The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mecha...
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The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of tkiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride;2) inhibitory effect of chloride on thiazide binding;3) stimulatory effect of sodium on thiazide binding;4) combined effects of sodium and chloride on thiazide binding;5) dependence of sodium influx on extracellular sodium and chloride;and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.
With the current rapid pace at which human disease genes are identified there is a need for practical, cost-efficient genetic screening tests. Two-dimensional electrophoretic separation of PCR-amplified gene fragments...
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With the current rapid pace at which human disease genes are identified there is a need for practical, cost-efficient genetic screening tests. Two-dimensional electrophoretic separation of PCR-amplified gene fragments on the basis of size and base pair sequence, in non-denaturing and denaturing gradient polyacrylamide gels respectively, provides a rapid parallel approach to gene mutational scanning. Accuracy of the denaturing gradient gel electrophoresis (DGGE) component of this system strongly depends on the design of the PCR primers and the melting characteristics of the fragments they encompass. We have developed a fully automated generally applicable procedure to generate optimal two-dimensional test designs at a minimum amount of time and effort. Designs were generated for the RB1, TP53, MLH1 and BRCA1 genes that can be readily implemented in research and clinical laboratories as low cost genetic screening tests.
A decision support system for planning small-scale agroforestry systems was developed (DESSAP). The program generates a set of feasible alternatives of culture combinations based on specified constraints. The constrai...
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A decision support system for planning small-scale agroforestry systems was developed (DESSAP). The program generates a set of feasible alternatives of culture combinations based on specified constraints. The constraints include land, labor, and cash. Labor used include own and/or hired, and cash is money spent for different items and activities such as fertilizer, harvesting, etc. The program utilizes a multiple objective linear programming model coupled with a management tool to generate alternatives. The system can be used by planners, managers, trainers, extension personnel, farmers, etc., to determine the optimum and desirable alternative(s) for an agroforestry farming system.
In this series of articles, a method is presented that performs (semi) quantitative phase analysis for nanocrystalline transmission electron microscope samples from selected area electron diffraction (SAED) patterns. ...
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In this series of articles, a method is presented that performs (semi) quantitative phase analysis for nanocrystalline transmission electron microscope samples from selected area electron diffraction (SAED) patterns. Volume fractions and degree of fiber texture are determined for the nanocrystalline components. The effect of the amorphous component is minimized by empirical background interpolation. First, the two-dimensional SAED pattern is converted into a one-dimensional distribution similar to X-ray diffraction. Volume fractions of the nanocrystalline components are determined by fitting the spectral components, calculated for the previously identified phases with a priori known structures. These Markers are calculated not only for kinematic conditions, but the Blackwell correction is also applied to take into account dynamic effects for medium thicknesses. Peak shapes and experimental parameters (camera length, etc.) are refined during the fitting iterations. Parameter space is explored with the help of the Downhill-SIMPLEX. The method is implemented in a computer program that runs under the Windows operating system. Part I presented the principles, while part II elaborated current implementation. The present part III demonstrates the usage and efficiency of the computer program by numerous examples. The suggested experimental protocol should be of benefit in experiments aimed at phase analysis using electron diffraction methods.
Initial assessment of cost estimation for constructing a building is one of the most challenging and critical tasks by all involved participants across the fields of Architecture, Engineering, and Construction (A/E/C)...
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Initial assessment of cost estimation for constructing a building is one of the most challenging and critical tasks by all involved participants across the fields of Architecture, Engineering, and Construction (A/E/C) industries. This may be contributed by the architects' subjectivity, owners' requirements, and a variety of possible design alternatives. Early decisions based on an estimate involve highly uncertain subsequent disputes between stakeholders. One of the most common uncertainty cost estimate factors of a project is selecting the building Architectural Design Variables (ADVs). Thus, this research identified seven ADVs with 40 design options that have conflicting contributions to the cost performance in construction. These options were quantitatively evaluated and combined to generate the cost of potential designs. Based on that, a novel Architectural-Based Construction Cost Impact Scoring System (ACCISS) was developed to reduce stakeholders' subjectivity, and accordingly, determine the most appropriate design decision that provides early cost advice and highlights the most cost-acceptable design alternatives. The proposed ACCISS is capable to automatically evaluate any combination of design alternatives, through its simple and user-friendly program. A case study of three design alternatives with three regression analyses models was incorporating to validate the ACCISS. The models' results showed the ability of ACCISS to work as an efficient assessing tool for providing cost-effective designs.
In a theoretical survey, the various advantages of orthogonal polynomial terms compared to ordinary powers of X are established. The coefficients in front of the polynomial terms are then not covariant. Simple formula...
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In a theoretical survey, the various advantages of orthogonal polynomial terms compared to ordinary powers of X are established. The coefficients in front of the polynomial terms are then not covariant. Simple formulae can be derived for the standard deviations of these coefficients. These standard deviations are proportional to the residual standard deviation and all have the same number of degrees of freedom. Additionally, matrix inversion is not necessary in the calculation procedure and so cannot boost computing errors. Testing whether these coefficients differ significantly from zero is shown to provide an excellent basis for cutting off the overall polynomial above a certain degree. The orthogonal polynomial terms are tested sequentially to see if their contribution is significant;in the procedure, the polynomial is cut off just before two adjacent terms which do not contribute significantly. This test proved to be far more robust than the usual F-tests which are based on changes of the overall polynomial. Possible outliers are detected earlier. For practical calibrations, five equidistant calibration levels should be selected to cover the orthogonal polynomial contributions adequately up to the fifth degree. During validation procedures, additional levels at 1/3 and 2/3 of the calibration range can be added. The use of other distributions of calibration levels should be discouraged. Replicate measurements at the different equidistant levels should be made at the ratio 3:1:2:1:3 (or at 8:3:2:4:2:3:8, in the other case). The absolute values of the calibration levels should be selected so that the unknown X falls in the upper part of the calibration range. The number of replicate measurements on the unknown should be at least 25% of the total number of measurements used in the calibration. In this way, the unknown can be evaluated optimally with minimal relative standard deviation. If the standard deviations of replicate standards do not change by more than a fa
A computer program, LESSDAD (LEast-Squares Spectrophotometric Determination by Absorbance Data), is described for computation of the best set of analytical concentrations of two ligands and/or metal ions from absorban...
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A computer program, LESSDAD (LEast-Squares Spectrophotometric Determination by Absorbance Data), is described for computation of the best set of analytical concentrations of two ligands and/or metal ions from absorbance measurements. At least-squares method is used to calculate the concentrations from the pH of the solution, spectrophotometric data (experimental absorbances and known molar absorptivities) and the relevant equilibtium constants. The Newton-Raphson iteration is used to solve the mass-balance equations. The program is rapid convenient to use and gives satisfactory results on a number of systems.
Objectives: Record linkage, the process of bringing together separately compiled but related records from different databases, is essential in many area's of biomedical research. We developed a, record linkage pro...
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Objectives: Record linkage, the process of bringing together separately compiled but related records from different databases, is essential in many area's of biomedical research. We developed a, record linkage program (EpiLink), which employs a simple mathematical approach. We describe the program and present results obtained testing it in a linkage task. Methods: EpiLink was designed to be flexible with user-friendly settings to tailor linkage and operating parameters to specific linkage tasks, and employ deterministic, probabilistic or sequential deterministic-probabilistic linkage strategies as required. The user con also standardize data format, examine linkage results and accept of discard them. We used EpiLink to link a subset of cases of the Lombardy Cancer Registry (20,724 records) with the Social Security file of the population (1,021,846 records) covered by the registry. I The linkage strategy was deterministic, followed by several probabilistic linkage steps. Results: Manual inspection of the-results showed that EpiLink achieved 98.8% specificity and 96.5% sensitivity. Conclusions. EpiLink is a practical and accurate means of linking records from different databases that con be used by non-statisticians and is efficient in terms of human and financial resources.
Genetic analysis is used to map genes, including disease loci, to positions within the human genome. Linkage analysis depends on the co-segregation of a gene (locus) and a phenotype through a pedigree, while associati...
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Genetic analysis is used to map genes, including disease loci, to positions within the human genome. Linkage analysis depends on the co-segregation of a gene (locus) and a phenotype through a pedigree, while association analysis, or linkage disequilibrium mapping, depends on measuring deviation from the random occurrence of alleles in a haplotype in unrelated individuals or nuclear families. Complex computer programs may be used in both forms of analysis. In recent years most interest has focused on identifying genes involved in common, multifactorial diseases. Here I review some current and developing techniques of genetic analysis and give references to where further information can be obtained.
For two independent samples with independent proportions, the significance level of the difference between them can be obtainedfrom joint binomial probabilities, assuming the population propor-tion is well estimated b...
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For two independent samples with independent proportions, the significance level of the difference between them can be obtainedfrom joint binomial probabilities, assuming the population propor-tion is well estimated by the samples' pooled proportion. An efficient computer program can be written for this binomial test. The x2test, using a continuity correction of .25 for equal sample sizes and .1 for unequal sample sizes, is in close agreement with the binomial test.
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