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PubMed2003

Comparison of tree-based methods for prognostic stratification of survival data.

Tree-based methods can be used to generate rules for prognostic classification of patients that are expressed as logical combinations of covariate values. Several splitting algorithms have been proposed for generating trees from survival data. However, the choice of an appropriate algorithm is difficult and may also depend on clinical considerations. By means of a prognostic study of patients with gallbladder stones and of a simulation study, we compare the following splitting algorithms: log-rank statistic adjusted for measurement scale with (AP) and without (AU) pruning, exponential log-likelihood loss (EP), Kaplan-Meier (KP) distance of survival curves, unadjusted log-rank statistic (LP), martingale residuals (MP), and node impurity (ZP). With the exception of the AU algorithm (based on a Bonferroni-adjusted p-value driven stopping rule), trees are pruned using the measure of split-complexity, and optimally-sized trees are selected using cross-validation. The integrated Brier score is used for the evaluation of predictive models. According to the results of our simulation study and of the clinical example, we conclude that the AU, AP, EP, and LP algorithm may yield superior predictive accuracy. The choice among these four algorithms may be based on the required parsimonity and on medical considerations.

Algorithms↗
PubMed2003

Gene tree parsimony vs uninode coding for phylogenetic reconstruction.

have suggested that there are important weaknesses of gene tree parsimony in reconstructing phylogeny in the face of gene duplication, weaknesses that are addressed by method of uninode coding. Here, we discuss Simmons and Freudenstein's criticisms and suggest a number of reasons why gene tree parsimony is preferable to uninode coding. During this discussion we introduce a number of recent developments of gene tree parsimony methods overlooked by Simmons and Freudenstein. Finally, we present a re-analysis of data from that produces a more reasonable phylogeny than that found by Simmons and Freudenstein, suggesting that gene tree parsimony outperforms uninode coding, at least on these data.

Algorithms↗
PubMed1999

Building large trees by combining phylogenetic information: a complete phylogeny of the extant Carnivora (Mammalia).

One way to build larger, more comprehensive phylogenies is to combine the vast amount of phylogenetic information already available. We review the two main strategies for accomplishing this (combining raw data versus combining trees), but employ a relatively new variant of the latter: supertree construction. The utility of one supertree technique, matrix representation using parsimony analysis (MRP), is demonstrated by deriving a complete phylogeny for all 271 extant species of the Carnivora from 177 literature sources. Beyond providing a 'consensus' estimate of carnivore phylogeny, the tree also indicates taxa for which the relationships remain controversial (e.g. the red panda; within canids, felids, and hyaenids) or have not been studied in any great detail (e.g. herpestids, viverrids, and intrageneric relationships in the procyonids). Times of divergence throughout the tree were also estimated from 74 literature sources based on both fossil and molecular data. We use the phylogeny to show that some lineages within the Mustelinae and Canidae contain significantly more species than expected for their age, illustrating the tree's utility for studies of macroevolution. It will also provide a useful foundation for comparative and conservational studies involving the carnivores.

Animals↗
PubMed1991

Rod bipolar cells in the cone-dominated retina of the tree shrew Tupaia belangeri.

The tree shrew has a cone-dominated retina with a rod proportion of 5%, in contrast to the common mammalian pattern of rod-dominated retinae. As a first step to elucidate the rod pathway in the tree shrew retina, we have demonstrated the presence of rod bipolar cells and studied their morphology and distribution by light and electron microscopy. Rod bipolar cells were labeled with an antiserum against the protein kinase C (PKC), a phosphorylating enzyme. Intense PKC immunoreactivity was found in perikarya, axons, and dendrites of rod bipolar cells. The cell bodies are located in the sclerad part of the inner nuclear layer, the dendrites ascend to the outer plexiform layer where they are postsynaptic to rod spherules, and an axon descends towards the inner plexiform layer (IPL). The axons branch, and terminate in the vitread third of the IPL where mammalian rod bipolar cells are known to terminate. Two amacrine cell processes are always seen as the postsynaptic elements (dyads). Dendritic and axonal arbors of rod bipolar cells are rather large, up to 100 microns in diameter. The topographical distribution of the rod bipolar cells was analyzed quantitatively in tangential sections. Their density ranges from 300 cells/mm2 in peripheral retina to 900 cells/mm2 more centrally. The distribution is rather flat with no local extremes. Consistent with the low rod proportion in tree shrew, the rod bipolar cell density is low compared to the rod-dominated cat retina for example (36,000-47,000 rod bipolar cells/mm2). Rod-to-rod bipolar cell ratios in the tree shrew retina range from smaller than 1 to about 7, and thus are also lower than in cat.

Animals↗
PubMedDate not supplied

Subdivisions of the visual system labeled with the Cat-301 antibody in tree shrews.

The monoclonal antibody Cat-301 was used to stain neurons and neuropil in the visual thalamus and cortex of tree shrews--small, highly visual mammals that are closely related to primates. Previously, this antibody has been found to label neurons associated with the Y-cell stream of processing in cats and the magnocellular or M-cell stream in macaque monkeys. In tree shrews, the antibody selectively labeled layers 1, 2, 4, and 5 of the dorsal lateral geniculate nucleus, layers that are likely to contain neurons previously classified as Y-cells. Of the two layers that contain W-cells, layer 3 was unlabeled and layer 6 was lightly labeled. In area 17, layer 3c was densely stained, as in cats and macaque monkeys. The external half of layer 5 was also densely stained, in contrast to cats where the internal half of layer 5 is stained and macaques where layer 5 is sparsely stained. Area 18 was characterized by dense, uniform staining of inner layer 3 and outer layer 5, but no pattern of alternating light and dense bands crossed the width of area 18 as in macaques. Dense labeling of these same sublayers occurred in cortical areas TA and TD just lateral to area 18. Area TD may be the homologue of area MT of primates, which also stains densely with Cat-301 in macaques. These results indicate that Cat-301 differentially labels layers and areas in the visual system of tree shrews, and raise intriguing issues of comparison among tree shrews, primates, and cats.

Animals↗
PubMedDate not supplied

Classification tree models for the prediction of blood-brain barrier passage of drugs.

The use of classification trees for modeling and predicting the passage of molecules through the blood-brain barrier was evaluated. The models were built and evaluated using a data set of 147 molecules extracted from the literature. In the first step, single classification trees were built and evaluated for their predictive abilities. In the second step, attempts were made to improve the predictive abilities using a set of 150 classification trees in a boosting approach. Two boosting algorithms, discrete and real adaptive boosting, were used and compared. High-predictive classification trees were obtained for the data set used, and the models could be improved with boosting. In the context of this research, discrete adaptive boosting gives slightly better results than real adaptive boosting.

Blood-Brain Barrier↗
PubMed2003

Reconstructing tritium exposure using tree rings at Lawrence Berkeley National Laboratory, California.

Annual tritium exposures were reconstructed using tree cores from Pinus jeffreyi and Eucalyptus globulus near a tritiated water vapor release stack. Both tritium (3H) and carbon-14 (14C) from the wood were measured from milligram samples using accelerator mass spectrometry. Because the annual nature of the eucalyptus tree rings was in doubt, 14C measurements provided growth rates used to estimate the age for 3H determinations. A 30-yr comparison of organically bound tritium (OBT) levels to reported 3H release data is achieved using OBT measurements from three trees nearthe stack. The annual average 3H, determined from atmospheric water vapor monitoring stations, is comparable to the OBT in proximal trees. For situations without adequate historical monitoring data, this measurement-based historical assessment provides the only independent means of assessing exposure as compared to fate and transport models that require prior knowledge of environmental conditions and 3H discharge patterns.

Environmental Exposure↗
PubMed2006

Structure-taste relationships for disubstituted phenylsulfamate tastants using classification and regression tree (CART) analysis.

Forty-two new disubstituted phenylsulfamates have been synthesized, and 30 of these have been combined with 40 already available from earlier work to create a training database of 70 compounds. On the basis of panel taste data these were divided into three categories, N (nonsweet), N/S (nonsweet/sweet), and (S) sweet, and a "sweetness value" or weighting was also calculated for each compound. Using these 70 compounds as a training set and a series of nine predictors derived from Corey-Pauling-Koltun (CPK) models, calculated from the PC SPARTAN PRO program and Hammett sigma values taken from the literature, a classification and regression tree analysis (CART) was carried out leading to a regression tree that correctly classified 62 of the 70 compounds (89% overall correct classification). The tree's predictive ability varies for the different taste categories, and for nonsweet compounds it is virtually 100%; for nonsweet/sweet compounds it is 66%, and for sweet compounds it is approximately 75%. This tree correctly predicted taste categories for 10 compounds from a test set of 12 randomly selected from among the 42 new compounds (83% correct classification). Therefore, it can be used with a good degree of confidence to predict the tastes of disubstituted phenylsulfamates. For the design of new sweeteners, appropriate values or ranges of the descriptors are derived.

Cyclamates↗
PubMed1999

Total system performance assessment for waste disposal using a logic tree approach.

The Electric Power Research Institute (EPRI) has sponsored the development of a model to assess the long-term, overall "performance" of the candidate spent fuel and high-level radioactive waste (HLW) disposal facility at Yucca Mountain, Nevada. The model simulates the processes that lead to HLW container corrosion, HLW mobilization from the spent fuel, and transport by groundwater, and contaminated groundwater usage by future hypothetical individuals leading to radiation doses to those individuals. The model must incorporate a multitude of complex, coupled processes across a variety of technical disciplines. Furthermore, because of the very long time frames involved in the modeling effort (>> 10(4) years), the relative lack of directly applicable data, and many uncertainties and variabilities in those data, a probabilistic approach to model development was necessary. The developers of the model chose a logic tree approach to represent uncertainties in both conceptual models and model parameter values. The developers felt the logic tree approach was the most appropriate. This paper discusses the value and use of logic trees applied to assessing the uncertainties in HLW disposal, the components of the model, and a few of the results of that model. The paper concludes with a comparison of logic trees and Monte Carlo approaches.

Geological Phenomena↗
PubMed2002

Stochastic trees and the StoTree modeling environment: models and software for medical decision analysis.

In this paper we present a review of stochastic trees, a convenient modeling approach for medical treatment decision analyses. Stochastic trees are a generalization of decision trees that incorporate useful features from continuous-time Markov chains. We also discuss StoTree, a freely available software tool for the formulation and solution of stochastic trees, implemented in the Excel spreadsheet environment.

Decision Support Systems, Clinical↗
PubMed2003

Antioxidants in the midgut fluids of a tannin-tolerant and a tannin-sensitive caterpillar: effects of seasonal changes in tree leaves.

The seasonal decline in foliar nutritional quality in deciduous trees also effects the availability of essential micronutrients, such as ascorbate and alpha-tocopherol, to herbivorous insects. This study first examined whether there are consistent patterns of seasonal change in antioxidant concentrations in deciduous tree leaves. Alpha-tocopherol concentrations increased substantially through time in late summer in sugar maple (Acer saccharum), red oak (Quercus rubra), and trembling aspen (Populus tremuloides). However, seasonal change in the concentrations of other antioxidants differed between each species: P. tremuloides had higher levels of ascorbate and glutathione in the spring, Q. rubra had higher levels of glutathione but lower levels of ascorbate in the spring, and A. saccharum had lower levels of both ascorbate and glutathione in the spring. To test the hypothesis that tannin-tolerant caterpillars maintain higher concentrations of antioxidants in their midgut fluids than do tannin-sensitive species, we measured antioxidants in Orgyia leucostigma (a spring- and summer-feeding, tannin-tolerant species) and Malacosoma disstria (a spring-feeding, tannin-sensitive species) that were fed tree leaves in the spring and summer. The midgut fluids of O. leucostigma larvae generally had higher concentrations of antioxidants in the summer than did those of M. disstria, and were significantly higher overall. The results of this study are consistent with the hypothesis that higher concentrations of antioxidants form an important component of the defenses of herbivores that feed on mature, phenol-rich tree leaves. Some limitations of the interpretation of total antioxidant capacity are also discussed.

Acer↗
PubMed1997

Beta-adrenoceptors in the tree shrew brain. I. Distribution and characterization of [125I]iodocyanopindolol binding sites.

1. The number and distribution pattern of beta-adrenergic receptors in the brain have been reported to be species specific. The aim of the present study was to describe binding of the beta-adrenoceptor ligand [125I]iodocyanopindolol in the brain of the tree shrew (Tupaia belangeri), a species which provides an appropriate model for studies of psychosocial stress and its consequences on central nervous processes. 2. 125I-Iodocyanopindolol (125ICYP) labeling revealed a high degree of nonspecific binding, which was due mainly to interactions of this ligand with serotonin binding sites. For a quantitative evaluation of beta 1- and beta 2-adrenoceptors, serotonin binding sites had to be blocked by 100 microM 5HT. 3. Binding of the radioligand to beta 1- and beta 2-adrenoceptors was characterized using the beta 1-specific antagonist CGP20712A and the beta 2-specific antagonist ICI118.551. beta 1-adrenoceptor binding is present in the whole brain, revealing low receptor numbers in most brain regions (up to 1.5 to 2.7 fmol/mg). A slight enrichment was observed in cortical areas (lateral orbital cortex: 4.0 +/- 0.7 fmol/mg) and in the cerebellar molecular layer (8.7 +/- 1.0 fmol/mg). 4. Competition experiments demonstrated high- and low-affinity binding sites with considerable variations in Ki values for CGP20712A, showing that various affinity states of beta 1-adrenoceptors are present in the brain (Ki: 0.61 nM to 67.1 microM). In the hippocampus, only low-affinity beta 1-adrenoceptors were detected (Ki: 1.3 +/- 0.2 microM). Since it is known that 125ICYP labels not only membrane bound but also internalized beta-adrenoceptors, it can be assumed that the large population of the low-affinity sites represents internalized receptors which may be abundant due to a high sequestration rate. 5. High numbers of beta 2-adrenoceptors are present in only a few brain structures of tree shrews (external layer of the olfactory bulb, 15.8 +/- 2.0 fmol/mg; claustrum, 19.3 +/- 1.5 fmol/mg; anteroventral thalamic nucleus, 19.4 +/- 1.5 fmol/mg; cerebellar molecular layer, 55.0 +/- 4.3 fmol/mg). Also for this class of beta-adrenoceptors, high- and low-affinity binding sites for the beta 2-selective antagonist ICI118.551 were observed, indicating that 125ICYP labels membrane bound and internalized beta 2-adrenoceptors. Only in the cerebellar molecular layer was a high percentage of high-affinity beta 2-adrenoceptors detected (Ki for ICI118.551 was 1.8 +/- 0.3 nM for 90% of the receptors). 6. In conclusion, beta 1- and beta 2-adrenoceptor binding can be localized and quantified by in vitro receptor autoradiography in the brains of tree shrews when serotonergic binding sites are blocked. Modulatory effects of long-term psychosocial conflict on the central nervous beta-adrenoceptor system in male tree shrews are described in the following paper.

Adrenergic beta-Antagonists↗
PubMed2004

A simple geometrical pattern for the branching distribution of the bronchial tree, useful to estimate optimality departures.

The design of the bronchial tree has largely been proposed as a model of optimal design from a physical-functional perspective. However, the distributive function of the airway may be more related to a geometrical than a physical problem. The bronchial tree must distribute a three dimensional volume of inspired air on a two dimensional alveolar surface, included in a limited volume. It is thus valid to ask whether an optimal bronchial tree from a physical perspective is also optimum from a geometrical point of view. In this paper we generate a simple geometric model for the branching pattern of the bronchial tree, deducing relationships that permit estimation of the departures from the geometrical optimum of each bifurcation. We also, for comparative purposes, estimate the departures from the physical optimum. From the geometrical assumptions: i) a symmetrical dichotomic fractal design, ii) with minimum volume and iii) maximum dispersion of the terminal points; and several simulations we suggest that the optimality is characterized by a bifurcation angle theta approximately 60 degrees and a length reduction scale gamma = (1/2)(1/3) = 0.7937. We propose distances from the physical and geometrical optimality defined as Euclidean distances from the expected optima. We show how the advanced relationships and the distances can be used to estimate departures from the optimality in bronchographs of four species. We found lower physical and geometrical departures in the distal zone than those of the proximal zones, as well as lower physical than geometrical departures from optimality.

Animals↗
PubMed2004

Impact of founder population, drift and selection on the genetic diversity of a recently translocated tree population.

Recently established, temperate tree populations combine a high level of differentiation for adaptive traits, suggesting rapid genetic evolution, with a high level of genetic diversity within population, suggesting a limited impact of genetic drift and purifying selection. To study experimentally the evolutionary forces in a recently established population, we assessed the spatial and temporal patterns of genetic diversity within a disjunct population of Cedrus atlantica established 140 years ago in south-eastern France from a North African source. The population is expanding through natural regeneration. Three generations were sampled, including founder trees. We analysed 12 isozyme loci, three of which were previously found in tight association with selected genes, and quantitative traits. No bottleneck effect was detected in the founder generation, but a simple test of allelic association revealed an initial disequilibrium which disappeared in the following generations. The impact of genetic drift during secondary evolution was limited, as suggested by the weak temporal differentiation. The genetic load was not reduced after 3 generations, and the quantitative variation for adaptive traits did not change either. Thus, initial genetic changes first proceed from a rapid re-organisation of the diversity through mating and recombination, whereas genetic erosion through drift and selection is delayed due to temporal and spatial stochasticity. Two life-history traits of trees contribute to slowing down the processes of genetic erosion: perenniality and large spatial scale. Thus, one would expect recently established tree populations to have a higher diversity than older ones, which seems in accordance with experimental surveys.

Biological Evolution↗
PubMed2005

Gene flow among established Puerto Rican populations of the exotic tree species, Albizia lebbeck.

We estimate gene flow and patterns of genetic diversity in Albizia lebbeck, an invasive leguminous tree in the dry forest of southwestern Puerto Rico. Genetic diversity estimates calculated for 10 populations of 24 trees each indicated that these populations may have been formed from multiple introductions. The presence of unique genotypes in the northernmost populations suggests that novel genotypes are still immigrating into the area. This combination of individuals from disparate locations led to high estimates of genetic diversity (He = 0.266, P = 0.67). Indirect estimates of gene flow indicate that only 0.69 migrants per generation move between populations, suggesting that genetic diversity within populations should decrease due to genetic drift. Since migration-drift equilibrium was not found, however, this estimate needs to be viewed with caution. The regular production of pods in this outcrossing species (tm = 0.979) indicates that sufficient outcross pollen is received to insure successful reproduction. Direct estimates of gene flow indicate that between 44 and 100% of pollen received by trees in four small stands of trees (n < 11) was foreign. The role of gene flow in facilitating the spread of this invasive plant species is discussed.

Albizzia↗
PubMed2000

Distribution of apoptotic cells and expression of apoptosis-related proteins along the intrahepatic biliary tree in normal and non-biliary diseased liver.

AIMS: The cell kinetics and homeostasis of biliary epithelial cells may be maintained differently along the biliary tree. In this study, the role of apoptosis in the maintenance and homeostasis of the intrahepatic biliary tree was evaluated. METHODS AND RESULTS: By counting apoptotic biliary cells and by immunostaining apoptosis-related proteins in normal liver, fatty liver, and those with acute viral hepatitis, chronic viral hepatitis, and hepatitis virus-related cirrhosis, it was found that the larger the intrahepatic bile ducts became, the more biliary epithelial cells underwent apoptosis. bcl-2, an inhibitor of apoptosis, was diffusely expressed in the interlobular bile ducts, but rarely detectable in the large and septal bile ducts. bcl-XL and mcl-1, inhibitors of apoptosis, and bax, a promoter of apoptosis, were diffusely expressed along the intrahepatic biliary tree. CD95, a direct inducer of apoptosis, was present in the large and septal bile ducts, but rarely in the interlobular bile ducts. CONCLUSION: The ratio of bax to bcl-2, as well as the expression of CD95 which differed at the interlobular versus large and septal bile ducts, may be responsible for the unique distribution of apoptotic biliary cells and involved in the homeostasis of the intrahepatic biliary tree.

Aged↗
PubMed2002

Islands within an island: phylogeography and conservation genetics of the endangered Hawaiian tree snail Achatinella mustelina.

Mitochondrial DNA (mtDNA) sequences were used to evaluate phylogeographic structure within and among populations of three endangered Hawaiian tree snail species (n = 86). The primary focus of this investigation was on setting conservation priorities for Achatinella mustelina. Limited data sets for two additional endangered Hawaiian tree snails, A. livida and A. sowerbyana, were also developed for comparative purposes. Pairwise genetic distance matrices and phylogenetic trees were generated, and an analysis of molecular variance was performed on 675-base pair cytochrome oxidase I gene sequences from multiple populations of Hawaiian tree snails. Sequence data were analysed under distance-based maximum-likelihood, and maximum-parsimony optimality criteria. Within the focal species, A. mustelina, numbers of variable and parsimony informative sites were 90 and 69, respectively. Pairwise intraspecific mtDNA sequence divergence ranged from 0 to 5.3% in A. mustelina, from 0 to 1.0% in A. livida and from 0 to 1.9% in A. sowerbyana. For A. mustelina, population genetic structure and mountain topography were strongly correlated. Maximum genetic distances were observed across deep, largely deforested valleys, and steep mountain peaks, independent of geographical distance. However, in certain areas where forest cover is presently fragmented, little mtDNA sequence divergence exists despite large geographical scales (8 km). Genetic data were used to define evolutionarily significant units for conservation purposes including decisions regarding placement of predator exclusion fences, captive propagation, re-introduction and translocation.

Animals↗
PubMed2004

The origin of a 'true' worker caste in termites: mapping the real world on the phylogenetic tree.

The evolution of the 'true' worker caste in termites is not decisively inferred by coding and mapping both this character and the foraging behaviour on a phylogenetic tree. Answering to Thompson et al. (2000, 2003), and with reference to Grandcolas and D'Haese (2002), we show that this indecisive inference depends on the correct consideration paid to the outgroups. These last ones could be non subsocial cockroaches, or some wood-eating subsocial cockroaches often considered misleadingly as living ancestors, or even any hemimetabolous insects, all of them would be unambiguously lacking 'true' worker caste and pseudergate caste and not showing the 'one-piece' life type foraging behaviour. These statements derive from observing, coding and mapping the real world on the tree without making ad hoc assumptions. In that respect, because termites do not exist in isolation, apart from the tree of life, mapping the character of interest on the tree must be applied to the outgroups as well.

Animals↗