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A quantitative trait locus influences coordinated variation in measures of ApoB-containing lipoproteins.

Lipoprotein phenotypes are known to be strongly intercorrelated. These intercorrelations are due to genetic and environmental effects on common metabolic pathways. The purpose of this study was to determine if we could localize genes that exert pleiotropic effects on multiple related lipoprotein traits in humans. Using data from the San Antonio Family Heart Study, we extracted principal components from a set of 12 intercorrelated lipoprotein traits that included phenotypes reflecting lipid and protein concentrations and size distributions for LDLs and HDLs. Five principal components were extracted from the data and all were significantly heritable (h(2) = 0.41-0.57). When subjected to linkage analyses, only one, Component 5, returned a LOD score > or = 3 (LOD score was 3.0 at 38cM on chromosome 15; genome-wide P-value = 0.039). LDL median diameter (-0.529), non-HDLC (-0.422), and ApoB (-0.403) concentrations were the only traits with loadings (absolute value) >0.4, suggesting Component 5 is related to LDL size or perhaps more generally to beta-lipoprotein metabolism. Surprisingly, none of the 12 original lipoprotein traits had a LOD >1 in this region of chromosome 15. These data provide evidence for a novel gene, influencing beta-lipoprotein phenotypes, whose effect(s) is detected only when several lipoprotein traits are considered together.

Adult↗

Strategies of shape representation in macaque visual area V2.

Contours and surface textures provide powerful cues used in image segmentation and the analysis of object shape. To learn more about how the visual system extracts and represents these visual cues, we studied the responses of V2 neurons in awake, fixating monkeys to complex contour stimuli (angles, intersections, arcs, and circles) and texture patterns such as non-Cartesian gratings, along with conventional bars and sinusoidal gratings. Substantial proportions of V2 cells conveyed information about many contour and texture characteristics associated with our stimuli, including shape, size, orientation, and spatial frequency. However, the cells differed considerably in terms of their degree of selectivity for the various stimulus characteristics. On average, V2 cells responded better to grating stimuli but were more selective for contour stimuli. Metric multidimensional scaling and principal components analysis showed that, as a population, V2 cells show strong correlations in how they respond to different stimulus types. The first two and five principal components accounted for 69% and 85% of the overall response variation, respectively, suggesting that the response correlations simplified the population representation of shape information with relatively little loss of information. Moreover, smaller random subsets of the population carried response correlation patterns very similar to the population as a whole, indicating that the response correlations were a widespread property of V2 cells. Thus, V2 cells extract information about a number of higher order shape cues related to contours and surface textures and about similarities among many of these shape cues. This may reflect an efficient strategy of representing cues for image segmentation and object shape using finite neuronal resources.

Animals↗

A new modulated Hebbian learning rule--biologically plausible method for local computation of a principal subspace.

This paper presents one possible implementation of a transformation that performs linear mapping to a lower-dimensional subspace. Principal component subspace will be the one that will be analyzed. Idea implemented in this paper represents generalization of the recently proposed infinity OH neural method for principal component extraction. The calculations in the newly proposed method are performed locally--a feature which is usually considered as desirable from the biological point of view. Comparing to some other wellknown methods, proposed synaptic efficacy learning rule requires less information about the value of the other efficacies to make single efficacy modification. Synaptic efficacies are modified by implementation of Modulated Hebb-type (MH) learning rule. Slightly modified MH algorithm named Modulated Hebb Oja (MHO) algorithm, will be also introduced. Structural similarity of the proposed network with part of the retinal circuit will be presented, too.

Models, Neurological↗

Selection of background electrolyte for CZE analysis by a chemometric approach. Part II. Separation of a mixture of basic beta-blocker drugs.

In the first part of this study a chemometric approach to choose a suitable background electrolyte for CZE analysis was introduced. Two hundred and twenty-two possible electrolytes were previously characterized by means of the descriptors pH, conductivity, ionic strength and relative viscosity and the approach was applied to the separation of a mixture of acidic drugs. In this second part, another application concerning the analysis of basic drugs is presented. The test mixture was made of eight beta-blocker drugs. According to the basic nature of the analytes, the original data set was reduced to a new subset of 117 objects with pH less than or equal to 7, and after computing principal components the new set of objects was represented in a two-dimensional space. Ten objects to be tested in CZE, capable of covering homogeneously the principal component space, were selected by means of Kennard-Stone algorithm. The data set was further reduced around the BGEs which gave the best results, and a new set of electrolytes to be tested was selected. Using pH 4 citrate buffer, an electropherogram with baseline resolution was obtained in 10 min. A Doehlert design was run to further reduce analysis time, and applying the optimized conditions (voltage, 23 kV; temperature, 26 degrees C) the separation was obtained in about 7 min.

Adrenergic beta-Antagonists↗

Factor validation of the Consideration of Future Consequences Scale: evidence for a short version.

The author examined the factor structure of the 12-item Consideration of Future Consequences (CFC) Scale (A. Strathman, F. Gleicher, D. S. Boninger, & S. Edwards, 1994) among 664 undergraduate university students enrolled in human development courses. A principal-components factor analysis with varimax rotation yielded 2 factors. The author used confirmatory factor analysis procedures to examine the fit of 4 models, according to the principal-components factor analysis findings, with the observed covariance. The author used a number of fit indices to compare the 4 models. Both sets of analysis provided the greatest support for an 8-item short version of the CFC Scale. The author discussed findings in regard to the CFC Scale as an instrument to measure future time perspective.

Adolescent↗

Chlorinated dibenzo-p-dioxins and dibenzofurans in the Baltic herring and sprat of Estonian coastal waters.

BACKGROUND, AIMS AND SCOPE: The concentration of chlorinated dibenzo-p-dioxins and dibenzofurans in many fish from the Baltic requires monitoring, since it approaches or exceeds the European Union threshold limit value of 4 pg TEQ/g wet weight of fish for human consumption. The concentrations, expressed in TEQs, are important for toxicology and regulations, but hide the concentrations of the individual congeners, which are important for other environmental sciences, source allocation, and for the detection of measurement errors. This report evaluates the results of a survey reported earlier only in the terms of the TEQ concentrations. METHODS: Principal Component Analysis (PCA) was used to reduce the dimensions of the data (17 = 7 chlorinated dibenzo-p-dioxin and 10 chlorinated dibenzofuran congeners) to three principal components. This facilitated the interpretation of the congener profiles. Slopes of the congener concentrations as a function of age of the fish were estimated by least squares regression. The results were compared with a large set of data for lake trout from Lake Ontario. RESULTS AND DISCUSSION: The congener profiles of Baltic herring are less scattered than those of sprat. The profiles of herring from the central Baltic differ from those of herring from the Gulf of Riga and both appear to be affected relatively minimally by the age of the fish. The congener profiles of herring from the western Gulf of Finland are similar to those from the central Baltic, those from middle Gulf of Finland are similar to those from the Gulf of Riga. Both seem to be more affected by age of the fish than the profiles of the first two groups. The concentrations of several pentachloro- and hexachloro-dibenzo-p-dioxins and dibenzofurans increase with the age of the fish CONCLUSION: PCA is a good technique for the evaluation of the congener profiles. The resulting loading and score plots provide a good graphic summary of the multidimensional data. Additional analyses are needed to confirm the observed profile patterns. A comparison with the results of a long-term monitoring from another area shows that the age of the fish is a more important factor than the year of capture. RECOMMENDATION AND OUTLOOK: The surveys should continue for a number of years and the results should be presented and evaluated both in terms of the TEQs as well as in terms of weight concentrations. Since the concentrations do not appear to change very much from year to year, it would be better to carry out surveys only every 3-4 years and, instead, stratify the sampling according to age and gender of the fish, and to analyze replicate extracts by replicate measurements. The inclusion of unmarked replicate samples would be a good quality assurance measure. It would be desirable to analyze additional parts of the food chain in order to understand the fate of the compounds in the ecosystem.

Age Factors↗

Temporal patient state characterization using Iterative Order and Noise (ION) estimation: applications to anesthesia patient monitoring.

OBJECTIVE: As more sensors are added to increasingly technology-dependent operating rooms (OR), physicians such as anesthesiologists must sift through an ever-increasing number of patient parameters every few seconds as part of their OR duties. To the extent these many parameters are correlated and redundant, manually monitoring all of them may not be an optimal physician strategy for assessing patient state or predicting future changes to guide their actions. METHODS: The method is illustrated by application to seventy-six anesthetized patients for which thirty-two fundamental and derived variables were recorded at 20-second intervals. The Iterative Order and Noise estimation algorithm (ION) estimated the noise on each parameter. The performance of principal components analysis (PCA) was improved by normalizing the noise estimated by ION to unity. A linear regression of the resulting seven high signal-to-noise ratio principal components (PC's) predicted tachycardia 140 seconds in advance. RESULTS: ION estimated the noise on each parameter with sufficient accuracy to increase the number of significant PC's from two to seven, all of which had identifiable physiological correlates. The resulting receiver operating characteristic (ROC) suggested that a 70 percent prediction rate with 5 percent false alarms could be achieved. CONCLUSIONS: This paper illustrates the use of ION to improve significantly the performance of PCA in the efficient representation of patient state and in improving the performance of linear predictors of clinically significant parameters.

Algorithms↗

The Bosnian version of the international self-report measure of posttraumatic stress disorder, the Posttraumatic Stress Diagnostic Scale, is reliable and valid in a variety of different adult samples affected by war.

BACKGROUND: The aim of the present study was to assess the internal consistency and discriminant and convergent validity of the Bosnian version of a self-report measure of posttraumatic stress disorder (PTSD), the Posttraumatic Stress Diagnostic Scale (PTDS). The PTDS yields both a PTSD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) and a measure of symptom severity. METHODS: 812 people living in Sarajevo or in Banja Luka in Bosnia-Herzegovina, of whom the majority had experienced a high number of traumatic war events, were administered the PTDS and other measures of trauma-related psychopathology. The psychometric properties of the instrument were assessed using Cronbach's alpha and principal components analysis, and its construct validity was assessed via Spearman correlation coefficients with the other instruments. RESULTS: The PTDS and its subscales demonstrated high internal consistency. The principal components revealed by an exploratory analysis are broadly consistent with the DSM-IV subscales except that they reproduce some previously reported difficulties with the "numbing" items from the avoidance subscale. The construct validity of the PTDS was supported by appropriate correlations with other relevant measures of trauma related psychopathology. CONCLUSION: The Bosnian version of the PTDS thus appears to be a time-economic and psychometrically sound measure for screening and assessing current PTSD. This self-report measure awaits further validation by interview methods.

Adolescent↗

Vector space classification of DNA sequences.

Revisiting the problem of intron-exon identification, we use a principal component analysis (PCA) to classify DNA sequences and present first results that validate our approach. Sequences are translated into document vectors that represent their word content; a principal component analysis then defines Gaussian-distributed sequence classes. The classification uses word content and variation of word usage to distinguish sequences. We test our approach with several data sets of genomic DNA and are able to classify introns and exons with an accuracy of up to 96%. We compare the method with the best traditional coding measure, the non-overlapping hexamer frequency count, and find that the PCA method produces better results. We also investigate the degree of cross-validation between different data sets of introns and exons and find evidence that the quality of a data set can be detected.

Animals↗

Dynamite: a simple way to gain insight into protein motions.

A public web-based facility to infer, analyse and graphically represent the likely modes of a protein motion, starting from a static structure, is presented. This facility is based on the use of CONCOORD to generate an ensemble of feasible protein structures that are subsequently analysed by principal component analysis to identify probable concerted motions. The user is returned the ensemble of feasible structures, together with associated analyses, including animations and graphical representations of both the principal component of the ensemble covariance and indicators of strongly correlated pairwise atomic motions. Whilst users are warned that completely reliable inferences about protein motion may be beyond even substantially more rigorous tools for exploring configurational space, it is hoped that the service will allow a much wider community to benefit from the insights that simple dynamic data may offer.

Algorithms↗

Spatio-temporal decomposition of the EEG: a general approach to the isolation and localization of sources.

The principal-component method of source localization for the background EEG is generalized to arbitrary spatio-temporal decompositions. It is shown that as long as the spatial patterns of the decomposition span the same signal space as the principal spatial components, the computational process of attempting to localize the sources is the same. Decompositions other than the principal components are shown to be superior for the EEG in that they appear to enable individual sources to be better isolated. An example is given using the common spatial pattern decomposition and using a raw varimax rotation of a subset of the common spatial patterns. The results show that the principal component decomposition is almost ineffective for isolating spike and sharp wave activity in an EEG from a patient with epilepsy, that the common spatial pattern decomposition is significantly better and that the varimax rotation is better yet. That the varimax rotation is best is demonstrated by attempting to locate dipole sources inside the brain which account for the spike and sharp wave activity on the scalp. The question which remains is whether there exists some oblique rotation of the basis vectors of the EEG signal space which is optimal for isolating individual sources.

Adult↗

Metabolomic discrimination of different grades of pine-mushroom (Tricholoma matsutake Sing.) using 1H NMR spectrometry and multivariate data analysis.

Metabolomic analysis of raw and cooked pine-mushrooms (Tricholoma matsutake Sing.) of different grades was performed using (1)H nuclear magnetic resonance (NMR) spectrometry and principal component analysis (PCA). PCA of the (1)H NMR spectra of aqueous fractions allowed different grades of raw pine-mushroom to be discriminated by a combination of principal component (PC) 1 and PC 2, which accounted cumulatively for 94.1% of the variation in all variables. The major peaks in the (1)H NMR spectra that contributed to discrimination of raw mushrooms were assigned to choline, trehalose, threonine, leucine/isoleucine, succinic acid, alanine, and fumaric acid. The combination of PC 1 (70.8%) and PC 3 (7.5%) allowed different grades of cooked pine-mushroom to be discriminated, and the major peaks in the (1)H NMR spectra that contributed to discrimination of cooked mushrooms were assigned to succinic acid, trehalose, and fumaric acid. This metabolomic analysis-based method allows different grades of pine-mushroom to be distinguished without any prepurification.

Agaricales↗

[Structural characteristics of arthropod community in grapery].

By the method of principal component analysis, this paper analyzed the characteristic parameters of arthropod community and its phytophagous and predacious sub-communities in grapery. The results showed that in the first principal component, the contribution of arthropod community, phytophagous sub-community and predacious sub-community was 66.70%, 73.39% and 54.17%, respectively. For arthropod community, the absolute values of normalized regressive coefficients of individuals' number N, Hill diversity index N1, Hill diversity index N2 and McIntosh index D(mc) were larger, indicating their greater contribution on the community. For phytophagous sub-community, N, N1, N2, N and S (total species) had greater contribution; while for predacious sub-community, the greater contribution was made by N1, N2, Shannon-Wiener diversity index H' and abundance R. Synthetically, N2 and N1 had greater contribution on the arthropod community and its phytophagous and predacious sub-communities in grapery, comparing with other characteristic parameters.

Animals↗

Y-chromosome genotyping and genetic structure of Zhuang populations.

Zhuang, the largest ethnic minority population in China, is one of the descendant groups of the ancient Bai-Yue. Linguistically, Zhuang languages are grouped into northern and southern dialects. To characterize its genetic structure, 13 East Asian-specific Y-chromosome biallelic markers and 7 Y-chromosome short tandem repeat (STR) markers were used to infer the haplogroups of Zhuang populations. Our results showed that O*, O2a, and O1 are the predominant haplogroups in Zhuang. Frequency distribution and principal component analysis showed that Zhuang was closely related to groups of Bai-Yue origin and therefore was likely to be the descendant of Bai-Yue. The results of principal component analysis and hierarchical clustering analysis contradicted the linguistically derived north-south division. Interestingly, a west-east clinal trend of haplotype frequency changes was observed, which was supported by AMOVA analysis that showed that between-population variance of east-west division was larger than that of north-south division. O* network suggested that the Hongshuihe branch was the center of Zhuang. Our study suggests that there are three major components in Zhuang. The O* and O2a constituted the original component; later, O1 was brought into Zhuang, especially eastern Zhuang; and finally, northern Han population brought O3 into the Zhuang populations.

Alleles↗

Independent representations of limb axis length and orientation in spinocerebellar response components.

Dorsal spinocerebellar tract (DSCT) neurons transmit sensory signals to the cerebellum that encode global hindlimb parameters, such as the hindlimb end-point position and its direction of movement. Here we use a population analysis approach to examine further the characteristics of DSCT neuronal responses during continuous movements of the hind foot. We used a robot to move the hind paw of anesthetized cats through the trajectories of a step or a figure-8 footpath in a parasagittal plane. Extracellular recordings from 82 cells converted to cycle histograms provided the basis for a principal-component analysis to determine the common features of the DSCT movement responses. Five principal components (PCs) accounted for about 80% of the total variance in the waveforms across units. The first two PCs accounted for about 60% of the variance and they were highly robust across samples. We examined the relationship between the responses and limb kinematic parameters by correlating the PC waveforms with waveforms of the joint angle and limb axis trajectories using multivariate linear regression models. Each PC waveform could be at least partly explained by a linear relationship to joint-angle trajectories, but except for the first PC, they required multiple angles. However, the limb axis parameters more closely related to both the first and second PC waveforms. In fact, linear regression models with limb axis length and orientation trajectories as predictors explained 94% of the variance in both PCs, and each was related to a particular linear combination of position and velocity. The first PC correlated with the limb axis orientation and orientation velocity trajectories, whereas second PC with the length and length velocity trajectories. These combinations were found to correspond to the dynamics of muscle spindle responses. The first two PCs were also most representative of the data set since about half the DSCT responses could be at least 85% accounted for by weighted linear combinations of these two PCs. Higher-order PCs were unrelated to limb axis trajectories and accounted instead for different dynamic components of the responses. The findings imply that an explicit and independent representation of the limb axis length and orientation may be present at the lowest levels of sensory processing in the spinal cord.

Anesthesia↗

Brownian dynamics simulation of helix-capping motifs.

Helix-capping motifs are believed to play an important role in stabilizing alpha-helices and defining helix start and stop signals. We performed microsecond scale Brownian dynamics simulations to study ten XAAD sequences, with X = (A,E,I,L,N,Q,S,T,V,Y), to examine their propensity to form helix capping motifs and correlate these results with those obtained from analyzing a structural database of proteins. For the widely studied capping box motif S**D, where the asterisk can be any amino acid residue, the simulations suggested that one of the two hydrogen bonds proposed earlier as a stabilizing factor might not be as important. On the other hand, side-chain interactions between the capping residue and the third residue downstream on the polypeptide chain might also play a role in stabilizing this motif. These results are consistent with explicit-solvent molecular dynamics simulations of two capping box motifs found in the proteins BPTI and alpha-dendrotoxin. Principal component analysis of the SAAD trajectory showed that the first three principal components, after those corresponding to translational-rotational motion were removed, accounted for more than half of the conformational fluctuations. The first component separated the conformational space into two parts with the all-helical conformation and the capping box motif lying largely in one part. The second component, on the other hand, could be used to describe conformational transitions between the all-helical form and the capping box motif.

Amino Acid Motifs↗

A cross-cultural comparative study of depressive symptoms in British and Turkish clinical samples.

A cross-cultural comparison of the symptomatology of depression in Britain and Turkey was conducted in outpatient samples selected according to the same criteria, and matched for age, sex and severity; the same standardized rating instruments were also used with each sample. Comparison of the frequency and severity of individual symptoms showed higher mean ratings in the British sample for core depressive symptoms and higher ratings in the Turkish sample for symptoms reflecting somatization and a tendency to emphasize symptoms. Principal component analysis produced similar dimensions, confirmed after factor rotation, but the principal components emerged in a different order, reflecting differing contributions to the variance. In the Turkish sample, the first, general component, accounting for the greatest variance, was the somatization factor, while in the British sample it was the component that reflects core depressive symptoms. These findings indicate that there are some similarities in the symptoms of depression in the two cultures, but also differences in their predominant mode of expression.

Adult↗

Multivariate analysis of the selectivity for a pentachlorophenol-imprinted polymer.

A pentachlorophenol (PCP)-imprinted polymer (MIP) was obtained by thermal polymerization of a mixture of template, 4-vinylpyridine and ethylene glycol dimethacrylate with molar ratio 1 +3 + 27, using as porogenic solvent methanol-water ( 3 + 1(v/v)). The polymer was packed in an HPLC column and selectivity towards 52 PCP-related phenols (22-chloro-, 21-alkyl-, 4-aryl-, 3-methoxy- and 6-polyphenols) was measured using acetonitrile-acetic acid (99 + 1(v/v)) as mobile phase. The same was made for a reference polymer obtained without pentachlorophenol (NIP). The molecular recognition properties of the imprinted polymer were expressed in terms of selectivity index (SI), calculated for each phenol as k(NIP)/k(MIP). Sixteen molecular descriptors were calculated for each molecule: qO, the partial charge of the phenolic oxygen atom; qH, the partial charge of the phenolic hydrogen atom; Deltaq, the absolute value of the difference qO - qH; HOMO, the highest occupied molecular orbital; LUMO, the lowest unoccupied molecular orbital; Deltaorb, absolute value of the difference HOMO - LUMO; micro(2), the square of total dipole moment; MW, the molecular weight; SAS, the solvent-accessible molecular surface area; hSAS, the hydrophobic solvent-accessible molecular surface area; Svdw, the van der Waals molecular surface area; hSvdw, the hydrophobic part of Svdw; MOv, the molecular ovality; RG, the radius of gyration; logP, the logarithm of n-octanol-water partition coefficient; pK, the phenolic dissociation constant. Correlations between selectivity index and these descriptors were searched utilizing multivariate principal component analysis (PCA). The multivariate model obtained by regression on the principal components correlate collectively several of the calculated descriptors with the polymer selectivity. The magnitude of the model's parameters shows that selectivity is strongly influenced by molecular descriptors having structural character, such as MW, hSvdw and logP, while the effect of molecular descriptors having electronic character, such as qO and pK, is much less marked.

Multivariate Analysis↗