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    Construction of exact D-optimal designs by tabu search

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    Tabu search (TS) has recently emerged as a promising heuristic method for solving complex combinatorial optimization problems. By guiding the search using the so-called tabu list and accepting disimproved solutions at some iterations, TS helps alleviate the risk of being trapped at a local optimum. In this article, we introduce the essential features of TS, apply TS to the problem of constructing an exact D-optimal design for a main-effect or a quadratic model with a finite design space, and compare performances of TS and the Fedorov exchange algorithm (FEA) as modified by Nguyen and Miller (1992). Computational results indicate that although TS requires more computing time per try than FEA, its overall performance is generally better except for the case of quadratic models with a small number of factors. For some test problems, TS also identifies designs with larger determinants than the corresponding designs obtained by FEA

    Characteristics of the Salivary Microbiota in Periodontal Diseases and Potential Roles of Individual Bacterial Species To Predict the Severity of Periodontal Disease

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    The purposes of this study were to examine the compositional changes in the salivary microbiota according to the severity of periodontal disease and to verify whether the distribution of specific bacterial species in saliva can distinguish the severity of disease. Saliva samples were collected from 8 periodontally healthy controls, 16 patients with gingivitis, 19 patients with moderate periodontitis, and 29 patients with severe periodontitis. The V3 and V4 regions of the 16S rRNA gene in the samples were sequenced, and the levels of 9 bacterial species showing significant differences among the groups by sequencing analysis were identified using quantitative real-time PCR (qPCR). The predictive performance of each bacterial species in distinguishing the severity of disease was evaluated using a receiver operating characteristic curve. Twenty-nine species, including Porphyromonas gingivalis, increased as the severity of disease increased, whereas 6 species, including Rothia denticola, decreased. The relative abundances of P. gingivalis, Tannerella forsythia, Filifactor alocis, and Prevotella intermedia determined by qPCR were significantly different among the groups. The three bacterial species P. gingivalis, T. forsythia, and F. alocis were positively correlated with the sum of the full-mouth probing depth and were moderately accurate at distinguishing the severity of periodontal disease. In conclusion, the salivary microbiota showed gradual compositional changes according to the severity of periodontitis, and the levels of P. gingivalis, T. forsythia, and F. alocis in mouth rinse saliva had the ability to distinguish the severity of periodontal disease. IMPORTANCE Periodontal disease is one of the most widespread medical conditions and the leading cause of tooth loss, imposing high economic costs and an increasing burden worldwide as life expectancy increases. Changes in the subgingival bacterial community during the progression of periodontal disease can affect the entire oral ecosystem, and bacteria in saliva can reflect the degree of bacterial imbalance in the oral cavity. This study explored whether the specific bacterial species in saliva can distinguish the severity of periodontal disease by analyzing the salivary microbiota and suggested P. gingivalis, T. forsythia, and F. alocis as biomarkers for distinguishing the severity of periodontal disease in saliva

    Salivary microbiota reflecting changes in subgingival microbiota

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    The purpose of this study was to determine whether subgingival microbial changes according to the severity of periodontal disease and following the nonsurgical periodontal treatment of periodontitis are reflected in the saliva microbiota. Subgingival and saliva samples were collected from 7 periodontally healthy controls, 14 patients with gingivitis, 12 with moderate periodontitis, and 18 with severe periodontitis. Among subjects who received treatment, seven moderate and seven severe periodontitis patients were selected for post-treatment microbial analysis, and their samples were analyzed at baseline and 6 months after treatment. The V3 and V4 regions of the 16S rRNA gene were sequenced, and correlations of the relative abundance of phyla and health- or periodontitis-dominant species between subgingival plaque and saliva samples were analyzed using Spearman signed-rank tests. Alpha diversity was higher in saliva than subgingival plaque samples, and beta diversity was significantly different between the two samples. However, levels of phyla and most health- or periodontitis-dominant species in salivary microbiota were significantly correlated with those in subgingival plaque. The improvement in clinical parameters following treatment was accompanied by a microbial shift not only in subgingival plaque but also in saliva. The abundance of 2 phyla including Bacteroidetes, 6 genera including Porphyromonas and Treponema, and 11 species including Porphyromonas gingivalis, Tannerella forsythia, and Filifactor alocis was significantly reduced in saliva following treatment. These results indicate that the salivary microbiota can reflect changes in the subgingival microbiota, suggesting that saliva can be used as a diagnostic tool to monitor the periodontal health status of individuals. IMPORTANCE The salivary microbiota has attracted increasing attention as a promising method for monitoring periodontal disease. With regard to the pathogenesis of periodontal disease, however, subgingival plaque microbiota is the dominant etiological factor. Although it has been established that periodontopathogenic bacteria exist in saliva and their distribution differs, depending on the severity of the disease, it is necessary to analyze the extent to which the salivary microbiota reflects the subgingival microbiota. This study explored whether subgingival microbial changes according to the severity of periodontal disease and following the non-surgical periodontal treatment of periodontitis are reflected in the saliva microbiota and concluded that the salivary microbiota can reflect changes in the subgingival microbiota. Saliva can be used as a diagnostic tool to monitor the periodontal health status of individuals

    Polarization of human gingival fibroblasts by Th1‐, Th2‐, Th17‐, and Treg‐derived cytokines

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    BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate whether gingival fibroblasts (GFs) can be differently activated and polarized into distinct functional subtypes by T-helper (Th) cytokines. METHODS: Gingival fibroblasts were stimulated with interferon (IFN)-gamma, interleukin (IL)-4, IL-17, and transforming growth factor (TGF)-beta, representative cytokines of Th1, Th2, Th17, and regulatory T cells, respectively, and the gene expression profiles were analyzed by microarray. Differentially expressed genes (DEGs) in GFs stimulated by 4 cytokines were screened, and a gene ontology (GO) analysis of the DEGs was conducted. To confirm the reliability of the microarray results, the DEGs that showed the largest differences compared with non-stimulated GFs were further analyzed by RT-PCR. To evaluate the effect of polarization on GFs responses to lipopolysaccharide (LPS), GFs stimulated by 4 cytokines were further stimulated with Escherichia coli LPS and mRNA levels of several genes were analyzed using RT-PCR. RESULTS: Differentially expressed genes by 4 Th cytokines were enriched in different GO terms, and the patterns of gene expression on GFs were shown functionally different. GFs stimulated with IFN-gamma (GF(IFN-gamma)) up-regulated the expression of chemokines (chemokine (C-X-C motif) ligand (CXCL)9, -10, -11, chemokine (C-C motif) ligand (CCL)8), molecules involved in antigen presentation, complement component 3 (C3), and other immune response-related molecules, whereas they down-regulated the expression of several types of collagen, extracellular matrix (ECM) components, and DNA replication and nuclear protein-related molecules. By contrast, GF(IL-4) up-regulated the expression of ECM components, cell adhesion molecules, and tissue development-related molecules and down-regulated the expression of chemokines (CXCL10 and CXCL8) and adaptive immune response-related molecules. GF(IL-17) up-regulated the expression of chemokines and other molecules for neutrophil infiltration and activation, the pro-inflammatory cytokine IL-6, and C3. GF(TGF-beta) up-regulated the expression of cell growth-related molecules, ECM components, several types of collagen, and cell adhesion molecules and down-regulated the expression of molecules related to complement activation and bacterial recognition. GFs stimulated by 4 cytokines responded differently to LPS. CONCLUSION: These results show that Th cytokines can polarize GFs into cells with functionally distinct features: immune-activating but tissue-destructive GF(IFN-gamma), tissue-reparative, and immune-inhibiting GF(IL-4), highly pro-inflammatory GF(IL-17), and potent tissue-reparative GF(TGF-beta)

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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