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Enabling proteomics discovery through visual analysis. The peptide permutation and protein prediction tool.

Proteins play a key role in cellular processes, making proteomics central to understanding systems biology. MS techniques provide a means to observe entire proteomes at a global level. Yet, high-throughput MS proteomics techniques generate data faster than it can currently be analyzed. The success of proteomics depends on high-throughput experimental techniques coupled with sophisticated visual analysis and data-mining methods. Visual analysis has been applied successfully in a number of fields plagued with huge, complex data sets and will likely be an important tool in proteomics discovery. PQuad, a novel visualization of MS proteomics data, provides powerful analysis capabilities that support a number of proteomic data applications. In particular, PQuad supports differential proteomics by simplifying the comparison of peptide sets from different experimental conditions as well as different protein identification or confidence scoring techniques. Finally, PQuad supports data validation and quality control by providing a variety of resolutions for huge amounts of data to reveal errors undetected by other methods.

Algorithms↗

A description of grip strength in preschool children.

The purpose of this research project was to provide occupational therapists with preliminary descriptive data on the spherical grip strength of 3- to 5 1/2-year-old children using the Martin Vigorimeter. Three hundred and eighty boys and girls were tested. Standardized positioning and instructions were followed. The mean of three trials was used as the grip strength score for each hand. The right and left hands were alternated during testing to allow a 20-second rest between trials. A repeated measures design multiple analysis of variance was used to analyze the data. The findings indicated that the mean grip strength scores increased linearly with an increase in age (p less than .001) and that the right grip strength score was greater than the left (p less than .001). The descriptive data were reported separately for the right and left hands by age increments of 6 months. Two tables of mean grip strength scores and their standard deviations were generated for clinical use.

Age Factors↗

The prevalence and risk factors analysis of serum antibody to hepatitis C virus in the elders in northeast Taiwan.

BACKGROUND: Hepatitis C virus (HCV) infection will result in liver cirrhosis and hepatocellular carcinoma, which are the leading causes of death in Taiwan. The prevalence of antibody to HCV (anti-HCV) was 2%-3% in Taipei city. However, it can be as high as 20% to 60% in Central and Southern part of Taiwan. In I-Lan, a county located in northern-east Taiwan, there is no large-scale investigation yet. The objective of this research is to evaluate the prevelance and risk factors of anti-HCV positivity in three towns of I-Lan county. METHODS: Blood sampled from people in San-Shing, Tou-Cheng and Tong-Shan was collected from October 1999 to June 2000. Totally, 1,316 persons (607 male, 790 female, mean age: 62 +/- 12 years old) were enrolled. Anti-HCV was measured by a second-generation enzyme immunoassay. Risk factors analysis was performed in anti-HCV positive subjects and age-sex matched anti-HCV negative controls. RESULTS: Sixty-seven persons (5.1%) had positive serum anti-HCV. The prevalence rate of anti-HCV increased with age. San-Shing and Tong-Shan showed a higher anti-HCV prevalence rate than Tou-Cheng (6.0% and 8.3% vs. 3.2%, p = 0.007). Risk factors analysis showed that people with positive serum anti-HCV had a significantly high rate of surgical history, usage of nondisposable needles injection, frequent nondisposable needles injection, frequent dental therapy, and a lower level of education than the anti-HCV negative counterpart (p < 0.05). Multivariate logistic regression analysis revealed that age > 60 years, surgical history and frequent nondisposable needles injection were significantly independent risk factors of positive anti-HCV (p < 0.05). CONCLUSIONS: The prevalence rate of anti-HCV in I-Lan county was 5.1%. Age > 60 years, surgical history and frequent nondisposable needles injection were the significant risk factors of HCV infection in I-Lan area.

Adult↗

Mass distributed clustering: a new algorithm for repeated measurements in gene expression data.

The availability of whole-genome sequence data and high-throughput techniques such as DNA microarray enable researchers to monitor the alteration of gene expression by a certain organ or tissue in a comprehensive manner. The quantity of gene expression data can be greater than 30,000 genes per one measurement, making data clustering methods for analysis essential. Biologists usually design experimental protocols so that statistical significance can be evaluated; often, they conduct experiments in triplicate to generate a mean and standard deviation. Existing clustering methods usually use these mean or median values, rather than the original data, and take significance into account by omitting data showing large standard deviations, which eliminates potentially useful information. We propose a clustering method that uses each of the triplicate data sets as a probability distribution function instead of pooling data points into a median or mean. This method permits truly unsupervised clustering of the data from DNA microarrays.

Algorithms↗

Preliminary assessment of an image analysis method for the evaluation of pharmaceutical coatings.

This article describes the development and preliminary assessment of an innovative image analysis method for the evaluation of pharmaceutical coatings. Nonpareils previously hot-melt coated with a red water-soluble dye incorporated into polyethylene glycol were employed to develop and evaluate the new method. Digital images of batch samples were acquired and transferred to a PC for evaluation by image analysis software. Standard deviations generated for the optical densities of individual nonpareils in each batch sample were utilized to evaluate coating uniformity. Mean optical densities generated for each batch sample were used to evaluate the mean coating thickness. Method precision determinations, using an average sample size of 221 nonpareils, returned a relative standard deviation of 2.47% for coating uniformity and 1.71% for coating thickness. The new method is rapid, objective, and relatively inexpensive. It proved to be both qualitative and quantitative for coating uniformity, qualitative for coating thickness, and maintained a high degree of precision. The method can be used independently or in conjunction with other methods to eliminate their subjective aspects regarding sample selection.

Chemistry, Pharmaceutical↗

Linear and nonlinear ARMA model parameter estimation using an artificial neural network.

This paper addresses parametric system identification of linear and nonlinear dynamic systems by analysis of the input and output signals. Specifically, we investigate the relationship between estimation of the system using a feedforward neural network model and estimation of the system by use of linear and nonlinear autoregressive moving-average (ARMA) models. By utilizing a neural network model incorporating a polynomial activation function, we show the equivalence of the artificial neural network to the linear and nonlinear ARMA models. We compare the parameterization of the estimated system using the neural network and ARMA approaches by utilizing data generated by means of computer simulations. Specifically, we show that the parameters of a simulated ARMA system can be obtained from the neural network analysis of the simulated data or by conventional least squares ARMA analysis. The feasibility of applying neural networks with polynomial activation functions to the analysis of experimental data is explored by application to measurements of heart rate (HR) and instantaneous lung volume (ILV) fluctuations.

Computer Simulation↗

A digital ion trap mass spectrometer coupled with atmospheric pressure ion sources.

In a digital ion trap (DIT), the quadrupole trapping and excitation waveforms are generated by the rapid switching between discrete d.c. voltage levels. As the timing of the switch can be controlled precisely by digital circuitry, the approach provides an opportunity to generate mass spectra by means of a frequency scan in contrast to the conventional voltage scan, thus providing a wider mass range of analysis. An instrument has been constructed which employs a 'non-stretched' ion trap and the field fault around the aperture of the end-cap electrode can be corrected electronically using a field-adjusting electrode. The ion trap was coupled with electrospray ionization (ESI) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) sources to demonstrate the capability of the digital method. AP-MALDI mass spectra of singly charged ions with mass-to-charge ratios upto 17 000 Th were generated using a trapping voltage of only 1000 V. Forward and reverse mass scans at resolutions up to 19 000 and precursor ion isolation at resolutions up to 3500 with subsequent tandem mass spectrometric analysis were demonstrated. The method of generating the digital waveforms and period scan is described. Discussion of the issues of mass range, scan speed, ion trapping efficiency and collision-induced dissociation efficiency are also provided.

Animals↗

Clinical usefulness of ultrashort-lived iridium-191m from a carbon-based generator system for the evaluation of the left ventricular function.

Ultrashort-lived 191mIr (4.96 sec; 63-74 and 129 keV photons) is potentially advantageous for first-pass radionuclide angiocardiography, offering the opportunity to perform repeat studies with very low absorbed radiation dose to the patient. Left ventricular (LV) first-pass studies were performed in 72 patients with 191mIr from a new bedside 1.3 Ci (48.1 GBq) 191Os/191mIr generator system using an activated carbon support that offers high 191mIr yields (15-18%) and consistent low 191Os breakthrough (2-4 x 10(-4)%/bolus). Using a single crystal digital gamma camera, uncorrected end-diastolic counts in the left ventricular representative cycle ranged from 10 up to 30 k counts. The reproducibility of repeated LV ejection fraction (LVEF) determination at 2-min intervals in 50 patients was r = 0.97, mean diff. = 2.08 +/- 1.55 EF units. Comparison between 191mIr (80-120 mCi; 2,960-4,400 MBq) and 99mTc (20-25 mCi; 750-925 MBq) LV count rates indicates a 3 wk useful shelf life of this new generator system for cardiac studies. Iridium-191m determined LVEF correlated closely with 99mTc determined LVEF in 32 patients (r = 0.96, mean diff. = 1.87 +/- 1.23 EF units). Parametric images for LV wall motion analysis were comparable with both isotopes. We conclude that rapid, repeat, and reproducible high count rate first-pass left ventricular studies can be obtained with 191mIr from this new 191Os/191mIr generator system using a single crystal digital gamma camera.

Adult↗

Analysis of polar organic pollutants in the Elbe river by flow injection analysis and high-performance liquid chromatography with tandem mass spectrometry.

Water extracts from the Elbe river and from one of its tributaries have been analyzed by gas chromatography-mass spectrometry (GC-MS) and by high-performance liquid chromatography combined with ultraviolet (UV) and/or MS detection. After column chromatography or flow injection analysis (FIA) bypassing the analytical column, ionization for MS was performed by either atmospheric pressure chemical ionization or electrospray. Since the reduction of the pollutant concentrations relative to the concentration of matrix components in the water samples had continued compared to earlier investigations [H.Fr. Schröder, J. Chromatogr. A 712 (1995) 123-140], substance-group-specific methods were applied for the screening for certain compound groups. For this purpose tandem mass spectrometry (MS-MS) was used to characterize the substance groups, with the help of parent-ion and neutral-loss scans. Identification then followed by means of daughter-ion spectra, which were generated by collisionally induced dissociation (CID) using FIA-MS-MS. The limitations of mixture analysis in the case of isomeric compounds present in the extracts are demonstrated.

Chromatography, High Pressure Liquid↗

[Estimation of height from leg lenght measured with tape measure].

Equations to predict height from several body segments have been developed. However, those that use the knee height are limited by the need of an instrument with high cost (anthropometer). Thus, the aim of this study was to develop a prediction equation from the leg length by using a tape measure. Leg length and height was measured in 180 subjects, with ages 30-59 years that attended the Ambulatorio Docente Asistencial of the University Hospital of Caracas, from April to June of 2002. In order to determine the correlation degree of each measurement with height, the existent correlation between height and each one of the studied variables (leg length, sex, age) and between the variables to one each other was calculated by means of the Pearson's correlation coefficient. Linear regression analysis was done to estimate the height in each gender and the results were tested on an independent sample. The generated equations achieved a very good correlation with the real height and the standard error was calculated. Thus, in those subjects in whom assessment of the real height is not possible by conventional means, it is possible to use height prediction equations from simple techniques and equipment accessible to the whole health care staff.

Adult↗

A prospective comparative clinical analysis of the first-generation knee replacements: polycentric vs. geometric knee arthroplasty.

A prospective study of 119 polycentric and 92 geometric knee replacements was performed to determine and compare the clinical effectiveness of these two prostheses. All kneex were followed for a minimum of 2 years and a mean time of 3 1/2 years (2--6 years). Data were collected using a specially designed proforma for subsequent computer analysis. Failure occurred in 11% of the polycentric and in 16% of the geometric knees. Males (8 of 47) and patients with osteoarthritic knees (22 of 68) failed most frequently. Both prostheses provided excellent relief of pain, the same degree of flexion and improvement in flexion contracture. However, walking, function, alignment, stability, muscle strength and patellar mobility varied as to the degree of improvement and the type of prosthesis. Present results with prosthetic knee replacement using a completely new operative technique can be used as a basis for comparison with other contemporary and future arthroplasty designs.

Adolescent↗

EEG bands during wakefulness, slow-wave, and paradoxical sleep as a result of principal component analysis in the rat.

Rat EEG has been empirically divided in bands that frequently do not correspond with EEG generators nor with the functional meaning of EEG rhythms. Power spectra from wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) of Wistar rats were submitted to Principal Component Analyses (PCA) to investigate which frequencies are covariant. Three independent eigenvectors were identified for SWS: a band between 1-6, an intermediate band between 7-15, and a fast band between 16-32 Hz (90.74% of the variance); two independent eigenvectors were extracted for PS: slow frequencies between 1-6 covarying together with frequencies between 11-16 Hz, and activity between 6-10 covarying together with fast frequencies between 17-32 Hz (80.38% of the variance); four eigen-vectors were obtained for W: 3-7, 8-9, 10-21 and 21-32 Hz (81.47% of the variance). Vigilance states showed significant differences in AP from 1 to 22 Hz. PCA extracted broad bands different for each vigilance state, which included the most representative EEG activities characteristic of them. These results indicate that during SWS, slow oscillations include frequencies up to 6 Hz, and spindle oscillations frequencies down to 7 Hz. No alpha frequencies were identified as an independent band. Frequencies within theta and beta were gathered in the same eigenvector during PS and in different eigenvectors during W suggesting coordinated activation of hippocampal and cortical systems during PS. These bands are consistent with the underlying neurophysiological mechanisms of sleep and wakefulness and with firing frequencies of generators of rhythmic activity obtained in cellular studies in animals.

Animals↗

The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer.

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.

Adipose Tissue↗

The biometrical genetics of competitive parameters in Drosophila melanogaster.

Despite the importance of competition as an evolutionary determinant in natural populations there have been few studies of the genetical control of competitive ability. Here, we report the results of a biometrical analysis of four continuously varying traits which, between them, describe the competitive interactions in mixed cultures of Drosophila melanogaster. The analysis involved the parental, F1, F2 and backcross generations (including all reciprocals) derived from crosses between two highly inbred lines isolated from the Texas population of D. melanogaster. The competitive performance of each genotype in monoculture and in duoculture with a phenotypically distinct tester were assessed using a yield-density regression analysis. Appropriate genetic models were fitted using a variance weighted least squares procedure and the resulting genetic components of the generation means used to define the genetical architecture of competition. Of the four competitive parameters investigated here the e-value, which describes the competitive performance of the indicator genotype at a fixed reference density, was found to be determined by simple additive genetic effects with no evidence of significant dominance. Conversely, competitive performance in monoculture (intra-genotypic competition) did display a significant net dominance component and the observed values in the F1 and parental generations indicated some degree of heterosis. Of the two competitive parameters determining performance in duoculture (inter-genotypic sensitivity and inter-genotypic pressure) the former was found to have a complex genetic determination involving not only additive and dominance components of the progeny's own genotype but also dominance components of the F1 maternal genotypes. There were also additive-dominance and dominance-dominance non-allelic interactions. Heterosis was evident, determined both by the progeny's own genotype and by one of the F1 maternal genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Can cardiac weight predict lung weight in patients with congenital diaphragmatic hernia?

Left ventricular disproportion (decreased left-to-right ventricular internal diameter ratio) has been correlated with fetal or neonatal survival in cases of congenital diaphragmatic hernia (CDH). Because cardiac development is intimately related to lung development in the normally developing fetus, the authors sought to determine whether cardiac weight correlates with lung weight in control and CDH lambs at term. Twenty lambs had CDH created surgically at 80 days' gestation and were sacrificed at term for measurement of lung and heart weight. Nine unoperated lambs served as controls. Analysis of the relationship between heart weight and lung weight was performed for both groups, and regression curves were generated as mean +/- 2 standard deviations (SD) for each group of lambs. All data are expressed in grams. For CDH lambs, the relationship between heart and lung weight is as follows: lung weight = 0.69 x heart weight + 37 g. For control lambs, the equation is: lung weight = -0.004 x heart weight + 135 g. There is no overlap of these regression curves at 2 SD of the mean. The curves differ significantly, and the P value exceeds .05. The results suggest that cardiac weight can be used to predict lung weight in CDH and control lambs at term. The authors speculate that this difference in weight is attributable to underdevelopment of the left ventricle in CDH. Given that left ventricular disproportion has been described as early as the pseudoglandular stage of lung development in human fetuses with CDH, it is hoped that echocardiographic parameters can be used to differentiate the fetuses with adequate lung volume from those whose lung volume is incompatible with extrauterine life. Patients in the latter group may benefit from surgical correction of the diaphragmatic defect in utero.

Analysis of Variance↗

Brain electrical tomography (BET) analysis of induced gamma band responses during a simple object recognition task.

The formation of cortical object representations requires the activation of cell assemblies, correlated by induced oscillatory bursts above 20 Hz (gamma band), which are characterized by trial-by-trial latency fluctuations around a mean of approximately 300 ms after stimulus onset. The present electroencephalogram (EEG) study was intended to uncover to the generators of induced gamma band responses (GBRs) and to analyze phase-synchronization between these sources. A standard object recognition task was used to elicit gamma activity. At the scalp surface (electrode space), we found an augmentation of induced GBRs after the presentation of meaningful (familiar) as opposed to meaningless (unfamiliar) stimuli, which was accompanied by a dense pattern of significant phase-locking values between distant recording sites. Subsequently, intracranial current density distributions compatible with the observed scalp voltage topographies were estimated by means of VARETA (Variable Resolution Electromagnetic Tomography). In source space brain electrical tomographies (BETs) revealed widespread generators of induced GBRs at temporal, parietal, posterior, and frontal areas. Phase-locking analysis was calculated between re-constructed electrode signals based on separate forward solutions of the observed generators, thereby eliminating the possibly confounding influence of activity from areas not under observation. The results support the view that induced GBRs signify synchronous neuronal activity in a broadly distributed network during object recognition. The localization of the generators of event-related potentials (ERPs), evoked gamma activity, and induced alpha activity revealed different sources as compared to the induced GBR and, thus, seem to mirror complementary functions during the present task as compared to induced high-frequency brain dynamics.

Adult↗

Digital signal and image processing in echocardiography. The American Society of Echocardiography.

Digital signal and image processing techniques are acquiring an increasingly important role in the generation and analysis of cardiac images. This is particularly true of 2D echocardiography, in which image acquisition, manipulation, and storage within the echocardiograph, as well as quantitative analysis of echocardiographic data by means of "off-line" systems, depend upon digital techniques. The increasing role of computers in echocardiography makes it essential that echocardiographers and technologists understand the basic principles of digital techniques applied to echocardiographic instrumentation and data analysis. In this article, we have discussed digital techniques as applied to image generation (digital scan conversion, preprocessing, and postprocessing) as well as to the analysis of image data (computer-assisted border detection, 3D reconstruction, tissue characterization, and contrast echocardiography); a general introduction to off-line analysis systems was also given. Experience with other cardiac imaging methods indicates that digital techniques will likely play a dominant role in the future of echocardiographic imaging.

Echocardiography↗

Comments on selected fundamental aspects of microarray analysis.

Microarrays are becoming a ubiquitous tool of research in life sciences. However, the working principles of microarray-based methodologies are often misunderstood or apparently ignored by the researchers who actually perform and interpret experiments. This in turn seems to lead to a common over-expectation regarding the explanatory and/or knowledge-generating power of microarray analyses. In this note we intend to explain basic principles of five (5) major groups of analytical techniques used in studies of microarray data and their interpretation: the principal component analysis (PCA), the independent component analysis (ICA), the t-test, the analysis of variance (ANOVA), and self organizing maps (SOM). We discuss answers to selected practical questions related to the analysis of microarray data. We also take a closer look at the experimental setup and the rules, which have to be observed in order to exploit microarrays efficiently. Finally, we discuss in detail the scope and limitations of microarray-based methods. We emphasize the fact that no amount of statistical analysis can compensate for (or replace) a well thought through experimental setup. We conclude that microarrays are indeed useful tools in life sciences but by no means should they be expected to generate complete answers to complex biological questions. We argue that even well posed questions, formulated within a microarray-specific terminology, cannot be completely answered with the use of microarray analyses alone.

Computational Biology↗