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PubMed2003

The influence of climate on the oxygen isotopes in tree rings.

Natural variations in the oxygen isotope ratio 18O/16O are occurring in the hydrological cycle as a result of isotope fractionations during evaporation and condensation. These processes imprint a valuable climatic signal in the precipitation, which is stored in ice caps as well as in the cellulose of trees. Recent developments in the continuous-flow analysis of 18O/16O of organic matter now enable a systematic application of this method in tree rings. It becomes possible to build maps of the past oxygen isotope distribution in continental areas, yielding important information on regional climate changes. In this paper, the factors influencing the isotope composition of tree rings are discussed with an example from trees in northern Eurasia. Oxygen isotope values of Larix, Picea and Pinus trees were measured over a large climatic gradient extending from Norway to Siberia. The spatial isotope variations were highly correlated to the annual mean temperature (r2 = 0.84), whereby the slope of the corresponding regression line was 0.35%/degrees C. When considering the changes in 18O/16O during the 20th century, not only the temperature, but also changes in the precipitation patterns have to be considered, in particular the observed increase in the amount of winter precipitation.

Asia↗

PubMed1990

Fate of grafted embryonic Purkinje cells in the cerebellum of the adult "Purkinje cell degeneration" mutant mouse. I. Development of reciprocal graft-host interactions.

In this paper, we have morphologically studied the developmental events underlying the neuronal replacement, 3-21 days after grafting. Despite their abnormal environment, Purkinje cell progenitors proceed with their proliferation in the grafted neuroepithelium, with a time window similar to that characterizing proliferation of this neuronal class in control mouse embryos. Only postmitotic Purkinje cells leave the grafts and migrate to the host molecular layer following stereotyped pathways. These neurons invade the host molecular layer, either through a tangential migration under the pial basal lamina from the graft/host interface or breaking locally the latter, and passing directly from the lateral swellings of the graft lying on the surface of the host folia. Whatever the pathway for host invasion, the migrating Purkinje cells penetrate radially and/or obliquely into the host molecular layer until their inward-oriented processes attain the molecular/granular layer interface, which occurs about 7 days after grafting. At the end of their migration, the grafted Purkinje cells with bipolar shapes and long and smooth processes begin to build up their ultimate dendritic trees. This dendritogenesis proceeds with constructive and regressive processes, passing through the same three developmental phases described by Ramón y Cajal (Trab. Lab. Invest. Biol. Univ. Madrid 24:215-251, 1926) for control Purkinje cells (phase of the fusiform cell, phase of the stellate cell with disoriented dendrons, and phase of orientation and flattening of the dendrites). In the grafted cerebella, the duration of the second and third phases is somewhat shorter than during normal cerebellar ontogenesis. Synaptogenesis between adult host axons and grafted Purkinje cells starts when the latter attain their second phase of dendritic development. Somatic filopodia emerging from grafted Purkinje cells begin, 10-11 days after grafting, to be synaptically contacted by axonal sprouts of the host climbing fibers resulting, 2 days later, in the formation of pericellular nests. Synaptogenesis between slender dendritic spines and host parallel fibers, together with that of axon terminals from host molecular layer interneurons and the smooth surface of the grafted Purkinje cell somata, begin earlier than in control mouse development, being almost simultaneous with climbing fiber/Purkinje cell synaptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2005

Region-growing segmentation of brain vessels: an atlas-based automatic approach.

PURPOSE: To propose an atlas-based method that uses both phase and magnitude images to integrate anatomical information in order to improve the segmentation of blood vessels in cerebral phase-contrast magnetic resonance angiography (PC-MRA). MATERIAL AND METHODS: An atlas of the whole head was developed to store the anatomical information. The atlas divides a magnitude image into several vascular areas, each of which has specific vessel properties. It can be applied to any magnitude image of an entire or nearly entire head by deformable matching, which helps to segment blood vessels from the associated phase image. The segmentation method used afterwards consists of a topology-preserving, region-growing algorithm that uses adaptive threshold values depending on the current region of the atlas. This algorithm builds the arterial and venous trees by iteratively adding voxels that are selected according to their grayscale value and the variation of values in their neighborhood. The topology preservation is guaranteed because only simple points are selected during the growing process. RESULTS: The method was performed on 40 PC-MRA images of the brain. The results were validated using maximum-intensity projection (MIP) and three-dimensional surface rendering visualization, and compared with results obtained with two non-atlas-based methods. CONCLUSION: The results show that the proposed method significantly improves the segmentation of cerebral vascular structures from PC-MRA. These experiments tend to prove that the use of vascular atlases is an effective way to optimize vessel segmentation of cerebral images.

Adult↗

PubMed2001

Evaluating the safety of microbial enzyme preparations used in food processing: update for a new century.

Microbial enzymes used in food processing are typically sold as enzyme preparations that contain not only a desired enzyme activity but also other metabolites of the production strain, as well as added materials such as preservatives and stabilizers. The added materials must be food grade and meet applicable regulatory standards. The purpose of this report is to present guidelines that can be used to evaluate the safety of the metabolites of the production strain that are also present in the enzyme preparation, including of course, but not limited to, the desired enzyme activity itself. This discussion builds on previously published decision tree mechanisms and includes consideration of new genetic modification technologies, for example, modifying the primary structure of enzymes to enhance specific properties that are commercially useful. The safety of the production strain remains the primary consideration in evaluating enzyme safety, in particular, the toxigenic potential of the production strain. Thoroughly characterized nonpathogenic, nontoxigenic microbial strains, particularly those with a history of safe use in food enzyme manufacture, are logical candidates for generating a safe strain lineage, through which improved strains may be derived via genetic modification by using either traditional/classical or rDNA strain improvement strategies. The elements needed to establish a safe strain lineage include thoroughly characterizing the host organism, determining the safety of all new DNA that has been introduced into the host organism, and ensuring that the procedure(s) that have been used to modify the host organism are appropriate for food use. Enzyme function may be changed by intentionally altering the amino acid sequence (e.g., protein engineering). It may be asked if such modifications might also affect the safety of an otherwise safe enzyme. We consider this question in light of what is known about the natural variation in enzyme structure and function and conclude that it is unlikely that changes which improve upon desired enzyme function will result in the creation of a toxic protein. It is prudent to assess such very small theoretical risks by conducting limited toxicological tests on engineered enzymes. The centerpiece of this report is a decision tree mechanism that updates previous enzyme safety evaluation mechanisms to accommodate advances in enzymology. We have concluded that separate mutagenicity testing is not needed if this decision tree is used to evaluate enzyme safety. Under the criteria of the decision tree, no new food enzyme can enter the market without critical evaluation of its safety.

Animals↗

PubMed2001

Point mutations and sequence variability in proteins: redistributions of preexisting populations.

Here we study the effect of point mutations in proteins on the redistributions of the conformational substates. We show that regardless of the location of a mutation in the protein structure and of its type, the observed movements of the backbone recur largely at the same positions in the structures. Despite the different interactions that are disrupted and formed by the residue substitution, not only are the conformations very similar, but the regions that move are also the same, regardless of their sequential or spatial distance from the mutation. This observation leads us to conclude that, apart from some extreme cases, the details of the interactions are not critically important in determining the protein conformation or in specifying which parts of the protein would be more prone to take on different local conformations in response to changes in the sequence. This finding further illustrates why proteins manifest a robustness toward many mutational events. This nonuniform distribution of the conformer population is consistently observed in a variety of protein structural types. Topology is critically important in determining folding pathways, kinetics, building block cutting, and anatomy trees. Here we show that topology is also very important in determining which regions of the protein structure will respond to sequence changes, regardless of the sequential or spatial location of the mutation.

Adenylate Kinase↗

PubMed2006

Cytokine expression patterns associated with systemic adverse events following smallpox immunization.

Vaccinia virus is reactogenic in a significant number of vaccinees, with the most common adverse events being fever, lymphadenopathy, and rash. Although the inoculation is given in the skin, these adverse events suggest a robust systemic inflammatory response. To elucidate the cytokine response signature of systemic adverse events, we used a protein microarray technique to precisely quantitate 108 serum cytokines and chemokines in vaccine recipients before and 1 week after primary immunization with Aventis Pasteur smallpox vaccine. We studied 74 individuals after vaccination, of whom 22 experienced a systemic adverse event and 52 did not. The soluble factors most associated with adverse events were selected on the basis of voting among a committee of machine-learning methods and statistical procedures, and the selected cytokines were used to build a final decision-tree model. On the basis of changes in protein expression, we identified 6 cytokines that accurately discriminate between individuals on the basis of adverse event status: granulocyte colony-stimulating factor, stem cell factor, monokine induced by interferon-gamma (CXCL9), intercellular adhesion molecule-1, eotaxin, and tissue inhibitor of metalloproteinases-2. This cytokine signature is characteristic of particular inflammatory response pathways and suggests that the secretion of cytokines by fibroblasts plays a central role in systemic adverse events.

Adolescent↗

PubMed2005

A method for calling gains and losses in array CGH data.

Array CGH is a powerful technique for genomic studies of cancer. It enables one to carry out genome-wide screening for regions of genetic alterations, such as chromosome gains and losses, or localized amplifications and deletions. In this paper, we propose a new algorithm 'Cluster along chromosomes' (CLAC) for the analysis of array CGH data. CLAC builds hierarchical clustering-style trees along each chromosome arm (or chromosome), and then selects the 'interesting' clusters by controlling the False Discovery Rate (FDR) at a certain level. In addition, it provides a consensus summary across a set of arrays, as well as an estimate of the corresponding FDR. We illustrate the method using an application of CLAC on a lung cancer microarray CGH data set as well as a BAC array CGH data set of aneuploid cell strains.

Algorithms↗

PubMed1995

The need for aggressive nutritional intervention in the injured patient: the development of a predictive model.

Early nutritional intervention has been advocated in trauma patients. We have developed a model to identify those patients who will most benefit from the invasive and costly measures that are required to provide injured patients with early enteral feedings. Four hundred forty-two patients admitted to a level I trauma center during a 2-month period were evaluated using 21 clinical variables. Time to tolerance of a regular diet was used as the dependent variable in a step-wise regression, and then the selected variables were used to build a classification and regression tree to predict tolerance of a regular diet within 5 days. Our findings demonstrate that intensive care unit disposition, Injury Severity Score, Abdominal Trauma Index, and the need for early surgical intervention are important predictors regarding the need for early nutritional intervention. When the model was applied to the study population, it had a sensitivity of 83%, a specificity of 84%, and an accuracy of 84%.

Adolescent↗

PubMed2005

On the building of binary spelling interfaces for augmentative communication.

A criterion for design of optimal binary spelling interfaces (SI)--the average expectation of number of writing steps (trials) required to write one letter--is presented and discussed. This criterion is relevant for practical usage of any menu-oriented alternative communication system, mechanical device or brain-computer-interface, when a user (typically, a patient with devastating neuromuscular handicap) can not create an intended single binary response with an absolute reliability. An algorithm for building of a corresponding binary tree is developed and evaluated. This algorithm is efficient, when selection probabilities have essentially different values (the worst case).

Algorithms↗

PubMed2004

Incorporation of nonnatural amino acids into proteins.

The genetic code is established by the aminoacylation of transfer RNA, reactions in which each amino acid is linked to its cognate tRNA that, in turn, harbors the nucleotide triplet (anticodon) specific to the amino acid. The accuracy of aminoacylation is essential for building and maintaining the universal tree of life. The ability to manipulate and expand the code holds promise for the development of new methods to create novel proteins and to understand the origins of life. Recent efforts to manipulate the genetic code have fulfilled much of this potential. These efforts have led to incorporation of nonnatural amino acids into proteins for a variety of applications and have demonstrated the plausibility of specific proposals for early evolution of the code.

Amino Acids↗

PubMedDate not supplied

[Kanjiza Spa: ninety years of healing].

"Kanjiza" spa was founded in 1903. It was an artesian bath at the beginning, but gradually it has grown into a modern rehabilitation center. Much of its existence the spa owes to Herman Gruenfeld, a local businessman who was the first one to invest in development of natural resources in medical purposes. In this work the author reviews some earlier analyses of the chemical composition of water in Kanjiza spa. Procedures are illustrated as well as laboratory findings in Budapest and Belgrade. The author brings to attention the current condition of certain parts of the Spa, which are supposed to be under governmental care and protection. Many of the older building are in bad condition. Trees are damaged in the park, and little has been renewed lately. This paper emphasizes the diversity and efficiency of medical procedures performed by 150 members of the team lead by 10 doctors, and many problems and hardships they successfully face in the health system of Serbia. Due to unpredicted circumstances the centennial anniversary of Kanjiza spa was not marked depriving the public of rare opportunity to recognize efforts and accomplishments of this many aspects unique institution belonging to the very top medical centers specialized in rehabilitation in our country.

Balneology↗

PubMed1996

Risk of dying after a free fall from height.

Falls from height are predominantly an urban phenomenon and represent an important form of blunt trauma. Disagreement predominates regarding the height at which death results. The aim of this study was to investigate the risk of dying after a free fall from height in relation to the distance fallen. Therefore, medical records of victims of a fall from height treated in 1989 at Viennese emergency units were analysed. In addition, post-mortem reports of deaths due to falls from height, examined in the same year at the Institute of Forensic Medicine in Vienna, were studied. For the purpose of an homogenous investigation sample in regard to physical condition, only people aged from 20 to 50 years were taken into account. A total of 11 females and 30 males suffered an accidental fall from buildings, seven men from scaffolding and two men from a tree. A total of 18 females and 18 males jumped from residential buildings. One woman and nine men intentionally fell from other buildings. All victims landed on concrete or pavement. Suicidal jumps occurred from significantly higher places than accidental falls. The results of this analysis suggest that death usually occurs when distance is more than five storeys.

Accidental Falls↗

PubMedDate not supplied

Application of the random forest method in studies of local lymph node assay based skin sensitization data.

The random forest and classification tree modeling methods are used to build predictive models of the skin sensitization activity of a chemical. A new two-stage backward elimination algorithm for descriptor selection in the random forest method is introduced. The predictive performance of the random forest model was maximized by tuning voting thresholds to reflect the unbalanced size of classification groups in available data. Our results show that random forest with a proposed backward elimination procedure outperforms a single classification tree and the standard random forest method in predicting Local Lymph Node Assay based skin sensitization activity. The proximity measure obtained from the random forest is a natural similarity measure that can be used for clustering of chemicals. Based on this measure, the clustering analysis partitioned the chemicals into several groups sharing similar molecular patterns. The improved random forest method demonstrates the potential for future QSAR studies based on a large number of descriptors or when the number of available data points is limited.

Algorithms↗

PubMed1998

Roost selection in the pipistrelle bat, Pipistrellus pipistrellus (Chiroptera: Vespertilionidae), in northeast Scotland.

Availability of suitable roost sites may limit bat distribution and abundance. We compared nine internal and 26 external features of 21 known roost buildings with those of 17 random buildings in northeast Scotland, U.K. (57 degreesN) to assess whether pipistrelle bats, Pipistrellus pipistrellus (55-kHz phonotype) are selective in their use of roosts. Bats did not select roosts with specific structural attributes. Compared with random buildings, roosts were closer to a tree over 10 m tall and had a greater percentage cover (of trees over 10 m tall) within a radius of 50 m. Trees may provide benefits by providing shelter and thus ameliorating the microclimate of the roost. Cover may also provide protection from predators so that bats are able to emerge earlier, thus increasing foraging time. Bats in the present study emerged 11 min earlier from roosts with 29% cover than from roosts with 3% cover, potentially gaining as much as 10% of their daily energy requirements in this extra time. Roosts were also more likely to have linear vegetation elements leading away from them. These features may be important for navigation, foraging or predator avoidance. Compared with random buildings roosts were closer to and surrounded by a greater area of deciduous woodland within a radius of 0.5 km, had a greater area of coniferous woodland within a radius of 0.5 km, and were more likely to be found within 0.5 km of a major river. All these factors are likely to be beneficial for foraging. A logistic regression model indicated that percentage cover within 50 m of the building was the best predictor of the presence or absence of bats roosting in a building. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMedDate not supplied

Boosting: an ensemble learning tool for compound classification and QSAR modeling.

A classification and regression tool, J. H. Friedman's Stochastic Gradient Boosting (SGB), is applied to predicting a compound's quantitative or categorical biological activity based on a quantitative description of the compound's molecular structure. Stochastic Gradient Boosting is a procedure for building a sequence of models, for instance regression trees (as in this paper), whose outputs are combined to form a predicted quantity, either an estimate of the biological activity, or a class label to which a molecule belongs. In particular, the SGB procedure builds a model in a stage-wise manner by fitting each tree to the gradient of a loss function: e.g., squared error for regression and binomial log-likelihood for classification. The values of the gradient are computed for each sample in the training set, but only a random sample of these gradients is used at each stage. (Friedman showed that the well-known boosting algorithm, AdaBoost of Freund and Schapire, could be considered as a particular case of SGB.) The SGB method is used to analyze 10 cheminformatics data sets, most of which are publicly available. The results show that SGB's performance is comparable to that of Random Forest, another ensemble learning method, and are generally competitive with or superior to those of other QSAR methods. The use of SGB's variable importance with partial dependence plots for model interpretation is also illustrated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Zinc accumulation by the slime mold Fuligo septica (L.) Wiggers in the former Soviet Union and North Korea.

Samples of the slime mold Fuligo septica (L.) Wiggers were collected from an ecologically diverse selection of sites across the former USSR and in North Korea to determine their Zn concentrations. Plasmodia were collected from trees, rocks, soils, the walls of buildings and a variety of other materials and structures from 1990 to 1996. The biomass collected ranged from 305 to 968 mg, whereas Zn concentrations in plasmodia of F. septica ranged from 8400 to 23,000 mg kg(-1) dry wt. (mean and standard error = 14,200 +/- 860 mg kg(-1) dry wt.). No clear trend as to which areas produced F. septica with the highest Zn concentrations was discernable. Nor was it possible to identify any particular substrate on which F. septica grew that produced noticeably high Zn concentrations. For example, forest litter on which F. septica was found had Zn concentrations of only 25 to 130 mg kg(-1) dry wt. Our data confirm the only other study showing hyperaccumulation of Zn in F. septica, which was carried out in Finland. This ability seems to be unique to this species, but how or why it does this, or why such high Zn concentrations are not toxic to F. septica, are questions requiring future research.

Animals↗

PubMed2000

NOTUNG: a program for dating gene duplications and optimizing gene family trees.

Large scale gene duplication is a major force driving the evolution of genetic functional innovation. Whole genome duplications are widely believed to have played an important role in the evolution of the maize, yeast, and vertebrate genomes. The use of evolutionary trees to analyze the history of gene duplication and estimate duplication times provides a powerful tool for studying this process. Many studies in the molecular evolution literature have used this approach on small data sets, using analyses performed by hand. The rapid growth of genetic sequence data will soon allow similar studies on a genomic scale, but such studies will be limited unless the analysis can be automated. Even existing data sets admit alternative hypotheses that would be too tedious to consider without automation. In this paper, we describe a program called NOTUNG that facilitates large scale analysis, using both rooted and unrooted trees. When tested on trees analyzed in the literature, NOTUNG consistently yielded results that agree with the assessments in the original publications. Thus, NOTUNG provides a basic building block for inferring duplication dates from gene trees automatically and can also be used as an exploratory analysis tool for evaluating alternative hypotheses.

Algorithms↗

PubMed2004

Constructing rooted supertrees using distances.

Suppose that a family of rooted phylogenetic trees Ti with different sets Xi of leaves is given. A supertree for the family is a single rooted tree T whose leaf set is the union of all the Xi, such that the branching information in T corresponds to the branching information in all the trees Ti. This paper proposes a polynomial-time method BUILD-WITH-DISTANCES that makes essential use of distance information provided by the trees Ti to construct a rooted tree S0. When a supertree also containing the distance information exists, then S0 is a supertree. The supertree S0 often shows increased resolution over the trees found by methods that utilize only the topology of the input trees. When no supertree exists because the input trees are incompatible, several variants of the method are described which still produce trees with provable properties.

Algorithms↗