master Equation with a partial integral differential equation that is solved by a semi-lagrangian method with high efficiency. Networks under consideration might involve multiple genes with self and cross regulations, in which genes can be regulated by different transcription factors. Moreover, the validity of the method is not restricted to a particular type of kinetics. The tool offers total flexibility regarding network topology, kinetics and parameterization, as well as simulation options. SELANSI runs under the MATLAB environment, and is available under GPLv3 license at https://sites.google.com/view/selansi. antonio@iim.csic.es. © The Author(s) 2017. Published by Oxford University Press.

Adapted J6/JFH1-based Hepatitis C virus recombinants with genotype-specific NS4A show similar efficacies against lead protease inhibitors, alpha interferon, and a putative NS4A inhibitor

DEFF Research Database (Denmark)

Gottwein, Judith M; Jensen, Sanne B; Serre, Stéphanie B N

2013-01-01

To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a...... (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10 focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A...... (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950...

Time concurrency/phase-time synchronization in digital communications networks

Science.gov (United States)

Kihara, Masami; Imaoka, Atsushi

1990-01-01

Digital communications networks have the intrinsic capability of time synchronization which makes it possible for networks to supply time signals to some applications and services. A practical estimation method for the time concurrency on terrestrial networks is presented. By using this method, time concurrency capability of the Nippon Telegraph and Telephone Corporation (NTT) digital communications network is estimated to be better than 300 ns rms at an advanced level, and 20 ns rms at final level.

Distributed Sleep Scheduling in Wireless Sensor Networks via Fractional Domatic Partitioning

Science.gov (United States)

Schumacher, André; Haanpää, Harri

We consider setting up sleep scheduling in sensor networks. We formulate the problem as an instance of the fractional domatic partition problem and obtain a distributed approximation algorithm by applying linear programming approximation techniques. Our algorithm is an application of the Garg-Könemann (GK) scheme that requires solving an instance of the minimum weight dominating set (MWDS) problem as a subroutine. Our two main contributions are a distributed implementation of the GK scheme for the sleep-scheduling problem and a novel asynchronous distributed algorithm for approximating MWDS based on a primal-dual analysis of Chvátal's set-cover algorithm. We evaluate our algorithm with ns2 simulations.

Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR.

Science.gov (United States)

Shukla, Mohan K; Singh, Neeru; Sharma, Ravendra K; Barde, Pradip V

2017-07-01

The objective of this study was to demonstrate the utility of dengue virus (DENV) non structural protein 1 (NS1) based rapid diagnostic test (RDT) for use in tribal and difficult to reach areas for early dengue (DEN) diagnosis in acute phase patients and evaluate its sensitivity and specificity against DENV NS1 enzyme linked immune sorbent assay (ELISA) and real time reverse transcriptase polymerase chain reaction (qRT-PCR). The DENV NS1 RDT was used for preliminary diagnosis during outbreaks in difficult to reach rural and tribal areas. The diagnosis was confirmed by DENV NS1 ELISA in the laboratory. The samples were also tested and serotyped by qRT-PCR. The results were evaluated using statistical tests. The DENV NS1 RDT showed 99.2% sensitivity and 96.0% specificity when analyzed using DENV NS1 ELISA as standard. The specificity and sensitivity of the RDT when compared with qRT-PCR was 93.6% and 91.1%, respectively. The serotype specific evaluation showed more than 90% sensitivity and specificity for DENV-1, 2, and 3. The RDT proved a good diagnostic tool in difficult to reach rural and tribal areas. Further evaluation studies with different commercially available RDTs in different field conditions are essential, that will help clinicians and patients for treatment and programme managers for timely intervention. © 2017 Wiley Periodicals, Inc.

Simulation technologies in networking and communications selecting the best tool for the test

CERN Document Server

Pathan, Al-Sakib Khan; Khan, Shafiullah

2014-01-01

Simulation is a widely used mechanism for validating the theoretical models of networking and communication systems. Although the claims made based on simulations are considered to be reliable, how reliable they really are is best determined with real-world implementation trials.Simulation Technologies in Networking and Communications: Selecting the Best Tool for the Test addresses the spectrum of issues regarding the different mechanisms related to simulation technologies in networking and communications fields. Focusing on the practice of simulation testing instead of the theory, it presents

Limits to high-speed simulations of spiking neural networks using general-purpose computers.

Science.gov (United States)

Zenke, Friedemann; Gerstner, Wulfram

2014-01-01

To understand how the central nervous system performs computations using recurrent neuronal circuitry, simulations have become an indispensable tool for theoretical neuroscience. To study neuronal circuits and their ability to self-organize, increasing attention has been directed toward synaptic plasticity. In particular spike-timing-dependent plasticity (STDP) creates specific demands for simulations of spiking neural networks. On the one hand a high temporal resolution is required to capture the millisecond timescale of typical STDP windows. On the other hand network simulations have to evolve over hours up to days, to capture the timescale of long-term plasticity. To do this efficiently, fast simulation speed is the crucial ingredient rather than large neuron numbers. Using different medium-sized network models consisting of several thousands of neurons and off-the-shelf hardware, we compare the simulation speed of the simulators: Brian, NEST and Neuron as well as our own simulator Auryn. Our results show that real-time simulations of different plastic network models are possible in parallel simulations in which numerical precision is not a primary concern. Even so, the speed-up margin of parallelism is limited and boosting simulation speeds beyond one tenth of real-time is difficult. By profiling simulation code we show that the run times of typical plastic network simulations encounter a hard boundary. This limit is partly due to latencies in the inter-process communications and thus cannot be overcome by increased parallelism. Overall, these results show that to study plasticity in medium-sized spiking neural networks, adequate simulation tools are readily available which run efficiently on small clusters. However, to run simulations substantially faster than real-time, special hardware is a prerequisite.

Small-angle X-Ray analysis of macromolecular structure: the structure of protein NS2 (NEP) in solution

Science.gov (United States)

Shtykova, E. V.; Bogacheva, E. N.; Dadinova, L. A.; Jeffries, C. M.; Fedorova, N. V.; Golovko, A. O.; Baratova, L. A.; Batishchev, O. V.

2017-11-01

A complex structural analysis of nuclear export protein NS2 (NEP) of influenza virus A has been performed using bioinformatics predictive methods and small-angle X-ray scattering data. The behavior of NEP molecules in a solution (their aggregation, oligomerization, and dissociation, depending on the buffer composition) has been investigated. It was shown that stable associates are formed even in a conventional aqueous salt solution at physiological pH value. For the first time we have managed to get NEP dimers in solution, to analyze their structure, and to compare the models obtained using the method of the molecular tectonics with the spatial protein structure predicted by us using the bioinformatics methods. The results of the study provide a new insight into the structural features of nuclear export protein NS2 (NEP) of the influenza virus A, which is very important for viral infection development.

XNsim: Internet-Enabled Collaborative Distributed Simulation via an Extensible Network

Science.gov (United States)

Novotny, John; Karpov, Igor; Zhang, Chendi; Bedrossian, Nazareth S.

2007-01-01

In this paper, the XNsim approach to achieve Internet-enabled, dynamically scalable collaborative distributed simulation capabilities is presented. With this approach, a complete simulation can be assembled from shared component subsystems written in different formats, that run on different computing platforms, with different sampling rates, in different geographic locations, and over singlelmultiple networks. The subsystems interact securely with each other via the Internet. Furthermore, the simulation topology can be dynamically modified. The distributed simulation uses a combination of hub-and-spoke and peer-topeer network topology. A proof-of-concept demonstrator is also presented. The XNsim demonstrator can be accessed at http://www.jsc.draver.corn/xn that hosts various examples of Internet enabled simulations.

Coarse-grained simulation of a real-time process control network under peak load

International Nuclear Information System (INIS)

George, A.D.; Clapp, N.E. Jr.

1992-01-01

This paper presents a simulation study on the real-time process control network proposed for the new ANS reactor system at ORNL. A background discussion is provided on networks, modeling, and simulation, followed by an overview of the ANS process control network, its three peak-load models, and the results of a series of coarse-grained simulation studies carried out on these models using implementations of 802.3, 802.4, and 802.5 standard local area networks

Exploring a model of human chemokine receptor CCR2 in presence of TAK779: A membrane based molecular dynamics study

Science.gov (United States)

Balupuri, Anand; Sobhia, M. Elizabeth

2014-04-01

Chemokine receptor 2 (CCR2) is a G-protein coupled receptor (GPCR) and a crucial target for various inflammation-driven diseases. In the present study, molecular docking and molecular dynamics simulations were performed on a CCR2 homology model. This work includes the comparative MD simulations of uncomplexed and ‘antagonist-complexed’ CCR2 models. These simulations yield insights into the binding mechanism of antagonist TAK779 and improve the understanding of various structural changes induced by the ligand in the CCR2 protein. Here, one 20 ns MD simulation was carried out on the uncomplexed CCR2 model in lipid bilayer to explore the effects of lipid membrane on the protein. Another 20 ns MD simulation was performed under the similar conditions on the docked CCR2-TAK779 complex. An alteration in the position and orientation of the ligand in binding site was observed after the simulation. Examination of protein-ligand complex suggested that TAK779 produced a greater structural change on the TM-III, TM-IV, TM-V and TM-VI than TM-I, TM-II and TM-VII. Interaction networks involving the conserved residues of uncomplexed and ‘antagonist-complexed’ CCR2 models were also examined. The major difference was observed to be the role of conserved residues of the DRY motif of TM-III and the NPxxY motif of TM-VII of CCR2.

Speeding Up Network Simulations Using Discrete Time

OpenAIRE

Lucas, Aaron; Armbruster, Benjamin

2013-01-01

We develop a way of simulating disease spread in networks faster at the cost of some accuracy. Instead of a discrete event simulation (DES) we use a discrete time simulation. This aggregates events into time periods. We prove a bound on the accuracy attained. We also discuss the choice of step size and do an analytical comparison of the computational costs. Our error bound concept comes from the theory of numerical methods for SDEs and the basic proof structure comes from the theory of numeri...

Distributed Sensor Network Software Development Testing through Simulation

Energy Technology Data Exchange (ETDEWEB)

Brennan, Sean M. [Univ. of New Mexico, Albuquerque, NM (United States)

2003-12-01

The distributed sensor network (DSN) presents a novel and highly complex computing platform with dif culties and opportunities that are just beginning to be explored. The potential of sensor networks extends from monitoring for threat reduction, to conducting instant and remote inventories, to ecological surveys. Developing and testing for robust and scalable applications is currently practiced almost exclusively in hardware. The Distributed Sensors Simulator (DSS) is an infrastructure that allows the user to debug and test software for DSNs independent of hardware constraints. The exibility of DSS allows developers and researchers to investigate topological, phenomenological, networking, robustness and scaling issues, to explore arbitrary algorithms for distributed sensors, and to defeat those algorithms through simulated failure. The user speci es the topology, the environment, the application, and any number of arbitrary failures; DSS provides the virtual environmental embedding.

X-ray structure of the pestivirus NS3 helicase and its conformation in solution.

Science.gov (United States)

Tortorici, M Alejandra; Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice; Rey, Félix A

2015-04-01

Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the

Enhancement of Adaptive Cluster Hierarchical Routing Protocol using Distance and Energy for Wireless Sensor Networks

International Nuclear Information System (INIS)

Nawar, N.M.; Soliman, S.E.; Kelash, H.M.; Ayad, N.M.

2014-01-01

The application of wireless networking is widely used in nuclear applications. This includes reactor control and fire dedication system. This paper is devoted to the application of this concept in the intrusion system of the Radioisotope Production Facility (RPF) of the Egyptian Atomic Energy Authority. This includes the tracking, monitoring and control components of this system. The design and implementation of wireless sensor networks has become a hot area of research due to the extensive use of sensor networks to enable applications that connect the physical world to the virtual world [1-2]. The original LEACH is named a communication protocol (clustering-based); the extended LEACH’s stochastic cluster head selection algorithm by a deterministic component. Depending on the network configuration an increase of network lifetime can be accomplished [3]. The proposed routing mechanisms after enhancement divide the nodes into clusters. A cluster head performs its task which is considerably more energy-intensive than the rest of the nodes inside sensor network. So, nodes rotate tasks at different rounds between a cluster head and other sensors throughout the lifetime of the network to balance the energy dissipation [4-5].The performance improvement when using routing protocol after enhancement of the algorithm which takes into consideration the distance and the remaining energy for choosing the cluster head by obtains from the advertise message. Network Simulator (Ns2 simulator) is used to prove that LEACH after enhancement performs better than the original LEACH protocol in terms of Average Energy, Network Life Time, Delay, Throughput and Overhead.

The design of a network emulation and simulation laboratory

CSIR Research Space (South Africa)

Von Solms, S

2015-07-01

Full Text Available The development of the Network Emulation and Simulation Laboratory is motivated by the drive to contribute to the enhancement of the security and resilience of South Africa's critical information infrastructure. The goal of the Network Emulation...

ESIM_DSN Web-Enabled Distributed Simulation Network

Science.gov (United States)

Bedrossian, Nazareth; Novotny, John

2002-01-01

In this paper, the eSim(sup DSN) approach to achieve distributed simulation capability using the Internet is presented. With this approach a complete simulation can be assembled from component subsystems that run on different computers. The subsystems interact with each other via the Internet The distributed simulation uses a hub-and-spoke type network topology. It provides the ability to dynamically link simulation subsystem models to different computers as well as the ability to assign a particular model to each computer. A proof-of-concept demonstrator is also presented. The eSim(sup DSN) demonstrator can be accessed at http://www.jsc.draper.com/esim which hosts various examples of Web enabled simulations.

Relativistic calculations of the fine-structure intervals of the ns2np2P terms and the ionization energies of the Ca-, Sr-and Ba- ions

International Nuclear Information System (INIS)

Wijesundera, W.P.; Vosko, S.H.; Parpia, F.A.

1996-01-01

We report new calculations of the energy differences between the ns 1/2 2 np 1/2 and ns 1/2 2 np 3/2 levels of the Ca - , Sr - and Ba - ions; here n 4, 5 and 6 for Ca - , Sr - and Ba - , respectively. The electron affinities of Ca, Ba and Sr have also been calculated. All estimates were obtained by performing a series of multiconfiguration Dirac-Fock calculations for the neutral atoms and their anions. Correlations among valence electrons in both the ground and excited states were included in these calculations. Our estimate of the fine structure of the ground state of Sr - is in good agreement with recent measurements. Our estimates of the electron affinities of Ca, Sr and Ba are in reasonable agreement with experiment. (author)

Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

Directory of Open Access Journals (Sweden)

Amol Hartalkar

2015-08-01

Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

Biochemical Network Stochastic Simulator (BioNetS: software for stochastic modeling of biochemical networks

Directory of Open Access Journals (Sweden)

Elston Timothy C

2004-03-01

Full Text Available Abstract Background Intrinsic fluctuations due to the stochastic nature of biochemical reactions can have large effects on the response of biochemical networks. This is particularly true for pathways that involve transcriptional regulation, where generally there are two copies of each gene and the number of messenger RNA (mRNA molecules can be small. Therefore, there is a need for computational tools for developing and investigating stochastic models of biochemical networks. Results We have developed the software package Biochemical Network Stochastic Simulator (BioNetS for efficientlyand accurately simulating stochastic models of biochemical networks. BioNetS has a graphical user interface that allows models to be entered in a straightforward manner, and allows the user to specify the type of random variable (discrete or continuous for each chemical species in the network. The discrete variables are simulated using an efficient implementation of the Gillespie algorithm. For the continuous random variables, BioNetS constructs and numerically solvesthe appropriate chemical Langevin equations. The software package has been developed to scale efficiently with network size, thereby allowing large systems to be studied. BioNetS runs as a BioSpice agent and can be downloaded from http://www.biospice.org. BioNetS also can be run as a stand alone package. All the required files are accessible from http://x.amath.unc.edu/BioNetS. Conclusions We have developed BioNetS to be a reliable tool for studying the stochastic dynamics of large biochemical networks. Important features of BioNetS are its ability to handle hybrid models that consist of both continuous and discrete random variables and its ability to model cell growth and division. We have verified the accuracy and efficiency of the numerical methods by considering several test systems.

Drug Abuse Warning Network US (DAWN-NS-1994)

Data.gov (United States)

U.S. Department of Health & Human Services — The Drug Abuse Warning Network (DAWN) survey is designed to capture data on emergency department (ED) episodes that are induced by or related to the use of an...

Drug Abuse Warning Network US (DAWN-NS-1997)

Data.gov (United States)

U.S. Department of Health & Human Services — The Drug Abuse Warning Network (DAWN) survey is designed to capture data on emergency department (ED) episodes that are induced by or related to the use of an...

Increased longevity of wireless Ad hoc network through fuzzy system

Directory of Open Access Journals (Sweden)

Fawzia Abdali Larki

2014-06-01

Full Text Available The Ad hoc network is one of the multistep-based self-organizing networks, which are dynamically changing and are taken more into account as the ways of connecting the terminals through the development of wireless communication terminals. We are faced with numerous challenges in designing a wireless network such as the dynamic topology, common and limited bandwidth, and the limited energy. The nodes are moving according to the continuous changes in the topology and the source-to-destination paths are completely broken. Therefore, the repeated route discovery enhances the delay and overload of routing. Thus, it is essential to consider the link stability while designing the path in order to choose the routing protocol. Providing the multiple paths may lead to the better performance than a path. The transmission energy control in the wireless Ad hoc networks is the option for the level of transmission energy in order to transmit each node packet in this system. Therefore, transmission energy control affects the wireless medium interface. Because of choosing the appropriate protocol, the routing operation can be improved and the energy consumption can be controlled properly as well as enhancing the durability and longevity of network. The main objective of this study is to enhance the network longevity. The proposed algorithm in this research considers the combination of 2 parameters including the rate of node energy and number of steps in Fuzzy System applied on AOMDV Protocol, which is a Multipath Routing Protocol. The results of simulation also indicate the improved performance of proposed algorithm (AOMDV-F compared to AODV and AOMDV Protocols in NS2 simulator.

Distributed dynamic simulations of networked control and building performance applications.

Science.gov (United States)

Yahiaoui, Azzedine

2018-02-01

The use of computer-based automation and control systems for smart sustainable buildings, often so-called Automated Buildings (ABs), has become an effective way to automatically control, optimize, and supervise a wide range of building performance applications over a network while achieving the minimum energy consumption possible, and in doing so generally refers to Building Automation and Control Systems (BACS) architecture. Instead of costly and time-consuming experiments, this paper focuses on using distributed dynamic simulations to analyze the real-time performance of network-based building control systems in ABs and improve the functions of the BACS technology. The paper also presents the development and design of a distributed dynamic simulation environment with the capability of representing the BACS architecture in simulation by run-time coupling two or more different software tools over a network. The application and capability of this new dynamic simulation environment are demonstrated by an experimental design in this paper.

Fuzzy Logic-based Intelligent Scheme for Enhancing QoS of Vertical Handover Decision in Vehicular Ad-hoc Networks

Science.gov (United States)

Azzali, F.; Ghazali, O.; Omar, M. H.

2017-08-01

The design of next generation networks in various technologies under the “Anywhere, Anytime” paradigm offers seamless connectivity across different coverage. A conventional algorithm such as RSSThreshold algorithm, that only uses the received strength signal (RSS) as a metric, will decrease handover performance regarding handover latency, delay, packet loss, and handover failure probability. Moreover, the RSS-based algorithm is only suitable for horizontal handover decision to examine the quality of service (QoS) compared to the vertical handover decision in advanced technologies. In the next generation network, vertical handover can be started based on the user’s convenience or choice rather than connectivity reasons. This study proposes a vertical handover decision algorithm that uses a Fuzzy Logic (FL) algorithm, to increase QoS performance in heterogeneous vehicular ad-hoc networks (VANET). The study uses network simulator 2.29 (NS 2.29) along with the mobility traffic network and generator to implement simulation scenarios and topologies. This helps the simulation to achieve a realistic VANET mobility scenario. The required analysis on the performance of QoS in the vertical handover can thus be conducted. The proposed Fuzzy Logic algorithm shows improvement over the conventional algorithm (RSSThreshold) in the average percentage of handover QoS whereby it achieves 20%, 21% and 13% improvement on handover latency, delay, and packet loss respectively. This is achieved through triggering a process in layer two and three that enhances the handover performance.

Cascading Denial of Service Attacks on Wi-Fi Networks

OpenAIRE

Xin, Liangxiao; Starobinski, David; Noubir, Guevara

2016-01-01

We unveil the existence of a vulnerability in Wi-Fi, which allows an adversary to remotely launch a Denial-of-Service (DoS) attack that propagates both in time and space. This vulnerability stems from a coupling effect induced by hidden nodes. Cascading DoS attacks can congest an entire network and do not require the adversary to violate any protocol. We demonstrate the feasibility of such attacks through experiments with real Wi-Fi cards, extensive ns-3 simulations, and theoretical analysis....

EEG simulation by 2D interconnected chaotic oscillators

Energy Technology Data Exchange (ETDEWEB)

Kubany, Adam, E-mail: adamku@bgu.ac.i [Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105 (Israel); Mhabary, Ziv; Gontar, Vladimir [Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105 (Israel)

2011-01-15

Research highlights: ANN of 2D interconnected chaotic oscillators is explored for EEG simulation. An inverse problem solution (PRCGA) is proposed. Good matching between the simulated and experimental EEG signals has been achieved. - Abstract: An artificial neuronal network composed by 2D interconnected chaotic oscillators is explored for brain waves (EEG) simulation. For the inverse problem solution a parallel real-coded genetic algorithm (PRCGA) is proposed. In order to conduct thorough comparison between the simulated and target signal characteristics, a spectrum analysis of the signals is undertaken. A good matching between the theoretical and experimental EEG signals has been achieved. Numerical results of calculations are presented and discussed.

EEG simulation by 2D interconnected chaotic oscillators

International Nuclear Information System (INIS)

Kubany, Adam; Mhabary, Ziv; Gontar, Vladimir

2011-01-01

Research highlights: → ANN of 2D interconnected chaotic oscillators is explored for EEG simulation. → An inverse problem solution (PRCGA) is proposed. → Good matching between the simulated and experimental EEG signals has been achieved. - Abstract: An artificial neuronal network composed by 2D interconnected chaotic oscillators is explored for brain waves (EEG) simulation. For the inverse problem solution a parallel real-coded genetic algorithm (PRCGA) is proposed. In order to conduct thorough comparison between the simulated and target signal characteristics, a spectrum analysis of the signals is undertaken. A good matching between the theoretical and experimental EEG signals has been achieved. Numerical results of calculations are presented and discussed.

Simulation studies of a wide area health care network.

Science.gov (United States)

McDaniel, J. G.

1994-01-01

There is an increasing number of efforts to install wide area health care networks. Some of these networks are being built to support several applications over a wide user base consisting primarily of medical practices, hospitals, pharmacies, medical laboratories, payors, and suppliers. Although on-line, multi-media telecommunication is desirable for some purposes such as cardiac monitoring, store-and-forward messaging is adequate for many common, high-volume applications. Laboratory test results and payment claims, for example, can be distributed using electronic messaging networks. Several network prototypes have been constructed to determine the technical problems and to assess the effectiveness of electronic messaging in wide area health care networks. Our project, Health Link, developed prototype software that was able to use the public switched telephone network to exchange messages automatically, reliably and securely. The network could be configured to accommodate the many different traffic patterns and cost constraints of its users. Discrete event simulations were performed on several network models. Canonical star and mesh networks, that were composed of nodes operating at steady state under equal loads, were modeled. Both topologies were found to support the throughput of a generic wide area health care network. The mean message delivery time of the mesh network was found to be less than that of the star network. Further simulations were conducted for a realistic large-scale health care network consisting of 1,553 doctors, 26 hospitals, four medical labs, one provincial lab and one insurer. Two network topologies were investigated: one using predominantly peer-to-peer communication, the other using client-server communication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7949966

PERFORMANCE EVALUATION OF INTEGRATED MACRO AND MICRO MOBILITY PROTOCOLS FOR WIDE AREA WIRELESS NETWORKS

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R.Gunasundari

2010-03-01

Full Text Available The success of next generation wireless networks will rely much on advanced mechanisms for seamless mobility support among emerging heterogeneous technologies. Currently, Mobile IP is the most promising solution for mobility management in the Internet. Several IP micro mobility approaches have been proposed to enhance the performance of Mobile IP which supports quality of service, minimum packet loss, limited handoff delay and scalability and power conservation but they are not scalable for macro mobility. A practical solution would therefore require integration of Mobile IP and Micro mobility protocols where Mobile IP handles macro mobility and micro mobility protocols handles micro mobility. In this paper an integrated mobility management protocol for IP based wireless networks is proposed and analyzed. Simulation results presented in this paper are based on ns 2.

Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses.

Science.gov (United States)

Aydillo, Teresa; Ayllon, Juan; Pavlisin, Amzie; Martinez-Romero, Carles; Tripathi, Shashank; Mena, Ignacio; Moreira-Soto, Andrés; Vicente-Santos, Amanda; Corrales-Aguilar, Eugenia; Schwemmle, Martin; García-Sastre, Adolfo

2018-04-01

Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1 -/- human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein. IMPORTANCE Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique

COEL: A Cloud-based Reaction Network Simulator

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Peter eBanda

2016-04-01

Full Text Available Chemical Reaction Networks (CRNs are a formalism to describe the macroscopic behavior of chemical systems. We introduce COEL, a web- and cloud-based CRN simulation framework that does not require a local installation, runs simulations on a large computational grid, provides reliable database storage, and offers a visually pleasing and intuitive user interface. We present an overview of the underlying software, the technologies, and the main architectural approaches employed. Some of COEL's key features include ODE-based simulations of CRNs and multicompartment reaction networks with rich interaction options, a built-in plotting engine, automatic DNA-strand displacement transformation and visualization, SBML/Octave/Matlab export, and a built-in genetic-algorithm-based optimization toolbox for rate constants.COEL is an open-source project hosted on GitHub (http://dx.doi.org/10.5281/zenodo.46544, which allows interested research groups to deploy it on their own sever. Regular users can simply use the web instance at no cost at http://coel-sim.org. The framework is ideally suited for a collaborative use in both research and education.

Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized by different immunoglobulin E-binding properties.

Science.gov (United States)

Bolla, Michela; Zenoni, Sara; Scheurer, Stephan; Vieths, Stefan; San Miguel Moncin, Maria Del Mar; Olivieri, Mario; Antico, Andrea; Ferrer, Marta; Berroa, Felicia; Enrique, Ernesto; Avesani, Linda; Marsano, Francesco; Zoccatelli, Gianni

2014-01-01

Pomegranate allergy is associated with sensitization to non-specific lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the non-specific nsLTPs expressed in pomegranate at the molecular level and to study their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross-reactivity with peach nsLTP (Pru p 3). A non-equilibrium two-dimensional (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera from pomegranate-allergic patients. For final identification, pomegranate nsLTPs were purified by chromatography and subjected to trypsin digestion and mass spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA cloning of three pomegranate nsLTPs were integrated in the database that was subsequently searched for MS data interpretation. Four nsLTPs were identified by 2-D immunoblotting. The detected proteins showed different IgE-binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS analyses led to the identification of three nsLTP isoforms with 66-68% amino acid sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. By 2-D electrophoresis, we could separate different nsLTP isoforms possessing different IgE-binding properties, which might reflect peculiar allergenic potencies. The contribution of Pru p 3 to prime sensitization is not central as in other plant nsLTPs. © 2014 S. Karger AG, Basel.

Simulated epidemics in an empirical spatiotemporal network of 50,185 sexual contacts.

Directory of Open Access Journals (Sweden)

Luis E C Rocha

2011-03-01

Full Text Available Sexual contact patterns, both in their temporal and network structure, can influence the spread of sexually transmitted infections (STI. Most previous literature has focused on effects of network topology; few studies have addressed the role of temporal structure. We simulate disease spread using SI and SIR models on an empirical temporal network of sexual contacts in high-end prostitution. We compare these results with several other approaches, including randomization of the data, classic mean-field approaches, and static network simulations. We observe that epidemic dynamics in this contact structure have well-defined, rather high epidemic thresholds. Temporal effects create a broad distribution of outbreak sizes, even if the per-contact transmission probability is taken to its hypothetical maximum of 100%. In general, we conclude that the temporal correlations of our network accelerate outbreaks, especially in the early phase of the epidemics, while the network topology (apart from the contact-rate distribution slows them down. We find that the temporal correlations of sexual contacts can significantly change simulated outbreaks in a large empirical sexual network. Thus, temporal structures are needed alongside network topology to fully understand the spread of STIs. On a side note, our simulations further suggest that the specific type of commercial sex we investigate is not a reservoir of major importance for HIV.

Experimental voyages of N.S. Mutsu

International Nuclear Information System (INIS)

Ochiai, Masaaki

1993-01-01

The first Japanese nuclear ship, N.S. MUTSU was commissioned by the Government on February 14 1991, after power up test and official sea trial with much success. Four experimental voyages of the ship were taken in the Pacific Ocean from March to December 1991 to study the performance of the nuclear power plant when it was influenced by marine conditions. In such an environment, incessant ship motion and load changes due to wave, wind, maneuvering, etc. are experienced. The ship sailed for a total of 110 days, a total distance of 64,180 km and for a total reactor operating time of 2,321 hours. Integrated reactor power was about 2,250 efph (effective full power hour) including that during the power up test. Zero power experiments were done again in Jan. 1992 to measure the core characteristics after finishing all the N.S. MUTSU plant operation program. Thus the most essential parts in the R ampersand D program on N.S. MUTSU was completed. The voyages demonstrated that the nuclear power plant worked well in any case and that the plant system had excellent capability as a marine engine. The data acquired through the experiments will contribute to the research and development program of the advanced marine reactor in Japan Atomic Energy Research Institute. This paper describes the technical informations obtained through the experimental voyages, such as load following abilities, system performances during the high sea sailing and the tropical sea sailing and behavior of system parameters accompanied with steering. The latest technical results yielded by the program are also summarized here

Future planning: default network activity couples with frontoparietal control network and reward-processing regions during process and outcome simulations.

Science.gov (United States)

Gerlach, Kathy D; Spreng, R Nathan; Madore, Kevin P; Schacter, Daniel L

2014-12-01

We spend much of our daily lives imagining how we can reach future goals and what will happen when we attain them. Despite the prevalence of such goal-directed simulations, neuroimaging studies on planning have mainly focused on executive processes in the frontal lobe. This experiment examined the neural basis of process simulations, during which participants imagined themselves going through steps toward attaining a goal, and outcome simulations, during which participants imagined events they associated with achieving a goal. In the scanner, participants engaged in these simulation tasks and an odd/even control task. We hypothesized that process simulations would recruit default and frontoparietal control network regions, and that outcome simulations, which allow us to anticipate the affective consequences of achieving goals, would recruit default and reward-processing regions. Our analysis of brain activity that covaried with process and outcome simulations confirmed these hypotheses. A functional connectivity analysis with posterior cingulate, dorsolateral prefrontal cortex and anterior inferior parietal lobule seeds showed that their activity was correlated during process simulations and associated with a distributed network of default and frontoparietal control network regions. During outcome simulations, medial prefrontal cortex and amygdala seeds covaried together and formed a functional network with default and reward-processing regions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Large-scale modeling of epileptic seizures: scaling properties of two parallel neuronal network simulation algorithms.

Science.gov (United States)

Pesce, Lorenzo L; Lee, Hyong C; Hereld, Mark; Visser, Sid; Stevens, Rick L; Wildeman, Albert; van Drongelen, Wim

2013-01-01

Our limited understanding of the relationship between the behavior of individual neurons and large neuronal networks is an important limitation in current epilepsy research and may be one of the main causes of our inadequate ability to treat it. Addressing this problem directly via experiments is impossibly complex; thus, we have been developing and studying medium-large-scale simulations of detailed neuronal networks to guide us. Flexibility in the connection schemas and a complete description of the cortical tissue seem necessary for this purpose. In this paper we examine some of the basic issues encountered in these multiscale simulations. We have determined the detailed behavior of two such simulators on parallel computer systems. The observed memory and computation-time scaling behavior for a distributed memory implementation were very good over the range studied, both in terms of network sizes (2,000 to 400,000 neurons) and processor pool sizes (1 to 256 processors). Our simulations required between a few megabytes and about 150 gigabytes of RAM and lasted between a few minutes and about a week, well within the capability of most multinode clusters. Therefore, simulations of epileptic seizures on networks with millions of cells should be feasible on current supercomputers.

Large-Scale Modeling of Epileptic Seizures: Scaling Properties of Two Parallel Neuronal Network Simulation Algorithms

Directory of Open Access Journals (Sweden)

Lorenzo L. Pesce

2013-01-01

Full Text Available Our limited understanding of the relationship between the behavior of individual neurons and large neuronal networks is an important limitation in current epilepsy research and may be one of the main causes of our inadequate ability to treat it. Addressing this problem directly via experiments is impossibly complex; thus, we have been developing and studying medium-large-scale simulations of detailed neuronal networks to guide us. Flexibility in the connection schemas and a complete description of the cortical tissue seem necessary for this purpose. In this paper we examine some of the basic issues encountered in these multiscale simulations. We have determined the detailed behavior of two such simulators on parallel computer systems. The observed memory and computation-time scaling behavior for a distributed memory implementation were very good over the range studied, both in terms of network sizes (2,000 to 400,000 neurons and processor pool sizes (1 to 256 processors. Our simulations required between a few megabytes and about 150 gigabytes of RAM and lasted between a few minutes and about a week, well within the capability of most multinode clusters. Therefore, simulations of epileptic seizures on networks with millions of cells should be feasible on current supercomputers.

Isolation and sequence analysis of the complete NS1 and VP2 genes of canine parvovirus from domestic dogs in 2013 and 2014 in China.

Science.gov (United States)

Wang, Hualei; Jin, Hongli; Li, Qian; Zhao, Guoxing; Cheng, Nan; Feng, Na; Zheng, Xuexing; Wang, Jianzhong; Zhao, Yongkun; Li, Ling; Cao, Zengguo; Yan, Feihu; Wang, Lina; Wang, Tiecheng; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu

2016-02-01

Canine parvovirus (CPV) can cause severe disease in animals and continuously generates new variant and recombinant strains in dogs that have a strong impact on sanitation. It is therefore necessary to investigate epidemic CPV strains to improve our understanding of CPV transmission and epidemic behavior. However, most studies have focused on the analysis of VP2, and therefore, information about recombination and relationships between strains is still lacking. Here, 14 strains of CPV were isolated from domestic dogs suspected of hosting CPV between 2013 and 2014 in China. The complete NS1 and VP2 genes were sequenced and analyzed. The results suggest that the new CPV-2a and new CPV-2b types are the prevalent strains in China. In addition to a few mutations (residues 19, 544, 545, 572 and 583 of NS1 and residues 267, 370, 377 and 440 of VP2) that were preserved during transmission, new mutations (residues 60, 630 of NS1, and residues 21, 310 of VP2) were found in the isolated strains. A phylogenetic tree based on VP2 sequences illustrated that the new CPV-2a and new CPV-2b strains from China form single clusters that are distinct from lineages from other countries. Moreover, recombination between the new CPV-2a and new CPV-2b types was also identified in the isolated strains. Due to differences in selection pressures or recombination, there were a small number of inconsistencies between the phylogenetic trees for VP2 and NS1, which indicated that phylogenetic relationships based on VP2 might not be representative of those based on NS1. The data indicated that mutations and recombination are constantly occurring along with the spread of CPV in China.

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

International Nuclear Information System (INIS)

Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan; Bi, Jing; Wang, Dang; Xiao, Shaobo

2016-01-01

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

Energy Technology Data Exchange (ETDEWEB)

Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Bi, Jing [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); Department of Immunology and Aetology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan 430065 (China); Wang, Dang [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Xiao, Shaobo, E-mail: vet@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China)

2016-12-15

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

Fracture network modeling and GoldSim simulation support

International Nuclear Information System (INIS)

Sugita, Kenichiro; Dershowitz, William

2004-01-01

During Heisei-15, Golder Associates provided support for JNC Tokai through discrete fracture network data analysis and simulation of the MIU Underground Rock Laboratory, participation in Task 6 of the Aespoe Task Force on Modelling of Groundwater Flow and Transport, and development of methodologies for analysis of repository site characterization strategies and safety assessment. MIU Underground Rock Laboratory support during H-15 involved development of new discrete fracture network (DFN) models for the MIU Shoba-sama Site, in the region of shaft development. Golder developed three DFN models for the site using discrete fracture network, equivalent porous medium (EPM), and nested DFN/EPM approaches. Each of these models were compared based upon criteria established for the multiple modeling project (MMP). Golder supported JNC participation in Task 6AB, 6D and 6E of the Aespoe Task Force on Modelling of Groundwater Flow and Transport during H-15. For Task 6AB, Golder implemented an updated microstructural model in GoldSim, and used this updated model to simulate the propagation of uncertainty from experimental to safety assessment time scales, for 5 m scale transport path lengths. Task 6D and 6E compared safety assessment (PA) and experimental time scale simulations in a 200 m scale discrete fracture network. For Task 6D, Golder implemented a DFN model using FracMan/PA Works, and determined the sensitivity of solute transport to a range of material property and geometric assumptions. For Task 6E, Golder carried out demonstration FracMan/PA Works transport calculations at a 1 million year time scale, to ensure that task specifications are realistic. The majority of work for Task 6E will be carried out during H-16. During H-15, Golder supported JNC's Total System Performance Assessment (TSPO) strategy by developing technologies for the analysis of precipitant concentration. These approaches were based on the GoldSim precipitant data management features, and were

Simulating individual-based models of epidemics in hierarchical networks

NARCIS (Netherlands)

Quax, R.; Bader, D.A.; Sloot, P.M.A.

2009-01-01

Current mathematical modeling methods for the spreading of infectious diseases are too simplified and do not scale well. We present the Simulator of Epidemic Evolution in Complex Networks (SEECN), an efficient simulator of detailed individual-based models by parameterizing separate dynamics

CoSimulating Communication Networks and Electrical System for Performance Evaluation in Smart Grid

Directory of Open Access Journals (Sweden)

Hwantae Kim

2018-01-01

Full Text Available In smart grid research domain, simulation study is the first choice, since the analytic complexity is too high and constructing a testbed is very expensive. However, since communication infrastructure and the power grid are tightly coupled with each other in the smart grid, a well-defined combination of simulation tools for the systems is required for the simulation study. Therefore, in this paper, we propose a cosimulation work called OOCoSim, which consists of OPNET (network simulation tool and OpenDSS (power system simulation tool. By employing the simulation tool, an organic and dynamic cosimulation can be realized since both simulators operate on the same computing platform and provide external interfaces through which the simulation can be managed dynamically. In this paper, we provide OOCoSim design principles including a synchronization scheme and detailed descriptions of its implementation. To present the effectiveness of OOCoSim, we define a smart grid application model and conduct a simulation study to see the impact of the defined application and the underlying network system on the distribution system. The simulation results show that the proposed OOCoSim can successfully simulate the integrated scenario of the power and network systems and produce the accurate effects of the networked control in the smart grid.

Analiza karakteristika MPLS simulatora / Characteristics analyse of the MPLS network simulator

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Boban Pavlović

2005-05-01

Full Text Available U ovom radu predstavljena je arhitektura i analizirane su karakteristike MPLS mrežnog simulatora MNS (Multiprotocol Label Switching Network Simulator, koji se koristi u projektovanju paketskih mreža zasnovanih na IP (Internet Protocol protokolu koje moraju podržavati saobraćaj u realnom vremenu i multimedijalni saobraćaj. Na bazi mrežnog simulatora prikazane su i opisane procedure simulacije saobraćaja različitog QoS, kao i simulacija posluživanja saobraćaja višeg prioriteta. / In this article are presented architecture and characteristics analyze of the MPLS Network Simulator (MNS. MNS is used for design packet networks based on Internet Protocol (IP which must support Real-time Traffic and Multimedia. In this document are presented and described simulation procedure for traffics -with different QoS and simulation for resource preemption.

Flash and Continuous Photolysis Studies of the Thionitrosyl Complex Cr(CH3CN)5(NS)2+ and the Nitric Oxide Analogs. Reactions of Nitrogen Monosulfide in Solution

DEFF Research Database (Denmark)

Dethlefsen, Johannes Wied; Hedegård, Erik; Rimmer, R. Dale

2009-01-01

Photolysis of the thionitrosyl complex Cr(CH3CN)5(NS)2+ (1) in acetonitrile solution leads to the dissociation of nitrogen monosulfide (NS).  In deaerated solution, this reaction is reversible, and flash photolysis studies demonstrate that NS reacts with Cr(CH3CN)62+ according to the rate law d[1...... dependent quantum yields of 0.3-1.0 mol/Einstein. Mass spectroscopic studies of the product solutions demonstrate formation of S8, presumably from the decomposition of NS. The quantitative photochemical behaviors of 1 and the nitrosyl analog 2 are compared. Udgivelsesdato: Jan....

Projection of future climate change conditions using IPCC simulations, neural networks and Bayesian statistics. Part 2: Precipitation mean state and seasonal cycle in South America

Energy Technology Data Exchange (ETDEWEB)

Boulanger, Jean-Philippe [LODYC, UMR CNRS/IRD/UPMC, Tour 45-55/Etage 4/Case 100, UPMC, Paris Cedex 05 (France); University of Buenos Aires, Departamento de Ciencias de la Atmosfera y los Oceanos, Facultad de Ciencias Exactas y Naturales, Buenos Aires (Argentina); Martinez, Fernando; Segura, Enrique C. [University of Buenos Aires, Departamento de Computacion, Facultad de Ciencias Exactas y Naturales, Buenos Aires (Argentina)

2007-02-15

Evaluating the response of climate to greenhouse gas forcing is a major objective of the climate community, and the use of large ensemble of simulations is considered as a significant step toward that goal. The present paper thus discusses a new methodology based on neural network to mix ensemble of climate model simulations. Our analysis consists of one simulation of seven Atmosphere-Ocean Global Climate Models, which participated in the IPCC Project and provided at least one simulation for the twentieth century (20c3m) and one simulation for each of three SRES scenarios: A2, A1B and B1. Our statistical method based on neural networks and Bayesian statistics computes a transfer function between models and observations. Such a transfer function was then used to project future conditions and to derive what we would call the optimal ensemble combination for twenty-first century climate change projections. Our approach is therefore based on one statement and one hypothesis. The statement is that an optimal ensemble projection should be built by giving larger weights to models, which have more skill in representing present climate conditions. The hypothesis is that our method based on neural network is actually weighting the models that way. While the statement is actually an open question, which answer may vary according to the region or climate signal under study, our results demonstrate that the neural network approach indeed allows to weighting models according to their skills. As such, our method is an improvement of existing Bayesian methods developed to mix ensembles of simulations. However, the general low skill of climate models in simulating precipitation mean climatology implies that the final projection maps (whatever the method used to compute them) may significantly change in the future as models improve. Therefore, the projection results for late twenty-first century conditions are presented as possible projections based on the &apos

Mesoscopic Simulations of Crosslinked Polymer Networks

Science.gov (United States)

Megariotis, Grigorios; Vogiatzis, Georgios G.; Schneider, Ludwig; Müller, Marcus; Theodorou, Doros N.

2016-08-01

A new methodology and the corresponding C++ code for mesoscopic simulations of elastomers are presented. The test system, crosslinked ds-1’4-polyisoprene’ is simulated with a Brownian Dynamics/kinetic Monte Carlo algorithm as a dense liquid of soft, coarse-grained beads, each representing 5-10 Kuhn segments. From the thermodynamic point of view, the system is described by a Helmholtz free-energy containing contributions from entropic springs between successive beads along a chain, slip-springs representing entanglements between beads on different chains, and non-bonded interactions. The methodology is employed for the calculation of the stress relaxation function from simulations of several microseconds at equilibrium, as well as for the prediction of stress-strain curves of crosslinked polymer networks under deformation.

Simbrain 3.0: A flexible, visually-oriented neural network simulator.

Science.gov (United States)

Tosi, Zachary; Yoshimi, Jeffrey

2016-11-01

Simbrain 3.0 is a software package for neural network design and analysis, which emphasizes flexibility (arbitrarily complex networks can be built using a suite of basic components) and a visually rich, intuitive interface. These features support both students and professionals. Students can study all of the major classes of neural networks in a familiar graphical setting, and can easily modify simulations, experimenting with networks and immediately seeing the results of their interventions. With the 3.0 release, Simbrain supports models on the order of thousands of neurons and a million synapses. This allows the same features that support education to support research professionals, who can now use the tool to quickly design, run, and analyze the behavior of large, highly customizable simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modelisation et simulation d'un PON (Passive Optical Network) base ...

African Journals Online (AJOL)

English Title: Modeling and simulation of a PON (Passive Optical Network) Based on hybrid technology WDM/TDM. English Abstract. This development is part of dynamism of design for a model combining WDM and TDM multiplexing in the optical network of PON (Passive Optical Network) type, in order to satisfy the high bit ...

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Science.gov (United States)

Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

2018-01-23

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex

Directory of Open Access Journals (Sweden)

Jihui Lin

2017-08-01

Full Text Available Classical swine fever virus (CSFV is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation.

Detection of antibodies against porcine parvovirus nonstructural protein NS1 may distinguish between vaccinated and infected pigs

DEFF Research Database (Denmark)

Madsen, Eva Smedegaard; Madsen, Knud Gert; Nielsen, Jens

1997-01-01

The humoral antibody response against the nonstructural protein NS1 and the structural protein VP2 of porcine parvovirus (PPV) was evaluated by immuno-peroxidase test (IPT) and enzyme linked immune sorbent assay (ELISA) using recombinant PPV antigens. The coding sequence for NS1 and VP2...... was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV) genome resulting in two recombinant baculoviruses AcNPV-NS1 and AcNPV-VP2, respectively. Sf9 cells (Spodoptora frugidiperda) inoculated with AcNPV-NS1 producing recombinant nonstructural protein (rNS1) and AcNPV-VP2...... producing recombinant virion protein (rVP2) were used in IPT and ELISA to analyse serum antibodies. Pigs vaccinated with an inactivated whole virus vaccine and experimentally infected pigs were studied. Significant titers against rVP2 were obtained in both vaccinated and infected pigs. Specific antibodies...

Networks and their traffic in multiplayer games

Directory of Open Access Journals (Sweden)

Cristian Andrés Melo López

2016-06-01

Full Text Available Computer games called multiplayer real-time, or (MCG are at the forefront of the use of the possibilities of the network. Research on this subject have been made for military simulations, virtual reality systems, computer support teamwork, the solutions diverge on the problems posed by MCG. With this in mind, this document provides an overview of the four issues affecting networking at the MCG. First, network resources (bandwidth, latency and computing capacity, together with the technical limits within which the MCG must operate. Second, the distribution concepts include communication architectures (peer-to-peer, client / server, server / network, and data and control architectures (centralized, distributed and reproduced .Thirdly, scalability allows the MCG to adapt to changes in parameterization resources. Finally, security is intended to fend off the traps and vandalism, which are common in online games; to check traffic, particularly these games we decided to take the massively multiplayer game League of Legends, a scene corresponding to a situation of real life in a network of ADSL access network is deployed has been simulated by using NS2 Three variants of TCP, it means SACK TCP, New Reno TCP, and TCP Vegas, have been considered for the cross traffic. The results show that TCP Vegas is able to maintain a constant speed while racing against the game traffic, since it avoids the packet loss and the delays in the tail caused by high peaks, without increasing the size of the sender window. SACK TCP and TCP New Reno, on the other hand, tend to increase continuously the sender window size, which could allow a greater loss of packages and also to cause unwanted delays for the game traffic.

Electron Cloud Observations during LHC Operation with 25 ns Beams

CERN Document Server

Li, Kevin; Iadarola, Giovanni; Mether, Lotta; Romano, Annalisa; Rumolo, Giovanni; Schenk, Michael

2016-01-01

While during the Run 1 (2010-2012) of the Large Hadron Collider (LHC) most of the integrated luminosity was produced with 50 ns bunch spacing, for the Run 2 start-up (2015) it was decided to move to the nominal bunch spacing of 25 ns. As expected, with this beam configuration strong electron cloud effects were observed in the machine, which had to be mitigated with dedicated 'scrubbing' periods at injection energy. This enabled to start the operation with 25 ns beams at 6.5 TeV, but e-cloud effects continued to pose challenges while gradually increasing the number of circulating bunch trains. This contribution will review the encountered limitations and the mitigation measures that where put in place and will discuss possible strategies for further performance gain.

PWR system simulation and parameter estimation with neural networks

Energy Technology Data Exchange (ETDEWEB)

Akkurt, Hatice; Colak, Uener E-mail: uc@nuke.hacettepe.edu.tr

2002-11-01

A detailed nonlinear model for a typical PWR system has been considered for the development of simulation software. Each component in the system has been represented by appropriate differential equations. The SCILAB software was used for solving nonlinear equations to simulate steady-state and transient operational conditions. Overall system has been constructed by connecting individual components to each other. The validity of models for individual components and overall system has been verified. The system response against given transients have been analyzed. A neural network has been utilized to estimate system parameters during transients. Different transients have been imposed in training and prediction stages with neural networks. Reactor power and system reactivity during the transient event have been predicted by the neural network. Results show that neural networks estimations are in good agreement with the calculated response of the reactor system. The maximum errors are within {+-}0.254% for power and between -0.146 and 0.353% for reactivity prediction cases. Steam generator parameters, pressure and water level, are also successfully predicted by the neural network employed in this study. The noise imposed on the input parameters of the neural network deteriorates the power estimation capability whereas the reactivity estimation capability is not significantly affected.

PWR system simulation and parameter estimation with neural networks

International Nuclear Information System (INIS)

Akkurt, Hatice; Colak, Uener

2002-01-01

A detailed nonlinear model for a typical PWR system has been considered for the development of simulation software. Each component in the system has been represented by appropriate differential equations. The SCILAB software was used for solving nonlinear equations to simulate steady-state and transient operational conditions. Overall system has been constructed by connecting individual components to each other. The validity of models for individual components and overall system has been verified. The system response against given transients have been analyzed. A neural network has been utilized to estimate system parameters during transients. Different transients have been imposed in training and prediction stages with neural networks. Reactor power and system reactivity during the transient event have been predicted by the neural network. Results show that neural networks estimations are in good agreement with the calculated response of the reactor system. The maximum errors are within ±0.254% for power and between -0.146 and 0.353% for reactivity prediction cases. Steam generator parameters, pressure and water level, are also successfully predicted by the neural network employed in this study. The noise imposed on the input parameters of the neural network deteriorates the power estimation capability whereas the reactivity estimation capability is not significantly affected

Modeling a Million-Node Slim Fly Network Using Parallel Discrete-Event Simulation

Energy Technology Data Exchange (ETDEWEB)

Wolfe, Noah; Carothers, Christopher; Mubarak, Misbah; Ross, Robert; Carns, Philip

2016-05-15

As supercomputers close in on exascale performance, the increased number of processors and processing power translates to an increased demand on the underlying network interconnect. The Slim Fly network topology, a new lowdiameter and low-latency interconnection network, is gaining interest as one possible solution for next-generation supercomputing interconnect systems. In this paper, we present a high-fidelity Slim Fly it-level model leveraging the Rensselaer Optimistic Simulation System (ROSS) and Co-Design of Exascale Storage (CODES) frameworks. We validate our Slim Fly model with the Kathareios et al. Slim Fly model results provided at moderately sized network scales. We further scale the model size up to n unprecedented 1 million compute nodes; and through visualization of network simulation metrics such as link bandwidth, packet latency, and port occupancy, we get an insight into the network behavior at the million-node scale. We also show linear strong scaling of the Slim Fly model on an Intel cluster achieving a peak event rate of 36 million events per second using 128 MPI tasks to process 7 billion events. Detailed analysis of the underlying discrete-event simulation performance shows that a million-node Slim Fly model simulation can execute in 198 seconds on the Intel cluster.

Hop-by-HopWorm Propagation with Carryover Epidemic Model in Mobile Sensor Networks

Directory of Open Access Journals (Sweden)

Jun-Won Ho

2015-10-01

Full Text Available In the internet, a worm is usually propagated in a random multi-hop contact manner. However, the attacker will not likely select this random multi-hop propagation approach in a mobile sensor network. This is because multi-hop worm route paths to random vulnerable targets can be often breached due to node mobility, leading to failure of fast worm spread under this strategy. Therefore, an appropriate propagation strategy is needed for mobile sensor worms. To meet this need, we discuss a hop-by-hop worm propagation model in mobile sensor networks. In a hop-by-hop worm propagation model, benign nodes are infected by worm in neighbor-to-neighbor spread manner. Since worm infection occurs in hop-by-hop contact, it is not substantially affected by a route breach incurred by node mobility. We also propose the carryover epidemic model to deal with the worm infection quota deficiency that might occur when employing an epidemic model in a mobile sensor network. We analyze worm infection capability under the carryover epidemic model. Moreover, we simulate hop-by-hop worm propagation with carryover epidemic model by using an ns-2 simulator. The simulation results demonstrate that infection quota carryovers are seldom observed where a node’s maximum speed is no less than 20 m/s.

Simulation of nonlinear random vibrations using artificial neural networks

Energy Technology Data Exchange (ETDEWEB)

Paez, T.L.; Tucker, S.; O`Gorman, C.

1997-02-01

The simulation of mechanical system random vibrations is important in structural dynamics, but it is particularly difficult when the system under consideration is nonlinear. Artificial neural networks provide a useful tool for the modeling of nonlinear systems, however, such modeling may be inefficient or insufficiently accurate when the system under consideration is complex. This paper shows that there are several transformations that can be used to uncouple and simplify the components of motion of a complex nonlinear system, thereby making its modeling and random vibration simulation, via component modeling with artificial neural networks, a much simpler problem. A numerical example is presented.

Structural modeling and molecular simulation analysis of HvAP2/EREBP from barley.

Science.gov (United States)

Pandey, Bharati; Sharma, Pradeep; Tyagi, Chetna; Goyal, Sukriti; Grover, Abhinav; Sharma, Indu

2016-06-01

AP2/ERF transcription factors play a critical role in plant development and stress adaptation. This study reports the three-dimensional ab initio-based model of AP2/EREBP protein of barley and its interaction with DNA. Full-length coding sequence of HvAP2/EREBP gene isolated from two Indian barley cultivars, RD 2503 and RD 31, was used to model the protein. Of five protein models obtained, the one with lowest C-score was chosen for further analysis. The N- and C-terminal regions of HvAP2 protein were found to be highly disordered. The dynamic properties of AP2/EREBP and its interaction with DNA were investigated by molecular dynamics simulation. Analysis of trajectories from simulation yielded the equilibrated conformation between 2-10ns for protein and 7-15ns for protein-DNA complex. We established relationship between DNA having GCC box and DNA-binding domain of HvAP2/EREBP was established by modeling 11-base-pair-long nucleotide sequence and HvAP2/EREBP protein using ab initio method. Analysis of protein-DNA interaction showed that a β-sheet motif constituting amino acid residues THR105, ARG100, ARG93, and ARG83 seems to play important role in stabilizing the complex as they form strong hydrogen bond interactions with the DNA motif. Taken together, this study provides first-hand comprehensive information detailing structural conformation and interactions of HvAP2/EREBP proteins in barley. The study intensifies the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information. It also provides molecular insight into protein-DNA binding for understanding and enhancing abiotic stress resistance for improving the water use efficiency in crop plants.

Decreasing the infusion rate reduces the proarrhythmic risk of NS-7

DEFF Research Database (Denmark)

Detre, Elke; Thomsen, Morten Bækgaard; Beekman, Jet D

2005-01-01

1 The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. 2 A fast (5 min...... intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg(-1), n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg(-1), n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs...... with chronic, complete AV block (CAVB), an animal model of TdP (n=6). 3 No electrophysiological effects were seen after 0.3 mg kg(-1) NS-7. Fast infusion of 3.0 mg kg(-1) caused prolongation of repolarisation, for example, heart rate corrected QT interval (QT(c)): in SR: 6+/-1%; in CAVB: 10+/-7%, which...

Modeling and simulation of different and representative engineering problems using Network Simulation Method.

Science.gov (United States)

Sánchez-Pérez, J F; Marín, F; Morales, J L; Cánovas, M; Alhama, F

2018-01-01

Mathematical models simulating different and representative engineering problem, atomic dry friction, the moving front problems and elastic and solid mechanics are presented in the form of a set of non-linear, coupled or not coupled differential equations. For different parameters values that influence the solution, the problem is numerically solved by the network method, which provides all the variables of the problems. Although the model is extremely sensitive to the above parameters, no assumptions are considered as regards the linearization of the variables. The design of the models, which are run on standard electrical circuit simulation software, is explained in detail. The network model results are compared with common numerical methods or experimental data, published in the scientific literature, to show the reliability of the model.

Trends in ns 2np 0 [M(CO)] q+ complexes: From germanium to element 114 (Uuq)

Science.gov (United States)

Gourlaouen, C.; Parisel, O.; Piquemal, J.-P.

2009-02-01

The present contribution reports investigations on the metal-ligand bond lengths and interaction energies in selected carbon monoxide complexes of metal cations sharing the ns2np0 valence configuration. 1- and 4-component DFT geometry optimizations have been performed for cations ranging from Ge2+ to Uuq2+, the dication of element 114 (Ununquadium). The nature of the bonding has been studied by means of energy decomposition analysis. The magnitude of the relativistic effects is shown to evolve slowly and to become predominant for Uuq for the molecular properties investigated.