Sensitivity of methods for calculating energy expenditure by use of doubly labeled water

Attempts to estimate human energy expenditure by use of doubly labeled water have produced three methods currently used for calculating carbon dioxide production from isotope disappearance data: 1) the two-point method, 2) the regression method, and 3) the integration method. An ideal data set was used to determine the error produced in the calculated energy expenditure for each method when specific variables were perturbed. The analysis indicates that some of the calculation methods are more susceptible to perturbations in certain variables than others. Results from an experiment on one adult human subject are used to illustrate the potential for error in actual data. Samples of second void urine, 24-h urine, and breath collected every other day for 21 days are used to calculate the average daily energy expenditure by three calculation methods. The difference between calculated energy expenditure and metabolizable energy on a weight-maintenance diet is used to estimate the error associated with the doubly labeled water method.     

Trajectory analysis of NMR structure calculations

Summary NMR as well as X-ray crystallography are used to determine the three-dimensional structures of macromolecules at atomic resolution. Structure calculation generates coordinates that are compatible with NMR data from randomly generated initial structures. We analyzed the trajectory taken by structures during NMR structure calculation in conformational space, assuming that the distance between two structures in conformational space is the root-mean-square deviation between the two structures. The coordinates of a structure in conformational space were obtained by applying the metric multidimensional scaling method. As an example, we used a 22-residue peptide, -Conotoxin GIIIA, and a simulated annealing protocol of XPLOR. We found that the three-dimensional solution of the multidimensional scaling analysis is sufficient to describe the overall configuration of the trajectories in conformational space. By comparing the trajectories of the entire calculation with those of the converged calculation, random sampling of conformational space is readily discernible. Trajectory analysis can also be used for optimization of protocols of NMR structure calculation, by examining individual trajectories.Abbreviations MD molecular dynamics - MDS multidimensional scaling - rmsd root-mean-square deviation - armsd angular rmsd - R multiple correlation coefficient - YASAP yet another simulated annealing protocol - PCA principal component analysis     

Movements of the lumbar spine measured by three-dimensional X-ray analysis

Techniques for the calculation from biplanar radiographs of the three-dimensional coordinates of anatomical landmarks on human lumbar vertebrae, and of the movements in three dimensions of the vertebrae between different positions of the spine are presented. The calculation of three-dimensional coordinates uses a calibration procedure based on direct linear transformation. Coordinate systems are used to define the orientations of each vertebra, and movements are derived from coordinate transformations between neighbouring vertebrae. The root mean square error in determining the absolute locations of anatomical landmarks was found to be less than 1 mm. For the movements of one vertebra relative to its neighbour the root mean square errors for translations were < 2 mm and for rotations were < 1.5 degrees. The system has been used to assess patients after spinal fusions and is currently being used in the diagnosis and assessment of patients with specific pathologies.     

Alignment of optical maps.

We introduce a new scoring method for calculation of alignments of optical maps. Missing cuts, false cuts, and sizing errors present in optical maps are addressed by our alignment score through calculation of corresponding likelihoods. The size error model is derived through the application of Central Limit Theorem and validated by residual plots collected from real data. Missing cuts and false cuts are modeled as Bernoulli and Poisson events, respectively, as suggested by previous studies. Likelihoods are used to derive an alignment score through calculation of likelihood ratios for a certain hypothesis test. This allows us to achieve maximal descriminative power for the alignment score. Our scoring method is naturally embedded within a well known DP framework for finding optimal alignments.     

Do calendrical savants use calculation to answer date questions? A functional magnetic resonance imaging study

Calendrical savants can name the weekdays for dates from different years with remarkable speed and accuracy. Whether calculation rather than just memory is involved is disputed. Grounds for doubting whether they can calculate are reviewed and criteria for attributing date calculation skills to them are discussed. At least some calendrical savants possess date calculation skills. A behavioural characteristic observed in many calendrical savants is increased response time for questions about more remote years. This may be because more remote years require more calculation or because closer years are more practised. An experiment is reported that used functional magnetic resonance imaging to attempt to discriminate between these explanations. Only two savants could be scanned and excessive head movement corrupted one savant''s mental arithmetic data. Nevertheless, there was increased parietal activation during both mental arithmetic and date questions and this region showed increased activity with more remote dates. These results suggest that the calendrical skills observed in savants result from intensive practice with calculations used in solving mental arithmetic problems. The mystery is not how they solve these problems, but why.     

The assessment of patient prognosis using an interactive computer program

The use of chronic disease probabilistic models to calculate patient prognosis is presented. The method relies on the calculation of transition probabilities between discrete disease states from a patient data bank. Maximum likelihood estimates are used for each age and unwanted fluctuations are removed by a moving average. An interactive computer program was written and the method applied to the calculation of the probability of stroke and myocardial infarction for male patients on antihypertensive therapy. A clinician could obtain the prognostic information for a patient in less than one minute. Applications in medical student education are also discussed.     

重液浮选对花粉浓度计算的影响

用重液浮选方法可获得富集、清洁的孢粉制片,但在浮选过程中不可避免地会在丢弃的底样中留下相当数量的孢粉。本文定量地探讨这些残留孢粉在重液不同比重条件下对花粉浓度计算的影响,结果表明,在重液浮选中,不同类型孢粉的漂浮率有所不同,并因此造成浓度计算中的误差,误差的大小因孢粉类型和重液比重的不同而不同,大体在1—15%之间。     

Improving the accuracy of protein pKa calculations: Conformational averaging versus the average structure

Several methods for including the conformational flexibility of proteins in the calculation of titration curves are compared. The methods use the linearized Poisson-Boltzmann equation to calculate the electrostatic free energies of solvation and are applied to bovine pancreatic trypsin inhibitor (BPTI) and hen egg-white lysozyme (HEWL). An ensemble of conformations is generated by a molecular dynamics simulation of the proteins with explicit solvent. The average titration curve of the ensemble is calculated in three different ways: an average structure is used for the pK_a calculation; the electrostatic interaction free energies are averaged and used for the pK_a calculation; and the titration curve for each structure is calculated and the curves are averaged. The three averaging methods give very similar results and improve the pK_a values to approximately the same degree. This suggests, in contrast to implications from other work, that the observed improvement of pK_a values in the present studies is due not to averaging over an ensemble of structures, but rather to the generation of a single properly averaged structure for the pK_a calculation. Proteins 33:145–158, 1998. © 1998 Wiley-Liss, Inc.     

Bacterial aerosol emission rates from municipal wastewater aeration tanks.

In this report we describe the results of a study conducted to determine the rates of bacterial aerosol emission from the surfaces of the aeration tanks of the Metropolitan Water Reclamation District of Greater Chicago John E. Egan Water Reclamation Plant. This study was accomplished by conducting test runs in which Andersen six-stage viable samplers were used to collect bacterial aerosol samples inside a walled tower positioned above an aeration tank liquid surface at the John E. Egan Water Reclamation Plant. The samples were analyzed for standard plate counts (SPC), total coliforms (TC), fecal coliforms, and fecal streptococci. Two methods of calculation were used to estimate the bacterial emission rate. The first method was a conventional stack emission rate calculation method in which the measured air concentration of bacteria was multiplied by the air flow rate emanating from the aeration tanks. The second method was a more empirical method in which an attempt was made to measure all of the bacteria emanating from an isolated area (0.37 m2) of the aeration tank surface over time. The data from six test runs were used to determine bacterial emission rates by both calculation methods. As determined by the conventional calculation method, the average SPC emission rate was 1.61 SPC/m2/s (range, 0.66 to 2.65 SPC/m2/s). As determined by the empirical calculation method, the average SPC emission rate was 2.18 SPC/m2/s (range, 1.25 to 2.66 SPC/m2/s). For TC, the average emission rate was 0.20 TC/m2/s (range, 0.02 to 0.40 TC/m2/s) when the conventional calculation method was used and 0.27 TC/m2/s (range, 0.04 to 0.53 TC/m2/s) when the empirical calculation method was used.(ABSTRACT TRUNCATED AT 250 WORDS)     

Semiautomated processing of systolic time intervals.

Systolic time intervals are commonly used to identify changes in ventricular function. The method described facilitates measurement and calculation of many such intervals. This method utilizes a printed polygraph recording of electrocardiogram, phonocardiogram, and carotid pulse contour; a digitizing device for reading the necessary coordinates from the record; and a minicomputer for calculation of the intervals and for data analysis. Intervals related to approximately 100 pulse beats can be read, calculated, printed in chart and graph form, and subjected to some analyses in about an hour.     

Calculation of the morbid risk in genetic-epidemiologic studies of age-dependent diseases

Distributions of age at onset are widely used in the genetic epidemiology of age-dependent diseases. Examples are estimation of recurrent risks in genetic counselling and testing genetic hypotheses in segregation and linkage analyses. In this study, morbidity parameters are defined, including age-specific morbidity rates, morbidity net risk (incidence), and cumulative incidence (population risk, an integrated measure of population susceptibility to the disease at the moment of the study). Age-specific morbidity risks are calculated from the respective morbidity rates, which are analogous to mortality rates used in demography. Population data typically used for calculation of morbidity rates are discussed. Methods of calculation of morbidity rates based on the data of single and interval epidemiological studies are described. Methods for calculating standard errors of these parameters, estimating their statistical reliability, and testing statistical hypotheses are discussed.     

A method for accurate inference of population size from serially sampled genealogies distorted by selection

The serial coalescent extends traditional coalescent theory to include genealogies in which not all individuals were sampled at the same time. Inference in this framework is powerful because population size and evolutionary rate may be estimated independently. However, when the sequences in question are affected by selection acting at many sites, the genealogies may differ significantly from their neutral expectation, and inference of demographic parameters may become inaccurate. I demonstrate that this inaccuracy is severe when the mutation rate and strength of selection are jointly large, and I develop a new likelihood calculation that, while approximate, improves the accuracy of population size estimates. When used in a Bayesian parameter estimation context, the new calculation allows for estimation of the shape of the pairwise coalescent rate function and can be used to detect the presence of selection acting at many sites in a sequence. Using the new method, I investigate two sets of dengue virus sequences from Puerto Rico and Thailand, and show that both genealogies are likely to have been distorted by selection.     

Improved estimates of environmental copper release rates from antifouling products

The US Navy Dome method for measuring copper release rates from antifouling paint in-service on ships' hulls can be considered to be the most reliable indicator of environmental release rates. In this paper, the relationship between the apparent copper release rate and the environmental release rate is established for a number of antifouling coating types using data from a variety of available laboratory, field and calculation methods. Apart from a modified Dome method using panels, all laboratory, field and calculation methods significantly overestimate the environmental release rate of copper from antifouling coatings. The difference is greatest for self-polishing copolymer antifoulings (SPCs) and smallest for certain erodible/ablative antifoulings, where the ASTM/ISO standard and the CEPE calculation method are seen to typically overestimate environmental release rates by factors of about 10 and 4, respectively. Where ASTM/ISO or CEPE copper release rate data are used for environmental risk assessment or regulatory purposes, it is proposed that the release rate values should be divided by a correction factor to enable more reliable generic environmental risk assessments to be made. Using a conservative approach based on a realistic worst case and accounting for experimental uncertainty in the data that are currently available, proposed default correction factors for use with all paint types are 5.4 for the ASTM/ISO method and 2.9 for the CEPE calculation method. Further work is required to expand this data-set and refine the correction factors through correlation of laboratory measured and calculated copper release rates with the direct in situ environmental release rate for different antifouling paints under a range of environmental conditions.     

PSEUDYANA for NMR structure calculation of paramagnetic metalloproteins using torsion angle molecular dynamics

The program DYANA, for calculation of solution structures of biomolecules with an algorithm based on simulated annealing by torsion angle dynamics, has been supplemented with a new routine, PSEUDYANA, that enables efficient use of pseudocontact shifts as additional constraints in structure calculations of paramagnetic metalloproteins. PSEUDYANA can determine the location of the metal ion inside the protein frame and allows to define a single tensor of magnetic susceptibility from a family of conformers. As an illustration, a PSEUDYANA structure calculation is provided for a metal-undecapeptide complex, where simulated pseudocontact shifts but no NOE restraints are used as conformational constraints.     

Genetically-designed Neural Networks for Error Reduction in an Optimized Biomechanical Model of the Human Elbow Joint Complex

A real time dynamic biomechanical model of the human elbow joint has been used as the first step in the process of calculating time varying joint position from the electromyograms (EMGs) of eight muscles crossing the joint. Since calculation of position has a high sensitivity to errors in the model torque calculation, a genetic algorithm (GA) neural network (NN) has been developed for automatic error reduction in the dynamic model. Genetic algorithms are used to design many neural network structures during a preliminary trial effort, and then each network's performance is ranked to choose a trained network that represents the most accurate result. Experimental results from three subjects have shown model error reduction in 84.2% of the data sets from a subject on which the model had been trained, and 52.6% of the data sets from the subjects on which the model had not been trained. Furthermore, the GA networks reduced the error standard deviation across all subjects, showing that progress in error reduction was made evenly across all data sets.     

Genetically-designed neural networks for error reduction in an optimized biomechanical model of the human elbow joint complex

A real time dynamic biomechanical model of the human elbow joint has been used as the first step in the process of calculating time varying joint position from the electromyograms (EMGs) of eight muscles crossing the joint. Since calculation of position has a high sensitivity to errors in the model torque calculation, a genetic algorithm (GA) neural network (NN) has been developed for automatic error reduction in the dynamic model. Genetic algorithms are used to design many neural network structures during a preliminary trial effort, and then each network's performance is ranked to choose a trained network that represents the most accurate result. Experimental results from three subjects have shown model error reduction in 84.2% of the data sets from a subject on which the model had been trained, and 52.6% of the data sets from the subjects on which the model had not been trained. Furthermore, the GA networks reduced the error standard deviation across all subjects, showing that progress in error reduction was made evenly across all data sets.     

On relationship inference using gamete identity by descent data.

Related individuals are identical by descent (IBD) at a genetic locus if they share the same DNA material from a common ancestor. Continuous gamete IBD data consist of the lengths of (in order) IBD and non-IBD regions along the genomes for gametes segregating from two related individuals and can be used to distinguish different relationships. Under the assumption that the crossovers follow a Poisson process, we show that the exact calculation of the likelihood of a particular relationship for a given gamete IBD datum is tractable. Greatgrandparent--greatgrandchild and cousin relationships are used as examples to illustrate our methods.     

Dynamic models of gene expression and classification

Powerful new methods, like expression profiles using cDNA arrays, have been used to monitor changes in gene expression levels as a result of a variety of metabolic, xenobiotic or pathogenic challenges. This potentially vast quantity of data enables, in principle, the dissection of the complex genetic networks that control the patterns and rhythms of gene expression in the cell. Here we present a general approach to developing dynamic models for analyzing time series of whole genome expression. In this approach, a self-consistent calculation is performed that involves both linear and non-linear response terms for interrelating gene expression levels. This calculation uses singular value decomposition (SVD) not as a statistical tool but as a means of inverting noisy and near-singular matrices. The linear transition matrix that is determined from this calculation can be used to calculate the underlying network reflected in the data. This suggests a direct method of classifying genes according to their place in the resulting network. In addition to providing a means to model such a large multivariate system this approach can be used to reduce the dimensionality of the problem in a rational and consistent way, and suppress the strong noise amplification effects often encountered with expression profile data. Non-linear and higher-order Markov behavior of the network are also determined in this self-consistent method. In data sets from yeast, we calculate the Markov matrix and the gene classes based on the linear-Markov network. These results compare favorably with previously used methods like cluster analysis. Our dynamic method appears to give a broad and general framework for data analysis and modeling of gene expression arrays. Electronic Publication     

Characterization of proteins with wide-angle X-ray solution scattering (WAXS)

X-ray solution scattering in both the small-angle (SAXS) and wide-angle (WAXS) regimes is making an increasing impact on our understanding of biomolecular complexes. The accurate calculation of WAXS patterns from atomic coordinates has positioned the approach for rapid growth and integration with existing Structural Genomics efforts. WAXS data are sensitive to small structural changes in proteins; useful for calculation of the pair-distribution function at relatively high resolution; provides a means to characterize the breadth of the structural ensemble in solution; and can be used to identify proteins with similar folds. WAXS data are often used to test structural models, identify structural similarities and characterize structural changes. WAXS is highly complementary to crystallography and NMR. It holds great potential for the testing of structural models of proteins; identification of proteins that may exhibit novel folds; characterization of unfolded or natively disordered proteins; and detection of structural changes associated with protein function.     

Calculation of the"Net Additions to Stock" Indicator for the Czech Republic Using a Direct Method

Abstract: Net additions to stock (NAS) are an indicator based on economy-wide material flow accounting and analysis. NAS, a measure of the physical growth rate of an economy, can be used for estimates of future waste flows. It is calculated using two methods: The indirect method of calculation is a simple difference between all input and output flows, whereas the direct method involves measuring the amounts of materials added to particular categories of physical stock and the amounts of waste flows from these stocks.
The study described in this article had one leading objective: to make available direct NAS data for the Czech Republic, which could later be used for predicting future waste flows. Two additional objectives emerged from the first: (1) to develop a method for direct NAS calculation from data availability in the Czech Republic; (2) to calculate NAS directly, compare the results with those achieved in indirect NAS calculation, and discuss the identified differences.
The NAS for the Czech Republic calculated by the direct method is equal to approximately 65 million tonnes on average in 2000–2002 and is approximately 27% lower than the NAS acquired by the indirect method of calculation. The actual values of directly calculated NAS and its uncertainties suggest that the indirect NAS is more likely to be an overestimation than an underestimation. Durables account for about 2% of the total direct NAS, whereas the rest is attributed to infrastructure and buildings. The direct NAS is dominated by nonmetal construction commodities such as building stone and bricks, which equal approximately 89% of the total direct NAS.
Calculation of NAS by the direct method has been proved to be feasible in the Czech Republic. Moreover, uncertainties related to direct NAS are lower than those related to indirectly acquired NAS.