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PubMed1988

Structural analysis of polymers of sickle cell hemoglobin. I. Sickle hemoglobin fibers.

The structure of fibers of deoxyhemoglobin S has been under investigation for several years and a number of different models have been proposed for the arrangement of molecules within the particles. We have used reconstruction and modeling techniques in our analysis of these structures. Several new approaches have been employed in this analysis in order to provide improved estimates of the co-ordinates, pairing, and polarity of the hemoglobin S molecules. Fibers have a variable pitch and, in order to minimize distortions in the reconstructed density maps associated with these variations in pitch, we have developed an iterative procedure to measure the instantaneous pitch and have modified the reconstruction algorithm to incorporate the measured values. This procedure improves the accuracy with which the hemoglobin S molecules can be located in the density maps. Furthermore, the determination of the instantaneous pitch allows us to measure directly the rotation of the individual hemoglobin molecules. These measurements are in excellent agreement with the values predicted using a random angular walk model (as originally proposed for F-actin) to describe the variable pitch. The reconstructions confirm that the fiber consists of 14 strands of hemoglobin S arranged in a hexagonally shaped cross-section. We have determined the pairing of the molecules to form double strands directly from the density maps by identifying the molecules that have intermolecular distances that conform to those of double strands in the Wishner-Love crystal. The seven double strands identified in this manner are consistent with the strand pairings proposed by Dykes et al. (1979) rather than the alternate pairings proposed by Rosen & Magdoff-Fairchild (1985). In addition, we have for the first time determined the polarity of the double strands directly from the reconstruction data. This was achieved using a procedure that amounts to essentially "dissecting" individual double strands from the reconstructed density maps so that their density distribution could be examined independently of the neighboring double strands. Knowledge of the relative polarities of the double strands is essential for determining the intermolecular interactions that stabilize the fiber.

Crystallography↗
PubMed1992

Automatic assessment of the quality of G-banded metaphases. A preliminary study.

Assessment of the quality of cytogenetic preparations is important for 1) a general quality control of the cytogenetic laboratory and 2) for determining the quality of individual cytogenetic analyses. It is generally accepted that good preparations allow a more detailed search for structural abnormalities than poor preparations. As part of a comprehensive study on automated assessment of slide quality we have developed a simple algorithm for automated measurement of metaphase resolution. During semi-automated karyotyping with the Magiscan chromosome analysis system (Joyce-Loebl) three measurements related to resolution are automatically extracted 1) the total number of dark bands of the chromosomes of the metaphase (TB), 2) the normalized average length of the chromosomes (NL), and 3) the average "thickness" of the chromosomes (T). The algorithm TB x NL/T has been tested on 35 metaphases of various quality and compared with visual assessment of the same 35 metaphases. The results indicate that the automatic assessment of metaphase resolution is superior to the visual.

Chromosome Banding↗
PubMed1989

Automatisation of the single-breath nitrogen washout test.

The paper presents a computer-based system for performance and analysis of the single-breath nitrogen washout test (Sb-N2 test). A pneumotachometer and a rapid gas analyser are used for volume flow rate and nitrogen fraction measurements. The data are acquired and analysed by a PDP-11/34 computer. Several sources of measurement errors are considered. An algorithm is proposed to reduce errors in flow measurements due to viscosity variation in respired air. The algorithm for closing volume (CV) detection and calculation of other Sb-N2 parameters is developed from 50 tracings of 18 subjects. The CV is obtained by an iterative linear fitting of the later half of the Sb-N2 curve. Comparisons between computer and hand measurements of three trained readers show good correlations (r = 0.87, 0.93, 0.91). The variability of computer CV measurements was comparable with that of the hand reader with the lowest variance. The coefficient of variation of residual volume and slope of alveolar plateau measurements are apparently reduced. The results demonstrate the adequacy and convenience of using the computer to analyse the Sb-N2 test and indicate that the automation allows for reduction of experimental errors and of test parameter variabilities.

Adult↗
PubMed1992

Assessment of protein coding measures.

A number of methods for recognizing protein coding genes in DNA sequence have been published over the last 13 years, and new, more comprehensive algorithms, drawing on the repertoire of existing techniques, continue to be developed. To optimize continued development, it is valuable to systematically review and evaluate published techniques. At the core of most gene recognition algorithms is one or more coding measures--functions which produce, given any sample window of sequence, a number or vector intended to measure the degree to which a sample sequence resembles a window of 'typical' exonic DNA. In this paper we review and synthesize the underlying coding measures from published algorithms. A standardized benchmark is described, and each of the measures is evaluated according to this benchmark. Our main conclusion is that a very simple and obvious measure--counting oligomers--is more effective than any of the more sophisticated measures. Different measures contain different information. However there is a great deal of redundancy in the current suite of measures. We show that in future development of gene recognition algorithms, attention can probably be limited to six of the twenty or so measures proposed to date.

Algorithms↗
PubMed1987

Automated temperature scanning for hyperthermia treatment monitoring.

Ideal descriptors of hyperthermia treatments will most likely depend on complete target temperature distributions. Although these distributions can be modeled numerically, the accuracy of models is limited by the sparseness of temperatures measured in vivo. Thus, the strategy of monitoring temperatures may play a key role in improving hyperthermia therapy. Scanning temperatures by manual translations of thermometers was found to be excessively time consuming. Consequently an automated system was developed consisting of linear actuators, outriggers, guide tubes, thermometry catheters, personal computer, and dedicated hardware and software. During treatments, scan patterns were created with algorithms using temperatures measured preceding each thermometer translation. Measurement position had a noteworthy influence on thermal dose estimated by current models. Relative to manual scanning, automated scanning increased measurement efficiency, reduced probe position uncertainty, reduced operator time, and provided improved data for modeling bioheat transfer and thermal dose.

Algorithms↗
PubMed1987

Electron arc therapy: beam data requirements and treatment planning.

In electron arc therapy a long narrow beam defined by a secondary collimator is used to sweep across the treatment area of the patient. Central axis percentage depth doses and off-axis ratios measured with such a collimator show variations with the source-to-surface distance (SSD). Errors may be introduced into isodose distributions calculated with the effective SSD method when beam data measured at a fixed SSD are used. A treatment planning algorithm using beam data measured at two SSDs to allow an interpolation and extrapolation procedure to account for SSD variations has been implemented. For calculations in off-axis planes, off-axis ratios normal to the plane of rotation are also required. Results of the calculations were checked with film dosimetry measurements and found to be in good agreement.

Electrons↗
PubMed1989

A theoretical and experimental study of the effects of non-uniform membrane resistance on the shape of single-cell charging curves.

The isolated Muller glial cell of the neotenous tiger salamander retina is used as an experimental model for studying the effects of non-uniform membrane conductance on the shape of charging curves in response to step current inputs. A simple cable model of the Muller cell is formulated and used to interpret the experimental data. The Muller cell model is completely described by three parameters: (a) electrotonic length L; (b) the membrane time constant tau m; and (c) the percentage of the total membrane conductance accounted for by the endfoot S. Model analysis indicates that increasing S produces monotonic decreases in the rise time of charging curves. This effect is greatest when L is small. In such cases charging curve rise time can be substantially faster than that of a semi-infinite cable. When S greater than 0, the first time constant obtained by fitting the late exponential tail of the charging curve is not the membrane time constant (as is the case when S = 0), but is instead an equalizing time constant equal to the membrane time constant times a scale factor in the range of 0 to 1. This scaling factor becomes quite small as S approaches 100%. We describe a convergent numerical procedure for generating unique estimates of all three model parameters from charging curves. Application of the algorithm to experimentally measured Muller cell charging curves confirms Newman's finding that a large fraction of membrane conductance in these cells is accounted for by the endfoot (greater than 90%). The model prediction that charging curve rise time may be substantially faster than that of the semi-infinite cable when S greater than 0 is also confirmed. The error that results from misinterpreting the first equalizing time constant tau l as the membrane time constant tau m can have a significant effect on estimates of specific membrane resistance and capacitance. The algorithm described in this paper provides a means for obtaining direct estimates of the membrane time constant and will make possible more accurate estimates of specific membrane resistance and capacitance in Muller glial cells. The fact that the estimation procedure is based on a simple electrophysiological measurement suggests that it may be useful for studying asymmetry of membrane conductance in glial and neural elements of the intact nervous system.

Animals↗
PubMed1991

DEXA measurement of spine density in the lateral projection. I: Methodology.

Bone mineral content and bone mineral density (BMC in g and BMD in g/cm2) were measured using dual-energy X-ray absorptiometry (DEXA). DEXA scans in the lateral decubitus position required about 12 minutes for the L2-L4 sequence at 0.75 mA (dose 5 mrem) and 4 minutes at 4.75 mA (7 mrem). The former scans were done with the Lunar DPX densitometer and the latter with the Lunar DPX-L. One test of the algorithms used for measurement is the equality of BMC in both AP and lateral projections. BMC in the lateral projection averaged about 1% lower than in the AP projection in phantoms and for L2 + L3 in 8 subjects, but the difference was not significant. Additional tests were done on the effects of tissue thickness and position from the tabletop. There was little or no influence of tissue thickness from 18 to 30 cm on BMD results, but there was a small influence of thickness below 18 cm (0.01 g/cm2; P = 0.01) and of distance from the tabletop at extremes of positioning (0.02 g/cm2; P = 0.06). The precision in vivo was similar for both 4- and 12-minute scans; the standard deviation of repeat measurements was about 0.02 g/cm2, which was about 2% relative to the mean BMD for a region within the vertebral body. The latter region included half the BMC of the body, or 24% of the entire vertebra. Results of 4-minute scans on the DPX and 12-minute scans on the DPX-L in 9 subjects were highly correlated (r = 0.98; P less than 0.001).

Absorptiometry, Photon↗
PubMedDate not supplied

Real-time measurement of microvascular dimensions using digital cross-correlation image processing.

A real-time automatic digital image-processing algorithm was developed for measuring microvascular dimensions. Using video microscopic images of the vasculature, the video images are digitized and analyzed using contrast enhancement, frame averaging, and pattern recognition, rather than edge detection. Performance of the algorithm was evaluated for second- and third-order vessels surrounded by the complex interfering features of in vivo skeletal muscle. Graded diameter changes and vasomotion were induced with pharmacological agents. Data obtained by auto-tracking agreed with data obtained by traditional manual methods of measurement. These findings indicate that a pattern recognition algorithm based on cross-correlation analysis provides a highly accurate method for real-time automatic tracking of microvessel diameters.

Animals↗
PubMedDate not supplied

Similarity searching in databases of three-dimensional molecules and macromolecules.

This paper discusses algorithmic techniques for measuring the degree of similarity between pairs of three-dimensional (3-D) chemical molecules represented by interatomic distance matrices. A comparison of four methods for the calculation of 3-D structural similarity suggests that the most effective one is a procedure that identifies pairs of atoms, one from each of the molecules that are being compared, that lie at the center of geometrically-related volumes of 3-D space. This atom mapping method enables the calculation of a wide range of types of intermolecular similarity coefficient, including measures that are based on physicochemical data. Massively-parallel implementations of the method are discussed, using the AMT Distributed Array Processor, that achieve a substantial increase in performance when compared with a sequential implementation on a UNIX workstation. Current work involves the use of angular information and the extension of the method to field-based similarity searching. Similarity searching in 3-D macromolecules is effected by the use of a maximal common subgraph (MCS) isomorphism algorithm with a novel, graph-based representation of the tertiary structures of proteins. This algorithm is being used to identify similarities between the 3-D structures of proteins in the Brookhaven Protein Data Bank; its use is exemplified by searches involving the NAD-binding fold motif.

Algorithms↗
PubMedDate not supplied

Automatic derivation of initial match points for paired digital images of skin.

Computerized matching of skin images has been suggested as a means of screening for changes indicative of malignant melanoma. Matching or "registering" each lesion in a pair of images plays an important role in this process. Point-pattern matching algorithms based upon correlation or geometric transformations of the image pairs have been shown to be effective for this registration but require knowledge of one or more "initial match" points which are known to be the same on both images. A method is described for automatically finding these initial match points with a high degree of success. Our algorithm uses the so-called "Gabriel graph" representation of the paired images to select sets of probable matching points. Performance of the algorithm has been measured in realistic trials, using images of patients with large numbers of pigmented lesions. Results show that the single best match chosen is correct greater than 99% of the time, while over 93% of the first three consecutive matches will be chosen correctly. It is likely that these results can be improved through the use of additional nonpositional information or additional image processing.

Algorithms↗
PubMed1979

Utilization of cross-plane rays for three-dimensional reconstruction by filtered back-projection.

Present popular computed tomography (CT) algorithms reconstruct an object from the ray measurements lying on a set of parallel planes. This paper presents an algorithm that can also utilize "cross-plane" rays (i.e., rays that cross through many planes) to reconstruct the object. In this reconstruction algorithm, the ray measurements are grouped into two-dimensional projections, filtered, and stored. The filtered projections can then be back-projected onto a three-dimensional matrix or any plane through the three-dimensional volume. General theoretical aspects are presented and then applied to the special case in which ray measurements have been made in all directions. The algorithm is tested using computer-generated data. Expressions for the noise power spectrum and the variance in the reconstruction are derived. It is shown that the noise-to-signal ratio per detected photon for this reconstruction method is close to a theoretical limit, as it also is for normal CT. The ability to use ray measurements that cross many planes is especially useful in emission CT, where order-of-magnitude improvements in image quality per unit dose can be achieved.

Computers↗
PubMed1990

Negligible effects of previous moderate physical activity and changes in environmental temperature on whole body electrical impedance.

Several studies have shown that the predictive power of various linear combinations of anthropometric data (body weight, height, sex, age, etc.) to estimate fat free mass is improved after inclusion of measurements of electrical impedance (see eg Khaled et al., 1988). Published algorithms are based on measurements performed under fairly standardized conditions with the subjects at stationary conditions of rest, of environmental temperature and of body fluids. Use of the method under less standardized conditions raises the question of possible effects of deviations from these standard conditions. Hydration and dehydration by 1-2 l of fluid increased or decreased, respectively, the electrical resistance by about 14 per cent and the effects persisted for more than 1 h (Khaled et al., 1988). A change in environmental temperature by 21 degrees C from 35 degrees C to 14 degrees C (with almost constant relative humidity) during 90 min caused an increase in the resistance of about 9 per cent (Caton et al., 1988). The perturbations used in the studies quoted above are fairly drastic and not likely to occur under reasonably controlled field conditions. Therefore, we report here results of measurements of whole body electrical impedance before, during and after a period of 10 degrees C increased environmental temperature and before and after a 5-min period of light to moderate physical exercise.

Electric Conductivity↗
PubMed1990

Application of new calculation algorithms to oxygenation parameters of cirrhotic patients. A comparison between calculated and measured data.

Oxygen status from both arterial and mixed venous blood was analyzed by reliable methods in 39 cirrhotic patients. These measured data were checked with computed oxygen parameters by new calculation algorithms. Calculated oxygen contents were higher than directly measured values but there was a highly significant correlation between them. Calculated and measured 2,3-DPG mean values were not significantly different but there was no correlation between them. A large difference was observed between measured and computed evaluation of oxygen-hemoglobin affinity without correlation between P50. In hyperkinetic patients, no correlation was observed between 'compensation factor' and the increase of cardiac index. So, in these patients the new iterative equations were not valid to determine traditional oxygen parameters from only Po2 and So2 arterial measurements. Moreover the new oxygenation parameters appeared frankly inadequate.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

Vertebral mineral determination by quantitative computed tomography (QCT): accuracy of single and dual energy measurements.

Quantitative CT (QCT) studies of trabecular vertebral bone tissue have been carried out in vitro on a GE CT/T 9800 scanner. Results of both single energy (SE) 80 kVp and dual energy (DE) 80/140 kVp QCT data are compared with chemical mineral analysis to determine accuracy. We examined 62 vertebral specimens, from 28 cadavers (19 male and 9 female with an age range of 19-93 years, mean = 60.4). Averaging the results of all vertebral bodies of the same individual for SEQCT versus ashweight, we found a correlation coefficient (r) of 0.94 (p less than 0.0001), a standard error of the estimate (SEE) of 12.2 mg/cm3 (calibrated to K2HPO4), with a coefficient of variation (CV) of 13.2% and an average underestimation of bone mineral content of 18.7 mg/cm3. The corresponding DEQCT results were r = 0.98 (p less than 0.0001), SEE = 7.4 mg/cm3, CV = 7.0%, and an average underestimation of 4.9 mg/cm3. The SE and DE results are correlated with r = 0.98 (p less than 0.0001), SEE = 8.0 mg/cm3, and CV = 8.7%. From our SEQCT data and the results of the chemical analysis of bone mineral and fat content we calculated a fat sensitivity of 7.7 mg/cm3 K2HPO4 per 100 mg/cm3 fat change for our scanner. Using an average fat variability of 87.5 mg/cm3, this leads to a fat-related uncertainty for the normative SEQCT data of 6.7 mg/cm3, which is far lower than the normal biological variation of 29.4 mg/cm3. Using tabulated normative data on fat content versus age and versus mineral content of 188 vertebral specimens from five collaborating centers, we derived a correction algorithm for QCT measurement that reduces our average underestimation to 0.88 mg/cm3 with an SEE of 12.1 mg/cm3. Hence, this correction procedure can be used to estimate the fat corrected absolute mineral density for research purposes or for scanners with high fat sensitivity. For the GE CT/T 9800 scanner, with a relatively low fat to mineral sensitivity at 80 kVp, the correction procedure is generally not recommended for clinical studies since it minimizes the average fat induced error but does not reduce the residual, partially fat related uncertainty. Finally, since the fat related uncertainty is small compared to biological variation, the correlation is high between SEQCT and DEQCT, and the radiation dose is lower and the precision higher for SEQCT, we suggest that most clinical diagnostic studies using the GE CT/T 9800 scanner for bone mineral determination employ SEQCT at 80 kVp.

Adult↗
PubMed1992

Results obtained by using a computerized image analysis system designed as an aid to diagnosis of cutaneous melanoma.

Results obtained using a computerized image analysis system as an aid to clinical diagnosis of melanoma are reported. The system comprises a colour television camera connected through a digitizing board to a 386 personal computer. By means of original algorithms able to measure the shape, the colours and texture of a pigmented lesion of the skin, the system provides eight on/off indicators that are matched with the histological diagnosis to identify benign and malignant pigmented lesions. The chances that a given lesion is malignant increase with the increasing number of positive indicators. The training field of the system was constituted of images and data of 169 cutaneous lesions in 165 patients. Taking two positive indicators as the threshold between pigmented benign and malignant lesions, the efficiency of the system is 0.98, the positive predictive value is 0.45 and the negative predictive value is 0.95. These values were confirmed in a series of 44 pigmented lesions, 10 of which were melanoma, that constitute the present test series. The authors conclude that this computerized image analysis system should be regarded as a useful aid to diagnosis for a non-expert clinician. The system limit is transformation within a naevus.

Adult↗
PubMedDate not supplied

Yield of the screening review of systems: a study on a general medical service.

STUDY OBJECTIVE: To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions. DESIGN: Case series. SETTING: General internal medicine ward of a university hospital. PATIENTS: 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease. INTERVENTIONS: Positive responses to screening systems review questions were evaluated using a standardized testing algorithm. MAIN OUTCOME MEASURES: Numbers of new diagnoses; potential for patient benefit. MAIN RESULTS: The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result. CONCLUSIONS: The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices.

Adult↗