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PubMed1997

Genetic and phenotypic correlations among size-related traits, and heritability variation between body parts in Drosophila buzzatii.

Recent studies have shown that body size is a heritable trait phenotypically correlated with several fitness components in wild populations of the cactophilic fly Drosophila buzzatii. To obtain further information on size-related variation, heritabilities as well as genetic and phenotypic correlations among size-related traits of several body parts (head, thorax and wings) were estimated. The study was carried out on an Argentinean natural population in which size-related selection was previously detected. The genetic parameters were estimated using offspring-parent regressions (105 families) in the laboratory G2 generation of a sample of wild flies. The traits were also scored in Wild-Caught Flies (WCF). Laboratory-Reared Flies (LRF) were larger and less variable than WCF. Although heritability estimates were significant for all traits, heritabilities were higher for thorax-wing traits than for head traits. Phenotypic and genetic correlations were all positive. The highest genetic correlations were found between traits which are both functionally and developmentally related. Genetic and phenotypic correlations estimated in the lab show similar correlation pattern (r = 0.49; P = 0.02, Mantel's test). However, phenotypic correlations were found to be typically larger in WCF than in LRF. The genetic correlation matrix estimated in the relatively homogeneous lab environment is not simply a constant multiplicative factor of the phenotypic correlation matrix estimated in WCF.

Animals↗

PubMed1988

Genetic, geographic, and linguistic distances in Europe.

Genetic and taxonomic distances were computed for 3466 samples of human populations in Europe based on 97 allele frequencies and 10 cranial variables. Since the actual samples employed differed among the genetic systems studied, the genetic distances were computed separately for each system, as were matrices of geographic distances and of linguistic distances based on membership in the same language family or phylum. Significant matrix correlations between genetics and geography were found for the majority of systems; somewhat less frequent are significant correlations between genetics and language. The effects of the two factors can be separated by means of partial matrix correlations. These show significant values for both genetics and geography, language kept constant, and genetics and language, geography kept constant, with a tendency for the former to be higher. These findings demonstrate that speakers of different language families in Europe differ genetically and that this difference remains even after geographic differentiation is allowed for. The greater effect of geography than of language may be due to the several factors that bring about spatial differentiation in human populations.

Europe↗

PubMed2006

Properties of correlated neural activity clusters in cat auditory cortex resemble those of neural assemblies.

Spiking activity was recorded from cat auditory cortex using multi-electrode arrays. Cross-correlograms were calculated for spikes recorded on separate microelectrodes. The pair-wise cross-correlation matrix was constructed for the peak values of the correlograms. Hierarchical clustering was performed on the cross-correlation matrix for six stimulus conditions. These were silence, three multi-tone stimulus ensembles with different spectral densities, low-pass amplitude-modulated noise, and Poisson-distributed click trains that each lasted 15 min. The resulting neuron clusters reflect patches in cortex of up to several mm(2) in size that expand and contract in response to different stimuli. Cluster positions and size were very similar for spontaneous activity and multi-tone stimulus-evoked activity but differed between those conditions and the noise and click stimuli. Cluster size was significantly larger in posterior auditory field (PAF) compared with primary auditory cortex (AI), whereas the fraction of common spikes (within a 10-ms window) across all electrode activity participating in a cluster was significantly higher in AI compared with PAF. Clusters crossed area boundaries in <5% of the cases were simultaneous recording were made in AI and PAF. Clusters are therefore similar to but not synonymous with the traditional view of neural assemblies. Common-spike spectrotemporal receptive fields (STRFs) were obtained for common-spike activity and all-spike activity within a cluster. Common-spike STRFs had higher signal-to-noise ratio than all-spike STRFs and showed generally spectral and temporal sharpening. The coincident and noncoincident output of the clusters could potentially act in parallel and may serve different modes of stimulus coding.

Acoustic Stimulation↗

PubMed1986

Innovative blood pressure measurements yield information not reflected by sitting measurements.

A study of 873 healthy adults and children from Utah kindreds was performed to identify redundant and unique information contained in multiple diverse blood pressure determinations. Systolic blood pressure, fourth-phase and fifth-phase diastolic blood pressures, and simultaneous heart rates were measured in subjects sitting, standing, supine, and tilting, during half-maximal handgrip exercise, and just before blood drawing. A correlation matrix of 57 blood pressure and pulse variables in 618 healthy adults was analyzed. Factor analysis of the correlation matrix showed that all systolic blood pressures loaded as a single factor, accounting for 44% of the total variance of the observed variables. All heart rates also loaded together as a single factor. Diastolic blood pressures showed much more heterogeneity of information distributed among five separate factors. The same basic factors were found in young adults (age, 18-35 years) and older adults (age, 36 + years). Children under 12 years of age showed very different factor patterns, and youths 12 to 17 years of age showed patterns intermediate between those of adults and children. In light of recent clinical trials, better definitions are being sought for hypertension. Information from blood pressures other than sitting determinations may improve the definition of hypertension or better predict which patients have the highest risk of hypertension and its cardiovascular complications.

Adolescent↗

PubMed2003

Validating internet research: a test of the psychometric equivalence of internet and in-person samples.

This study evaluated the psychometric equivalency of Web-based research. The Sexual Boredom Scale was presented via the World-Wide Web along with five additional scales used to validate it. A subset of 533 participants that matched a previously published sample (Watt & Ewing, 1996) on age, gender, and race was identified. An 8 x 8 correlation matrix from the matched Internet sample was compared via structural equation modeling with a similar 8 x 8 correlation matrix from the previously published study. The Internet and previously published samples were psychometrically equivalent. Coefficient alpha values calculated on the matched Internet sample yielded reliability coefficients almost identical to those for the previously published sample. Factors such as computer administration and uncontrollable administration settings did not appear to affect the results. Demographic data indicated an overrepresentation of males by about 6% and Caucasians by about 13% relative to the U.S. Census (2000). A total of 2,230 participants were obtained in about 8 months without remuneration. These results suggest that data collection on the Web is (1) reliable, (2) valid, (3) reasonably representative, (4) cost effective, and (5) efficient.

Adult↗

PubMed1998

Factors affecting population variation in eastern Adriatic isolates (Croatia).

Inhabitants of the Croatian islands of Brac, Hvar, Korcula, and the Peljesac Peninsula have been the subject of extensive previous studies of local population differentiation. Most of these studies used biological and ecological variables, but some also considered historical and sociological factors. In this study we use genetic, morphological, kinship, and language distance data, collected for individuals from 26 rural communities on the islands of Brac, Hvar, Korcula, and the Peljesac Peninsula in the Adriatic, to further explore the interaction of historical, sociological, and biological factors in small populations and to test the significance of some of these proposed causes. First, we use matrix correlation methods to evaluate the relationships among different types of distance measures. The specific measures of genetic distance used here do not correlate well with other measures of population distance, and it appears that for the studied genetic systems the populations are not strongly differentiated. As expected, kinship and language distances have a high degree of association. Morphological differences among populations seem to be more closely tied to kinship distances than to genetic distances. This may result from modification of some morphological features by environmental rather than genetic factors, or it may be attributed to extensive, selective, nonrandom emigration of the population during the first decade of the twentieth century. In the second part of our analysis we use matrix correlation methods to evaluate and possibly identify the external factors that have contributed to the population differences. Specifically, we use design matrices to test hypotheses that population differences can be explained by one of the following factors: geographic isolation on the islands and peninsula, distance from the mainland, geographic barriers within the islands and peninsula, and the historical factors that differentially affected the three islands and the peninsula. Most of these design matrices reflect geographic distances; although correlations between morphological variables and simple geographic distance between localities were not significant, correlations between these localities and a design matrix incorporating geographic distance along with geographic barriers, such as bodies of water and mountain ranges, are particularly important for explaining distances among kin. Design matrices provide an important tool for quantifying the relationship between historical and geographic factors, and measures of population distance.

Anthropometry↗

PubMed1998

A geometric study of the amino acid sequence of class I HLA molecules.

HLA class I alleles are studied by representing them in a metric space where each dimension corresponds to each one of the amino acid positions. Their similarity in reference to their ability to present peptides to T cells is then evaluated by calculating the correlation matrix between the amino-acid-composition tables (or binding affinity tables) for the sets of peptides presented by each allele. This correlation matrix is considered an empirical similarity matrix between HLA alleles, and is modeled in terms of possible structures defined in the metric space of HLA class I amino acid sequences. These geometric structures are adequate models of the peptide-binding data currently available. The following clusters of HLA class I molecules are identified in reference to their ability to present peptides: Cluster I) HLA-A3/ HLA-A11/ HLA-A31/ HLA-A33/ HLA-A68; Cluster II) HLA-B35/ HLA-B51/ HLA-B53/ HLA-B54/ HLA-B7; and Cluster III) HLA-A29/ HLA-B61/HLA-B44; the last cluster showing possible similarities between alleles from different loci. In modeling these natural clusters, the geometric structures with more predictive power confirm the importance of those positions in the peptide-binding groove, particularly those in the B pocket. In addition, other positions (46, 79, 113, 131, 144, and 177) appeared to bear some relevance in determining which peptides can be presented by which HLA alleles.

Amino Acid Sequence↗

PubMed2007

Phylogenetic tree information aids supervised learning for predicting protein-protein interaction based on distance matrices.

BACKGROUND: Protein-protein interactions are critical for cellular functions. Recently developed computational approaches for predicting protein-protein interactions utilize co-evolutionary information of the interacting partners, e.g., correlations between distance matrices, where each matrix stores the pairwise distances between a protein and its orthologs from a group of reference genomes. RESULTS: We proposed a novel, simple method to account for some of the intra-matrix correlations in improving the prediction accuracy. Specifically, the phylogenetic species tree of the reference genomes is used as a guide tree for hierarchical clustering of the orthologous proteins. The distances between these clusters, derived from the original pairwise distance matrix using the Neighbor Joining algorithm, form intermediate distance matrices, which are then transformed and concatenated into a super phylogenetic vector. A support vector machine is trained and tested on pairs of proteins, represented as super phylogenetic vectors, whose interactions are known. The performance, measured as ROC score in cross validation experiments, shows significant improvement of our method (ROC score 0.8446) over that of using Pearson correlations (0.6587). CONCLUSION: We have shown that the phylogenetic tree can be used as a guide to extract intra-matrix correlations in the distance matrices of orthologous proteins, where these correlations are represented as intermediate distance matrices of the ancestral orthologous proteins. Both the unsupervised and supervised learning paradigms benefit from the explicit inclusion of these intermediate distance matrices, and particularly so in the latter case, which offers a better balance between sensitivity and specificity in the prediction of protein-protein interactions.

Computational Biology↗

PubMed2005

Neurophysiological architecture of functional magnetic resonance images of human brain.

We investigated large-scale systems organization of the whole human brain using functional magnetic resonance imaging (fMRI) data acquired from healthy volunteers in a no-task or 'resting' state. Images were parcellated using a prior anatomical template, yielding regional mean time series for each of 90 regions (major cortical gyri and subcortical nuclei) in each subject. Significant pairwise functional connections, defined by the group mean inter-regional partial correlation matrix, were mostly either local and intrahemispheric or symmetrically interhemispheric. Low-frequency components in the time series subtended stronger inter-regional correlations than high-frequency components. Intrahemispheric connectivity was generally related to anatomical distance by an inverse square law; many symmetrical interhemispheric connections were stronger than predicted by the anatomical distance between bilaterally homologous regions. Strong interhemispheric connectivity was notably absent in data acquired from a single patient, minimally conscious following a brainstem lesion. Multivariate analysis by hierarchical clustering and multidimensional scaling consistently defined six major systems in healthy volunteers-- corresponding approximately to four neocortical lobes, medial temporal lobe and subcortical nuclei- - that could be further decomposed into anatomically and functionally plausible subsystems, e.g. dorsal and ventral divisions of occipital cortex. An undirected graph derived by thresholding the healthy group mean partial correlation matrix demonstrated local clustering or cliquishness of connectivity and short mean path length compatible with prior data on small world characteristics of non-human cortical anatomy. Functional MRI demonstrates a neurophysiological architecture of the normal human brain that is anatomically sensible, strongly symmetrical, disrupted by acute brain injury, subtended predominantly by low frequencies and consistent with a small world network topology.

Adult↗

PubMed2002

Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion.

BACKGROUND: The actions of the extracellular-matrix degrading enzymes, matrix metalloproteinases (MMPs), are implicated in tumorigenesis. The cellular localization of MMP-2, MMP-9, membrane type 1 (MT1)-MMP, tissue inhibitors of metalloproteinases (TIMPs) 1-3, and the presence of active gelatinases were investigated in endometrial carcinoma. METHODS: Endometrial carcinomas were grouped according to histologic grade (Grades 1-3), depth of myometrial invasion (0, < 50%, > 50%) and the presence of vascular/lymphatic invasion. Twenty-nine endometrial carcinoma biopsies were investigated immunohistochemically to determine the tissue localization of MMP-2 (gelatinase A), MMP-9 (gelatinase B), MT1-MMP, and TIMPs 1-3. In situ hybridization was performed to localize MMP-2 and MMP-9 mRNA. The presence of active gelatinases was assessed using in situ zymography. RESULTS: Epithelial tumor cells were the main site of MMP-2, MMP-9, and MT1-MMP protein. Variable stromal cell localization was also observed, particularly in areas adjacent to tumor nests. Semiquantitative analysis revealed increases in MMP-9 and MMP-2 but not MT1-MMP staining scores in tumor epithelial cells in the transition from histologic Grade 1 to Grades 2 and 3. Matrix metalloproteinase-9 and MT1-MMP staining scores in tumor cells were significantly associated with the presence of myometrial invasion and vascular/lymphatic invasion, while MMP-2 did not correlate with these factors. In addition, MT1-MMP was co-localized with MMP-2, supporting its role in the activation of proMMP-2. Tumor cells from all histologic grades stained intensely for TIMP-2 and TIMP-3 proteins, while variable stromal staining was observed. In Grade 1 carcinomas TIMP-1 was predominantly immunolocalized to the stromal compartment with variable tumor cell localization being observed in Grades 2 and 3 carcinomas. Matrix metalloproteinase-9 and MMP-2 mRNAs were predominantly observed in tumor epithelial cells as well as in the stroma to varying degrees. In situ zymography revealed active forms of gelatinases at the cellular surface and in association with tumor epithelial cells within endometrial carcinoma tissues. CONCLUSIONS: These data suggest that increasing expression of MMPs and endometrial carcinoma progression are closely related. Active gelatinases are present in endometrial carcinoma, resulting in alterations to the microenvironment that promote tumor invasion and metastasis.

Biopsy↗

PubMed1992

Genetic expression of extracellular matrix proteins correlates with histologic changes during fracture repair.

We characterized gene expression in the reparative callus that formed after fracture of the rat femur. The callus was divided into regions of bone formation (hard callus) and cartilage formation (soft callus), and gene expression was examined separately in each region. Expression of extracellular matrix protein genes varied with the progression of repair and differed between hard and soft calluses. Messenger ribonucleic acids (mRNAs) for osteonectin, alkaline phosphatase, and type I procollagen were detected in the hard callus at maximal levels during endochondral ossification and bone remodeling (day 15) and at 50% maximal levels during intramembranous bone formation (day 7). Messenger RNAs for these proteins in the soft callus were detected at low levels during chondrogenesis (day 9) but increased to 80% of maximal levels with chondrocyte hypertrophy and mineralization of the cartilage matrix (day 13). Messenger RNAs for type II procollagen and proteoglycan core protein were detected at maximal levels in the soft callus during chondrogenesis (day 9). Osteocalcin gene expression was detected in the hard callus during endochondral ossification and remodeling but not during intramembranous bone formation or at any time in the soft callus. Osteonectin mRNA was detected in both the hard and soft callus throughout the entire course of fracture repair. Expression of cartilage and bone-related genes correlated with the temporal sequence of histologic changes, suggesting transcriptional regulation of gene expression during repair. Differences in gene expression between hard and soft callus and in each of these regions as repair progressed suggest local regulation of gene expression during cell differentiation and matrix synthesis.

Alkaline Phosphatase↗

PubMed2004

Path integrals and fluctuations in irreversible thermodynamics.

We express the set of stochastic differential equations which describe fluctuations in linear irreversible thermodynamics in terms of path integrals. The stochastic terms which are added to the linearized macroscopic equations have a correlation matrix that is singular, which implies that the straightforward formulation of the problem in terms of path integrals fails. We therefore begin by constructing a path-integral representation which is valid whether or not the correlation matrix is singular. We apply this to linearized irreversible thermodynamics, but the technique is designed to be applicable to more general versions of the theory. The approach emphasizes the role of the response and correlation functions as basic elements of the theory, and we calculate these quantities explicitly for the case of density fluctuations in a fluid.

Journal Article↗

PubMed2001

Correlations between matrix metalloproteinase-9 and adenosine deaminase isozymes in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVE: To clarify the significance of increased adenosine deaminase (ADA) isozyme activities in synovial fluid (SF) from patients with rheumatoid arthritis (RA). METHODS: ADA isozyme activities were measured using colorimetric assays. Concentrations of matrix metalloproteinase-9 (MMP-9) were measured by ELISA. RESULTS: Levels of ADA isozyme activities in RA SF were significantly higher than those from patients with osteoarthritis and patients with traumatic injuries. Significant positive correlations between MMP-9 concentration and ADA activities were observed in RA SF (MMP-9 vs total ADA: r = 0.880; vs ADA1: r = 0.829; vs ADA2: r = 0.823; p < 0.001). CONCLUSION: Elevated levels of ADA activities were found in SF from patients with RA. There were significant positive correlations between MMP-9 and ADA isozymes. These results may reflect the inflammatory condition of patients with RA.

Adenosine Deaminase↗

PubMed1991

Comparison of two principal component analysis methods to evaluate reversed-phase retention data.

The retention of twelve 2-nitro-4-cyanophenyl esters showing marked herbicidal activity was determined in 23 reversed-phase thin-layer chromatographic systems. The retention data set was evaluated by principal component analysis (PCA). To assess the effect of the information loss caused by normalization, PCA was separately carried out on the covariance (method A) and on the correlation matrix (method B). The ratio of the variances explained was very similar for both methods, however, the PC loadings and the coordinates of the two-dimensional nonlinear maps showed poor correlation. The distribution of the 2-nitro-4-cyanophenyl esters and that of chromatographic systems showed differences on the two-dimensional nonlinear maps of PC loadings and PC variables, however, the general trend was similar independently of the application of method A or B. The findings indicate that the application of the correlation matrix as basis for the PCA calculations may lead to slightly distorted results that strongly advocates the use of covariance matrix in PCA.

Chromatography, Thin Layer↗

PubMed2000

On the accuracy of efficiency of estimating equation approach.

Liang and Zeger (1986, Biometrika 73, 13-22) introduced a generalized estimating equation (GEE) approach based on a working correlation matrix to obtain efficient estimators of regression parameters in the class of generalized linear models for repeated measures data. As demonstrated by Crowder (1995, Biometrika 82, 407-410), because of uncertainty of the definition of the working correlation matrix, the Liang-Zeger approach may, in some cases, lead to a complete breakdown of the estimation of the regression parameters. After taking this comment of Crowder into account, recently Sutradhar and Das (1999, Biometrika 86, 459-465) examined the loss of efficiency of the regression estimators due to misspecification of the correlation structures. But their study was confined to the regression estimation with cluster-level covariates, as in the original paper of Liang and Zeger. In this paper, we study this efficiency loss problem for the generalized regression models with within-cluster covariates by utilizing the approach of Sutradhar and Das (1999).

Biometry↗

PubMed2000

Correspondence analysis of genes and tissue types and finding genetic links from microarray data.

In this paper, we propose and use two novel procedures for the analysis of microarray gene expression data. The first is correspondence analysis which visualizes the relationship between genes and tissues as two 2 dimensional graphs, oriented so that distances between genes are preserved, distances between tissues are preserved, and so that genes which primarily distinguish certain types of tissue are spatially close to those tissues. For the inference of genetic links, partial correlations rather than correlations are the key issue. A partial correlation between i and j is the relationship between i and j after the effect of surrounding genes has been subtracted out of their pairwise correlation. This leads to the area of graphical modeling. A limitation of the graphical modeling approach is that the correlation matrix of expression profiles between genes is degenerate whenever the number of genes to be analyzed exceeds the number of distinct expression measurements. This can cause considerable problems, as calculation of partial correlations typically uses the inverse of the correlation matrix. To avoid this limitation, we propose two practical multiple regression procedures with variable selection to measure the net, screened, relationship between pairs of genes. Possible biases arising from the analysis of a subset of genes from the genome are examined in the worked examples. It seems that both these approaches are more natural ways of analyzing gene expression data than the currently popular approach of two way clustering.

Carbonates↗

PubMed1989

Heat shock-induced appearance of RNA polymerase II in karyoskeletal protein-enriched (nuclear "matrix") fractions correlates with transcriptional shutdown in Drosophila melanogaster.

Heat shock in vivo or brief incubation at moderately elevated temperatures (15 min at 37 degrees C) in vitro is required for the structural stability of proteinaceous karyoskeletal elements purified from Drosophila melanogaster (McConnell, M., Whalen, A. M., Smith, D. E., and Fisher, P. A. (1987) J. Cell Biol. 105, 1087-1098). We have found that the appearance of the two largest subunits of RNA polymerase II in karyoskeletal preparations is promoted by conditions identical to those which promote in vitro stability of karyoskeletal elements overall. Increased levels of polymerase II in karyoskeletal protein-enriched fractions correlate with decreased levels of nucleotide incorporation in nuclear transcription run-on assays. These results are not easily reconciled with the proposal that putative karyoskeletal elements such as the internal nuclear "matrix" are sites of active transcription in vivo.

Animals↗

PubMed1980

A model of distributed type associative memory with quantized Hadamard transform.

This paper proposes a new correlation matrix network model of associative memory in brain. Each memorized pattern which consists of binary (+1 or -1) elements is preprocessed by a quantized Hadamard transform to increase selectivity. The association ability of a correlation matrix network model depends on the orthogonality between key patterns by which the corresponding memorized patterns are associatively recalled. In a brain model, however, it is rare that the key patterns are mutually orthogonal since they are memorized patterns themselves. The quantized Hadamard transform, presented in this paper, renders the memorized patterns approximately orthogonal. The model is tested by computer simulation.

Animals↗