Averaging of strongly varying signals.

Forces acting at the hip joint during a given activity often vary much between trials and subjects. Large variations are also encountered in many other biomechanical signals. Arithmetic mean curves then lead to falsified results, especially if extreme values occur at very different times. A method was developed for calculating a typical curve from such varying, time dependent signals. All cycle times are first averaged and the signals are then more and more smoothed using Fourier series with decreasing numbers of harmonics. The remaining extrema are analysed to decide whether they are typical for all curves or not. This is done by systematically cutting off a varying number of extrema at the beginning or end of all curves. After this an equal number of extrema remains in all curves. These extrema are then shifted to average positions in time, i.e. the times between consecutive extrema are compressed or expanded, and the standard deviation of all curves is calculated. The combination of cut off extrema which results in the smallest standard deviation is then used further on. The same time distortions are applied to the original curves and their arithmetic mean finally results in the typical signal. This procedure is well suited for averaging hip contact forces and other varying signals as long as their complexity and variation is not extremely large.     

Determination of strongly overlapping signaling activity from microarray data

Background  

As numerous diseases involve errors in signal transduction, modern therapeutics often target proteins involved in cellular signaling. Interpretation of the activity of signaling pathways during disease development or therapeutic intervention would assist in drug development, design of therapy, and target identification. Microarrays provide a global measure of cellular response, however linking these responses to signaling pathways requires an analytic approach tuned to the underlying biology. An ongoing issue in pattern recognition in microarrays has been how to determine the number of patterns (or clusters) to use for data interpretation, and this is a critical issue as measures of statistical significance in gene ontology or pathways rely on proper separation of genes into groups.     

Determination of strongly overlapping signaling activity from microarray data

Background

The Tissue Microarray (TMA) facilitates high-throughput analysis of hundreds of tissue specimens simultaneously. However, bottlenecks in the storage and manipulation of the data generated from TMA reviews have become apparent. A number of software applications have been developed to assist in image and data management; however no solution currently facilitates the easy online review, scoring and subsequent storage of images and data associated with TMA experimentation.

Results

This paper describes the design, development and validation of the Virtual Tissue Matrix (VTM). Through an intuitive HTML driven user interface, the VTM provides digital/virtual slide based images of each TMA core and a means to record observations on each TMA spot. Data generated from a TMA review is stored in an associated relational database, which facilitates the use of flexible scoring forms. The system allows multiple users to record their interpretation of each TMA spot for any parameters assessed. Images generated for the VTM were captured using a standard background lighting intensity and corrective algorithms were applied to each image to eliminate any background lighting hue inconsistencies or vignetting. Validation of the VTM involved examination of inter-and intra-observer variability between microscope and digital TMA reviews. Six bladder TMAs were immunohistochemically stained for E-Cadherin, β-Catenin and PhosphoMet and were assessed by two reviewers for the amount of core and tumour present, the amount and intensity of membrane, cytoplasmic and nuclear staining.

Conclusion

Results show that digital VTM images are representative of the original tissue viewed with a microscope. There were equivalent levels of inter-and intra-observer agreement for five out of the eight parameters assessed. Results also suggest that digital reviews may correct potential problems experienced when reviewing TMAs using a microscope, for example, removal of background lighting variance and tint, and potential disorientation of the reviewer, which may have resulted in the discrepancies evident in the remaining three parameters.     

Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns

Voltage-sensitive fluorescent dyes are commonly used to measure cardiac electrical activity. Recent studies indicate, however, that optical action potentials (OAPs) recorded from the myocardial surface originate from a widely distributed volume beneath the surface and may contain useful information regarding intramural activation. The first step toward obtaining this information is to predict OAPs from known patterns of three-dimensional (3-D) electrical activity. To achieve this goal, we developed a two-stage model in which the output of a 3-D ionic model of electrical excitation serves as the input to an optical model of light scattering and absorption inside heart tissue. The two-stage model permits unique optical signatures to be obtained for given 3-D patterns of electrical activity for direct comparison with experimental data, thus yielding information about intramural electrical activity. To illustrate applications of the model, we simulated surface fluorescence signals produced by 3-D electrical activity during epicardial and endocardial pacing. We discovered that OAP upstroke morphology was highly sensitive to the transmural component of wave front velocity and could be used to predict wave front orientation with respect to the surface. These findings demonstrate the potential of the model for obtaining useful 3-D information about intramural propagation.     

Processing local signals into global patterns

Perceptual organization or grouping is one of the central issues in vision research. Recent reports in the neuroimaging literature suggest that perceptual organization is mediated by distributed visual areas that range from the primary visual cortex (V1) to higher visual areas, depending on the availability of grouping cues and on the weight of contribution of each visual area. Evidence suggests that grouping by proximity and collinearity, and also perhaps filling-in, involve V1, whereas grouping by similarity and symmetry seems to depend on activation of higher visual areas. Further studies should include deliberate controls for confounding factors such as attentional artifacts and radial orientation bias, to clarify how spatiotemporal information in visual areas is integrated to give rise to perceptual organization.     

Macrograzers strongly influence patterns of epiphytic assemblages in seagrass meadows

The influence of factors, both abiotic (light and nutrients) and biotic (meadow structure, herbivory and seagrass shoot length) in the abundance and distribution of epiphytes on the Mediterranean seagrass Posidonia oceanica was investigated by means of a correlational approach over a spatial scale of ca. 500 km and at two different depths (5 and 15 m). Variability was examined from the double perspective of integrative community measures (biomass, species richness and alpha-diversity) and species composition. We assessed the influence of biotic and abiotic factors on integrative community measures using multiple correlation analyses. The influence of these factors in the structure of the whole community was investigated using a distance-based RDA for a linear model. A total of 129 taxa, mostly epiphytic algae, were recorded across all sites and depths. A large part of the variability in species composition (51%) was explained by the variables investigated. In particular, variability caused by differences in grazing pressure was the most important (25%), followed by variables related to nutrient availability (11%), meadow structure (6%), light (5%) and seagrass shoot length (4%). Among integrative community variables investigated, species richness was also best explained by grazing and nutrients.     

Sexual signals and mating patterns in Syngnathidae

Male pregnancy in the family Syngnathidae (pipefishes, seahorses and seadragons) predisposes males to limit female reproductive success; sexual selection may then operate more strongly on females and female sexual signals may evolve (sex-role reversal). A bewildering array of female signals has evolved in Syngnathids, e.g. skin folds, large body size, colouration, markings on the body and elaborate courtship. These female sexual signals do not seem quantitatively or qualitatively different from those that evolve in males in species with conventional sex roles where males provide females or offspring with direct benefits. In several syngnathid species, males also evolve ornaments, females are choosy in addition to being competitive and males compete as well as choosing partners. Thus, sex roles form a continuum, spanning from conventional to reversed within this group of fishes. Cases are presented here suggesting that stronger sexual selection on females may be most extreme in species showing classical polyandry (one male mates with several females, such as many species where males brood their eggs on the trunk), intermediate in polygynandrous species (males and females both mate with more than one partner, as in many species where males brood their eggs on the tail) and least extreme, even exhibiting conventional sex roles, in monogamous species (one male mates solely with one female, as in many seahorses and tropical pipefishes). At the same time caution is needed before unanimously establishing this pattern: first, the connection between mating patterns, strength of sexual selection, sex roles and ornament expression is far from simple and straightforward, and second, knowledge of the actual morphology, ecology and behaviour of most syngnathid species is scanty. Basically only a few Nerophis, Syngnathus and Hippocampus species have been studied in any detail. It is known, however, that this group of fishes exhibits a remarkable variation in sex roles and ornamentation, making them an ideal group for the study of mating patterns, sexual selection and sexually selected signals.     

Altitudinal patterns for latitudinally varying traits and polymorphic markers in Drosophila melanogaster from eastern Australia

Altitudinal changes in traits and genetic markers can complement the studies on latitudinal patterns and provide evidence of natural selection because of climatic factors. In Drosophila melanogaster, latitudinal variation is well known but altitudinal patterns have rarely been investigated. Here, we examine five traits and five genetic markers on chromosome 3R in D. melanogaster collected at high and low altitudes from five latitudes along the eastern coast of Australia. Significant altitudinal differentiation was observed for cold tolerance, development time, ovariole number in unmated females, and the microsatellite marker DMU25686. Differences tended to match latitudinal patterns, in that trait values at high altitudes were also found at high latitudes, suggesting that factors linked to temperature are likely selective agents. Cold tolerance was closely associated with average temperature and other climatic factors, but no significant associations were detected for the other traits. Genes around DMU25686 represent good candidates for climatic adaptation.     

Discrepancies in dbSNP confirmation rates and allele frequency distributions from varying genotyping error rates and patterns

SUMMARY: Three recent publications have examined the quality and completeness of public database single nucleotide polymorphism (dbSNP) and have come to dramatically different conclusions regarding dbSNPs false positive rate and the proportion of dbSNPs that are expected to be common. These studies employed different genotyping technologies and different protocols in determining minimum acceptable genotyping quality thresholds. Because heterozygous sites typically have lower quality scores than homozygous sites, a higher minimum quality threshold reduces the number of false positive SNPs, but yields fewer heterozygotes and leads to fewer confirmed SNPs. To account for the different confirmation rates and distributions of minor allele frequencies, we propose that the three confirmation studies have different false positive and false negative rates. We developed a mathematical model to predict SNP confirmation rates and the apparent distribution of minor allele frequencies under user-specified false positive and false negative rates. We applied this model to the three published studies and to our own resequencing effort. We conclude that the dbSNP false positive rate is approximately 15-17% and that the reported confirmation studies have vastly different genotyping error rates and patterns.     

天津于桥水库流域典型景观类型时空演变分析

流域典型景观类型变化影响着流域生态水文过程,从而也关乎流域水环境安全。本研究以天津于桥水库流域为例,基于5期不同的卫星影像,利用轨迹分析及景观格局指数等方法,研究流域土地利用变化轨迹模型以及研究时间段内典型景观类型的空间分布格局及近30年的演变过程。结果表明:1984—2013年于桥水库流域景观格局变化显著,城镇、园地和草地增加明显,林地、耕地减少显著,林地面积减幅达50%;30年来流域土地利用变化面积占整个流域面积的63.11%,其中,人为因素引起的变化轨迹占所有变化轨迹的96.65%,变化类型主要包括耕地-城镇、林地-耕地/园地、林地-草地等的转化,变化轨迹主要分布于北部丘陵与北部平原等地区;典型景观类型的变化趋势与整个流域变化趋势基本一致,各景观类型破碎化程度总体呈上升趋势,连通性降低,景观多样性缓慢上升,景观格局异质性变高。     

Targeted metabolomics profiles are strongly correlated with nutritional patterns in women

Nutrition plays an important role in human metabolism and health. Metabolomics is a promising tool for clinical, genetic and nutritional studies. A key question is to what extent metabolomic profiles reflect nutritional patterns in an epidemiological setting. We assessed the relationship between metabolomic profiles and nutritional intake in women from a large cross-sectional community study. Food frequency questionnaires (FFQs) were applied to 1,003 women from the TwinsUK cohort with targeted metabolomic analyses of serum samples using the Biocrates Absolute-IDQ? Kit p150 (163 metabolites). We analyzed seven nutritional parameters: coffee intake, garlic intake and nutritional scores derived from the FFQs summarizing fruit and vegetable intake, alcohol intake, meat intake, hypo-caloric dieting and a “traditional English” diet. We studied the correlation between metabolite levels and dietary intake patterns in the larger population and identified for each trait between 14 and 20 independent monozygotic twins pairs discordant for nutritional intake and replicated results in this set. Results from both analyses were then meta-analyzed. For the metabolites associated with nutritional patterns, we calculated heritability using structural equation modelling. 42 metabolite nutrient intake associations were statistically significant in the discovery samples (Bonferroni P < 4 × 10^?5) and 11 metabolite nutrient intake associations remained significant after validation. We found the strongest associations for fruit and vegetables intake and a glycerophospholipid (Phosphatidylcholine diacyl C38:6, P = 1.39 × 10^?9) and a sphingolipid (Sphingomyeline C26:1, P = 6.95 × 10^?13). We also found significant associations for coffee (confirming a previous association with C10 reported in an independent study), garlic intake and hypo-caloric dieting. Using the twin study design we find that two thirds the metabolites associated with nutritional patterns have a significant genetic contribution, and the remaining third are solely environmentally determined. Our data confirm the value of metabolomic studies for nutritional epidemiologic research.     

Compensation of the picture distortions of moving patterns typical for time filters

The image distortions which usually occur in time filters when stimulated with moving patterns can be compensated through co-ordination of the temporal and spatial components of the filter. Moreover, special types of filter can be developed by the method presented in this paper which solve important special problems. The effort required in realisation is considerable since, in the ideal case, each possible direction of movement must have an individual space-time filter. However, the effort required is not a criterion of quality in biological systems.     

Regularized common spatial patterns with subject-to-subject transfer of EEG signals

In the context of brain-computer interface (BCI) system, the common spatial patterns (CSP) method has been used to extract discriminative spatial filters for the classification of electroencephalogram (EEG) signals. However, the classification performance of CSP typically deteriorates when a few training samples are collected from a new BCI user. In this paper, we propose an approach that maintains or improves the recognition accuracy of the system with only a small size of training data set. The proposed approach is formulated by regularizing the classical CSP technique with the strategy of transfer learning. Specifically, we incorporate into the CSP analysis inter-subject information involving the same task, by minimizing the difference between the inter-subject features. Experimental results on two data sets from BCI competitions show that the proposed approach greatly improves the classification performance over that of the conventional CSP method; the transformed variant proved to be successful in almost every case, based on a small number of available training samples.     

Metastatic breast cancer cells adhere strongly on varying stiffness substrates,initially without adjusting their morphology

We show that metastatic breast cancer cells are quantitatively identifiable from benign cells during adherence onto soft, elastic gels. We identify differences in time-dependent morphology and strength of adherence of single breast cells that are likely related to their malignancy and metastatic potential (MP). Specifically, we compare high and low MP breast cancer cells with benign cells as a control on collagen-coated, polyacrylamide gels with Young’s modulus in the physiological range of 2.4–10.6 kPa. We observe that the evaluated metastatic breast cancer cells remain rounded, with small contact area, up to 6.5 h following seeding. In contrast, the benign cells spread and become more elongated on stiffer gels. We identify measurable differences in the two-dimensional, lateral, traction forces exerted by the cells, where the rounded, metastatic cells apply significantly larger, traction forces, as compared to the benign cells, on gels stiffer than 2.4 kPa. The metastatic cell lines exhibited gel-stiffness-dependent differences in traction forces, strain energies, and morphologies during the initial stages of adhesion, which may relate to their MP or invasiveness.     

Frequency modulation patterns in the echolocation signals of two vespertilionid bats

In this study we measure and classify frequency modulation patterns in echolocation signals of two species of bats. By using the derivative of an exponential model fitted to pulses emitted by Pipistrellus pipistrellus and Myotis myotis, we show that the modulation functions differ fundamentally between the two species and also vary within each species. This variation makes it unlikely that pulse design and the concomitant modulation pattern can be explained by a single common principle as previously suggested.     

Simple identification of anaerobic bacteria to genus level using typical antibiotic susceptibility patterns

Simple yet comprehensive identification of anaerobic bacilli is possible to genus level when typical susceptibility patterns of antimicrobial substances are used in combination with the morphological characteristics of the bacteria. Paper discs were soaked with fosfomycin (100 μg), colistin (10 μg), everninomicin B (10 μg) and metronidazole (2 μg) and tested on sheep blood agar in a jar under anaerobic conditions. A dichotomous scheme has been suggested for the differentiation of the following genera: Actinomyces, Bacteroides, Bifidobacterium, Clostridium, Eubacterium, Fusobacterium, Lactobacillus, Leptotrichia, Propionibacterium and Selenomonas. The method gave preliminary results which can be used as guidance for subsequent species identification and for therapeutic advice, as antibiotic susceptibility depends very much on the genus of anaerobic bacilli.