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PubMed2005

Approaches to detecting gene x gene interaction in Genetic Analysis Workshop 14 pedigrees.

Whether driven by the general lack of success in finding single-gene contributions to complex disease, by increased knowledge about the potential involvement of specific biological interactions in complex disease, or by recent dramatic increases in computational power, a large number of approaches to detect locus x locus interactions were recently proposed and implemented. The six Genetic Analysis Workshop 14 (GAW14) papers summarized here each applied either existing or refined approaches with the goal of detecting gene x gene, or locus x locus, interactions in the GAW14 data. Five of six papers analyzed the simulated data; the other analyzed the Collaborative Study on the Genetics of Alcoholism data. The analytic strategies implemented for detecting interactions included multifactor dimensionality reduction, conditional linkage analysis, nonparametric linkage correlation, two-locus parametric linkage analysis, and a joint test of linkage and association. Overall, most of the groups found limited success in consistently detecting all of the simulated interactions due, in large part, to the nature of the generating model.

Alcoholism↗

PubMed1978

[Effect of Triton X-100 on properties of acetylcholinesterase from human erythrocytes].

The effect of Triton X-100 on catalytic properties of acetylcholinesterase from human erythrocytes under acetylcholine hydrolysis, on sensitivity of acetylcholinesterase to specific phosphoorganic inhibitors and eserine, and on the mobility and isoenyme spectrum under analytical electrophoresis in polyacrylamide gel is investigated. Triton X-100, independently on its concentration within 0.05-1.0%, slightly changes V and [S]opt values and increases Km value in 2-3 times. The inhibitory effect of Triton X-100 is mainly competitive, 0.5% Triton X-100 decreases bimolecular constant (kII) of the interaction of acetylcholinesterase with phosphoorganic inhibitor and eserine in 2.5-4 times. In the presence of phosphoorganic inhibitor, kII sharply decreased when 0.02% Triton X-100 was added, and then it did not change under the increase of Triton X-100 concentration up to 1.0%. On the basis of these data, an analytical method of estimating Triton X-100 content in protein solution is proposed. The introduction of 0.1% Triton X-100 into polyacrylamide gel results in considerable quantitative redistribution of acetylcholinesterase isoenzyme fractions and in the change of the mobility of one fraction under electrophoresis.

Acetylcholinesterase↗

PubMedDate not supplied

Analytic representation of electron central-axis depth dose data.

We have examined a number of analytic representations of electron central-axis depth dose data current in the literature, testing them against sets of standard depth dose data. One of them, a two-parameter model of Shabason and Hendee, is recommended in situations in which good accuracy (approximately 2%) is desired, with the values of the parameters determined by an approximation formula which we have developed elsewhere. For higher accuracy, we have developed a polynomial model which gives, typically, a standard deviation of the fitting polynomial from the data points of 1%, and a maximum deviation of 2%. Fitting polynomials obtained with this method possess the property of having zero slope at the position of actual maximum dose, and generally a fifth-order polynomial (requiring four nonzero coefficients) provided the most acceptable fit. The four parameters involved are determined through inversion of a 4 x 4 matrix, and we have tabulated these four coefficients for the standard data sets. The polynomial model is designed for interpolation in the range between the 100% dose depth and the 10% dose depth, and another fitting curve of the same type can be adjoined to cover depths less than the 100% dose depth.

Computers↗

PubMed2003

Human capital, schooling and health.

A consensus has been forged in the last decade that recent periods of sustained growth in total factor productivity and reduced poverty are closely associated with improvements in a population's child nutrition, adult health, and schooling, particularly in low-income countries. Estimates of the productive returns from these three forms of human capital investment are nonetheless qualified by a number of limitations in our data and analytical methods. This paper reviews the problems that occupy researchers in this field and summarizes accumulating evidence of empirical regularities. Social experiments must be designed to assess how randomized policy interventions motivate families and individuals to invest in human capital, and then measure the changed wage opportunities of those who have been induced to make these investments. Statistical estimation of wage functions that seek to represent the relationship between wage rates and a variety of human capital stocks may yield biased estimates of private rates of return from these investments for a variety of reasons. The paper summarizes several of these problems and illustrates how data and statistical methods can be used to deal with some of them. The measures of labor productivity and the proxies specified for schooling and adult health are first discussed, and then the functional relationships between human capital and wages are described. Three types of estimation problem are discussed: (1) bias due to omitted variables, such as ability or frailty; (2) bias due to the measurement of an aggregation of multiple sources of human capital, e.g. genetic and socially reproducible variation, which may contribute to different gains in worker productivity; and (3) errors in measurement of the human capital stocks. Empirical examples and illustrative estimates are surveyed.

Educational Status↗

PubMed2003

Theoretical and analytical characterization of a flow-through permeation liquid membrane with controlled flux for metal speciation measurements.

Speciation measurements with the permeation liquid membrane (PLM) technology require necessarily a good control of the flux of the analyte. In this perspective, a PLM-based multichannel flow-through cell has been designed. The first objective of this study has been to adapt the classical Levich model commonly used for electrochemical flow devices to the characteristic geometry of the PLM cell. In the latter case and contrary to the Levich model, the effects of the channel lateral walls on the flux of active species through the membrane have to be taken into account. The problem was solved by considering the existence of two parabolic Poiseuille profiles perpendicular to each other and developing along the fluid motion. The theoretical results obtained match satisfactorily with experimental data. The analytical study of this PLM system has been performed with copper(II) ions as test species and has shown that the preconcentration factor is (1) linear at least for preconcentration times of < or = 120 min, (2) reproducible on the same membrane as well as on different membranes, and (3) independent of the initial test metal ion concentration in the sample solution. The capabilities of this cell to determine metal speciation by considering lability of complexes and the flux of metal at variable flow rates of the test solution is also discussed by means of Cu(II)/sulfosalicylic complexes.

Journal Article↗

PubMed2005

IR spectroscopy together with multivariate data analysis as a process analytical tool for in-line monitoring of crystallization process and solid-state analysis of crystalline product.

Crystalline product should exist in optimal polymorphic form. Robust and reliable method for polymorph characterization is of great importance. In this work, infra red (IR) spectroscopy is applied for monitoring of crystallization process in situ. The results show that attenuated total reflection Fourier transform infra red (ATR-FTIR) spectroscopy provides valuable information on process, which can be utilized for more controlled crystallization processes. Diffuse reflectance Fourier transform infra red (DRIFT-IR) is applied for polymorphic characterization of crystalline product using X-ray powder diffraction (XRPD) as a reference technique. In order to fully utilize DRIFT, the application of multivariate techniques are needed, e.g., multivariate statistical process control (MSPC), principal component analysis (PCA) and partial least squares (PLS). The results demonstrate that multivariate techniques provide the powerful tool for rapid evaluation of spectral data and also enable more reliable quantification of polymorphic composition of samples being mixtures of two or more polymorphs. This opens new perspectives for understanding crystallization processes and increases the level of safety within the manufacture of pharmaceutics.

Algorithms↗

PubMed1989

A new method of assessing fetal heart rates with potential for analytical quantification.

We devised a method using a matrix to condense the large scale of fetal heart rates (FHR) without altering their characteristics. This matrix was arranged by FHRs at one beat per minute (bpm) intervals in rows, beat-to-beat differences (DFHRs) at one bpm intervals in columns and probabilities in the corresponding elements, respectively. Three matrices were calculated for Groups I, II and III: from 22 fetuses at 18-24 weeks, from 27 at 28-32 weeks and from 66 at 37-41 weeks of gestation, respectively. It was evident that the FHRs within the cumulative probability of 0.98 moved at 138-170 bpm in Group I, through 126-170 bpm in Group II onto 124-170 bpm in Group III. DFHRs spread symmetrically around zero bpm of DFHR for the entire scope of FHR values, irrespective of the age of gestation. This method can also be used for assimilating FHR data for analytical quantitation.

Diagnosis, Computer-Assisted↗

PubMed2002

Finding the findings in qualitative studies.

PURPOSE: To describe the challenges of finding the findings in qualitative studies. METHOD: Review of literature on representation in qualitative research and analysis of 99 reports of qualitative studies of women with HIV infection. FINDINGS: Factors complicating finding the findings in qualitative studies include varied reporting styles, misrepresentation of data and analytic procedures as findings, misuse of quotes and theory, and lack of clarity concerning pattern and theme. Theses and dissertations present special challenges because they often contain several of these problems. CONCLUSIONS: Given the varied beliefs about findings among qualitative researchers, the challenge is to find ways to present findings that will make them discernible to the diverse audiences for whom they are intended, including researchers and practitioners.

Data Interpretation, Statistical↗

PubMed1997

An extended difference of coherence test for comparing and combining several independent coherence estimates: theory and application to the study of motor units and physiological tremor.

Recently there has been an increase in the use of spectral methods for the analysis of experimental data. These analytical methods allow the study of interactions between simultaneously recorded signals and are particularly suited to the study of systems displaying rhythmic behaviour. A useful parameter in this context is the coherence function which provides a bounded measure of linear association between two signals. In this report we introduce two new techniques for dealing with an arbitrary number of independent coherence estimates. The first technique provides a test to compare the coherence estimates for statistically significant differences. The second allows the original coherence estimates to be combined, or 'pooled' into a single representative estimate. These two measures, taken together, provide a powerful tool for characterising and summarising the correlations within data sets. Applications of the techniques are illustrated by analysing the interactions between single motor unit discharges and finger tremor, and between pairs of motor unit discharges in human subjects.

Humans↗

PubMed2005

Quasielastic light scattering for protein assembly studies.

Quasielastic light scattering (QLS) spectroscopy is an optical method for the determination of diffusion coefficients of particles in solution. In this chapter, we discuss the principles and practice of QLS with respect to protein assembly reactions. Particles undergoing Brownian motion produce fluctuations in scattered light intensity. We describe how the temporal correlation function of these fluctuations can be measured and how this correlation function provides information about the distribution of diffusion coefficients of the particles in solution. We discuss the intricacies of deconvolution of the correlation function and the assumptions incorporated into data analysis procedures. We explain how the Stokes-Einstein relationship can be used to convert distributions of diffusion coefficients into distributions of particle size. Noninvasive observation of the temporal evolution of particles sizes provides a powerful tool for studying protein aggregation and self-assembly. We use examples from studies of Abeta fibrillogenesis to illustrate QLS application for understanding the molecular mechanisms of the nucleation and growth of amyloid fibrils.

Chemistry Techniques, Analytical↗

PubMed2001

B-type natriuretic peptide (BNP)--validation of an immediate response assay.

B-type natriuretic peptide, a proteohormone secreted by the left ventricle in response to wall-tension, is a promising laboratory parameter for the detection and follow-up of heart failure. In this report analytical validation data of a non-isotopic point-of-care testing system for the quantitative determination of BNP (Triage BNP, Biosite, USA) are given. Despite a very short turn-around time of about 10 minutes the assay proved to be reproducible (interassay coefficient of variation (n=10) of 8.4% and 8.0% at concentrations of 19.3 ng/l and 392 ng/l, respectively), linear (r=0.998, from 5 ng/l to 818 ng/l), and rugged with respect to common interferents; compared to the widely used SHIONORIA BNP assay (CIS, France) higher results were found (Triage-BNP = 1.52 x SHIONORIA BNP - 7.0 ng/l; n=70) with a relatively close correlation of the results (r=0.935). It is concluded that the Triage BNP assay meets the analytical requirements for further clinical validation and may allow a more widespread clinical use of BNP determination in contrast to competing assays with long turn-around times.

Atrial Natriuretic Factor↗

PubMedDate not supplied

Epidemiology of digestive tract cancers in India. III. Liver.

Liver cancer or hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer deaths in the world. The condition is extremely common in Southeast Asia and Africa. In this report the available data on the epidemiology of HCC from India are summarized. We estimate that 12,750 new patients will be diagnosed to have HCC in India in the year 2001; this will comprise 1.6% of all incident cancers. Published studies from India and those involving Indian immigrants to other countries suggest that the prevalence of HCC is relatively lower in Indians than in most parts of the world. This contrasts with the widespread contamination of foods with aflatoxin and the moderately high prevalence of hepatitis B (HBV) and hepatitis C (HCV) virus-related chronic liver disease in India. There are no studies available to explain this observation. There are several articles on HBV and HCC in India but there is a paucity of analytical epidemiological data on HCV and HCC from India. Published studies indicate HBV to be the single most important etiologic association, with HCV playing a lesser but important role. About 80% of Indian patients with HCC have hepatitis virus-associated liver disease. Multicenter epidemiological studies are needed to solve some of the enigmas and observations peculiar to India.

Aflatoxins↗

PubMed2004

Towards clarifying the N-M vibrational nature of metallo-phthalocyanines. Infrared spectrum of phthalocyanine magnesium complex: density functional calculations.

Infrared frequencies and intensities for the magnesium phthalocyanine complex MgPc have been calculated at density functional B3LYP level using the 6-31G(d) basis set. Detailed assignments of the metal-nitrogen (N-M) vibrational bands in the IR spectrum have been made on the basis of comparison of the calculated data of MgPc with the experimental result and also with that of H(2)Pc. The empirical controversial assignment of the characteristic band at 886-919 cm(-1) for metallo-phthalocyanines is also clearly interpreted. Nevertheless, the previous assignments of N-H stretchings, in-plane bending (IPB) and out-of-plane bending (OPB) modes made based on the comparative calculation of H(2)Pc and D(2)Pc are confirmed again by the present research result.

Chemistry Techniques, Analytical↗

PubMedDate not supplied

Ratio of alpha 1-antichymotrypsin--prostate specific antigen to total prostate specific antigen in prostate cancer diagnosis.

OBJECTIVE: To evaluate the analytical performance and diagnostic utility of prostate specific antigen (PSA) bound to alpha 1-antichymotrypsin (ACT) in serum to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: A total of 351 white men 21 to 88 years old were analysed. Serum concentration of tPSA, free PSA (fPSA) and ACT-PSA were measured in 163 untreated PCa patients (median age 66 years), 94 patients with histologically or clinically confirmed BPH (median age 65 years) and 94 men without prostate disease considered as controls (median age 54 years). The Elecsys system 2010 (Roche Diagnostics, Germany) was used for the determinations of tPSA and fPSA. The ACT-PSA assay is a new developed prototype on the ES system (Roche Diagnostics, Germany). RESULTS: The ACT-PSA assay showed reliable data of analytical performance in comparison to established assays for tPSA and fPSA. The median concentrations of tPSA (PCa: 9.22 micrograms/L, BPH: 2.28 micrograms/L, controls: 0.99 microgram/L) and ACT-PSA (7.99 micrograms/L vs. 1.63 micrograms/L vs. 0.58 microgram/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12.3%, BPH: 25.4%), ACT-PSA/tPSA (90.5% vs. 66.6%) and fPSA/ACT-PSA (14.0% vs. 38.6%) were significantly different between PCa and BPH patients. Significant differences of ratios between BPH and controls were not observed. Receiver operating characteristics analysis (tPSA up to 20 micrograms/L) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.861) and fPSA/ACT-PSA (0.847) were significantly different from tPSA (0.663), but ACT-PSA (0.733) alone and also the ratio of ACT-PSA/tPSA (0.780) were not significantly different from tPSA (0.663). CONCLUSION: The ratio fPSA/tPSA showed the best discrimination between BPH and PCa. The single or additional determination of ACT-PSA to tPSA does not improve the differentiation between the two groups of patients.

Adult↗

PubMed1999

Indications for treatment of subcondylar mandibular fractures.

BACKGROUND AND OBJECTIVES: The purpose of this study was to establish a reliable criteria for implementation of either an open surgical or a closed conservative treatment of subcondylar fractures, based on clinical data and analytical mathematical model. METHODS AND MATERIALS: A total of 512 subcondylar fractures were treated during a 3-year period. Of these, 256 were fractures characterized by either displacement or dislocation of the proximal (condylar) segment. Patients were treated with open reduction and internal fixation (ORIF) or closed reduction (CR) techniques. Patients were evaluated pre- and postoperatively by clinical examination, 3-dimensional axiography, radiographic imaging, and ultrasonography. A mathematical model was developed for estimating the loss of vertical ramus height. RESULTS AND/OR CONCLUSIONS: When the displacements were less than 37 degrees from the sagittal axis of the ascending ramus, the ensuing loss of vertical height was negligible when fractures were treated by conservative techniques. When the displacements exceeded 37 degrees, the fractures resulted in a significant decrease of vertical ramus height. Based on these data, 37 degrees appears to be the point for decision of whether to use closed or open treatment.

Adolescent↗

PubMed1999

NOE data demonstrating a compact unfolded state for an SH3 domain under non-denaturing conditions.

The N-terminal SH3 domain of drk (drkN SH3) is unstable, existing in equilibrium between a folded state (Fexch) and an unfolded state (Uexch) under non-denaturing buffer conditions. Using a15N/2H-labeled sample, long range amide NOEs can be observed in the Uexchstate as a result of reduced relaxation, in some cases correlating protons over 40 residues apart. These long range NOEs disappear upon addition of 2 M guanidinium chloride, demonstrating that there are substantial differences between the Uexchand the guanidine denatured states. Calculations using the long range NOEs of the Uexchstate yield highly compact structures having non-native turns and a non-native buried tryptophan residue. These structures agree with experimental stopped-flow fluorescence data and analytical ultracentrifugation results. Since protein stability depends on the structural and dynamic properties of both the folded and unfolded states, this study provides insights into the stability of the drkN SH3 domain. These results provide the first strong NOE-based evidence for compact unfolded states of proteins and suggest that some unfolded states under physiological conditions have specific interactions leading to compact structures.

Amino Acid Sequence↗

PubMed2004

A cation exchange model to describe Cs+ sorption at high ionic strength in subsurface sediments at Hanford site, USA.

A theoretical and experimental study of cation exchange in high ionic strength electrolytes was performed using pristine subsurface sediments from the U.S. Department of Energy Hanford site. These sediments are representative of the site contaminated sediments impacted by release of high level waste (HLW) solutions containing 137Cs+ in NaNO3 brine. The binary exchange behavior of Cs+-Na+, Cs+-K+, and Na+-K+ was measured over a range in electrolyte concentration. Vanselow selectivity coefficients (Kv) that were calculated from the experimental data using Pitzer model ion activity corrections for aqueous species showed monotonic increases with increasing electrolyte concentrations. The influence of electrolyte concentration was greater on the exchange of Na+-Cs+ than K+-Cs+, an observation consistent with the differences in ion hydration energy of the exchanging cations. A previously developed two-site ion exchange model [Geochimica et Cosmochimica Acta 66 (2002) 193] was modified to include solvent (water) activity changes in the exchanger phase through application of the Gibbs-Duhem equation. This water activity-corrected model well described the ionic strength effect on binary Cs+ exchange, and was extended to the ternary exchange system of Cs+-Na+-K+ on the pristine sediment. The model was also used to predict 137Cs+ distribution between sediment and aqueous phase (Kd) beneath a leaked HLW tank in Hanfordd's S-SX tank using the analytical aqueous data from the field and the binary ion exchange coefficients for the pristine sediment. The Kd predictions closely followed the trend in the field data and were improved by consideration of water activity effects that were considerable in certain regions of the vadose zone plume.

Cations↗

PubMed1999

Increased risk of iodine deficiency with vegetarian nutrition.

Observational studies primarily based on diet questionnaires or food records have reported that vegetarians can have a very low I intake. However, analytically ascertained data on the possible degree of I deficiency with this form of diet is lacking. Six healthy adult volunteers participated in the present controlled experimental diet study carried out in four separate 5 d diet periods. The study diets, normal, protein-rich, lactovegetarian, and repeat of the initial normal diet, were almost isoenergetic and contained no fish, sea food, iodized salt or processed foods fortified with I. During the last 48 h of each diet period two 24 h urine samples were obtained from each subject. I analyses were performed in the urine samples and in representative samples taken from all ingested diets. Urinary I excretion was significantly lower with the lactovegetarian diet (36.6 (SD 8.8) micrograms/d) than with the normal and the protein-rich diets (50.2 (SD 14.0) and 61.0 (SD 8.0) micrograms/d respectively). Accordingly, a markedly reduced I intake was confirmed analytically for the lactovegetarian diet (15.6 micrograms/d v. 35.2 and 44.5 micrograms/d respectively). Our results provide experimental confirmation of literature findings indicating that I supply is higher with non-vegetarian than with vegetarian diets. Specifically, the extremely low intake and urinary output of I as analytically determined for one exemplary vegetarian diet, demonstrate that dietary I may be limiting when strict forms of vegetarian dietary practices (no iodized salt, no I supplements) are followed. The present study is, therefore, the first diet-experiment-based pointer to the potential danger of I deficiency disorders due to strict forms of vegetarian nutrition, especially when fruits and vegetables grown in soils with low I levels are ingested.

Adult↗