bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Control ofMycobacterium bovisBCG Infection in the Absence of Toll-Like Receptors (TLRs): Investigation of TLR2-, TLR6-, or TLR2-TLR4-Deficient Mice
Authors: Nicolle Delphine , Fremond Cécile , Pichon Xavier , Bouchot André , Maillet Isabelle , Ryffel Bernhard , Quesniaux Valerie J. F. 
Published: November 2004

ABSTRACTLive mycobacteria have been reported to signal through both Toll-like receptor 2 (TLR2) and TLR4 in vitro. Here, we investigated the role of TLR2 in the long-term control of the infection by the attenuatedMycobacterium,Mycobacterium bovisBCG, in vivo. We sought to determine whether the reported initial defect of bacterial control (K. A. Heldwein et al., J. Leukoc. Biol. 74:277-286, 2003) resolved in the chronic phase of BCG infection. Here we show that TLR2-deficient mice survived a 6-month infection period withM. bovisBCG and were able to control bacterial growth. Granuloma formation, T-cell and macrophage recruitment, and activation were normal. Furthermore, the TLR2 coreceptor, TLR6, is also not required since TLR6-deficient mice were able to control chronic BCG infection. Finally, TLR2-TLR4-deficient mice infected with BCG survived the 8-month observation period. Interestingly, the adaptive response of TLR2- and/or TLR4-deficient mice seemed essentially normal on day 14 or 56 after infection, since T cells responded normally to soluble BCG antigens. In conclusion, our data demonstrate that TLR2, TLR4, or TLR6 are redundant for the control ofM. bovisBCG mycobacterial infection.
Polymorphisms in the
Chlamydia trachomatis
Cytotoxin Locus Associated with Ocular and Genital Isolates
Authors: Carlson John H. , Hughes Scott , Hogan Daniel , Cieplak Gordon , Sturdevant Daniel E. , McClarty Grant , Caldwell Harlan D. , Belland Robert J. 
Published: November 2004

ABSTRACT

Chlamydia trachomatis
is a strict human pathogen producing infections that cause medically important chronic inflammatory diseases, such as blinding trachoma and tubal factor infertility. Isolates exist as serotypes that fall into distinct biologic and pathological groups corresponding to differences in infection tissue tropism and invasion properties. Paradoxically, genome sequencing of several diverse strains has revealed a remarkable level of genomic synteny, suggesting that minor genetic differences determine the pathogen host- and tissue-specific infection characteristics. To better understand the genetic basis of chlamydial pathobiologic diversity, we performed comparative DNA-DNA microarray genomic hybridizations with all 15
C. trachomatis
serovariants. We found there are few major genetic differences among the 15 serovars. An exception was the cytotoxin locus located in the plasticity zone, a region that exhibited significant polymorphisms among serovars. We therefore sequenced this region from all 15 serovars. The cytotoxin gene was interrupted by extensive mutations and deletions among the different serovars; however, three basic open reading frame motifs were discovered that correlated with noninvasive oculotropic, urogenitotropic, and invasive serovars. Of interest, only noninvasive genitotropic serovars possessed an intact N-terminal portion of the putative toxin gene. This region contains the UDP-glucose binding domain and the glycosyltransferase domain required for enzymatic activity of the clostridial toxin homologs, suggesting a role in urogenital infection or pathogenesis.
A Mutant of
Mycobacterium tuberculosis
H37Rv That Lacks Expression of Antigen 85A Is Attenuated in Mice but Retains Vaccinogenic Potential
Authors: Copenhaver Robert H. , Sepulveda Eliud , Armitige Lisa Y. , Actor Jeffrey K. , Wanger Audrey , Norris Steven J. , Hunter Robert L. , Jagannath Chinnaswamy 
Published: November 2004

ABSTRACT

The
fbpA
and
fbpB
genes encoding the 85A and 85B proteins of
Mycobacterium tuberculosis
H37Rv, respectively, were disrupted, the mutants were examined for their ability to survive, and the strain lacking 85A (Δ
fbpA
) was tested for its ability to immunize mice. The Δ
fbpA
mutant was attenuated in mice after intravenous or aerosol infection, while replication of the Δ
fbpB
mutant was similar to that of the wild type. Complementation of the
fbpA
gene in Δ
fbpA
restored its ability to grow in the lungs of mice. The Δ
fbpA
mutant induced a stronger expression of pulmonary mRNA messages in mice for tumor necrosis factor alpha, interleukin-1 beta (IL-1β), gamma interferon, IL-6, IL-2, and inducible nitric oxide (NO) synthase, which led to its decline, while H37Rv persisted despite strong immune responses. H37Rv and Δ
fbpA
both induced NO in macrophages and were equally susceptible to NO donors, although Δ
fbpA
was more susceptible in vitro to peroxynitrite and its growth was enhanced by NO inhibitors in mice and macrophages. Aerosol-infected mice, which cleared a low-dose Δ
fbpA
infection, resisted a challenge with virulent
M. tuberculosis
. Mice subcutaneously immunized with Δ
fbpA
or
Mycobacterium bovis
BCG and challenged with
M. tuberculosis
also showed similar levels of protection, marked by a reduction in the growth of challenged
M. tuberculosis
. The Δ
fbpA
mutant was thus attenuated, unlike Δ
fbpB
, but was also vaccinogenic against tuberculosis. Attenuation was incomplete, however, since Δ
fbpA
revived in normal mice after 370 days, suggesting that revival was due to immunosenescence but not compensation by the
fbpB
or
fbpC
gene. Antigen 85A thus affects susceptibility to peroxynitrite in
M. tuberculosis
and appears to be necessary for its optimal growth in mice.
Interactions of Pulmonary Collectins with
Bordetella bronchiseptica
and
Bordetella pertussis
Lipopolysaccharide Elucidate the Structural Basis of Their Antimicrobial Activities
Authors: Schaeffer Lyndsay M. , McCormack Francis X. , Wu Huixing , Weiss Alison A. 
Published: November 2004

ABSTRACT

Surfactant proteins A (SP-A) and D (SP-D) play an important role in the innate immune defenses of the respiratory tract. SP-A binds to the lipid A region of lipopolysaccharide (LPS), and SP-D binds to the core oligosaccharide region. Both proteins induce aggregation, act as opsonins for neutrophils and macrophages, and have direct antimicrobial activity.
Bordetella pertussis
LPS has a branched core structure and a nonrepeating terminal trisaccharide.
Bordetella bronchiseptica
LPS has the same structure, but lipid A is palmitoylated and there is a repeating O-antigen polysaccharide. The ability of SP-A and SP-D to agglutinate and permeabilize wild-type and LPS mutants of
B. pertussis
and
B. bronchiseptica
was examined. Previously, wild-type
B. pertussis
was shown to resist the effects of SP-A; however, LPS mutants lacking the terminal trisaccharide were susceptible to SP-A. In this study, SP-A was found to aggregate and permeabilize a
B. bronchiseptica
mutant lacking the terminal trisaccharide, while wild-type
B. bronchiseptica
and mutants lacking only the palmitoyl transferase or O antigen were resistant to SP-A. Wild-type
B. pertussis
and
B. bronchiseptica
were both resistant to SP-D; however, LPS mutants of either strain lacking the terminal trisaccharide were aggregated and permeabilized by SP-D. We conclude that the terminal trisaccharide protects
Bordetella
species from the bactericidal functions of SP-A and SP-D. The O antigen and palmitoylated lipid A of
B. bronchiseptica
play no role in this resistance.
Human Antibody Responses to a Chlamydia-Secreted Protease Factor
Authors: Sharma Jyotika , Bosnic Anthony M. , Piper Jeanna M. , Zhong Guangming 
Published: November 2004

ABSTRACTWe have previously identified a chlamydia-secreted protein (designated chlamydial proteasome/protease-like activity factor, or CPAF) in the cytosol of chlamydia-infected cells. Although CPAF is known to degrade host transcription factors required for major histocompatibility complex antigen expression in cultured cells, it is not clear whether CPAF is produced and maintains similar functions in humans infected with chlamydial organisms. We now report that CPAF does not preexist in chlamydial organisms and that CPAF synthesis requires live organism replication in cultured cells. Mice inoculated with live, but not mice inoculated with dead, chlamydial organisms produced a strong antibody response to CPAF, correlating CPAF-specific antibody production with CPAF synthesis in animals. Sera from women diagnosed withChlamydia trachomatiscervicitis displayed higher levels of antibodies to CPAF than to either chlamydial major outer membrane protein or heat shock protein 60, suggesting that CPAF is both produced and immunogenic during human chlamydial infection.
Identification of a Novel
Anaplasma marginale
Appendage-Associated Protein That Localizes with Actin Filaments during Intraerythrocytic Infection
Authors: Stich Roger W. , Olah Glenn A. , Brayton Kelly A. , Brown Wendy C. , Fechheimer Marcus , Green-Church Kari , Jittapalapong Sathaporn , Kocan Katherine M. , McGuire Travis C. , Rurangirwa Fred R. , Palmer Guy H. 
Published: November 2004

ABSTRACT

The rickettsial pathogen
Anaplasma marginale
assembles an actin filament bundle during intracellular infection. Unlike other bacterial pathogens that generate actin filament tails,
A. marginale
infects mature erythrocytes, and the F-actin appendages are assembled on the cytoplasmic surface of a vacuole containing several organisms. To identify
A. marginale
molecules associated with these filaments, two complementary approaches were used: matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and tandem mass spectrometry of
A. marginale
proteins identified with an appendage-specific monoclonal antibody and expression screening of an
A. marginale
phage library. Amino acid and nucleotide sequences were mapped to a full-length gene in the genome of the St. Maries strain of
A. marginale
; the correct identification was confirmed by expression of full-length recombinant protein and its reactivity with appendage-specific antibodies. Interestingly, there is marked variation in the abilities of diverse
A. marginale
strains to assemble the F-actin appendages. Comparison of four strains, the Florida, Illinois, St. Maries, and Virginia strains, revealed substantial polymorphism in the gene encoding the appendage-associated protein, with amino acid sequence identity of as low as 34% among strains. However, this variation does not underlie the differences in expression, as there is no specific polymorphism associated with loss of ability to assemble actin appendages. In contrast, the ability to assemble an actin filament bundle reflected dramatic strain-specific differences in the expression level of the appendage-associated protein. Understanding how this protein influences the cycle of invasion, replication, and egress in the host cell may provide new insights into pathogen-host interactions.
Mannose-Resistant
Proteus
-Like Fimbriae Are Produced by Most
Proteus mirabilis
Strains Infecting the Urinary Tract, Dictate the In Vivo Localization of Bacteria, and Contribute to Biofilm Formation
Authors: Jansen Angela M. , Lockatell Virginia , Johnson David E. , Mobley Harry L. T. 
Published: November 2004

ABSTRACT

Proteus mirabilis
, an etiologic agent of complicated urinary tract infections, expresses mannose-resistant
Proteus
-like (MR/P) fimbriae whose expression is phase variable. Here we examine the role of these fimbriae in biofilm formation and colonization of the urinary tract. The majority of wild-type
P. mirabilis
cells in transurethrally infected mice produced MR/P fimbriae. Mutants that were phase-locked for either constitutive expression (MR/P ON) or the inability to express MR/P fimbriae (MR/P OFF) were phenotypically distinct and swarmed at different rates. The number of
P. mirabilis
cells adhering to bladder tissue did not appear to be affected by MR/P fimbriation. However, the pattern of adherence to the bladder surface was strikingly different. MR/P OFF colonized the lamina propria underlying exfoliated uroepithelium, while MR/P ON colonized the luminal surfaces of bladder umbrella cells and not the exfoliated regions. Wild-type
P. mirabilis
was usually found colonizing intact uroepithelium, but it occasionally adhered to exfoliated areas. MR/P ON formed significantly more biofilm than either
P. mirabilis
HI4320 (
P
= 0.03) or MR/P OFF (
P
= 0.05). MR/P OFF was able to form a biofilm similar to that of the wild type. MR/P ON formed a three-dimensional biofilm structure as early as 18 h after the initiation of the biofilm, while MR/P OFF and the wild type did not. After 7 days, however,
P. mirabilis
HI4320 formed a 65-μm-thick biofilm, while the thickest MR/P ON and MR/P OFF biofilms were only 12 μm thick. We concluded that MR/P fimbriae are expressed by most
P. mirabilis
cells infecting the urinary tract, dictate the localization of bacteria in the bladder, and contribute to biofilm formation.
Use of Translational Fusion of the MrpH Fimbrial Adhesin-Binding Domain with the Cholera Toxin A2 Domain, Coexpressed with the Cholera Toxin B Subunit, as an Intranasal Vaccine To Prevent Experimental Urinary Tract Infection byProteus mirabilis
Authors: Li Xin , Erbe Jarrod L. , Lockatell C. Virginia , Johnson David E. , Jobling Michael G. , Holmes Randall K. , Mobley Harry L. T. 
Published: November 2004

ABSTRACTThis is a follow-up to our previous study using an intranasal vaccine composed of MrpH, the tip adhesin of the MR/P fimbria, and cholera toxin to prevent urinary tract infection byProteus mirabilis(X. Li, C. V. Lockatell, D. E. Johnson, M. C. Lane, J. W. Warren, and H. L. Mobley, Infect. Immun. 72:66-75, 2004). Here, we have expressed a cholera toxin-like chimera in which the MrpH adhesin-binding domain (residues 23 to 157) replaces the cholera toxin A1 ADP-ribosyltransferase domain. This chimera, when administered intranasally without additional adjuvant, is sufficient to induce protective immunity in mice.
STRONGLY FREE ACTIONS ON SUBFACTORS
Authors: WINSLØW CARL 
Published: November 2004

For actions on arbitrary inclusions of factors with finite index, we define an algebraic property called "strong freeness". In the case of strongly amenable subfactors of type II∞ or IIIλ (0 < λ < 1), this property is shown to be a characterization of centrally free actions. We then classify strongly free actions of discrete amenable groups on strongly amenable subfactors of type II∞, and strongly free actions of a class of discrete amenable groups (which include ℤn, n ∈ ℕ) on strongly amenable subfactors of type IIIλ. Namely, we show that the (generalized) fundamental homomorphism is a complete invariant for cocycle conjugacy in both cases.
CLUSTER SIMULATIONS OF THE ISING MODEL ON DYNAMICALLY TRIANGULATED LATTICE
Authors: BEN-AV R. , KINAR J. , SOLOMON S. 
Published: November 2004

We have performed high precision finite size scaling measurements of the critical behavior of the Ising model on dynamically triangulated surfaces of genus 0. The results are in perfect agreement with the matrix model predictions.1,2 Values of the critical exponents equal to the regular lattice 2D Ising model are excluded by our error bars. In order to accumulate sufficient statistics we used cluster methods which eliminated critical slowing down to a great extent.
DKRL — AN OBJECT-ORIENTED LANGUAGE TO SUPPORT PROBLEM SOLVING IN DISTRIBUTED BLACKBOARD SYSTEMS
Authors: SAXENA MANOJ K. , BISWAS K.K. , BHATT P.C.P. 
Published: November 2004

For distributed problem solving systems, there is a need to define knowledge at two levels, one external to the agents and the other internal to the agents. External knowledge is required to achieve cooperation among agents and global convergence of the problem solving process, whereas internal knowledge is required to solve the sub-problems assigned to the agents. External knowledge specifies the role of each agent and its relationship with other agents in the system. Internal knowledge specifies knowledge structure and the problem solving process within each agent. DKRL is an object-oriented language for describing distributed blackboard systems. In DKRL a problem solving system is described as a collection of distributed intelligent, autonomous agents (modelled as objects), cooperating to solve the problem. An agent consists of a knowledge base, a behaviour part, a local controller, a monitor, and a communication controller. DKRL has characteristics of a dynamic nature, i.e. the agents can be created dynamically and the relationship among them also changes dynamically. An agent in DKRL’s computational model cannot be activated by more than one message at the same time and uses a virtual synchrony environment for message transmission among agents. This model combines the advantages of remote procedure calls with those of asynchronous message passing. DKRL allows object-oriented programming techniques to be used for system development and facilitates the development by allowing one-to-one mapping between the objects in the knowledge model and the knowledge base of the agent. In this paper, we give an overview of the distributed blackboard paradigm for which DKRL was developed as well as the design considerations. We also propose and formally describe the underlying models of DKRL and explain how concurrency is exploited by DKRL. We conclude with the current status of and preliminary experience with DKRL in using it for the development of a gate assignment problem.
BLACKBOARD CONCEPTS FOR DATA FUSION APPLICATIONS
Authors: LLINAS J. , ANTONY RICHARD T. 
Published: November 2004

Data fusion has been defined as a process dealing with the association, correlation, and combination of data and information from multiple sources to achieve refined position and identity estimates for entities, and complete and timely assessments of related situations and threats, and their significance. This process (sometimes labeled a “technology”) is pervasive, i.e. capable of broad, multi-domain application. Indeed, data fusion has found extensive application in the commercial/industrial sector as well, in areas such as robotics and process control, and for numerous applications requiring intelligent, autonomous processes and capabilities. One of the purposes of this paper is to describe the evolving standard description of the data fusion process ascribed to by the U.S. Joint Directors of Laboratories (JDL) Data Fusion Subpanel (a Department of Defense organization), as well as components of the attendant lexicon and taxonomy. While the specific definitions of a “situation assessment (SA)” and a “threat assessment (TA)” have proven to be problem-dependent for most defense applications, these notions generally encompass a large quantity of knowledge which reflect the (dynamic) constituency-dependency relationships among objects of various classes as well as events and activities of interest. Formulation of hypotheses about situations and threats is a process having the following properties: • it employs many types of knowledge • it must consider multiple, asynchronous activities • multiple types of dynamic and static data must be processed • numerous sub-networks of interest in the situation/threat picture (numerous constituency-dependency relationships) exist—this leads to feedforward/backward inferencing requirements • information-processing strategies are required to produce estimates of aggregated force structures (given individual unit positions and identities), as well as aggregated behaviors (given individual events or activities) • the situational or threat state is often ephemeral and thus temporal reasoning capabilities must be part of the process The paper expands on the processes and techniques involved in SA and TA analysis, and describes, from various points of view, why the blackboard paradigm is properly applicable to problems of SA and TA analysis. This assessment includes various trade-off factors (features, benefits, and disadvantages or complexities) in applying blackboard concepts to data fusion related reasoning processes. Specific research and development by the authors and synthesis of the results of a survey on data fusion applications (shown within) has led to the formulation of a recommended generic, ideal blackboard architecture for these defense problems described in the paper.
BUILDING MODELS FOR QUALITATIVE PREDICTION OF SYSTEM DYNAMIC BEHAVIOR
Authors: LEE SUKHAN , CHEN JUDY 
Published: November 2004

This paper presents a method of automatically constructing a model or a set of constraints from domain principles for solving the dynamic behavior of a mechanical system through qualitative simulation. It emphasizes the following issues: the extraction of a set of necessary and sufficient constraints which provides the minimum uncertainty associated with qualitative simulation, from the fundamental principles and laws of physics based solely on the physical description of a given mechanical system; and the modification of constraints through time by detecting and identifying “system discontinuities” due to collisions, separations, and other critical states associated with each of the object primitives. The first is accomplished by describing a mechanical system by a collection of object and inter-connection primitives, which allows direct instantiating of all the relevant physics laws from the knowledge base. Then, the final set of constraints having the minimum complexity and uncertainty is extracted from the relevant physics laws, based on an A* algorithm with heuristics providing the problem solving expertise. The second is accomplished by monitoring whether the states of any individual sub-systems evolve to system discontinuities represented by intra/inter subsystem critical states.
RECENT RESULTS IN HIERARCHICAL CLUSTERING: I–THE REDUCIBLE NEIGHBORHOODS CLUSTERING ALGORITHM
Authors: BRUYNOOGHE MICHEL 
Published: November 2004

The clustering of large data sets is of great interest in fields such as pattern recognition, numerical taxonomy, image or speech processing. The traditional Ascendant Hierarchical Algorithm (AHC) cannot be run for sets of more than a few thousand elements. The reducible neighborhoods clustering algorithm, which is presented in this paper, has overtaken the limits of the traditional hierarchical clustering algorithm by generating an exact hierarchy on a large data set. The theoretical justification of this algorithm is the so-called Bruynooghe reducibility principle, that lays down the condition under which the exact hierarchy may be constructed locally, by carrying out aggregations in restricted regions of the representation space. As for the Day and Edelsbrunner algorithm, the maximum theoretical time complexity of the reducible neighborhoods clustering algorithm is O(n2 log n), regardless of the chosen clustering strategy. But the reducible neighborhoods clustering algorithm uses the original data table and its practical performances are by far better than Day and Edelsbrunner’s algorithm, thus allowing the hierarchical clustering of large data sets, i.e. composed of more than 10 000 objects.