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Hierarchical Clustering (hierarchical + clustering)
Terms modified by Hierarchical Clustering Selected AbstractsSympathectomy suppresses tumor growth and alters gene-expression profiles in rat tongue cancerEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2009Bina Raju Sympathetic nerves are known to affect carcinogenesis. Recently we found that sympathetic denervation decreases the size of rat tongue tumors. To identify genes involved in rat tongue carcinogenesis and to study the effect of sympathetic nerves on these genes, we compared gene-expression profiles in normal rat tongue (control) and in tumor-induced tongues with (SCGx) and without (Sham) bilateral sympathectomy. Significance analysis of microarrays revealed 280 genes (168 up-regulated, 112 down-regulated) that showed at least a twofold differential expression between Sham and SCGx tumors (false discovery rate < 5%). These included genes associated with cell adhesion, signaling, structure, proliferation, metabolism, angiogenesis, development, and immunity. Hierarchical clustering demonstrated that controls and sympathectomized tumors grouped together, while Sham tumors grouped separately. We identified 34 genes, known to be involved in carcinogenesis, that were not differentially expressed between sympathectomized tumors and control tongues, but which showed a significant change in expression in Sham tumors. Microarray results of 12 of these genes were confirmed by quantitative reverse transcription,polymerase chain reaction. In conclusion, sympathectomy significantly altered the gene-expression profile and inhibited tumor growth. The expression of several cancer genes were increased more than threefold in Sham tumors, but unaltered in the sympathectomized tumors when compared with controls, indicating that these genes may be of significance in rat tongue carcinogenesis. [source] Hydrophilic interaction LC of peptides: Columns comparison and clusteringJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2010Sylvia Van Dorpe Abstract A wide variety of hydrophilic interaction chromatography (HILIC) stationary phase surface chemistries are currently available. Although their selectivity can be considerably different, column comparison or clustering using peptides is limited. In this study, ten pharmaceutically relevant model peptides are analyzed on seven different HILIC columns (bare silica, amide, poly-hydroxyethyl aspartamide, diol and zwitterionic) for the evaluation of their performance and classification. The responses examined include single and multiple responses: plate number, asymmetry factor, LOD, geometric mean resolution, resolution product, time corrected resolution product, peak capacity and chromatographic response function. Column classification was performed using hierarchical clustering and principal component analysis. Moreover, the overall performance quality of the HILIC columns was compared using a linear desirability function. Hierarchical clustering and principal component analysis showed consistent clusters. The zwitterionic phase was clustered apart from the other HILIC columns and both poly-aspartamide columns were clustered together. In addition, the two bare silica phases represent two different clusters, and thus different selectivities. Overall, the responses showed the best performance for one of the bare silica columns (Alltima-Alltech), followed by the zwitterionic phase (ZIC)-HILIC. Thus, these columns, belonging to different clusters, were found to be the best performing systems in pharmaceutical peptide analysis for the selected peptide set. [source] Structuring Chemical Space: Similarity-Based Characterization of the PubChem DatabaseMOLECULAR INFORMATICS, Issue 1-2 2010Giovanni Cincilla Abstract The ensemble of conceivable molecules is referred to as the Chemical Space. In this article we describe a hierarchical version of the Affinity Propagation (AP) clustering algorithm and apply it to analyze the LINGO-based similarity matrix of a 500 000-molecule subset of the PubChem database, which contains more than 19,million compounds. The combination of two highly efficient methods, namely the AP clustering algorithm and LINGO-based molecular similarity calculations, allows the unbiased analysis of large databases. Hierarchical clustering generates a numerical diagonalization of the similarity matrix. The target-independent, intrinsic structure of the database , derived without any previous information on the physical or biological properties of the compounds, maps together molecules experimentally shown to bind the same biological target or to have similar physical properties. [source] A method for selecting and monitoring medication sales for surveillance of gastroenteritis,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2010Camille Pelat Abstract Purpose Monitoring appropriate categories of medication sales can provide early warning of certain disease outbreaks. This paper presents a methodology for choosing and monitoring medication sales relevant for the surveillance of gastroenteritis and assesses the operational characteristics of the selected medications for early warning. Methods Acute diarrhoea incidences in mainland France were obtained from the Sentinelles network surveillance system for the period 2000,2009. Medication sales grouped by therapeutic classes were obtained on the same period. Hierarchical clustering was used to select therapeutic classes correlating with disease incidence over the period. Alert thresholds were defined for the selected therapeutic classes. Single and multiple voter algorithms were investigated for outbreak detection based on sales crossing the thresholds. Sensitivity and specificity were calculated respective to known outbreaks periods. Results Four therapeutic classes were found to cluster with acute diarrhoea incidence. The therapeutic class other antiemetic and antinauseants had the best sensitivity (100%) and timeliness (1.625 weeks before official alerts), for a false alarm rate of 5%. Multiple voter algorithm was the most efficient with the rule: ,Emit an outbreak alert when at least three therapeutic classes are over their threshold' (sensitivity 100%, specificity 95%, timeliness 1.750 weeks before official alerts). Conclusions The presented method allowed selection of relevant therapeutic classes for surveillance of a specific condition. Multiple voter algorithm based on several therapeutic classes performed slightly better than the best therapeutic class alone, while improving robustness against abrupt changes occurring in a single therapeutic class. Copyright © 2010 John Wiley & Sons, Ltd. [source] Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stageTHE JOURNAL OF PATHOLOGY, Issue 1 2004Astrid Koehler Abstract Gene expression profiling of matched colorectal carcinomas and metastases could reveal key molecular events involved in tumour progression and metastasis. Expression profiles have been created from 25 colorectal carcinomas (CRCs, pT1,4), corresponding normal colonic mucosa, and 14 liver metastases using cDNA arrays containing 1176 cancer-related genes (Clontech). Hierarchical clustering clearly distinguished carcinomas from non-cancerous tissues, separated tumours into high-stage (pT4 and extensive lymph node or distant metastases) and low-stage (,pT3) groups, and correlated with the histopathological classification in 87% (33/38 cases). Most primary tumours and matched liver metastases clustered on terminal branches of the dendrogram. Statistical analysis (Mann,Whitney U -test) revealed 40 tumour-specific genes (29 up-regulated, 11 down-regulated) which allowed identification of malignant tissue samples by cluster analysis. A specific expression signature in matching metastases was not found, but a set of 23 classifier genes with statistically significant expression patterns in high- and low-stage tumours was identified. These genes may represent important targets in colorectal carcinogenesis and might provide useful clinicopathological tools in the management of colorectal cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsetsARTHRITIS & RHEUMATISM, Issue 7 2009Thomas A. Griffin Objective To determine whether peripheral blood mononuclear cells (PBMCs) from children with recent-onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures. Methods Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second-line medications, such as methotrexate or biologic agents. RNA was extracted from isolated mononuclear cells, fluorescence labeled, and hybridized to commercial gene expression microarrays (Affymetrix HG-U133 Plus 2.0). Data were analyzed using analysis of variance at a 5% false discovery rate threshold after robust multichip analysis preprocessing and distance-weighted discrimination normalization. Results Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA patients and healthy controls. Hierarchical clustering of these probe sets distinguished 3 subgroups within the polyarticular JIA group. Prototypical patients within each subgroup were identified and used to define subgroup-specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor ,,inducible genes, and a third with immediate early genes. Correlation of gene expression signatures with clinical and biologic features of JIA subgroups suggested relevance to aspects of disease activity and supported the division of polyarticular JIA into distinct subsets. Conclusion Gene expression signatures in PBMCs from patients with recent-onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease. [source] Mesoscale Patterns in the Floristic Composition of Forests in the Central Western Ghats of Karnataka, IndiaBIOTROPICA, Issue 4 2010B. R. Ramesh ABSTRACT We describe the mesoscale floristic patterns in the central Western Ghats of Karnataka, India, through combined analysis of woody species abundance and stand structure data from a network of ninety-six 1-ha sampling plots spread across 22,000 km2. A total of 61,906 individuals (,10 cm gbh) comprising 400 plant species from 254 genera and 75 families were recorded. Euphorbiaceae, Rubiaceae, Lauraceae and Moraceae families constituted 23.5 percent of the total number of species encountered. The relative dominance of species was skewed with Poecilonueron indicum, Xylia xylocarpa, Terminalia tomentosa and Anogeissus latifolia being dominant in some plots. Correspondence analysis (CA) and a nonmetric multidimensional scaling (NMDS) of plots by species abundances data showed similar arching patterns, with significant correlation between the first axis of CA and NMDS (r=0.77). Hierarchical clustering of plot scores along the three first CA axes resulted in splitting the plots into five different categories that broadly reflect the major bioclimatic features of the region. A multiscale bootstrapping test indicated that categorization of the wettest (wet evergreen group 1 and 2) and driest (dry deciduous) groups were robust (P<0.05 with 1000 bootstraps), while the remaining two transitional groups were uncertain (P=0.12 and 0.26 for moist deciduous and semi-evergreen group, respectively). Principal component analysis revealed that plots with similar floristic composition can encompass contrastingly different physiognomic structures (canopy cover, canopy height and mean tree diameter) probably in relation to their levels of disturbance. Observed patterns in the floristic composition have been discussed in the light of the complex interaction between the bioclimatic and disturbance regimes that characterize the region. [source] Gene expression studies in cultured dendritic cells: new indicators for the discrimination of skin sensitizers and irritants in vitroCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2009S. Szameit Summary Background The replacement of animal tests for the detection of the sensitizing potential of chemicals is of great importance due to current legislation. One promising approach for the development of an in vitro assay is the exposure of immature dendritic cells (iDCs) to contact sensitizers and irritants, followed by an analysis of the maturation status of the cells. Objective The aim of this study was to further investigate the performance of our previously developed targeted microarray, the immune toxicity chip. In addition, we aimed to identify new marker genes for the discrimination of allergens and irritants using whole-genome microarrays. Methods Monocyte-derived iDCs were exposed to contact sensitizers and irritants in concentrations resulting in 10,20% cytotoxicity, as determined by dose,response curves. Changes in gene expression were analysed using the immune toxicity chip and a commercially available whole-genome microarray. Results Using the immune toxicity chip, we could identify a panel of marker genes suitable to discriminate strong allergens and irritants. Analysis with the whole-genome array revealed additional genes that are differentially expressed after allergen exposure, but not after irritant exposure. Hierarchical clustering of these genes showed distinct groups representing the different chemicals. Conclusion Here we show that our test system based on an immune-specific microarray is suitable for the discrimination of strong allergens and irritants. Genes detected as differentially expressed with the whole-genome array and previously not connected to the maturation process of DCs might be suitable candidate genes for the identification of weaker sensitizers. [source] Metagenomic signatures of 86 microbial and viral metagenomesENVIRONMENTAL MICROBIOLOGY, Issue 7 2009Dana Willner Summary Previous studies have shown that dinucleotide abundances capture the majority of variation in genome signatures and are useful for quantifying lateral gene transfer and building molecular phylogenies. Metagenomes contain a mixture of individual genomes, and might be expected to lack compositional signatures. In many metagenomic data sets the majority of sequences have no significant similarities to known sequences and are effectively excluded from subsequent analyses. To circumvent this limitation, di-, tri- and tetranucleotide abundances of 86 microbial and viral metagenomes consisting of short pyrosequencing reads were analysed to provide a method which includes all sequences that can be used in combination with other analysis to increase our knowledge about microbial and viral communities. Both principal component analysis and hierarchical clustering showed definitive groupings of metagenomes drawn from similar environments. Together these analyses showed that dinucleotide composition, as opposed to tri- and tetranucleotides, defines a metagenomic signature which can explain up to 80% of the variance between biomes, which is comparable to that obtained by functional genomics. Metagenomes with anomalous content were also identified using dinucleotide abundances. Subsequent analyses determined that these metagenomes were contaminated with exogenous DNA, suggesting that this approach is a useful metric for quality control. The predictive strength of the dinucleotide composition also opens the possibility of assigning ecological classifications to unknown fragments. Environmental selection may be responsible for this dinucleotide signature through direct selection of specific compositional signals; however, simulations suggest that the environment may select indirectly by promoting the increased abundance of a few dominant taxa. [source] Hourly surface wind monitor consistency checking over an extended observation periodENVIRONMETRICS, Issue 4 2009Scott Beaver Abstract A consistency checking methodology is presented to aid in identifying biased values in extended historical records of hourly surface wind measurements obtained from a single station. The method is intended for screening extended observation periods for values which do not fail physical consistency checks (i.e., standard or complex quality assurance methods), yet nonetheless exhibit statistical properties which differ from the bulk of the record. Several specific types of inconsistencies common in surface wind monitoring datasets are considered: annual biases, unexpected values, and discontinuities. The purely empirical method checks for self-consistency in the temporal distribution of the wind measurements by explicitly modeling the diurnal variability. Each year of data is modeled using principal component analysis (PCA) (or empirical orthogonal functions, EOF), then hierarchical clustering with nearest neighbor linkage is used to visualize any annual biases existing in the measurements. The diurnal distributions for wind speed and direction are additionally estimated and visualized to determine any periods of time which are inconsistent with the typical diurnal cycle for a given monitor. The robust consistency checking method is applied to a set of 44 monitors operating in the San Joaquin Valley (SJV) of Central California over a 9-year period. Monitors from the SLAMS, CIMIS, and RAWS networks are considered. Similar inconsistencies are detected in all three networks; however, network-specific types of inconsistencies are found as well. Copyright © 2008 John Wiley & Sons, Ltd. [source] Clustering technique for risk classification and prediction of claim costs in the automobile insurance industryINTELLIGENT SYSTEMS IN ACCOUNTING, FINANCE & MANAGEMENT, Issue 1 2001Ai Cheo Yeo This paper considers the problem of predicting claim costs in the automobile insurance industry. The first stage involves classifying policy holders according to their perceived risk, followed by modelling the claim costs within each risk group. Two methods are compared for the risk classification stage: a data-driven approach based on hierarchical clustering, and a previously published heuristic method that groups policy holders according to pre-defined factors. Regression is used to model the expected claim costs within a risk group. A case study is presented utilizing real data, and both risk classification methods are compared according to a variety of accuracy measures. The results of the case study show the benefits of employing a data-driven approach. © 2001 John Wiley & Sons, Ltd. [source] A kernel-based core growing clustering methodINTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 4 2009T. W. Hsieh In this paper, a novel clustering method in the kernel space is proposed. It effectively integrates several existing algorithms to become an iterative clustering scheme, which can handle clusters with arbitrary shapes. In our proposed approach, a reasonable initial core for each of the cluster is estimated. This allows us to adopt a cluster growing technique, and the growing cores offer partial hints on the cluster association. Consequently, the methods used for classification, such as support vector machines (SVMs), can be useful in our approach. To obtain initial clusters effectively, the notion of the incomplete Cholesky decomposition is adopted so that the fuzzy c-means (FCM) can be used to partition the data in a kernel defined-like space. Then a one-class and a multiclass soft margin SVMs are adopted to detect the data within the main distributions (the cores) of the clusters and to repartition the data into new clusters iteratively. The structure of the data set is explored by pruning the data in the low-density region of the clusters. Then data are gradually added back to the main distributions to assure exact cluster boundaries. Unlike the ordinary SVM algorithm, whose performance relies heavily on the kernel parameters given by the user, the parameters are estimated from the data set naturally in our approach. The experimental evaluations on two synthetic data sets and four University of California Irvine real data benchmarks indicate that the proposed algorithms outperform several popular clustering algorithms, such as FCM, support vector clustering (SVC), hierarchical clustering (HC), self-organizing maps (SOM), and non-Euclidean norm fuzzy c-means (NEFCM). © 2009 Wiley Periodicals, Inc.4 [source] Spatial analysis of taxonomic and genetic patterns and their potential for understanding evolutionary historiesJOURNAL OF BIOGEOGRAPHY, Issue 11 2004Sophia A. Bickford Abstract Aim, The aim of this research is to develop and investigate methods for the spatial analysis of diversity based on genetic and taxonomic units of difference. We use monophyletic groups of species to assess the potential for these diversity indices to elucidate the geographical components of macro-scaled evolutionary processes. Location, The range occupied by Pultenaea species in temperate and sub-tropical eastern Australia, extending from western South Australia (133° E,32° S) to Tasmania (146° E,43° S) to coastal central Queensland (148° E,20° S). Methods, We applied a series of both spatially explicit and spatially implicit analyses to explore the nature of diversity patterns in the genus Pultenaea, Fabaceae. We first analysed the eastern species as a whole and then the phylogenetic groups within them. We delineated patterns of endemism and biotic (taxon) regions that have been traditionally circumscribed in biogeographical studies of taxa. Centres of endemism were calculated using corrected weighted endemism at a range of spatial scales. Biotic regions were defined by comparing the similarity of species assemblages of grid cells using the Jaccard index and clustering similar cells using hierarchical clustering. On the basis that genetically coherent areas were likely to be more evolutionary informative than species patterns, genetic indices of similarity and difference were derived. A matrix of similarity distances between taxa was generated based on the number of shared informative characters of two sections of trnL-F and ndhF chloroplast nuclear regions. To identify genetically similar areas, we clustered cells using the mean genetic similarities of the species contained within each pair of cells. Measures of the mean genetic similarity of species in areas were delineated using a geographically local multi-scalar approach. Resultant patterns of genetic diversity are interpreted in relation to theories of the evolutionary relationships between species and species groups. Results, Centres of Pultenaea endemism were defined, those of clades 1 congruent with the spatially separated centres of clades 2 and 3. The taxonomic classification analysis defined cells with shared groups of species, which in some cases clustered when plotted in geographic space, defining biotic regions. In some instances the distribution of biotic regions was congruent with centres of endemism, however larger scale groupings were also apparent. In clade 1 one set of species was replaced by another along the extent of the range, with some connectivity between some geographically disjunct regions due to the presence of widespread species. In the combined analysis of clade 2 and 3 species the major biotic (taxonomic) groups with geographic coherence were defined by species in the respective clades, representing the geographic separation of these clades. However distinctive biotic regions within these main groupings of clades 2 and 3 were also apparent. Clustering cells using the mean genetic similarities of the species contained within each pair of cells indicated that some of the taxonomically defined biotic boundaries were the result of changes in composition of closely related species. This was most apparent in clades 1 and 2 where most cells were highly genetically similar. In clade 3 genetically distinct groups remained and were in part defined by sister taxa with disjunct distributions. Gradients in mean genetic similarity became more apparent from small to larger scales of analysis. At larger scales of analysis, regions of different levels of genetic diversity were delineated. Regions with highest diversity levels (lowest level of similarity) often represented regions where the ranges of phylogenetically distinctive species intergraded. Main conclusions, The combined analysis of diversity, phylogeny and geography has potential to reveal macro-scaled evolutionary patterns from which evolutionary processes may be inferred. The spatial genetic diversity indices developed in this study contribute new methods for identifying coherent evolutionary units in the landscape, which overcome some of the limitations of using taxonomic data, and from which the role of geography in evolutionary processes can be tested. We also conclude that a multiple-index approach to diversity pattern analysis is useful, especially where patterns may be the result of a long history of different environmental changes and related evolutionary events. The analysis contributes to the knowledge of large-scale diversity patterns of Pultenaea which has relevance for the assessment of the conservation status of the genus. [source] Serum IgG to heat shock proteins and Porphyromonas gingivalis antigens in diabetic patients with periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2002Tom J. Sims Abstract Background: Past studies have reported a correlation between the presence and severity of periodontitis and serum antibody titers to species-specific antigens of Porphyromonas gingivalis or to cross-reactive antigens, such as lipopolysaccharide (LPS) and heat shock proteins (HSP), shared between P. gingivalis and other bacteria. Our recent study of periodontal treatment outcome in insulin-dependent (type 1) diabetes mellitus patients with severe periodontitis (IDDMI/periodontitis) resulted in two key findings: 1. serum glutamic acid decarboxylase autoantibody (GAD65 Ab) levels were significantly associated with periodontal pocket depth change (PDC) and 2. serum IgG titers to P. gingivalis cells were positively associated with GAD65 Ab level in seropositive (GAD65 Ab +) patients. We have therefore hypothesized that profiles of serum autoantibody levels and IgG titers, to P. gingivalis -specific antigens may be useful in assessing risk for refractory periodontitis in such patients. Aim: To determine whether PDC resulting from non-surgical periodontal treatment can be predicted using profiles of baseline IgG titers to P. gingivalisspecific antigens, human HSP, and GAD65. Methods: PDC was assessed two months after non-surgical periodontal treatment of 7 GAD65 Ab + and 11 GAD65 AbIDDM/periodontitis patients. Pretreatment titers to GAD65, recombinant human heat shock proteins (HSP90, HSP70, and HSP60), and various P. gingivalis antigens were measured using radioligand precipitation or enzyme-linked immunosorbent (ELISA) assays and compared to the same measurements for 154 recent-onset IDDM patients and 46 non-diabetic controls. Results: Median titers (ELISA units) to HSP90 and HSP70 were significantly higher than non-diabetic controls for GAD65 Ab + (p°= 0.002) and GAD65 Ab- (p =,0.034) IDDM/periodontitis patients, respectively. Multivariate regression analysis indicated significant partial correlation of PDC with log-transformed titers to HSP90 (r =,, 0.62, p = 0.008), HSP70 (r =,+ 0.62, p = 0.009), GAD65 (r =,, 0.60, p = 0.01) and P. gingivalis LPS (r = , 0.5 1, p = 0.04). Furthermore, hierarchical clustering of baseline profiles of log-transformed HSP90, HSP70, and GAD65 Ab titers sorted patients into two distinct clusters with significantly different median PDC (1.45 min, n = 10 vs. 0.65 min, n = 8; p = 0.016, Mann,Whitney). Conclusion: Pretreatment profiles of serum antibody titers to HSP90, HSP70, GAD65, and P. gingivalis LPS may be useful for predicting which patients with IDDM/periodontitis will have a poor response to non-surgical periodontal therapy. [source] Genes Associated With Alcohol Abuse and Tobacco Smoking in the Human Nucleus Accumbens and Ventral Tegmental AreaALCOHOLISM, Issue 7 2010Traute Flatscher-Bader Background:, The incidence of alcohol and tobacco co-abuse is as high as 80%. The molecular mechanism underlying this comorbidity is virtually unknown, but interactions between these drugs have important implications for the development of and recovery from drug dependence. Methods:, We investigated the effects of chronic tobacco and alcohol abuse and the interaction of the 2 behaviors on global gene expression in the human nucleus accumbens using cDNA microarrays and 20 alcoholic and control cases, with and without smoking comorbidity. Changes in gene expression were established by factorial ANOVA. Unsupervised hierarchical clustering was utilized to probe the strength of the data sets. Applying real-time PCR differential expression of candidate genes was confirmed in the nucleus accumbens and explored further in a second core region of the mesolimbic system, the ventral tegmental area. Results:, Subjecting the data sets derived from microarray gene expression screening to unsupervised hierarchical clustering tied the cases into distinct groups. When considering all alcohol-responsive genes, alcoholics were separated from nonalcoholics with the exception of 1 control case. All smokers were distinguished from nonsmokers based on similarity in expression of smoking-sensitive genes. In the nucleus accumbens, alcohol-responsive genes were associated with transcription, lipid metabolism, and signaling. Smoking-sensitive genes were predominantly assigned to functional groups concerned with RNA processing and the endoplasmic reticulum. Both drugs influenced the expression of genes involved in matrix remodeling, proliferation, and cell morphogenesis. Additionally, a gene set encoding proteins involved in the canonical pathway "regulation of the actin cytoskeleton" was induced in response to alcohol and tobacco co-abuse and included. Alcohol abuse elevated the expression of candidate genes in this pathway in the nucleus accumbens and ventral tegmental area, while smoking comorbidity blunted this induction in the ventral tegmental area. Conclusions:, The region-specific modulation of alcohol-sensitive gene expression by smoking may have important consequences for alcohol-induced aberrations within the mesolimbic dopaminergic system. [source] DESCRIPTIVE ANALYSIS OF COMMERCIALLY AVAILABLE CREAMY STYLE PEANUT BUTTERS,JOURNAL OF SENSORY STUDIES, Issue 5 2002KAY L. McNEILL ABSTRACT This study was undertaken to establish category and product descriptive characteristics of commercial creamy style peanut butters for use in subsequent modeling of consumer response. An established descriptive lexicon for peanut flavor was modified with additional appearance and texture terminology to describe these samples. To determine the full category space for the appearance, flavor and texture characteristics for commercial creamy style peanut butters, a highly trained descriptive panel screened 42 brands. A subset of 22 peanut butters was identified which represented the available range of appearance, flavor and texture variations and determined the product category. These 22 commercial creamy style peanut butters were subsequently evaluated and quantitatively described using 4 appearance, 19 flavor and 12 texture descriptors. Using both hierarchical clustering and principal component analysis, 4 logical associative groupings of products were identified: store and name brands, natural brands, reduced fat brands, and some store or name brands with unique or unusual appearance, flavor or texture characteristics. Omission of products with redundant characteristics within a factor grouping enabled further reduction to 15 products for subsequent quantitative consumer testing to establish a model for descriptive analysis as a predictor of consumer research responses. [source] Hydrophilic interaction LC of peptides: Columns comparison and clusteringJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2010Sylvia Van Dorpe Abstract A wide variety of hydrophilic interaction chromatography (HILIC) stationary phase surface chemistries are currently available. Although their selectivity can be considerably different, column comparison or clustering using peptides is limited. In this study, ten pharmaceutically relevant model peptides are analyzed on seven different HILIC columns (bare silica, amide, poly-hydroxyethyl aspartamide, diol and zwitterionic) for the evaluation of their performance and classification. The responses examined include single and multiple responses: plate number, asymmetry factor, LOD, geometric mean resolution, resolution product, time corrected resolution product, peak capacity and chromatographic response function. Column classification was performed using hierarchical clustering and principal component analysis. Moreover, the overall performance quality of the HILIC columns was compared using a linear desirability function. Hierarchical clustering and principal component analysis showed consistent clusters. The zwitterionic phase was clustered apart from the other HILIC columns and both poly-aspartamide columns were clustered together. In addition, the two bare silica phases represent two different clusters, and thus different selectivities. Overall, the responses showed the best performance for one of the bare silica columns (Alltima-Alltech), followed by the zwitterionic phase (ZIC)-HILIC. Thus, these columns, belonging to different clusters, were found to be the best performing systems in pharmaceutical peptide analysis for the selected peptide set. [source] Application of agglomerative hierarchical clustering to identify consumer tomato preferences: influence of physicochemical and sensory characteristics on consumer responseJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 4 2006Marta Serrano-Megías Abstract A multiple regression model was developed to predict the acceptability of the four tomato varieties studied (Aranka, Cherry, Beef and Pitenza). Agglomerative hierarchical clustering showed the presence of four consumer clusters. One cluster preferred small tomatoes (Aranka and Cherry) and another cluster the larger tomatoes (Beef and Pitenza). In the sensorial analysis Aranka was the preferred variety, scoring more highly in taste, odour, acidity, sweetness and hardness. In the physicochemical analysis Aranka also obtained the highest values for titratable acidity (TA) and sugars (SSC), confirming that these parameters are important in tomato flavour. Lower values for both sets of parameters were reflected by lower consumer acceptability, with Beef and Pitenza receiving the lowest score for these flavours attributes (except odour). A significant correlation between the sensorial and physicochemical parameters was also observed: odour was positively correlated with calibre, while taste, acidity, hardness and acceptability were negatively correlated with calibre, pH and SSC/TA and positively correlated with SSC and TA. Copyright © 2005 Society of Chemical Industry [source] Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humansLIVER TRANSPLANTATION, Issue 9 2007Hiroto Egawa We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8+ alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8+CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27,CD28, subsets, interferon-gamma (IFN-,), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12R,1+ cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance. Liver Transpl 13:1262,1271, 2007, © 2007 AASLD. [source] Cytotoxic T-cell-mediated defense against infections in human liver transplant recipientsLIVER TRANSPLANTATION, Issue 2 2007Koichi Tanaka Previous studies have shown that postoperative infection is highest in transplant recipients with preexisting high levels of cytotoxic T lymphocytes (CTLs). To study this phenomenon, 106 adult liver transplant recipients were divided into 3 groups, based on hierarchical clustering of the CD3+CD8+CD45 isoform fractions prior to living donor liver transplantation (LDLT). Group I had the highest naive T-cell levels (subset CD45RO,CCR7+), Group II had the highest effector/memory (EM) T-cell levels (subset CD45RO+CCR7,), and Group III had the highest effector T-cell levels (subset CD45RO,CCR7,). In Group I, CTLs upregulated in response to invading pathogens much earlier and more rapidly than the other groups; this response was associated with CD4+ T-cell help, downregulation of CD27+CD28+ subsets, and upregulation of interferon-gamma and perforin expression. In contrast, in Groups II and III, CTLs upregulated slowly following persistent viral infection and did not respond efficiently to acute infection. In addition, Group II's cytolytic responses were due mainly to upregulation of the CD8+ EM T-cell fraction, whereas Group III's cytolytic responses were attributable to upregulation of effector T cells. The prevalence of EM or effector T cells was dependent on differentiation of the CD8+ phenotype before LDLT. In conclusion, in most infected transplant recipients who died, generation of CD8+ CTLs had been suppressed without associated CD4+ T-cell help. Liver Transpl 13:287,293, 2007. © 2007 AASLD. [source] Elemental abundance survey of the Galactic thick discMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2006Bacham E. Reddy ABSTRACT We have performed an abundance analysis for F- and G- dwarfs of the Galactic thick-disc component. A sample of 176 nearby (d, 150 pc) thick-disc candidate stars was chosen from the Hipparcos catalogue and subjected to a high-resolution spectroscopic analysis. Using accurate radial velocities combined with the Hipparcos astrometry, kinematics (U, V and W) and Galactic orbital parameters were computed. We estimate the probability for a star to belong to the thin disc, the thick disc or the halo. With a probability P, 70 per cent taken as certain membership, we assigned 95 stars to the thick disc, 13 to the thin disc, and 20 to the halo. The remaining 48 stars in the sample cannot be assigned with reasonable certainty to one of the three components. Abundances of C, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Ba, Ce, Nd and Eu have been obtained. The abundances for the thick-disc stars are compared with those for the thin-disc members from Reddy et al. The ratios of ,-elements (O, Mg, Si, Ca and Ti) to iron for thick-disc stars show a clear enhancement compared to thin-disc members in the range ,0.3 < [Fe/H] < ,1.2. There are also other elements , Al, Sc, V, Co, and possibly Zn , which show enhanced ratios to iron in the thick disc relative to the thin disc. The abundances of Na, Cr, Mn, Ni and Cu (relative to Fe) are very similar for thin- and thick-disc stars. The dispersion in abundance ratios [X/Fe] at given [Fe/H] for thick-disc stars is consistent with the expected scatter due to measurement errors, suggesting a lack of ,cosmic' scatter. A few stars classified as members of the thick disc by our kinematic criteria show thin-disc abundances. These stars, which appear older than most thin-disc stars, are also, on average, younger than the thick-disc population. They may have originated early in the thin-disc history, and been subsequently scattered to hotter orbits by collisions. The thick disc may not include stars with [Fe/H] > ,0.3. The observed compositions of the thin and thick discs seem to be consistent with the models of galaxy formation by hierarchical clustering in a Lambda cold dark matter (,CDM) universe. [source] An excursion set model of hierarchical clustering: ellipsoidal collapse and the moving barrierMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2002Ravi K. Sheth The excursion set approach allows one to estimate the abundance and spatial distribution of virialized dark matter haloes efficiently and accurately. The predictions of this approach depend on how the non-linear processes of collapse and virialization are modelled. We present simple analytic approximations that allow us to compare the excursion set predictions associated with spherical and ellipsoidal collapse. In particular, we present formulae for the universal unconditional mass function of bound objects and the conditional mass function which describes the mass function of the progenitors of haloes in a given mass range today. We show that the ellipsoidal collapse based moving barrier model provides a better description of what we measure in the numerical simulations than the spherical collapse based constant barrier model, although the agreement between model and simulations is better at large lookback times. Our results for the conditional mass function can be used to compute accurate approximations to the local-density mass function, which quantifies the tendency for massive haloes to populate denser regions than less massive haloes. This happens because low-density regions can be thought of as being collapsed haloes viewed at large lookback times, whereas high-density regions are collapsed haloes viewed at small lookback times. Although we have applied our analytic formulae only to two simple barrier shapes, we show that they are, in fact, accurate for a wide variety of moving barriers. We suggest how they can be used to study the case in which the initial dark matter distribution is not completely cold. [source] Dynamics of global gene expression changes during brain metastasis formationNEUROPATHOLOGY, Issue 4 2009Norihiko Saito As methods of cancer diagnosis and treatment improve, interest in metastatic brain tumors continues to increase. In the present study, we attempted to characterize genetically the dynamic changes occurring during brain metastasis formation by DNA microarray, and attempted to compare these findings with histological observations. Lewis lung carcinoma cells were injected into C57BL/6Ncrj mice carotid arteries. The mice were sacrificed at days 1,9 after injection. We performed histological observation and genome-wide expression profiling using a DNA microarray. In histological observation, tumor cells were observed in capillary vessels at day 1 after injection. At day 3, the tumor cells had begun to proliferate. At day 6, the metastatic foci showed "perivascular proliferations". Next, we performed a pairwise comparison of gene expression microarray data from day 1 to day 9 after injection. The first major change occurred between Phase Two and Phase Three. When hierarchical clustering was performed between different samples using the 867 genes, they could be classified into identical clusters for days 1 and 2, identical clusters for day 3 to day 5, and identical clusters for day 6 to day 9. For time course analysis, we extracted 623 genes by the pairwise comparison. By using the quality threshold (QT) nonhierarchical clustering method, we identified 37 expression patterns. These patterns can be separated into eight clusters by using the k-means method. The microarray results reported here strongly suggest that a large number of genes exhibit a spike pattern, which is tantamount to phase-specific expression. [source] A typology of community opportunity and vulnerability in metropolitan Australia,PAPERS IN REGIONAL SCIENCE, Issue 1 2001Robert Stimson Socio-economic performance; community opportunity and vulnerability; metropolitan regions Abstract. A multivariate model using hierarchical clustering and discriminant analysis is used to identify clusters of community opportunity and community vulnerability across Australia's mega metropolitan regions. Variables used in the model measure aspects of structural economic change, occupational change, human capital, income, unemployment, family/household disadvantage, and housing stress. A nine-cluster solution is used to categorise communities across metropolitan space. Significant between-city variations in the incidence of these clusters of opportunity and vulnerability are apparent, suggesting the emergence of marked differentiation between Australia's mega metropolitan regions in their adjustments to changing economic and social conditions. [source] In vivo proteome dynamics during early bovine myogenesisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 20 2008Thibault Chaze Abstract Myogenesis is a complex process of which the underlying mechanisms are conserved between species, including birds and mammals. Despite a good understanding of the stages of myogenesis, many of the mechanisms involved in the regulation of proliferation of the successive myoblast generations, the cellular transitions cell proliferation/alignment of myoblasts/fusion of myoblasts into myotubes/differentiation of myofibres and the control of total myofibre number still remain unknown. An in vivo proteomic analysis of the semitendinosus muscle from Charolais foetuses, at three specific stages of myogenesis (60, 110 and 180,days postconception), was conducted using 2-DE and MS. Expression profiles of more than 170 proteins were revealed and analysed using two way hierarchical clustering and statistical analysis. Our studies identify, for the first time, distinct proteins of varied biological functions and protein clusters with myogenic processes, such as the control of cell cycle activity and apoptosis, the establishment of cellular metabolism and muscle contractile properties and muscle cell reorganisation. These results are of fundamental interest to the field of myogenesis in general, and more specifically to the control of muscle development in meat producing animals. [source] Consistency of a two clinical site sample collection: A proteomics studyPROTEOMICS - CLINICAL APPLICATIONS, Issue 8-9 2010Cedric Wiesner Abstract Purpose: We investigated the ability to perform a clinical proteomic study using samples collected at different times from two independent clinical sites. Experimental Design: Label-free 2-D-LC-MS proteomic analysis was used to differentially quantify tens of thousands of peptides from human plasma. We have asked whether samples collected from two sites, when analyzed by this type of peptide profiling, reproducibly contain detectable peptide markers that are differentially expressed in the plasma of disease (advanced renal cancer) patients relative to healthy normals. Results: We have demonstrated that plasma proteins enriched in disease patients are indeed detected reproducibly in both clinical collections. Regression analysis, unsupervised hierarchical clustering and PCA detected no systematic bias in the data related to site of sample collection and processing. Using a genetic algorithm, support vector machine classification method, we were able to correctly classify disease samples at 88% sensitivity and 94% specificity using the second site as an independent validation set. Conclusions and clinical relevance: We conclude that multiple site collection, when analyzed by label-free 2-D-LC-MS, generates data that are sufficiently reproducible to guide reliable biomarker discovery. [source] A phase I clinical trial of interferon-beta gene therapy for high-grade glioma: novel findings from gene expression profiling and autopsyTHE JOURNAL OF GENE MEDICINE, Issue 4 2008Toshihiko Wakabayashi Background High-grade gliomas are highly lethal neoplasms representing approximately 20% of all intracranial tumors. Cationic liposome-mediated interferon-beta (IFN- ,) gene transfer has been found to induce regression of experimental glioma. We have previously performed a pilot clinical trial to evaluate the safety and effectiveness of this IFN- , gene therapy in five patients with high-grade glioma. Two patients showed more than 50% reduction while others had stable disease 10 weeks after treatment initiation. Methods To identify alterations in gene expression in brain tumors 2 weeks after the gene therapy trial, we used a microarray technology and Gene Ontology analysis. The results were validated by patients' clinical course and findings of histology and autopsy. Results and conclusions Using hierarchical clustering and principal component analysis, five series of gene therapy trials were classified according to the response to IFN- , gene therapy. Significant changes in gene expression related to immunoresponse and apoptosis were observed. Moreover, novel patterns of altered gene expression, such as inhibition of neovascularization, were identified, suggesting the involvement of pathways reported previously as not involved. Autopsy and histological examinations revealed dramatic changes in the tumor tissues after therapy in all patients. Many tumor cells showed necrotic changes, and immunohistochemistry identified numerous CD8-positive lymphocytes and macrophages infiltrating the tumor and surrounding tissues; these were probably the effects of therapy. Simultaneously, CD34-immunoreactive vessels were notably decreased in the vector-injected brain. This study facilitates the understanding of the antitumor mechanism and helps identify candidate target molecules for new approaches. However, additional clinical trials are warranted. Copyright © 2008 John Wiley & Sons, Ltd. [source] Genome-wide profiling of oral squamous cell carcinomaTHE JOURNAL OF PATHOLOGY, Issue 3 2004Yann-Jang Chen Abstract Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c- Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21,tel; 20q; 11q13; 3q27,29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Cluster Analysis of Lesions in Nonselected Kidney Transplant Biopsies: Microcirculation Changes, Tubulointerstitial Inflammation and ScarringAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010B. Sis Banff classification empirically established scoring of histologic lesions, but the relationships of lesions to each other and to underlying biologic processes remain unclear. We hypothesized that class discovery tools would reveal new relationships between individual lesions, and relate lesions to C4d staining, anti-HLA donor-specific antibody (DSA) and time posttransplant. We studied 234 nonselected renal allograft biopsies for clinical indications from 173 patients. Silhouette plotting and principal component analysis revealed three groups of lesions: microcirculation changes, including inflammation (glomerulitis, capillaritis) and deterioration (double contours, mesangial expansion); scarring/hyalinosis; and tubulointerstitial inflammation. DSA and C4d grouped with microcirculation inflammation, whereas time posttransplant grouped with scarring/hyalinosis lesions. Intimal arteritis clustered with DSA, C4d and microcirculation inflammation, but also showed correlations with tubulitis. Fibrous intimal thickening in arteries clustered with scarring/hyalinosis. Capillary basement membrane multilayering showed intermediary relationships between microcirculation deterioration and time-dependent scarring. Correlation analysis and hierarchical clustering confirmed the lesion relationships. Thus, we propose that the pathologic lesions in biopsies are not independent but are members of groups that represent distinct pathogenic forces: microcirculation changes, reflecting the stress of DSA; scarring, hyalinosis and arterial fibrosis, reflecting the cumulative burden of injury over time; and tubulointerstitial inflammation. Interpretation of lesions should reflect these associations. [source] Community-based Participatory Research: Development of an Emergency Department,based Youth Violence Intervention Using Concept MappingACADEMIC EMERGENCY MEDICINE, Issue 8 2010Carolyn E. Snider MD, FRCPC ACADEMIC EMERGENCY MEDICINE 2010; 17:1,9 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Emergency departments (EDs) see a high number of youths injured by violence. In Ontario, the most common cause of injury for youths visiting EDs is assault. Secondary prevention strategies using the teachable moment (i.e., events that can lead individuals to make positive changes in their lives) are ideal for use by clinicians. An opportunity exists to take advantage of the teachable moment in the ED in an effort to prevent future occurrences of injury in at-risk youths. However, little is known about perceptions of youths, parents, and community organizations about such interventions in EDs. The aims of this study were to engage youths, parents, and frontline community workers in conceptualizing a hospital-based violence prevention intervention and to identify outcomes relevant to the community. Methods:, Concept mapping is an innovative, mixed-method research approach. It combines structured qualitative processes such as brainstorming and group sorting, with various statistical analyses such as multidimensional scaling and hierarchical clustering, to develop a conceptual framework, and allows for an objective presentation of qualitative data. Concept mapping involves multiple structured steps: 1) brainstorming, 2) sorting, 3) rating, and 4) interpretation. For this study, the first three steps occurred online, and the fourth step occurred during a community meeting. Results:, Over 90 participants were involved, including youths, parents, and community youth workers. A two-dimensional point map was created and clusters formed to create a visual display of participant ideas on an ED-based youth violence prevention intervention. Issues related to youth violence prevention that were rated of highest importance and most realistic for hospital involvement included mentorship, the development of youth support groups in the hospital, training doctors and nurses to ask questions about the violent event, and treating youth with respect. Small-group discussions on the various clusters developed job descriptions, a list of essential services, and suggestions on ways to create a more youth-friendly environment in the hospital. A large-group discussion revealed outcomes that participants felt should be measured to determine the success of an intervention program. Conclusions:, This study has been the springboard for the development of an ED-based youth violence intervention that is supported by the community and affected youth. Using information generated by youth that is grounded in their experience through participatory research methods is feasible for the development of successful and meaningful youth violence prevention interventions. [source] | |||||||||||||||||||||||||||||||