bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of HIV-1 Replication by a Bis-Thiadiazolbenzene-1,2-Diamine That Chelates Zinc Ions from Retroviral Nucleocapsid Zinc Fingers
Authors: Pannecouque Christophe , Szafarowicz Beata , Volkova Natalia , Bakulev Vasiliy , Dehaen Wim , Mély Yves , Daelemans Dirk 
Published: February 2010

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1) nucleocapsid p7 (NCp7) protein holds two highly conserved “CCHC” zinc finger domains that are required for several phases of viral replication. Basic residues flank the zinc fingers, and both determinants are required for high-affinity binding to RNA. Several compounds were previously found to target NCp7 by reacting with the sulfhydryl group of cysteine residues from the zinc fingers. Here, we have identified an
N
,
N
′-bis(1,2,3-thiadiazol-5-yl)benzene-1,2-diamine (NV038) that efficiently blocks the replication of a wide spectrum of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) strains. Time-of-addition experiments indicate that NV038 interferes with a step of the viral replication cycle following the viral entry but preceding or coinciding with the early reverse transcription reaction, pointing toward an interaction with the nucleocapsid protein p7. In fact,
in vitro
, NV038 efficiently depletes zinc from NCp7, which is paralleled by the inhibition of the NCp7-induced destabilization of cTAR (complementary DNA sequence of TAR). A chemical model suggests that the two carbonyl oxygens of the esters in this compound are involved in the chelation of the Zn
2+
ion. This compound thus acts via a different mechanism than the previously reported zinc ejectors, as its structural features do not allow an acyl transfer to Cys or a thiol-disulfide interchange. This new lead and the mechanistic study presented provide insight into the design of a future generation of anti-NCp7 compounds.
Pathogenicity Islands PAPI-1 and PAPI-2 Contribute Individually and Synergistically to the Virulence of
Pseudomonas aeruginosa
Strain PA14
Authors: Harrison Ewan M. , Carter Melissa E. K. , Luck Shelley , Ou Hong-Yu , He Xinyi , Deng Zixin , O'Callaghan Chris , Kadioglu Aras , Rajakumar Kumar 
Published: February 2010

ABSTRACT

Pseudomonas aeruginosa
is a leading cause of hospital-acquired pneumonia and severe chronic lung infections in cystic fibrosis patients. The reference strains PA14 and PAO1 have been studied extensively, revealing that PA14 is more virulent than PAO1 in diverse infection models. Among other factors, this may be due to two pathogenicity islands, PAPI-1 and PAPI-2, both present in PA14 but not in PAO1. We compared the global contributions to virulence of PAPI-1 and PAPI-2, rather than that of individual island-borne genes, using murine models of acute pneumonia and bacteremia. Three isogenic island-minus mutants (PAPI-1-minus, PAPI-2-minus, and PAPI-1-minus, PAPI-2-minus mutants) were compared with the wild-type parent strain PA14 and with PAO1. Our results showed that both islands contributed significantly to the virulence of PA14 in acute pneumonia and bacteremia models. However, in contrast to the results for the bacteremia model, where each island was found to contribute individually, loss of the 108-kb PAPI-1 island alone was insufficient to measurably attenuate the mutant in the acute pneumonia model. Nevertheless, the double mutant was substantially more attenuated, and exhibited a lesser degree of virulence, than even PAO1 in the acute pneumonia model. In particular, its ability to disseminate from the lungs to the bloodstream was markedly inhibited. We conclude that both PAPI-1 and PAPI-2 contribute directly and synergistically in a major way to the virulence of PA14, and we suggest that analysis of island-minus strains may be a more appropriate way than individual gene knockouts to assess the contributions to virulence of large, horizontally acquired segments of DNA.
Acute Immune Response toMycobacterium massiliensein C57BL/6 and BALB/c Mice
Authors: Martins de Sousa Eduardo , Bonfim de Bortoli Fernando , Amaral Eduardo Pinheiro , Batista Aline Carvalho , Liberman Kipnis Thereza , Marques Cardoso Alessandra , Kipnis André , Junqueira-Kipnis Ana Paula 
Published: February 2010

ABSTRACTMycobacterium massilienseis an environmental opportunistic pathogen that has been associated with soft tissue infection after minor surgery. We studied the acute immune response of C57BL/6 and BALB/c mice infected intravenously with 106CFU of anM. massiliensestrain isolated from a nosocomial infection in Brazil. The results presented here show thatM. massilienseis virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells, and natural killer cells induced by gamma interferon and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice.
Toll-Like Receptor 3 Agonist Protection against ExperimentalFrancisella tularensisRespiratory Tract Infection
Authors: Pyles Richard B. , Jezek G. Eric , Eaves-Pyles Tonyia D. 
Published: February 2010

ABSTRACTWe investigated whether Toll-like receptor 3 (TLR3) stimulation would protect the host from inhaledFrancisella tularensis. TLR3 is expressed by respiratory epithelial cells and macrophages and can be activated by a synthetic double-stranded RNA ligand called polyinosine-polycytosine [poly(I:C)]. Thus, we evaluated poly(I:C) as a novel treatment against inhaledF. tularensis.In vivo, BALB/c mice intranasally (i.n.) treated with poly(I:C) (100 μg/mouse) 1 h before or after Schu 4 or LVS (100 CFU) i.n. challenge showed that poly(I:C) treatment significantly reduced bacterial load in the lungs (P< 0.05). Bronchoalveolar lavage from poly(I:C)-treated mice alone or combined withF. tularensisinfection significantly increased cytokine secretion and enhanced neutrophil influx to lung tissues. Poly(I:C) responses were transient but significantly prolonged the survival of treated mice after i.n.F. tularensischallenge relative to mock treated animals. This prolonged survival providing a longer window for initiation of levofloxacin (LEVO) treatment (40 mg/kg). Animals treated with poly(I:C), challenged withF. tularensis, and then treated with LEVO 5 days later had 100% survival relative to 0% survival in animals receiving LEVO alone. Mechanistically, poly(I:C) given to human monocyte-derived macrophages before or after Schu 4 or LVS challenge (multiplicity of infection, 20:1) had significantly reduced intracellular bacterial replication (P< 0.05). These data suggest that poly(I:C) may represent a potential therapeutic agent against inhaledF. tularensisthat prolongs survival and the opportunity to initiate standard antibiotic therapy (i.e., LEVO).
Contribution of Each of Four Superantigens toStreptococcus equi-Induced Mitogenicity, Gamma Interferon Synthesis, and Immunity
Authors: Paillot Romain , Robinson Carl , Steward Karen , Wright Nicola , Jourdan Thibaud , Butcher Nicola , Heather Zoe , Waller Andrew S. 
Published: February 2010

ABSTRACTStreptococcus equiis the causative agent of strangles, the most frequently diagnosed infectious disease of horses worldwide. The disease is characterized by abscessation and swelling of the lymph nodes of the head and neck, which can literally strangle the horse to death.S. equiproduces four recently acquired phage-associated bacterial superantigens (sAgs; SeeH, SeeI, SeeL, and SeeM) that share homology with the mitogenic toxins ofStreptococcus pyogenes. The aim of this study was to characterize the contribution of each of theseS. equisAgs to mitogenic activityin vitroand quantify the sAg-neutralizing capacity of sera from naturally infected horses in order to better understand their role in pathogenicity. Each of the sAgs was successfully cloned, and soluble proteins were produced inEscherichia coli. SeeI, SeeL, and SeeM induced a dose-dependent proliferative response in equine CD4 T lymphocytes and synthesis of gamma interferon (IFN-γ). SeeH did not stimulate equine peripheral blood mononuclear cells (PBMC) but induced proliferation of asinine PBMC. Allelic replacement mutants ofS. equistrain 4047 with sequential deletion of the superantigen genes were generated. Deletion ofseeI, seeL, andseeMcompletely abrogated the mitogenic activity and synthesis of IFN-γ, in equine PBMC, of the strain 4047 culture supernatant. Sera from naturally infected convalescent horses had only limited sAg-neutralizing activities. We propose thatS. equisAgs play an important role inS. equipathogenicity by stimulating an overzealous and inappropriate Th1 response that may interfere with the development of an effective immune response.
Virulence Plasmid Harbored by UropathogenicEscherichia coliFunctions in Acute Stages of Pathogenesis
Authors: Cusumano Corinne K. , Hung Chia S. , Chen Swaine L. , Hultgren Scott J. 
Published: February 2010

ABSTRACTUrinary tract infections (UTIs), the majority of which are caused by uropathogenicEscherichia coli(UPEC), afflict nearly 60% of women within their lifetimes. Studies in mice and humans have revealed that UPEC strains undergo a complex pathogenesis cycle that involves both the formation of intracellular bacterial communities (IBC) and the colonization of extracellular niches. Despite the commonality of the UPEC pathogenesis cycle, no specific urovirulence genetic profile has been determined; this is likely due to the fluid nature of the UPEC genome as the result of horizontal gene transfer and numerous genes of unknown function. UTI89 has a large extrachromosomal element termed pUTI89 with many characteristics of UPEC pathogenicity islands and that likely arose due to horizontal gene transfer. The pUTI89 plasmid has characteristics of both F plasmids and other known virulence plasmids. We sought to determine whether pUTI89 is important for virulence. Bothin vitroandin vivoassays were used to examine the function of pUTI89 using plasmid-cured UTI89. No differences were observed between UTI89 and plasmid-cured UTI89 based on growth, type 1 pilus expression, or biofilm formation. However, in a mouse model of UTI, a significant decrease in bacterial invasion, CFU and IBC formation of the pUTI89-cured strain was observed at early time points postinfection compared to the wild type. Through directed deletions of specific operons on pUTI89, thecjroperon was partially implicated in this observed defect. Our findings implicate pUTI89 in the early aspects of infection.
Local Host Response to Chlamydial Urethral Infection in Male Guinea Pigs
Authors: Wang Yin , Nagarajan Uma , Hennings Leah , Bowlin Anne K. , Rank Roger G. 
Published: February 2010

ABSTRACT

Very little is known about the host response to chlamydial genital infection in the male, particularly about the nature of the local response in the urethra. In this study, the pathological and immunologic responses to urethral infection of the male guinea pig with
Chlamydia caviae
(
Chlamydophila caviae
) were characterized both during a primary infection and following a challenge infection. A dose-response experiment found that the 50% infectious dose for male urethral infection was 78 inclusion-forming units. The histopathologic response was similar to that of the female, with an initial acute inflammatory response followed by a chronic inflammatory response and plasma cell infiltration. Production of IgG and IgA antibodies in local urethral secretions developed following infection, and levels of both increased in a typical anamnestic response following a challenge infection. CD4 and CD8 T cells, as well as B cells, were observed in the local site by flow cytometry, with a slightly increased number of CD8 cells. Following challenge infection, the dominant anamnestic response was solely in the B-cell compartment, with only a minimal number of T cells. The T-cell response was clearly a Th1 response, as judged by increased levels of gamma interferon (IFN-γ), interleukin-12 p40 (IL-12p40), and IL-2. The proinflammatory cytokines and chemokines IL-8, IL-1β, tumor necrosis factor alpha (TNF-α), CCL2 (monocyte chemoattractant protein 1 [MCP-1]), and CCL5 (RANTES) were elicited in the urethra following primary infection, but only CCL5 showed increased levels upon challenge. This study represents the first comprehensive analysis of the local immune response in the male urethra to a chlamydial genital infection.
Design and implementation of Sator
Authors: Brogi Antonio , Popescu Razvan , Tanca Matteo 
Published: February 2010

Our long-term objective is to develop a general methodology for deploying (Web) service aggregation and adaptation middleware, capable of suitably overcoming syntactic and behavioral mismatches in view of application integration within and across organizational boundaries.
This article focuses on describing the core aggregation process, which generates the workflow of a composite service from a set of service workflows to be aggregated and a data-flow mapping linking service parameters.
An experimental study of recent hotlink assignment algorithms
Authors: Jacobs Tobias 
Published: February 2010

The concept of
hotlink assignment
aims at enhancing the structure of Web sites such that the user's expected navigation effort is minimized. We concentrate on sites that are representable by trees and assume that each leaf carries a weight representing its popularity.

The problem of optimally adding at most one additional outgoing edge (“hotlink”) to each inner node has been widely studied. A considerable number of approximation algorithms have been proposed and worst-case bounds for the quality of the computed solutions have been given. However, only little is known about the practical behavior of most of these algorithms.
This article contributes to closing this gap by evaluating all recently proposed strategies experimentally. Our experiments are based on trees extracted from real Web sites, as well as on synthetic instances. The latter are generated by a new method that simulates the growth of a Web site over time. Finally, we present a new heuristic that is easy to implement and exhibits excellent behavior in practice.
OMF
Authors: Rakotoarivelo Thierry , Ott Maximilian , Jourjon Guillaume , Seskar Ivan 
Published: February 2010

Networking testbeds are playing an increasingly important role in the development of new communication technologies. Testbeds are traditionally built for a particular project or to study a specific technology. An alternative approach is to federate existing testbeds to a) cater for experimenter needs which cannot be fullled by a single testbed, and b) provide a wider variety of environmental settings at different scales. These heterogenous settings allow the study of new approaches in environments similar to what one finds in the real world.
This paper presents OMF, a control, measurement, and management framework for testbeds. It describes through some examples the versatility of OMF's current architecture and gives directions for federation of testbeds through OMF. In addition, this paper introduces a comprehensive experiment description language that allows an experimenter to describe resource requirements and their configurations, as well as experiment orchestration. Researchers would thus be able to reproduce their experiment on the same testbed or in a different environment with little changes. Along with the efficient support for large scale experiments, the use of testbeds and support for repeatable experiments will allow the networking field to build a culture of cross verification and therefore strengthen its scientific approach.
Signet
Authors: Paik Michael , Subramanian Lakshminarayanan 
Published: February 2010

The absence of reliable network connectivity in the developing world has resulted in the use of paper receipts remaining the de facto standard for tracking transactions of various types. This includes both cash transactions (microfinancerelated disbursements and repayments, purchases, money transfers) and noncash goods (food commodities to/from godowns or warehouses).
Such receipts are susceptible to loss, damage and alteration, with the last in particular severely compromising systems which depend on quotas or disbursement and repayment. Similarly, they allow go-betweens and agents to falsify payment or disbursement information and embezzle or misdirect funds or goods.
This paper describes Signet, a system which uses the computational power of commodity mobile telephones and security enabled Subscriber Identity Module (SIM) cards to create a secure and auditable record for atomic in-person transactions in the developing world. Signet performs this function at very low operating cost and without requiring continuous connectivity to a trusted third party.
Application of TRMM PR and TMI Measurements to Assess Cloud Microphysical Schemes in the MM5 for a Winter Storm
Authors: Han Mei , Braun Scott A. , Olson William S. , Persson P. Ola G. , Bao Jian-Wen 
Published: February 2010

AbstractThis paper uses observations from Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and microwave imager (TMI) to evaluate the cloud microphysical schemes in the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5; version 3.7.4) for a wintertime frontal precipitation system over the eastern Pacific Ocean. By incorporating a forward radiative transfer model, the radar reflectivity and brightness temperatures are simulated and compared with the observations at PR and TMI frequencies. The main purpose of this study is to identify key differences among the five schemes [including Simple ice, Reisner1, Reisner2, Schultz, and Goddard Space Flight Center (GSFC) microphysics scheme] in the MM5 that may lead to significant departures of simulated precipitation properties from both active (PR) and passive (TMI) microwave observations. Radiative properties, including radar reflectivity, attenuation, and scattering in precipitation liquid and ice layers are investigated. In the rain layer, most schemes are capable of reproducing the observed radiative properties to a reasonable degree; the Reisner2 simulation, however, produces weaker reflectivity and stronger attenuation than the observations, which is possibly attributable to the larger intercept parameter (N0r) applied in this run. In the precipitation ice layer, strong evidence regarding the differences in the microphysical and radiative properties between a narrow cold-frontal rainband (NCFR) and a wide cold-frontal rainband (WCFR) within this frontal precipitation system is found. The performances of these schemes vary significantly on simulating the microphysical and radiative properties of the frontal rainband. The GSFC scheme shows the least bias, while the Reisner1 scheme has the largest bias in the reflectivity comparison. It appears more challenging for the model to replicate the scattering signatures obtained by the passive sensor (TMI). Despite the common problem of excessive scattering in the WCFR (stratiform precipitation) region in every simulation, the magnitude of the scattering maximum seems better represented in the Reisner2 scheme. The different types of precipitation ice, snow, and graupel are found to behave differently in the relationship of scattering versus reflectivity. The determinative role of the precipitation ice particle size distribution (intercept parameters) is extensively discussed through sensitivity tests and a single-layer radiative transfer model.
Source of Gravity Waves within a Vortex-Dipole Jet Revealed by a Linear Model
Authors: Wang Shuguang , Zhang Fuqing 
Published: February 2010

Abstract
This study develops a linear numerical model to address the source mechanism of the gravity waves generated within a vortex dipole simulated in a fully nonlinear nonhydrostatic mesoscale model. The background flow for this linear model is obtained from potential vorticity inversion constrained by the nonlinear balance equation. The forcing imposed in the linear model is derived from an imbalance in the large-scale flow—that is, the forcing or imbalance in the vorticity, divergence, and thermodynamic equations, respectively. The response from the sum of these imbalanced forcings obtained from the linear dynamics shows well-defined gravity wave signals, which compare reasonably well in terms of location, phase, and amplitude with the gravity waves simulated in a fully nonlinear nonhydrostatic mesoscale model. It is found that the vorticity forcing, largely due to the advection of balanced relative vorticity, is the leading contributor to the gravity waves in the exit region of the vortex-dipole jet.
Precipitation in Boreal Summer Simulated by a GCM with Two Convective Parameterization Schemes: Implications of the Intraseasonal Oscillation for Dynamic Seasonal Prediction
Authors: Park Suhee , Hong Song-You , Byun Young-Hwa 
Published: February 2010

Abstract
In this paper, the intraseasonal oscillation (ISO) and its possible link to dynamical seasonal predictability within a general circulation model framework is investigated. Two experiments with different convection scheme algorithms, namely, the simplified Arakawa–Schubert (SAS) and the relaxed Arakawa–Schubert (RAS) convection algorithms, were designed to compare seasonal simulations from 1979 to 2002 on a seasonal model intercomparison project (SMIP)-type simulation test bed. Furthermore, the wave characteristics (wave intensity, period, and propagation) of the simulated ISO signal provided by the model with two different convection schemes for extended boreal summers from 1997 to 2004 were compared to the observational ISO signal. Precipitation in the boreal summer was fairly well simulated by the model irrespective of the convection scheme used, but the RAS run outperformed the SAS run with respect to tabulated skill scores. Decomposition of the interannual variability of boreal summer precipitation based on observations and model results demonstrates that the seasonal predictability of precipitation is dominated by the intraseasonal component over the warm pool area and the SST-forced signal over the equatorial Pacific Ocean, implying that the seasonal mean anomalies are more predictable under active ISO conditions as well as strong ENSO conditions. Comparison of the ISO simulations with the observations revealed that the main features, such as the intensity of precipitation variance in the intraseasonal time scale and the evolution of propagating ISOs, were reproduced fairly well by the model; however, the wave characteristics associated with the ISO signals were better captured by the experiment with the RAS scheme than the SAS scheme. This study further suggests that accurate simulation of the ISO can improve the seasonal predictability of dynamical seasonal prediction systems.