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Clustering binary fingerprint vectors with missing values for DNA array data analysis.

Oligonucleotide fingerprinting is a powerful DNA array based method to characterize cDNA and ribosomal RNA gene (rDNA) libraries and has many applications including gene expression profiling and DNA clone classification. We are especially interested in the latter application. A key step in the method is the cluster analysis of fingerprint data obtained from DNA array hybridization experiments. Most of the existing approaches to clustering use (normalized) real intensity values and thus do not treat positive and negative hybridization signals equally (positive signals are much more emphasized). In this paper, we consider a discrete approach. Fingerprint data are first normalized and binarized using control DNA clones. Because there may exist unresolved (or missing) values in this binarization process, we formulate the clustering of (binary) oligonucleotide fingerprints as a combinatorial optimization problem that attempts to identify clusters and resolve the missing values in the fingerprints simultaneously. We study the computational complexity of this clustering problem and a natural parameterized version, and present an efficient greedy algorithm based on MINIMUM CLIQUE PARTITION on graphs. The algorithm takes advantage of some unique properties of the graphs considered here, which allow us to efficiently find the maximum cliques as well as some special maximal cliques. Our experimental results on simulated and real data demonstrate that the algorithm runs faster and performs better than some popular hierarchical and graph-based clustering methods. The results on real data from DNA clone classification also suggest that this discrete approach is more accurate than clustering methods based on real intensity values, in terms of separating clones that have different characteristics with respect to the given oligonucleotide probes.

Algorithms↗

Therapeutic donor insemination: a prospective randomized study of scheduling methods.

OBJECTIVE: To compare basal body temperature (BBT) graphs and urinary luteinizing hormone (LH) monitoring in scheduling therapeutic donor insemination. DESIGN: Participants were prospectively randomized to the BBT or LH groups. SETTING: Participants were private patients of the Reproductive Endocrine Division at Washington University School of Medicine. PATIENTS: Inclusion criteria were designed to assure an isolated male factor. Seventy-four of 113 patients completed the study; 18 had ongoing treatment at the end of the study. INTERVENTIONS: Basal body temperature graphs were physician interpreted and appointments prospectively chosen. Luteinizing hormone patients monitored daily urine samples and scheduled an appointment the day after the detected surge. MAIN OUTCOME MEASURES: Fecundity rates, cumulative pregnancy rates, and cost per pregnancy were all prospectively evaluated. RESULTS: Life table analysis yielded a 6-month cumulative probability of pregnancy of 36.3% in the LH group and 65.1% in the BBT group (P less than 0.025). The total cost per pregnancy was lower in the BBT group (+6,212 versus +3,997; P less than 0.001). CONCLUSIONS: This randomized prospective study demonstrates significant therapeutic and economic advantages when therapeutic donor insemination is prospectively scheduled by BBT graphs.

Body Temperature↗

Visual inspection of single-subject data: an empirical analysis.

The ability of therapists and educators to reliably analyze data from single-subject designs using visual inspection of graphed data was investigated. Sixty-one examiners provided a rating of whether a significant change in performance occurred across the baseline and treatment phases of six graphs of hypothetical data. Results revealed considerable disagreement among the raters on four of them. Further analysis suggested that the visual characteristics of a change in variability or change in slope across the baseline and treatment phases were associated with the most disagreement. The advantages and limitations of visual analysis of graphed data were discussed and the argument made that additional information is needed on the process of visual inspection to ensure reliable interpretation of single-subject data.

Combined Modality Therapy↗

[Glucose-6-phosphate dehydrogenase activity as a marker of resolution in the separation of rabbit erythroblasts according to their stage of maturation].

The glucose 6 phosphate dehydrogenase (G6PD) activity of erythroblasts, separated at different advancing stages of development by the velocity sedimentation technique at unit gravity, shows a characteristic sigmoidal curve. The G6PD activity is high and constant in the dividing compartment, steeply declines between the polychromatic and the orthochromatic stage, and returns almost constant during the development from the orthochromatic to the reticulocyte stage. This report focuses on the possibility to use the G6PD activity curve to indicate a loss of resolution in the fractionation process. For this purpose two parameters of the graph were used: (h) which represents the distance between the two constant phases of the curve and (s) the slope of the decreasing part of the graph. In this view we have fractionated on a 400 ml linear gradient of sucrose (1%-2% in PBS), increasing amounts of bone marrow cells from anaemic rabbit. Suspensions of 100, 200, 350 and 700 millions of cells (25 ml in PBS) were separated in different experiments and the obtained G6PD activity curves were compared. We have seen that the two parameters h and s remained constant up to 200 millions of cells, while they declined markedly when the number of cells loaded on the gradient increased to 350 and 700 millions. The separated cells were grouped into three sets of fractions: fraction I with cells belonging to the high and constant phase of the graph, fraction II to the decreasing phase and fraction III to the low and constant activity phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Examining population structure through the use of surname matrices: methodology for visualizing nonrandom mating.

The analysis of nonrandom mating using the frequency of marital isonymy indirectly measures the degree of population structure. However, population structure is the result of all matings in a population. Difficulties with large surname matrices have resulted in data being summarized into a single statistic or collapsed into brief tables, with considerable loss of information. By using sophisticated computer graphing procedures and displays, it is possible to directly analyze the mating structure of a community. If P is a vector of proportions for each male surname i (i = 1, 2, 3, ..., n), Q a similar vector of female surnames j(j = 1, 2, 3, ...,m), then the expected frequency matrix E of each possible mating is P x Q. The difference D between the observed frequency matrix O and the expected matrix is O-E. The D matrix is graphed with the x axis containing the male surnames, the y axis the female surnames, and the z axis the difference values dij. Negative values represent negative nonrandom mating and positive values positive nonrandom mating. From 5417 marriages (1840-1963) in the Midlands of Tasmania, those between spouses having 1 of 194 core names were extracted. We analyze these marriages utilizing the new technique and examine the surface of the graph and statistical analysis of its finer structure. Among the results was the demonstration of frequency-dependent selection of surnames. This finding has significant implications for microevolution of human populations, as surnames have existed for possibly 700 years.

Computer Simulation↗

[Tissucol in septorhinoplasties].

There are two major indications for Tissucol: 1. Stabilization of structures separated by the operative procedure or of graphs, in particular cartilaginous, whether placed along the crest of the nose or at the level of the columella in sagittal position between the mesials, or frontal position under their lower edges. 2. The construction of grafts. a) Mixing of bone powder and Tissucol provides "laminated" graphs which, when placed laterally and below iliac bone grafts, avoid the grooves which all too often form along the edges of such grafts. b) Coherent moulding graphs can be obtained using Tissucol with crushed cartilage (from septum or auricular concha).

Aprotinin↗

Computer-aided pattern analysis of temperature differentials.

Chiropractic analysis often incorporates the evaluation of heat distribution patterns observed in skin temperature profiles. Historically, temperature recordings of the spine have been made with a heat detection instrument using a thermocouple design. The advent of refinements in infrared technology, however, have greatly enhanced temperature detection in terms of accuracy and reliability. The present research reflects the development of computer software designed to express the data obtained with a dual channel heat sensing instrument. Two phases are involved: a) digital information, received from the sensing instrument, is standardized, stored for future analysis, and retrieved for comparisons with other graphs; b) stored data is graphically displayed, statistically analyzed, and otherwise compared. The data is displayed for visual observation as a) temperature data received from either channel of the sensing instrument or b) relative temperature differences between data from both channels of the sending instrument. For statistical evaluation, corresponding readings (comparisons between graphs) are plotted against one another and analyzed by a moving Pearson Product Moment correlation and moving t-test. This evaluation is graphically represented with a numeric display of pertinent statistical values. Current work indicates that a 10 point moving correlation and t-test will yield accurate comparisons between graphs.

Algorithms↗

Interpretation of pathophysiology by laboratory data (2). Graphic display of data, dynamic pattern.

In order to display the pathophysiology of a patient more efficiently and adequately than in the static radar chart presented in the first report, a dynamic radar chart and serial line graphs using colored lines were presented. A dynamic radar chart prepared as described particularly in this report, shows the whole data of a patient along with the time course of illness by the space-saving "overlapped-drawing". Moreover serial line graphs are employed for items important for the understanding of a patient's pathophysiology or for items which show obscure change due to overlapping in the dynamic radar chart. Although this line graph is space-occupying it reveals more clearly the changes of data throughout the entire course of a patient's disease. In this second report the dynamic presentation of data and its interpretation, were presented for nine cases. This was done more efficiently and adequately than in the cases described in the first report where the display and interpretation of pathophysiology of a patient was made using merely the data of a single point.

Biometry↗

An equation for DNA electrophoretic mobility in agarose gels.

Assignment of molecular weight to DNA fragments on the basis of electrophoretic mobility in agarose gels is complicated by nonlinearity of the relationship between mobility and molecular weight. Graphical methods that linearize sigmoidal curves provide a simplified description of the mobility function when applied to normalized mobility data. This description is valid over a wide range of molecular weights. Linear duplex molecules of lengths ranging from 118 to 169,200 base pairs were electrophoresed at voltage gradients of 1 to 6 V/cm through horizontal slab gels ranging from 0.2 to 1.6% agarose. A logit transformation of the mobility graphed versus the logarithm of molecular weight, analogous to a Hill plot of enzyme kinetics, is a straight line. Changes in the voltage gradient or gel composition alter the position but not the slope or linearity of the data plotted by this method. The logistic representation is compared with the conventional graph of log molecular weight versus mobility, with the graph of molecular weight versus reciprocal mobility, and with Probit analysis of the mobility function. Parameters were determined for one equation that accurately describes DNA mobility as a function of the three tested variables. Curves are presented that are useful in predicting fragment length, migration, resolution, and gel performance.

DNA, Viral↗

[Vital capacity restitution curve: prognostic value in chronic decompensated respiratory insufficiency].

From a series of 50 patients with acute decompensation of chronic obstructive lung disease (38 of whom were treated by mechanical ventilation), the authors demonstrate the prognostic value of an easily obtained parameter of respiratory function: the vital capacity restitution curve (VCRC). From daily measurements of vital capacity, beginning on the day of admission, a graph is constructed which shows an initial period of increase in the degree of restitution, followed by stabilization of the values. An analysis of the various parameters embodied in this graph provides information about the prognosis. Such graphs can be divided into 3 zones of prognostic value: a favourable zone, an intermediate zone (mediocre survival with or without mechanical ventilation) and an unfavourable zone (death during the acute phase). Although a favourable prognosis can be made after 4 days of observation and almost always by the 10th day, an unfavourable prognosis cannot be made before the 21st day.

Aged↗

Screening term LGA neonates for hypoglycemia: the Colorado vs. the Portland Intrauterine Growth Chart.

It was postulated that identification of term (LGA) large for gestational age newborns by the Portland Intrauterine Growth Curve rather than the Colorado Curve would classify a lesser number of neonates as LGA, but would identify the LGA neonates at risk for hypoglycemia. One hundred inborn neonates who plotted LGA on the Colorado Chart were reviewed. Sixty-one infants were LGA on the Portland Chart. Of the 100 infants, 17 were found to have dextrostix less than 45 mg% in the first two hours of life, 15 of these had quantitative blood glucose (BG) test performed. Eleven of the 15 neonates had a BG less than 40 mg%; all 11 hypoglycemic neonates were identified LGA on the Colorado Graph whereas only seven were identified LGA by the Portland Graph. The authors conclude that the Colorado Graph is a better tool in their population than the Portland in identifying term LGA neonates at risk for hypoglycemia.

Embryonic and Fetal Development↗

Prediction of ovulation with basal body temperature.

Basal body temperature (BBT) is used extensively to monitor ovulation in the treatment of infertility. There are well-defined methods of interpreting the BBT graph retrospectively that identify a presumptive day of ovulation. The prediction of ovulation through utilization of the BBT graph (strictly concurrent interpretation) is adversely influenced by temperature fluctuation and cycle length variability. The BBT graph can be very useful when its interpretation is well defined and its limitations understood.

Body Temperature↗

Quantum chemical and other theoretical studies of carcinogens, their metabolic activation and attack on DNA constituents.

We have carried out a variety of different types of studies on carcinogens: ab-initio quantum chemical, including generation of electrostatic molecular potential contour (EMPC) maps and graph theoretical generation of polycyclic aromatic hydrocarbon (PAH) structures and characterization of the "carcinogenic" bay regions. Polycyclic aromatic hydrocarbon (PAH) carcinogens are activated metabolically from precarcinogen (PAH's) through proximate carcinogens (PAH epoxides and dihydrodiols) to ultimate carcinogens (PAH dihydrodiolepoxides) which then attack DNA constituents. We carried out ab-initio MODPOT/VRDDO/MERGE calculations on a variety of these molecules using our own ab-initio programs which incorporate as options a number of desirable options for ab-initio calculation on large molecules. From these electronic wave functions, we generated electrostatic molecular potential contour (EMPC) maps around these molecules. These EMPC maps indicated predictively the positions at which epoxides would form and the propensity and geometrical preference to form dihydrodiols and dihydrodiolepoxides. We performed spin and symmetry analyses for attack of O adding across C = C bonds or inserting in C-H or N-H bonds. We also carried out ab-initio calculations for attack of ultimate carcinogens on DNA constituents. Using graph theory we generated all possible structures for any arbitrary numbers of aromatic rings and also set up a graph theoretical characterization of the "carcinogenic" bay region. Most recently, we have incorporated this into a computer program for global prediction of toxicity.

Biotransformation↗

[Comparison of different nystagmus-parameters with the measured so-called maximal velocity of the slow phase in connexion with caloric vestibular examination (author's transl)].

The adequate stimulus of the semicircular canals by a rotatory acceleration is producing a nystagmus, whose graph of the postrotatorius I is adequate to a decreasing e-function. The constants of the function are calculabe, the variance is very small. The inadequate stimulus of the semicircular canals by caloric stimulation effects a nystagmus, which shows an intensive changing course of the graph with a large variance. Only smoothings and standardisations by counting of an individual coefficient of the reaction-intensity lead to a graph, which is nearly adequate to an increasing and decreasing e-function. The variance of the single nystagmus-parameters grows with its range of reaction. The velocity of the slow phase shows the largest variance. Each experimental arrangement, which enlarges the nystagmus-intensity, is enlarging the variance coincident. The experimental conditions are neither to form by illumination of the eyes nor by increasing of the mental activity in such a uniform way that the variance would be reduced. The valuation of the singular nystagmus-parameters for the clinic is only to confirm by the examination of otoneurologic syndroms.

Hot Temperature↗

Topological properties of the molecular electrostatic potential as a tool for prediction of biological activity.

The paper is an attempt to reveal a relation between the structure and biological activity. Topological properties of molecular electrostatic potentials were investigated. These properties are represented by tree graphs. Based on known experimental data concerning biological activity of a series of various compounds, a relation between the biological activity and the characteristics of the tree graph was searched for. Such a relation might be used to predict biological activity of compounds other than investigated. Characteristic graphs are presented enabling prediction of activity of compounds.

Electrochemistry↗

[Hemo- and lymphomicrocirculatory bed of the broad ligament of the uterus in the presence of collateral circulation].

Structural adaptation of the vascular bed in the broad ligament of the dog uterus has been studied at various time of the experimental phlebohypertension. Restitution of the circulation after the posterior vena cava occulsion occurs phasically. The venous collateralies are not formed at one time and it is connected with the venous pressure level in the inferiocaval system and with some changes in the construction of the microcirculatory bed. Basing on the morphometry data, a general equation has been derived which reflects dynamics of the microangiological parameters and demonstrates unidirectionness of the adaptive reactions in the vascular bed at the disturbed venous circulation. Using principles of the system-structural analysis and the mathematical graph theory, we consider the microcirculatory system of the broad ligament of the uterus as a graph-system and study the reorganization of the microcirculatory network at a venous congestion. Realization of the compensatory possibilities is reached in the microcirculatory bed by a changed relationships in the number of the intervascular connections. The latter are estimated according to the graph-schemes of the microvascular bed. Morphokinetics of the connections between the vessels is characterized by widening or narrowing the borders of the "adaptive norm" and by changing the microangioarchitectonics. At the same time, there is noted formation of specialized microhemoangioconstructions. Morphofunctional state of the lymphatic system is connected with reorganization of the angioarchitectonics. This is certain manifestation of the law of the lymphatic and blood beds "synergism". Thus, the structural changes of the vascular bed are aimed to support a certain hemodynamic level.

Animals↗

[Evaluation of the errors in analog recording of radionuclide dilution and clearance curves].

The mathematical expression for the function of changes in the output signal of the analog medium frequency pulse meter (MFPM), supplied on the input of the dilution curve (clearance) of a radioactive indicator, is obtained. The graphs illustrating the deformation of the initial curve at different MFPM time constants and different rates of the increase and decrease in the input signal, corresponding to the real conditions occurring in the study of the regional cerebral and muscular blood flow with the use of 133Xe clearance and the study of the blood flow volume through heart and large vessels with the use of RISA-131 dilution, are plotted. The errors introduced by the MFPM to the obtained data of the basic informative parameters--a period of half-dilution, the maximum value and the area under the curve are calculated. The graphs of the errors versus the MFPM time constants are normalized by the time units relative to the maximum of the corresponding initial curves thus enabling one to use the graphs as a versatile means in the course of assessment of the dilution and clearance curves' distortions introduced by the analogous MFPM. The analysis of the results obtained is presented.

Blood Volume Determination↗

An approach to completely automatic comparison of two-dimensional electrophoresis gels.

The problem addressed is that of determining the similarities and differences appearing in a sequence of two-dimensional polyacrylamide gels where we have no a priori knowledge of the intensity and spatial distribution of the protein spots. It is assumed that the gels are not in precise registration. An attempt is being made to develop a completely automatic program for use in genetic studies, which will compare a sequence of three gels run on samples from father, mother, and child. The program constructs a graph by using as nodes those spot cues that exceed a given intensity threshold. The graphs are then compared to determine an initial subset of spots that are common to all three gels. From this subset of common spots the program then determines whether the remaining graph differences are real or result from quantitative variation causing spots to fall below threshold.

Adult↗