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Myoglobin function reassessed.

The heart and those striated muscles that contract for long periods, having available almost limitless oxygen, operate in sustained steady states of low sarcoplasmic oxygen pressure that resist change in response to changing muscle work or oxygen supply. Most of the oxygen pressure drop from the erythrocyte to the mitochondrion occurs across the capillary wall. Within the sarcoplasm, myoglobin, a mobile carrier of oxygen, is developed in response to mitochondrial demand and augments the flow of oxygen to the mitochondria. Myoglobin-facilitated oxygen diffusion, perhaps by virtue of reduction of dimensionality of diffusion from three dimensions towards two dimensions in the narrow spaces available between mitochondria, is rapid relative to other parameters of cell respiration. Consequently, intracellular gradients of oxygen pressure are shallow, and sarcoplasmic oxygen pressure is nearly the same everywhere. Sarcoplasmic oxygen pressure, buffered near 0.33 kPa (2.5 torr; equivalent to approximately 4 micro mol l(-1) oxygen) by equilibrium with myoglobin, falls close to the operational K(m) of cytochrome oxidase for oxygen, and any small increment in sarcoplasmic oxygen pressure will be countered by increased oxygen utilization. The concentration of nitric oxide within the myocyte results from a balance of endogenous synthesis and removal by oxymyoglobin-catalyzed dioxygenation to the innocuous nitrate. Oxymyoglobin, by controlling sarcoplasmic nitric oxide concentration, helps assure the steady state in which inflow of oxygen into the myocyte equals the rate of oxygen consumption.

Animals↗

Mandible analysis of NOD and NON strains of mice.

10 inbred strains of mice including NOD and NON were identified by discriminant and canonical discriminant analysis of the mandible measurements. The number of erroneous discriminations was 0.5% (1/199) for the females and 0% for males (0/232). In canonical discriminant analysis (discriminant analysis with reduction of dimensionality), NOD and NON inbred strains were separately located on 2-dimensional planes, Z1-Z2, Z1-Z3, and Z2-Z3. These results clearly indicate that the genetic constitution of NOD and NON differs, although they have been established from a common ancestor ICR mouse. Causes of divergence between NOD and NON mice are discussed.

Analysis of Variance↗

Pattern recognition methods in evaluation of the structure of the laboratory data biominerals, antioxidant enzymes, selected biochemical parameters, and pulmonary function of welders.

A wide set of biochemical and spirometrical parameters was applied to a group of 41 welders. The obtained parameters were analyzed by the pattern recognition method: principal-components analysis (PCA) and mutual contribution analysis (MCA). The aim of the investigation was to find out which of 23 parameters had an influence on the pulmonological indices of COPD. It was found that PCA gave a substantial reduction of dimensionality. The most relevant parameters were Fe, Zn, Cu (all elements in blood, not in hair), FEV1, MEF50, bilirubin, TAS, and SOD. Only the relationships of MEF50, Cu, and TAS were statistically valid.

Adult↗

Spatio-temporal autoregressive models defined over brain manifolds.

Multivariate Autoregressive time series models (MAR) are an increasingly used tool for exploring functional connectivity in Neuroimaging. They provide the framework for analyzing the Granger Causality of a given brain region on others. In this article, we shall limit our attention to linear MAR models, in which a set of matrices of autoregressive coefficients Ak (k = 1,...,p) describe the dependence of present values of the image on lagged values of its past. Methods for estimating the Ak and determining which elements that are zero are well-known and are the basis for directed measures of influence. However, to date, MAR models are limited in the number of time series they can handle, forcing the a priori selection of a (small) number of voxels or regions of interest for analysis. This ignores the full spatio-temporal nature of functional brain data which are, in fact, collections of time series sampled over an underlying continuous spatial manifold the brain. A fully spatio-temporal MAR model (ST-MAR) is developed within the framework of functional data analysis. For spatial data, each row of a matrix Ak is the influence field of a given voxel. A Bayesian ST-MAR model is specified in which the influence fields for all voxels are required to vary smoothly over space. This requirement is enforced by penalizing the spatial roughness of the influence fields. This roughness is calculated with a discrete version of the spatial Laplacian operator. A massive reduction in dimensionality of computations is achieved via the singular value decomposition, making an interactive exploration of the model feasible. Use of the model is illustrated with an fMRI time series that was gathered concurrently with EEG in order to analyze the origin of resting brain rhythms.

Bayes Theorem↗

[Discriminant analysis of hematological and serum biochemical values in cynomolgus monkey (Macaca fascicularis) bred and reared under the indoor individually-caged conditions].

The data on hematological and serum biochemical properties of laboratory-bred cynomolgus monkeys (Macaca fascicularis) at different ages were analyzed by discriminant analysis. All the animals had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N.I.H., Japan. The items used were as follows: red blood cell count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), mean corpuscular volume (MCV), white blood cell count (WBC), glutamic oxaloacetic transaminase activity (GOT), glutamic pyruvic transaminase activity (GPT), total protein concentration (TP), albumin concentration (ALB), albumin-globulin ratio (A/G), blood urea nitrogen (BUN), glucose concentration (GLU), total cholesterol concentration (TCHO), free cholesterol concentration (FCHO), triglyceride concentration (TG) and alkaline phosphatase activity (ALP). In total, 1086 animals in 10 age groups were examined. Data analyses were done with respect to the difference of sex. Discrimination was possible by Mahalanobis' generalized distance between centroids of groups. In canonical discriminant analysis (discriminant analysis with reduction of dimensionality), age was highly correlated to the value of the first canonical variate. From the approximate relative value of the eigenvector of the first canonical variate, the most discriminant variables are WBC, TP, ALB, A/G, TCHO, FCHO, TG, and ALP. It can be concluded that periodic measurement of these 8 parameters is necessary and sufficient to monitor the physiological conditions of growing monkeys.

Age Factors↗

[Multivariate analysis of hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis) aged less than a year].

Hematological and serum biochemical data obtained from 91 laboratory-bred cynomolgus monkeys (Macaca fascicularis) aged 11 to 362 days were analyzed by the discriminant analysis. All animals used had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. The examination items were as follows: red blood cell count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), mean corpuscular volume (MCV), white blood cell count (WBC), glutamic oxaloacetic transaminase activity (GOT), glutamic pyruvic transaminase activity (GPT), total protein concentration (TP), albumin concentration (ALB), albumin-globulin ratio (A/G), blood urea nitrogen (BUN), glucose concentration (GLU), total cholesterol concentration (TCHO), free cholesterol concentration (FCHO), triglyceride concentration (TG), alkaline phosphatase activity (ALP) and calcium concentration (Ca). The animals were divided into four groups (A: Suckling infants, less than 176 days old. B, C, D: Weanlings and juveniles, 121 to 220 days old, 221 to 280 days old, and 281 to 362 days old, respectively). Discrimination was possible among these four groups on the basis of the Mahalanobis' generalized distance. Regarding the canonical discriminant analysis (discriminant analysis with reduction of dimensionality), discrimination was possible. The suckling infant group could be discriminated from the juvenile groups by the first canonical variate. Concerning the juvenile groups, age was highly correlated to the value of the second canonical variate.2+ Judging from an approximate relative eigenvector value for the second canonical variate, the effective discriminant variables were WBC, TP, ALB, A/G, FCHO, TG, and ALP. It can be concluded that these eight parameters are important and useful for monitoring the physiologicals conditions of growing juvenile monkeys.

Aging↗

[Discriminant analyses for pregnancy-related changes in hematological and serum biochemical values in cynomolgus monkeys (Macaca fascicularis)].

Hematological and serum biochemical data obtained from 45 non-pregnant and 142 pregnant cynomolgus monkeys (Macaca fascicularis) were analyzed by discriminant analyses. All animals used had been reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. The examination items were as follows: red blood cell count(RBC), hematocrit value(Ht), hemoglobin concentration(Hb), mean corpuscular volume(MCV), white blood cell count(WBC), total protein (TP), albumin (ALB), glucose (GLU), total cholesterol (TCHO), free cholesterol (FCHO), triglyceride (TG), and albumin-globulin ratio (A/G). The pregnant animals were divided into four groups according to their gestation ages (Group I: 1-40 days; II: 41-80 days; III: 81-120 days; and IV: more than 121 days). During pregnancy period (Groups II, III and IV), significant decrease of TP, ALB, TCHO, FCHO and TG was observed. RBC, Ht and Hb decreased in the last of the four periods of pregnancy (Group IV). Discrimination was possible between each of these four pregnant groups and the non-pregnant group on the basis of the Mahalanobis' generalized distance. To clarify the relationship among groups, canonical discriminant analysis (discriminant analysis with reduction of dimensionality) was carried out. As a result, the non-pregnant group and the pregnant I group could be clearly discriminated from the other pregnant groups (II, III, and IV) by the first canonical variate. Judging from the relative eigenvector value of each variable for the first canonical variate, the effective discriminant variables were RBC, Ht, Hb, MCV, TP and A/G.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

[Canonical discriminant analysis for pregnancy-related changes in hematological and serum biochemical values in tamarins (Saguinus spp].

Hematological and biochemical values obtained from 9 monkeys (Saguinus labiatus and S. mistax) during pre- and postpartum periods were analyzed by canonical discriminant analysis (discriminant analysis with reduction of dimensionality). All animals used were of wild origin and had been maintained under uniform environmental conditions at N. I. H., Japan. The items examined were as follows: white blood cell count (WBC), red blood cell count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), total protein concentration (TP), blood urea nitrogen (BUN), albumin concentration (ALB), albumin-globulin ratio (A/G), glutamic oxaloacetic transaminase activity (GGT), glutamic pyruvic transaminase activity (GPT), alkaline phosphatase activity (ALP) and total cholesterol concentration (CHO). The data obtained in the pre- and postpartum periods were divided into six chronological groups. The prepartum period was divided into Group I: weeks 15-10; Group II: weeks 9-7; Group III: weeks 6-4; and Group IV: weeks 3-0. The postpartum period was divided into Group V: weeks 0-4 and Group VI: weeks 5-7). In the later pregnancy period (Groups III and IV), significant decreases in RBC, Ht, Hb, TP and ALB, and a significant increase in CHO were observed. These values in the blood and serum continued after delivery (Groups V and VI). Results of canonical discriminant analysis showed that the value of the first canonical variate decreased according to the progress of pregnancy. The postpartum groups showed negative values. Although groups in the early

Analysis of Variance↗

[A comparison of hematological and serum biochemical values between two groups of female cynomolgus monkeys reared under different conditions].

The influence of long term rearing conditions on the hematological and serum biochemical values in laboratory-bred female cynomolgus monkeys (Macaca fascicularis) was studied under the following two conditions. Group A: New born infants were nursed by their mothers for at least 12 weeks after birth. After weaning, four monkeys of approximately equal age and body weight were kept in a relatively small cage (90 cm W x 60 cm D x 60 cm H) and reared to five years of age. These rearing conditions are commonly used in the breeding program of our primate center. Group B: One male and five females of wild origin were introduced into a relatively large cage (180 cm W x 180 cm D x 160 cm H). Female monkeys born in these cages were used in this study. All of them were reared by their own mothers and grew well in these cages. Male monkeys born in these cages were removed at about 3.5 years of age. Hematological and serum biochemical values between the two groups in each age class were compared and analyzed by the canonical discriminant analysis (the discriminant analysis with reduction of dimensionality). Age correlated highly with the value of the first canonical variate. The second canonical variate detected a difference in the blood hematology and biochemistry probably induced by the difference in rearing conditions.

Age Factors↗

[Canonical discriminant analysis for hematological and serum biochemical changes during pregnancy period in squirrel monkeys (Saimiri sciurea)].

Hematological and serum biochemical data obtained from non-pregnant, pregnant and post-partum squirrel monkeys (Saimiri sciurea) were analyzed by canonical discriminant analysis (discriminant analysis with reduction of dimensionality). All animals were of wild origin and had been maintained under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N.I.H., Japan. Months were standardized by the day of parturition. The calculated arithmetic means and standard deviations were listed for each item of measurement performed. Items detected statistically significant difference (p less than 0.01) between months were as follows: red blood cell count (RBC), mean corpuscular volume (MCV), hematocrit value (Ht), hemoglobin concentration (Hb), white blood cell count (WBC), albumin concentration (ALB), blood urea nitrogen concentration (BUN), total cholesterol concentration (T-CHO), triglyceride concentration (TG), alkaline phosphatase activity (ALP) and calcium concentration (Ca). Results of canonical discriminant analysis showed that the value of the first canonical variate (Z1) decreased from the early period of pregnancy to the middle period, and that the second canonical variate (Z2) decreased from the middle period of pregnancy to the end of pregnancy. The meaning of their changes were discussed.

Alkaline Phosphatase↗

Studies on multiple trait and random regression models for genetic evaluation of beef cattle for growth.

A simulation study examined issues important for genetic evaluation of growth in beef cattle by random regression models with cubic Legendre polynomials (RRML) and linear splines with three knots (RRMS) compared with multiple-trait models (MTM). Parameters for RRML were obtained by conversion from covariance functions. Parameters for MTM and RRMS were extracted from RRML at 1, 205, and 365 d; parameters for RRMS were the same as MTM for all effects except the permanent environment and the residual. Four data sets were generated assuming RRML included records at 1, 205, and 365 d; at 1, 160 to 250, and 320 to 410 d; at 1, 100, 205, 300, and 365 d; and at 1, 55 to 145, 160 to 250, 275 to 325, and 320 to 410 d. Accuracies were computed as correlations between the true (simulated) and predicted breeding values. With the first data set, excellent agreement in accuracy was obtained for all models. With the second data set, the accuracy of MTM dropped by up to 1.5% compared with the first data set, but accuracy was unchanged for both RRML and RRMS. With the third (fourth) data set, accuracies of RRML were up to 2.4% (2.5%) higher than with the first (second) data set. Small differences in accuracy between RRML and RRMS were found with the third and fourth data sets, which were traced to inflated correlations especially between 1 and 205 d in RRMS; inflation could be decreased by adding one extra knot at 100 d to RRMS. Diagonalization of random coefficients was crucial for RRML but not for RRMS, resulting in approximately six (two) times faster convergence with RRML (RRMS). Reduction of dimensionality in RRML associated with small eigenvalues caused a less accurate evaluation for birth weight. Genetic evaluation of growth by RRM requires careful implementation. The RRMS is simpler to implement than the RRML.

Age Factors↗

Multihost, multiparasite systems: an application of bifurcation theory.

The local analysis of multihost multiparasite models has been hampered by algebraic intractability. There have been two responses to this difficulty: extensive numerical investigation, and simplification to a level where analytical techniques work. In this paper we describe another approach, based on bifurcation theory, in which the qualitative properties of the model equilibrium structure are realized on an array of maps drawn in parameter space. This approach is described in the context of two models: the basic two-host shared microparasite S-I model and the single-host two-microparasite S-I (susceptible-infective) model. The procedure involved does not require model simplification through a reduction in dimensionality. It can handle intraspecific as well as parasite-mediated competition and, in the second model, single-host parasite coexistence. The map arrays provide a concise catalogue of the possible modes of behaviour of a system and an explanation for changes in that behaviour. In particular, the reasons why the conjectures made about the behaviour of the first of these models do not hold throughout parameter space are immediately clear from the map structure, as are the conditions for collusive and competitive behaviour between the two types of parasite in the second model.

Animals↗

Genetic relationships among 5 inbred strains established from common ancestor, dd mouse, as assessed by mandible analysis.

By multivariate analysis using mandible measurements genetic relationships were investigated among 5 inbred strains, DDD, DDK, DSD, DD/Tbr and DDY, derived from the common ancestor, dd mouse. (1) In canonical discriminant analysis (discriminant analysis with reduction of dimensionality), 3 DD strains, DDD, DSD, and DDY, were closer to one another than to any control strain on planes Z1-Z2, Z1-Z3, and Z2-Z3. Only the DDK strain was quite far from those 3 strains. (2) In the discriminant analysis, however, the 5 inbred strains could be classified correctly at the rate of 100%. They were genetically different from one another. (3) The causes for this genetical difference seemed to be the genetic heterogeneity of the ancestor dd mouse and the method of inbreeding which had been independent since the separation.

Analysis of Variance↗

Genetic relationships between sublines of inbred strains of mice as assessed by mandible analysis.

Genetic relationships between sublines of inbred strains of mice were investigated by using mandible measurements. (1) Canonical discriminant analysis (discriminant analysis with reduction of dimensionality) was applied to the investigation of genetic relationships between sublines on two kinds of dimensionality. As a result, it was made clear that all the sublines of the same strains mapped closer to each other than they were to other strains on the plane of z1--z2, except the sublines of strain AA. (2) According to the result of discriminant analysis, misclassification among the sublines of the other strains was only 0 head/302 head, or 0%, for the male mice and 6 head/302 head, or 1.99%, for the female mice. Misidentification between the sublines of the same strain was also of low rate; that is, 28/302, or 9.27%, or the males and 9/302, or 2.98%, for the females. These results suggested that the mice of the sublines of the same strain might be genetically different from one another. (3) The cause for the occurrence of such subline divergence as this seemed to be mainly due to the spontaneous mutation of each colony after the separation of mice. It appeared that the subline divergence of strain AA might be due to the genetic heterozygosity of an original stock before the separation of mice.

Animals↗

The use of Markovian metapopulation models: a comparison of three methods reducing the dimensionality of transition matrices.

The use of Markovian models is an established way for deriving the complete distribution of the size of a population and the probability of extinction. However, computationally impractical transition matrices frequently result if this mathematical approach is applied to natural populations. Binning, or aggregating population sizes, has been used to permit a reduction in the dimensionality of matrices. Here, we present three deterministic binning methods and study the errors due to binning for a metapopulation model. Our results indicate that estimation errors of the investigated methods are not consistent and one cannot make generalizations about the quality of a method. For some compared output variables of populations studied, binning methods that caused a strong reduction in dimensionality of matrices resulted in better estimations than methods that produced a weaker reduction. The main problem with deterministic binning methods is that they do not properly take into account the stochastic population process itself. Straightforward usage of binning methods may lead to substantial errors in population-dynamical predictions.

Markov Chains↗

Intensity-modulated radiotherapy in patients with locally advanced rectal cancer reduces volume of bowel treated to high dose levels.

PURPOSE: To investigate the potential for intensity-modulated radiotherapy (IMRT) to spare the bowel in rectal tumors. METHODS AND MATERIALS: The targets (pelvic nodal and rectal volumes), bowel, and bladder were outlined in 5 patients. All had conventional, three-dimensional conformal RT and forward-planned multisegment three-field IMRT plans compared with inverse-planned simultaneous integrated boost nine-field equally spaced IMRT plans. Equally spaced seven-field and five-field and five-field, customized, segmented IMRT plans were also evaluated. RESULTS: Ninety-five percent of the prescribed dose covered at least 95% of both planning target volumes using all but the conventional plan (mean primary and pelvic planning target volume receiving 95% of the prescribed dose was 32.8 +/- 13.7 Gy and 23.7 +/- 4.87 Gy, respectively), reflecting a significant lack of coverage. The three-field forward planned IMRT plans reduced the volume of bowel irradiated to 45 Gy and 50 Gy by 26% +/- 16% and 42% +/- 27% compared with three-dimensional conformal RT. Additional reductions to 69 +/- 51 cm(3) to 45 Gy and 20 +/- 21 cm(3) to 50 Gy were obtained with the nine-field equally spaced IMRT plans-64% +/- 11% and 64% +/- 20% reductions compared with three-dimensional conformal RT. Reducing the number of beams and customizing the angles for the five-field equally spaced IMRT plan did not significantly reduce bowel sparing. CONCLUSION: The bowel volume irradiated to 45 Gy and 50 Gy was significantly reduced with IMRT, which could potentially lead to less bowel toxicity. Reducing the number of beams did not reduce bowel sparing and the five-field customized segmented IMRT plan is a reasonable technique to be tested in clinical trials.

Humans↗

[A model of color vision in trichromats and protans].

A model which explains the human vision protanopic deficiency and its biologic prototype with the absence of red-absorbing pigment (rabbit) was constructed from neuron-like elements. In behavioral experiments and by means of evoked potential technique it was shown that the rabbit's color space is characterized by a spherical four-dimensional with a reduction of red-coding area. Similar spherical four-dimensional structure of color space is characteristic for a group of protanopic human subjects. The perceptive space of another group of protanopic subjects (protanomals) is characterized by a reduction of both parts of the red-green opponent axis. These disorders are reproduced in the model either by a loss of some color-coding elements (the absence of the red-absorbing pigment as in protanops) or a shift of the spectral characteristics of the red pigment towards those of the green one (protanomals).

Animals↗