Decompositions for 2-Ratios-Parameter Symmetry Model in Square Contingency Tables with Ordered Categoriesat

For square contingency tables with ordered categories, Agresti (1983) considered the linear diagonals-parameter symmetry model. An extended model including that model is proposed which has only one more parameter than that model. The model also includes the conditional symmetry model considered by McCullagh (1978). Decompositions for the proposed model and Agresti's model are given.     

Linear Diagonals‐Parameter Symmetry and Quasi‐Symmetry Models for Cumulative Probabilities in Square Contingency Tables with Ordered Categories

For the analysis of square contingency tables with ordered categories, Caussinus (1965) considered the quasi‐symmetry (QS) model, Goodman (1979) considered the diagonals‐parameter symmetry (DPS) model, and Agresti (1983) considered the linear diagonals‐parameter symmetry (LDPS) model. These models show the structures of symmetry for cell probabilities. Tomizawa (1993) proposed another DPS model which has a similar multiplicative form for cumulative probabilities that an observation will fall in row (column) category i or below and column (row) category j (>i) or above. This paper proposes another LDPS and QS models that have the corresponding similar multiplicative forms for cumulative probabilities instead of cell probabilities. Special cases of the proposed models include symmetry. Two kinds of unaided distance vision data and endometrial cancer data are analyzed using these models. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Symmetry and Asymmetry Models for Rectangular Tables

The models of complete, quasi and conditional symmetry as well as marginal homogeneity and diagonal asymmetry, applicable to square contingency tables are extended to non-square ones. Several properties of the models are investigated and estimation and test theory is presented. The utility of the new proposed models is discussed and illustrated by reanalyzing classical data sets.     

Population Model of Quorum Sensing with Multiple Parallel Pathways

Quorum sensing (QS) is a bacterial communication mechanism that uses signal-receptor binding to regulate gene expression based on cell density, resulting in group behaviors such as biofilm formation, bioluminescence and stress response. In certain bacterial species such as Vibrio harveyi, several parallel QS signaling pathways drive a single phosphorylation–dephosphorylation cycle, which in turn regulates QS target genes. In this paper, we investigate the possible role of parallel signaling pathways by developing a mathematical model of QS in V. harveyi at both the single-cell and population levels. First we explore how signal integration may be achieved at the single-cell level, and how different model parameters influence the process. We then consider two examples of signal integration at the population level: a one-population model responding to two environmental cues (cell density and mass transfer), and a two-population model with distinct cell densities. In each case, we use contraction analysis to reduce the population model to an effective single-cell model.     

Interpretation of H-NMR Experiments on the Orientation of the Transmembrane Helix WALP23 by Computer Simulations

Orientation, dynamics, and packing of transmembrane helical peptides are important determinants of membrane protein structure, dynamics, and function. Because it is difficult to investigate these aspects by studying real membrane proteins, model transmembrane helical peptides are widely used. NMR experiments provide information on both orientation and dynamics of peptides, but they require that motional models be interpreted. Different motional models yield different interpretations of quadrupolar splittings (QS) in terms of helix orientation and dynamics. Here, we use coarse-grained (CG) molecular dynamics (MD) simulations to investigate the behavior of a well-known model transmembrane peptide, WALP23, under different hydrophobic matching/mismatching conditions. We compare experimental ²H-NMR QS (directly measured in experiments), as well as helix tilt angle and azimuthal rotation (not directly measured), with CG MD simulation results. For QS, the agreement is significantly better than previously obtained with atomistic simulations, indicating that equilibrium sampling is more important than atomistic details for reproducing experimental QS. Calculations of helix orientation confirm that the interpretation of QS depends on the motional model used. Our simulations suggest that WALP23 can form dimers, which are more stable in an antiparallel arrangement. The origin of the preference for the antiparallel orientation lies not only in electrostatic interactions but also in better surface complementarity. In most cases, a mixture of monomers and antiparallel dimers provides better agreement with NMR data compared to the monomer and the parallel dimer. CG MD simulations allow predictions of helix orientation and dynamics and interpretation of QS data without requiring any assumption about the motional model.     

The Decompositions for Point Symmetry Models in Two-way Contingency Tables

The decomposition for the complete point symmetry model in a rectangular contingency table is shown. Also the respective decompositions for the local point symmetry model and the reverse local point symmetry model in a square contingency table are given. Moreover test procedures for the decomposed models and an example are given.     

Cross-Strain Quorum Sensing Inhibition by Staphylococcus Aureus. Part 2: A Spatially Inhomogeneous Model

Staphylococcus aureus uses quorum sensing (QS) to enhance its pathogenicity. An intriguing aspect of this is that different strains are capable of inactivating the QS systems of opposing strains. In Part 1 of this study, we presented a model of this phenomenon in a well-mixed environment; here, we incorporate spatial structure. Two competitive strains occupying adjacent habitats with freely diffusing QS signal molecules (QSSMs) are considered. We investigate the effect of the QSSM diffusion coefficient and the relative size of the two populations on the ability of one population to dominate the other. Regarding population size, a larger population is generally at an advantage (initial conditions permitting), while the implications of different diffusivities are more complex and depend upon the sizes of the populations.     

Three-Dimensional Numerical Simulations of Biofilm Dynamics with Quorum Sensing in a Flow Cell

We develop a multiphasic hydrodynamic theory for biofilms taking into account interactions among various bacterial phenotypes, extracellular polymeric substance (EPS), quorum sensing (QS) molecules, solvent, and antibiotics. In the model, bacteria are classified into down-regulated QS, up-regulated QS, and non-QS cells based on their QS ability. The model is first benchmarked against an experiment yielding an excellent fit to experimental measurements on the concentration of QS molecules and the cell density during biofilm development. It is then applied to study development of heterogeneous structures in biofilms due to interactions of QS regulation, hydrodynamics, and antimicrobial treatment. Our 3D numerical simulations have confirmed that (i). QS is beneficial for biofilm development in a long run by building a robust EPS population to protect the biofilm; (ii). biofilms located upstream can induce QS downstream when the colonies are close enough spatially; (iii). QS induction may not be fully operational and can even be compromised in strong laminar flows; (v). the hydrodynamic stress alters the biofilm morphology. Through further numerical investigations, our model suggests that (i). QS-regulated EPS production contributes to the structural formation of heterogeneous biofilms; (ii) QS down-regulated cells tend to grow at the surface of the biofilm while QS up-regulated ones tend to grow in the bulk; (iii) when nutrient supply is sufficient, QS induction might be more effective upstream than downstream; (iv) QS may be of little benefit in a short timescale in term of fighting against invading strain/species; (v) the material properties of biomass (bacteria and EPS) have strong impact on the dilution of QS molecules under strong shear flow. In addition, with this modeling framework, hydrodynamic details and rheological quantities associated with biofilm formation under QS regulation can be resolved.     

Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa

The biofilm formation of Pseudomonas aeruginosa, an opportunistic human pathogen, is developed by cell-to-cell signaling, so-called quorum sensing (QS). To control the biofilm formation, we designed and synthesized new QS inhibitors of P. aeruginosa based on the structure of the previously known QS inhibitor, furanone. Newly synthesized compounds were a series of analogs of (5-oxo-2,5-dihydrofuran-3-yl)methyl alkanoate, and the structures of all six synthesized compounds was confirmed by NMR and GC/MS analyses. These new QS inhibitor candidates could remarkably inhibit both Pseudomonas QS signaling and biofilm formation, which were assayed by using the recombinant reporter system and flow cell confocal microscopy. The degree of QS inhibition by these new inhibitors varied from 20% to 90%. For the profound understanding about inhibition mechanism, we tried to estimate the binding energy between QS receptor, LasR, and our inhibitors from the in silico modeling system. The predicted binding pattern from the modeling system and our experimental data about QS inhibition were in good agreement. From these results, we suggest a new approach to develop the QS inhibitors and biofilm control agents based on structural modeling.     

Quorum sensing has an unexpected role in virulence in the model pathogen Citrobacter rodentium

The bacterial mouse pathogen Citrobacter rodentium causes attaching and effacing (AE) lesions in the same manner as pathogenic Escherichia coli, and is an important model for this mode of pathogenesis. Quorum sensing (QS) involves chemical signalling by bacteria to regulate gene expression in response to cell density. E. coli has never been reported to have N-acylhomoserine lactone (AHL) QS, but it does utilize luxS-dependent signalling. We found production of AHL QS signalling molecules by an AE pathogen, C. rodentium. AHL QS is directed by the croIR locus and a croI mutant is affected in its surface attachment, although not in Type III secretion. AHL QS has an important role in virulence in the mouse as, unexpectedly, the QS mutant is hypervirulent; by contrast, we detected no impact of luxS inactivation. Further study of QS in Citrobacter should provide new insights into AE pathogenesis. As the croIR locus might have been horizontally acquired, AHL QS might exist in some strains of pathogenic E. coli.     

Effects of Deprivation of the Quick-Wave Sleep in Rats with Inherited Predisposition to Audiogenic Convulsions

In experiments on rats of Krushinskii–Molodkina line (KM) with genetic predisposition to audiogenic convulsions, effects of the 3- and 6-h periods of the absence of the quick-wave sleep (QS) were studied in animals under natural conditions as well as of selective deprivations of QS on EEG spectral characteristics in the wakening–sleep cycle, on organization of the cycle, and on intensity of convulsive symptoms. The QS deprivation for 3, 6, 9, and 12 h was produced by the classic methods of small platforms or of soft awakening. The data are presented about changes of the cycle parameters in the course of natural and experimental deprivations as well as about the dynamics of restoration of the cycle structure for 12 h of the post-deprivation period. It was established that during and after the QS deprivations (by any duration), in EEG of the hippocampus, caudate nucleus, medial central nucleus of thalamus, somato-sensory, visual and auditory cortex of the KM rat brain, no appearance of the paroxysmal fires was revealed in any of the states of the wakening–sleep cycle. It was also found that the selective QS deprivation did not affect duration of the latent period and parameters of the generalized tonic-clonic audiogenic convulsions. It is stated that in rats of the KM line that have the hidden convulsive syndrome, the used kinds and methods of QS deprivation fail to activate the epileptiform manifestations.     

Modeling the effect of acylated homoserine lactone antagonists in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a gram-negative bacterium that causes serious illnesses, particularly in immunocompromised individuals, often with a fatal outcome. The finding that the acylated homoserine lactone quorum sensing (QS) system controls the production of virulence factors in P. aeruginosa makes this system a possible target for antimicrobial therapy. It has been suggested that an N-(3-oxododecanoyl)-homoserine lactone (3O-C12-HSL) antagonist, a QS blocker (QSB), would interfere efficiently with the quorum sensing system in P. aeruginosa and thus reduce the virulence of this pathogen. In this work, a mathematical model of the QS system in P. aeruginosa has been developed. The model was used to virtually add 3O-C12-HSL antagonists that differed in their affinity for the receptor protein and for their ability to mediate degradation of the receptor. The model suggests that very small differences in these parameters for different 3O-C12-HSL antagonists can greatly affect the success of QSB based inhibition of the QS system in P. aeruginosa. Most importantly, it is proposed that the ability of the 3O-C12-HSL antagonist to mediate degradation of LasR is the core parameter for successful QSB based inhibition of the QS system in P. aeruginosa. Finally, this study demonstrates that QSBs can shift the system to a low steady state, corresponding to an uninduced state and thus, suggests that the use of 3O-C12-HSL antagonists may constitute a promising therapeutic approach against P. aeruginosa involved infections.     

Responses of toad's tectal neurons to in-phase and anti-phase movements of object and textured background

Summary Pigeons (Columba livia) were trained to find hidden food in a sunken well within a square box. After learning the location, they were tested occasionally with the well and food absent. The resulting search distributions were symmetric about the peak, implying a linear scale of measurement for distance. The spread of the distribution was a constant proportion of the distance to the nearest landmark, supporting Weber's Law. As well, in one test in which a landmark was shifted in a diagonal direction, the pigeons shifted their peak place of search both in the direction of landmark shift and in the direction orthogonal to the direction of landmark shift. This contradicted a pattern found earlier: For landmark shifts along the principal axes of the square box, pigeons only shifted their peak place of search in the direction of landmark shift, not in the orthogonal direction. The vector sum model, which predicts shifts of the peak place of search only in the direction of landmark shift, is disconfirmed and must be revised.     

Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa

The macrolide antibiotic, azithromycin (AZM), has been reported to improve the clinical outcome of cystic fibrosis patients, many of whom are chronically-infected with Pseudomonas aeruginosa. However, the highest clinically-achievable concentrations of this drug are well-below the minimum inhibitory concentration for P. aeruginosa, raising the question of why AZM exhibits therapeutic activity. One possibility that has been raised by earlier studies is that AZM inhibits quorum sensing (QS) by P. aeruginosa. To explicitly test this hypothesis the changes brought about by AZM treatment need to be compared with those associated with specific QS mutants grown alongside in the same growth medium, but this has not been done. In this work, we used quantitative 2D-difference gel electrophoresis and ¹H-NMR spectroscopy footprint analysis to examine whether a range of clinically-relevant AZM concentrations elicited proteomic and metabolomic changes in wild-type cultures that were similar to those seen in cultures of defined QS mutants. Consistent with earlier reports, over half of the AZM-induced spot changes on the 2D gels were found to affect QS-regulated proteins. However, AZM modulated very few protein spots overall (compared with QS) and collectively, these modulated proteins comprised only a small fraction (12–13%) of the global QS regulon. We conclude that AZM perturbs a sub-regulon of the QS system but does not block QS per se. Reinforcing this notion, we further show that AZM is capable of attenuating virulence factor production in another Gram-negative species that secretes copious quantities of exoenzymes (Serratia marcescens), even in the absence of a functional QS system.     

Association,Symmetry and Diagonal Models for Occupational Mobility and Other Similar Square Contingency Tables Having Ordered Categorical Variables

This paper examines various association, symmetry and “diagonal band” class models for both the British and Danish social mobility data. Composite models are also fitted to these data and the variety of models considered ensures that for most square tables, parsimonious models within the class of models examined in this study can always be found that will adequately describe such tables. The models considered in this study, which have been described in various forms by Goodman (1984), Upton (1985) and Tomizawa (1986) can suit most square tables having ordered classificatory variables. A model selection procedure is also examined.     

油松毛虫的空间分布型及抽样技术

采用Iwao(1968—1977)的(m)对m的回归方法以测定油松毛虫Dendrolimus tabulaeformis Tsai et Liu越冬幼虫、茧、卵块的空间分布型, 并用不同的抽样方法比较了抽样精确度.油松毛虫越冬幼虫, 茧、卵块在油松人工林内都呈聚集分布.幼虫和茧分布的基本成分是双重个体群.卵块分布的基本成分是卵块个体, 其遵从有一公共K值的负二项分布.抽样方法:当越冬幼虫在低密度情况下以单对角线法最佳, 茧在中密度情况下, 卵块在中低密度条件下均以双对角线法为最佳.     

Multiple roles of TorD-like chaperones in the biogenesis of molybdoenzymes

Studies on cultured cells and in infection models have shown that cell density-dependent quorum-sensing (QS) controls many of the known virulence factors of Pseudomonas aeruginosa . However, it is less clear what role QS plays in chronic human lung infections associated with cystic fibrosis (CF). The involvement of QS in biofilm development, crucial to the establishment of long-term infections, suggests a role in the early stages of infection. However, the accumulation of QS mutants during chronic CF infections has been taken to indicate that any role diminishes thereafter. Here, we discuss the evidence for a continuing role for QS in P. aeruginosa CF infections, including QS activity in CF sputa and CF-relevant effects of QS-regulated products, such as pyocyanin. Bacterial population behaviour in CF is complex, and the exact roles of QS remains unclear. Therapeutic strategies directed against QS suggest that a greater understanding of bacterial populations during infection would be a valuable research goal from a clinical perspective.     

Analysis of Square Contingency Tables with Ordered Categories by a New Method of Applying the 1-Weight Modified Marginal Homogeneity Models

For square contingency tables with ordered categories, this note proposes a new method of applying Tomizawa's (1987) 1-weight modified marginal homogeneity models and applies to the 4×4 tables on unaided vision analysed by Tomizawa (1987) and by Stuart (1955). A possible explanation which is derived from fitting those models is first obtained using this new method.     

Quorum-sensing regulation of gene expression: Fundamental and applied aspects and the role in bacterial communication

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density. QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches a critical level of density, autoinducers accumulate to a necessary threshold value and abrupt activation (induction) of certain genes and operons occurs. By means of low-molecular-weight regulators, bacteria accomplish communication between cells belonging to the same or different species, genera, and even families. QS systems have been shown to play a key role in the regulation of various metabolic processes in bacteria and to function as global regulators of the expression of bacterial genes. Data are presented on different types of QS systems present in bacteria of various taxonomic groups, on the species specificity of these systems, and on communication of bacteria by means of QS systems. The possibility is considered of using QS regulation systems as targets while combating bacterial infections; other applied aspects of QS investigation are discussed.