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Measurement-based evaluation of optical pathlength distributions reconstructed from simulated differential interference contrast images.

Recently a method was presented for reconstructing optical pathlength distributions (OPDs) from images of weak phase objects obtained by a conventional differential interference contrast (DIC) microscope. A potential application of this technique is the determination of the mass of biological objects: by integrating the optical pathlength over the projected surface of the image of an object, a measure of the dry mass, i.e. the total mass of all solid constituents present in the object, is obtained. To assess the possibilities of DIC microscopy for this application, simulations were performed on computer-generated DIC images of objects of various sizes, shapes and orientation angles. After reconstructing the OPDs from these images, the integrated optical pathlength of each of the test objects was determined, and compared with the expected results. The parameter settings used in the reconstruction algorithm were found to be very important in obtaining a reliable measurement. Using optimal parameter settings, errors in the integrated OPD could be limited to a few per cent for circular objects within the investigated size range. For non-circular objects, however, the orientation angle of the object relative to the lateral shift was found to influence the measured values. Ellipses with their long axes perpendicular to the shift direction had a significantly higher integrated OPD than ellipses orientated parallel to the shift. By adjusting the reconstruction parameters the effect could be limited, but complete elimination of the artefact was not possible within the parameter range investigated.

Journal Article↗

Optimum parameters of TLD100 powder used for radiotherapy beams calibration check.

External audit of the absorbed dose determination from radiotherapy machines is performed using Lithium fluoride (LiF) TLD-100. Optimal parameters needed to obtain highly accurate dosage from LiF powder was investigated, including the setup of the Harshaw 4000 reader. A linear correspondence between the thermoluminescent signal and the mass of the powder was observed, demonstrating that the dose can be evaluated with small samples of powder. The reproducibility of the thermoluminescence dosimeter (TLD) readings obtained with up to 10 samples from 1 capsule containing 160 mg of powder was around 1.5% (1 standard deviation [SD]). The time required for the manual evaluation of TLDs can be improved by 3 readings without loss of accuracy. Better reproducibility is achieved if the capsules are evaluated 7 days after irradiation using a nitrogen flow of 300 cc/min.

Calibration↗

Intensity-modulated radiotherapy of breast cancer using direct aperture optimization.

BACKGROUND AND PURPOSE: To design a clinically reliable and efficient step-and-shoot IMRT delivery technique for the treatment of breast cancer using direct aperture optimization (DAO). Using DAO, segments are created and optimized within the same optimization process. PATIENTS AND METHODS: The DAO technique implemented in the Pinnacle treatment planning system, which is called direct machine parameter optimization (DMPO), was used to generate IMRT plans for twelve breast cancer patients. The prescribed dose was 50 Gy. Two DMPO plans were generated. The first approach uses DMPO only; the second technique combines DMPO with two predefined segments (DMPO(segm)), having shapes identical to the conventional tangential fields. The weight of these predefined segments is optimized simultaneously with DMPO. The DMPO plans were compared with normal two-step (TS) IMRT, creating segments after optimizing the intensity. RESULTS: Dose homogeneity within the target volume was 4.8+/-0.6, 4.3+/-0.5 and 3.8+/-0.5 Gy for the TS, DMPO and DMPO(segm) plans, respectively. Comparing the IMRT plans with an idealized dose distribution obtained using only beamlet optimization, the degradation of the dose distribution was less for the DMPO plans compared with the two-step IMRT approach. Furthermore, this degradation was similar for all patients, while for the two-step IMRT approach it was patient specific. CONCLUSIONS: An efficient step-and-shoot IMRT solution was developed for the treatment of breast cancer using DMPO combined with two predefined segments.

Algorithms↗

Improving the in vivo X-ray fluorescence (XRF) measurement of renal mercury.

In vivo polarised X-ray fluorescence (XRF) measurements of renal mercury have previously been reported (Börjesson J, Barregård L, Sällsten G, Schütz A, Jonson R, Alpsten M, Mattsson S, 1995. In vivo XRF analysis of mercury: the relation between concentrations in the kidney and the urine. Phys. Med. Biol. 40, 413-426). However, with the detection limit reported therein, this system is limited to measurements in cases of significant mercury exposure. An improvement in detection limit is desirable to produce a tool capable of occupational monitoring in cases of mild to moderate exposure. Therefore, design changes have been investigated to improve system performance. Through Monte Carlo simulation and experiment, optimal parameters were determined with respect to polarisation and filtration, as well as the ideal X-ray tube voltage. The optimal configuration will be discussed. A preliminary comparison in terms of minimum detectable limit (MDL) will be made with the preceding polarised XRF renal mercury system.

Filtration↗

Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model.

Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dosing initiated 2 days after intravenous tumor challenge. Quantitative structure-activity relationships have been discovered in the GTC series with survival enhancement correlated to substituent parameters. Optimal correlations were found between the probit transform of the drug-induced increased lifespan (ILS) and field and pi parameters. Among the most effective analogues in this series was N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide.

Adenocarcinoma↗

The mechanism of reaction of fully reduced membrane-bound cytochrome oxidase with oxygen at 176K.

1. The results of non-linear optimization studies on the mechanism of reaction of fully reduced cytochrome oxidase with O2 at 176K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at three wavelength pairs (604-630, 608-630 and 830-940 nm) and at three O2 concentrations (60, 200 and 1180 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, good determination of the optimized parameters and a random distribution of residuals is a three-species sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from low-temperature trapping, e.p.r. and magnetic-susceptibility studies, the possible valence states of the metal centres in each of the intermediates are discussed.

Chemical Phenomena↗

Medical image segmentation with knowledge-guided robust active contours.

Medical image segmentation techniques typically require some form of expert human supervision to provide accurate and consistent identification of anatomic structures of interest. A novel segmentation technique was developed that combines a knowledge-based segmentation system with a sophisticated active contour model. This approach exploits the guidance of a higher-level process to robustly perform the segmentation of various anatomic structures. The user need not provide initial contour placement, and the high-level process carries out the required parameter optimization automatically. Knowledge about the anatomic structures to be segmented is defined statistically in terms of probability density functions of parameters such as location, size, and image intensity (eg, computed tomographic [CT] attenuation value). Preliminary results suggest that the performance of the algorithm at chest and abdominal CT is comparable to that of more traditional segmentation techniques like region growing and morphologic operators. In some cases, the active contour-based technique may outperform standard segmentation methods due to its capacity to fully enforce the available a priori knowledge concerning the anatomic structure of interest. The active contour algorithm is particularly suitable for integration with high-level image understanding frameworks, providing a robust and easily controlled low-level segmentation tool. Further study is required to determine whether the proposed algorithm is indeed capable of providing consistently superior segmentation.

Algorithms↗

Potential gain from optimizing multigeneration selection on an identified quantitative trait locus.

The potential extra response that can be obtained from the optimal use of a known QTL in selection by optimizing weights in an index of breeding value for the QTL and polygenic EBV was investigated for a range of parameters. Optimal strategies were derived for a deterministic model of simultaneous selection on a QTL and polygenic effects using optimal control theory. Responses over 10 generations to the following selection strategies were compared: 1) standard QTL selection, with QTL weights equal to 1, 2) optimal QTL selection, 3) stepwise single-generation optimal QTL selection, and 4) non-QTL selection based on phenotype. Cumulative discounted response with discount rates of 10 or 30% per generation were evaluated and used as objective for optimal selection strategies. Optimal selection balanced the conflict between short- and long-term responses and gave greater cumulative discounted response than standard QTL selection of up to 20%, but less than 5% for most cases. Discount rate had limited impact. For a QTL with an additive effect of one polygenic standard deviation, cumulative discounted response from optimal QTL selection was less than 5% greater than response for non-QTL selection for most cases. Exceptions were traits with low heritability and recessive QTL at low frequency, for which extra response was up to 55% greater. Stepwise optimal selection resulted in less cumulative discounted response than standard QTL selection for QTL with negative dominance. The benefit of optimal over stepwise optimal selection was limited (less than 4%) for most cases, except for overdominant QTL. These results indicate that optimizing selection on an identified QTL can result in greater responses to selection but that extra responses tend to be limited for the situations studied here of single-stage purebred selection on a single QTL for a trait observed on both sexes.

Animals↗

[Recovery process of nitric acid, copper and nickel in deplating wastewater].

The recovery process of nitric acid, copper and nickel in deplating wastewater was developed by using the combined technique of distillation, solvent extraction and precipitation. The conditions of the separation of copper and nickel by solvent extraction using P507 in kerosene and stripping copper with H2SO4 were specially investigated and the optimal parameters were determined. The results of experiment indicated that the recovery ratio of nitric acid was 97.8%, and under the optimized conditions of extraction process, concentration of original effluence ranged in 15-20 mg/mL copper, 5-10 mg/mL nickel, pH 1-2, concentration of extractant was 35% (V/V), saponification degree was 60%, phase ratio was 1:1, reaction time was 2 min, temperature ranged in 20 degrees C-25 degrees C, the one stage extraction efficiency of copper was higher than 90%, the separation ratio of copper and nickel was up to 75; copper and nickel could be completely separated by a continuous countercurrent three-stage extraction. The nickel could be recovered from the water phase by precipitating with NaOH and the recovery ratio of nickel reached up to 99.9% by controlling pH in solution within 10-11. After these treatment, the effluent could meet the national standards of wastewater discharge.

Copper↗

Model-based optimization of infectivity parameters: a study of the early epidemic in San Francisco.

By combining dynamic modeling of human immunodeficiency virus (HIV) transmission with mathematical optimization techniques, we calculate values of epidemiological parameters characterizing the early epidemic (1978-1986) among homosexual and bisexual men in San Francisco. The seroconversion fraction data reported by the San Francisco hepatitis B vaccine trials cohort study for this period is accurately simulated by a model assuming varying infectivity among three stages of HIV infection (early antigen stage, HIV antibody-positive stage, and AIDS stage). Using optimization techniques, we generate curves of the annual number of new partners and the annual number of risk contacts as functions of time. We project future case rates using optimized parameter values, and we study the sensitivity of these projections to variations in parameters, including the population size and the incubation period.

Bisexuality↗

Evaluation of a long-pulsed Nd:YAG laser at different parameters: an analysis of both fluence and pulse duration.

BACKGROUND: Effective hair removal continues to pose a challenge to the physician. The use of lasers represents a significant advance in epilation, but still requires further refinement. The long-pulsed Nd:YAG laser may offer advantages over other systems because of its significant depth of penetration and minimal absorption by epidermal melanin, but ideal parameters need to be determined. OBJECTIVE: To evaluate the efficacy of a long-pulsed Nd:YAG laser system and determine the optimal parameters for hair removal. METHODS: Twenty-two subjects were treated with a cryogen spray-cooled long-pulsed Nd:YAG laser. Four adjacent sites were assigned to each subject, where the following sets of parameters were utilized: 50 J/cm2 with a 25-msec pulse duration, 60 J/cm2 with a 50-msec pulse duration, 80 J/cm2 with a 50-msec pulse duration, and control. Hair counts were obtained immediately, 1 week, 1 month, and 3 months after treatment, and multivariate regression analysis was used to determine the significance of hair reduction. Acute reactions and adverse events were also evaluated. RESULTS: Treatment at all three sets of parameters resulted in significant mean hair reductions immediately, at 1 week, and at 1 month (P <.001). At 3 months, the higher settings of 60 J/cm2 and 50 msec and 80 J/cm2 and 50 msec were statistically significant for reduced mean hair counts (P =.014, P =.042, respectively), while the lowest setting at 50 J/cm2 and 25 msec was not significant (P =.079). Patient and physician assessments suggested optimal hair reduction at the highest fluence (80 J/cm2) and longest pulse duration (50 msec). The most common acute reactions were pain during treatment, erythema, and perifollicular edema, all of which were more severe with higher fluences. CONCLUSION: The long-pulsed Nd:YAG laser is a safe and effective method of hair removal. Increased fluence (60-80 J/cm2) and longer pulse duration (50 msec) settings were generally correlated with reduced hair counts and improved clinical outcome.

Adult↗

Assessment of the accuracy of a human arm model with seven degrees of freedom.

We are proposing a human arm model that consists of three rigid segments with seven degrees of freedom. The shoulder joint was modeled as a ball-and-socket joint and the elbow and wrist joints were modelled as skew-oblique joints. Optimal parameters for this model were calculated on the base of in vivo recordings with a spatial tracking system. The criterion of optimality was defined as the minimum of the mean-square deviation between the experimentally obtained sensor positions and orientations and their positions and orientations calculated by solving the direct kinematics problem. The minimal value of the direct kinematics error was found to be 0.5-0.6cm for sensor positions and 5-7 degrees for sensor orientations. We are proposing that these values serve as the assessment for the accuracy of the arm model.

Adult↗

An enhanced RNA alignment benchmark for sequence alignment programs.

BACKGROUND: The performance of alignment programs is traditionally tested on sets of protein sequences, of which a reference alignment is known. Conclusions drawn from such protein benchmarks do not necessarily hold for the RNA alignment problem, as was demonstrated in the first RNA alignment benchmark published so far. For example, the twilight zone - the similarity range where alignment quality drops drastically - starts at 60 % for RNAs in comparison to 20 % for proteins. In this study we enhance the previous benchmark. RESULTS: The RNA sequence sets in the benchmark database are taken from an increased number of RNA families to avoid unintended impact by using only a few families. The size of sets varies from 2 to 15 sequences to assess the influence of the number of sequences on program performance. Alignment quality is scored by two measures: one takes into account only nucleotide matches, the other measures structural conservation. The performance order of parameters--like nucleotide substitution matrices and gap-costs--as well as of programs is rated by rank tests. CONCLUSION: Most sequence alignment programs perform equally well on RNA sequence sets with high sequence identity, that is with an average pairwise sequence identity (APSI) above 75 %. Parameters for gap-open and gap-extension have a large influence on alignment quality lower than APSI < or = 75 %; optimal parameter combinations are shown for several programs. The use of different 4 x 4 substitution matrices improved program performance only in some cases. The performance of iterative programs drastically increases with increasing sequence numbers and/or decreasing sequence identity, which makes them clearly superior to programs using a purely non-iterative, progressive approach. The best sequence alignment programs produce alignments of high quality down to APSI > 55 %; at lower APSI the use of sequence+structure alignment programs is recommended.

Journal Article↗

Processing of myoelectric signals for estimating the location of innervation zones in the skeletal muscles.

An electrical activity associated with the excitement of muscle fibers arises from the myoneural junctions located at the middle length of the fibers and propagates to the both ends. This propagation can be detected with a multi-electrode array placed on the skin surface. Therefore, the position of the myoneural junctions, or of the innervation zones as a collection of myoneural junctions, can be estimated from the source of the propagation. The authors propose a method for determining the position of the propagation sources automatically with a computer. The method was based on the line-source model of muscle fibers. The positions of the propagation sources were treated as parameters in the model. When some values are assigned to the parameters, the surface potentials are calculated from the currents assumed to propagate on the muscle fibers. The computer searched for the optimal parameters which gave the best fit between the calculated and the measured potentials on the skin surface. Using this method some separate sources of propagation were detected at the middle length of the biceps brachii. The activity of the individual innervation zones was quantitatively described by the average amplitude of the potentials arising from the corresponding sources. This description clarified the changes in the activity of innervation zones when the contraction forces were varied.

Action Potentials↗

Identification of metabolic system parameters using global optimization methods.

BACKGROUND: The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. METHODS AND RESULTS: Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. CONCLUSION: The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.

Algorithms↗

[Transcranial electroanalgesia in rats: an optimal regimen of electrical stimuli].

According to earlier experimental results in rabbits the maximal analgesic effect in rats as determined by vocalization test was elicited by transcranial application of combination of direct current and rectangular pulses (70 Hz, 3.0-3.5 ms) with optimal ratio of amplitudes of direct and mean pulse currents being about 2:1. In anesthetized rats during the transcranial application of the current with parameters optimal for analgesia the most prominent inhibition of the nociceptive blood pressure reflexes were also shown. The similar results obtained in different species of animals confirmed our earlier conclusion that the most pronounced transcranial analgesia may be elicited by the narrow band current parameters only. Directions of further investigation on the electroanalgesia mechanisms using transcranial current application in rats as an experimental model are discussed.

Animals↗

Optimization of electroporation for transfection of mammalian cell lines.

Electroporation can be a highly efficient method for introducing DNA molecules into cultured cells for transient expression of genes or for permanent genetic modification. However, effective transformation by electroporation requires careful optimization of electric field strength and pulse characteristics. We have used the transient expression of the firefly luciferase gene as a rapid and sensitive indicator of gene expression to describe the effects on transfection efficiency of altering electroporation field strength and shape. Using the luciferase assay, we investigated the correlation of cell viability with optimal transfection efficiency and determined the optimal parameters for a number of phenotypically distinct mammalian cell lines derived from the nervous and immune systems. The efficiency of electroporation under optimal conditions was compared with that obtained using DEAE-dextran or calcium phosphate-mediated transformation. Transfection by electroporation using square wave pulses, as opposed to exponentially decaying pulses, was found to be significantly increased by repetitive pulses. These methods improve the ability to obtain high efficiency gene transfer into many mammalian cell types.

Animals↗

Experimental design for parameter estimation through sensitivity analysis.

Parameter estimates can be obtained by fitting a numerical simulation model to experimental data, but these estimates may be biased and/or imprecise because of noise in the experimental data. Appropriate choice of experimental conditions, such as exposure or substrate concentrations and sampling times, can minimize the effect of experimental noise on parameter estimates, thus reducing bias and improving precision. This article describes a technique for selecting experimental (initial) conditions and measurement times for optimal parameter estimation. The technique makes use of a user-supplied mathematical simulation model for the process under study with a set of "current" parameter values specified. These "current" parameter values are the best that can be obtained using all available experimental data and/or literature information at the time when design calculations are performed. Early in a modeling study, the "current" parameter values will be tentative--based on a relatively small amount of information. Later in a study, the "current" parameter values may be known to reasonable accuracy, but final confirmation is desired. The technique uses the simulation model to calculate a numerical index for each possible experimental design. The numerical index, or Information Index, is a measure of the response of a simulation model to changes in parameter values, described by Kalogerakis and Luus (1983, 1984). The experimental design with the greatest value of Information Index is the one under which parameters can be most precisely estimated. Computation of the Information Index, described in detail, can be somewhat complicated, depending on the software available. The results, however, are simple to interpret and provide valuable information on the quality of alternate proposed experiments. The technique is applicable to a broad range of dynamical systems. Its use is demonstrated by application to a simulation model being developed to describe the in vitro metabolism of benzene by mouse liver microsomes.

Animals↗