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At least 1,261 records · Page 70Linked to original sources

PubMed2003

Role of progesterone in structural and biochemical remodeling of endometrium.

The endometrial response to the varying levels of ovarian steroids is exhibited as alterations in its form and function. These changes in endometrial morphology and physiology, especially those observed during the implantation window are prerequisites to support embryo attachment and invasion. However the state of endometrial receptivity to embryo results from an operative network of several molecular events triggered by estrogen, progesterone and probably some other factors, yet to be discovered. It is well established that estrogen and progesterone are the critical endocrine determinants of endometrial functions. However the precise delineation of hormone driven events and their interaction is yet to be ascertained. Several attempts have been made to understand these cascades, however most of these studies have been conducted in vitro using one or the other component of endometrial tissues. We have attempted to investigate in vivo morphological and biochemical/molecular changes in endometrium in response to neutralization of progesterone synthesis/ function in two primate animal models. In one of the models, ovariectomized rhesus monkeys, artificial menstrual cycles were simulated and subsequent effects on the _expression of various genes were investigated in presence and absence of sufficient progesterone levels. The results coincided with those observed in the endometrium of the other model, bonnet monkeys presenting normal hypothalamus-ovarian-pituitary function but displaying retarded endometrial growth due to blocked progesterone receptor. A significant decline was observed in the expression of transforming growth factor beta, transforming growth factor beta receptor, leukaemia inhibitory factor, whereas no remarkable changes were observed in the expression of estrogen receptor and progesterone receptors in response to neutralization of progesterone synthesis/function in these two animal models. Taking support from the inferences drawn from previously published in vitro studies and our data from in vivo studies conducted in these two models, we propose a hypothesis supporting a potential link between the expressions of transforming growth factor beta, leukaemia inhibitory factor, cyclooxygenases and integrins.

Animals↗

PubMed2005

A neuro-fuzzy inference system for modeling and prediction of heart rate variability in the neuro-intensive care unit.

In the neurological intensive care unit (NICU), prediction of impending changes in patient condition would be highly beneficial. In this paper, we employ a neuro-fuzzy inference system (NFIS) for short-term prediction of heart rate variability in the NICU. An NFIS was selected because it allows for a "gray-box" approach through which a system identification procedure is used in conjunction with fuzzy modeling. The NFIS is described in detail and is compared to an auto-regressive moving average (ARMA) model for its ability to model both simulated and measured data from NICU patients. We found that the NFIS is capable of predicting changes in heart rate to a reasonable extent, and that the NFIS has both advantages and limitations over the ARMA model. The NFIS may therefore be a reasonable technique to consider for more extensive prediction purposes in ICU settings.

Blood Pressure↗

PubMed2006

Bacterial regulatory networks are extremely flexible in evolution.

Over millions of years the structure and complexity of the transcriptional regulatory network (TRN) in bacteria has changed, reorganized and enabled them to adapt to almost every environmental niche on earth. In order to understand the plasticity of TRNs in bacteria, we studied the conservation of currently known TRNs of the two model organisms Escherichia coli K12 and Bacillus subtilis across complete genomes including Bacteria, Archaea and Eukarya at three different levels: individual components of the TRN, pairs of interactions and regulons. We found that transcription factors (TFs) evolve much faster than the target genes (TGs) across phyla. We show that global regulators are poorly conserved across the phylogenetic spectrum and hence TFs could be the major players responsible for the plasticity and evolvability of the TRNs. We also found that there is only a small fraction of significantly conserved transcriptional regulatory interactions among different phyla of bacteria and that there is no constraint on the elements of the interaction to co-evolve. Finally our results suggest that majority of the regulons in bacteria are rapidly lost implying a high-order flexibility in the TRNs. We hypothesize that during the divergence of bacteria certain essential cellular processes like the synthesis of arginine, biotine and ribose, transport of amino acids and iron, availability of phosphate, replication process and the SOS response are well conserved in evolution. From our comparative analysis, it is possible to infer that transcriptional regulation is more flexible than the genetic component of the organisms and its complexity and structure plays an important role in the phenotypic adaptation.

Bacillus subtilis↗

PubMed1998

Frame: detection of genomic sequencing errors.

MOTIVATION: The underlying error rate for genomic sequencing sometimes results in the introduction of artificial frameshifts and in-frame stop codons into putative protein encoding genes. Severe errors are then introduced into the inferred transcripts through mis-translation or premature termination. RESULTS: We describe a system for screening segments of DNA for frameshift and in-frame stop errors in coding regions. The method is based on homology matching using blastx to compare all six reading frames of the query nucleotide sequence against selected protein sequence databases. Fragments of protein matching neighbouring regions of the query DNA are united and extended laterally to define candidate open reading frames, within which, frameshifts and stops are identified. Suitable targets include prokaryotic or other intron-free genomic sequence and complementary DNAs. As an example of its use, we report here two frameshifted ORFs that deviate from the original TIGR sequence annotations for the recently released Helicobacter pylori genome. AVAILABILITY: The tool is accessible via the URL http://www.sander.ebi.ac.uk/frame/. CONTACT: brown@ebi.ac.uk.

Amino Acid Sequence↗

PubMed2006

Watershed nitrogen and mercury geochemical fluxes integrate landscape factors in long-term research watersheds at Acadia National Park, Maine, USA.

This paper is an overview of this special issue devoted to watershed research in Acadia National Park (Acadia NP). The papers address components of an integrated research program on two upland watersheds at Acadia NP, USA (44 degrees 20' N latitude; 68 degrees 15' E longitude). These watersheds were instrumented in 1998 to provide a long-term foundation for regional ecological and watershed research. The research was initiated as part of EPA/NPS PRIMENet (Park Research and Intensive Monitoring of Ecosystems Network), a system of UV-monitoring stations and long-term watershed research sites located in US national parks. The initial goals at Acadia NP were to address research questions about mercury, acid rain, and nitrogen saturation developed from prior research. The project design was based on natural differences in forests and soils induced by an intense wildfire in one watershed in 1947. There is no evidence of fire in the reference watershed for several hundred years. We are testing hypotheses about controls on surface water chemistry, and bioavailability of contaminants in the contrasting watersheds. The unburned 47-ha Hadlock Brook watershed is 70% spruce-fir mature conifer forest. In contrast, burned 32-ha Cadillac Brook watershed, 4 km northeast of the Hadlock watershed, is 20% regenerating mixed northern hardwoods and 60% shrub/rocky balds. Differences in atmospheric deposition are controlled primarily by forest stand composition and age. The watersheds are gauged and have water chemistry stations at 122 m (Cadillac) and 137 m (Hadlock); watershed maximum elevations are 468 and 380 m, respectively. The stream water chemistry patterns reflect, in part, the legacy of the intense fire, which, in turn, controls differences in forest vegetation and soil characteristics. These factors result in higher nitrogen and mercury flux from the unburned watershed, reflecting differences in atmospheric deposition, contrasting ecosystem pools of nitrogen and mercury, and inferred differences in internal cycling and bioavailabilty.

Acid Rain↗

PubMed2003

AnaBench: a Web/CORBA-based workbench for biomolecular sequence analysis.

BACKGROUND: Sequence data analyses such as gene identification, structure modeling or phylogenetic tree inference involve a variety of bioinformatics software tools. Due to the heterogeneity of bioinformatics tools in usage and data requirements, scientists spend much effort on technical issues including data format, storage and management of input and output, and memorization of numerous parameters and multi-step analysis procedures. RESULTS: In this paper, we present the design and implementation of AnaBench, an interactive, Web-based bioinformatics Analysis workBench allowing streamlined data analysis. Our philosophy was to minimize the technical effort not only for the scientist who uses this environment to analyze data, but also for the administrator who manages and maintains the workbench. With new bioinformatics tools published daily, AnaBench permits easy incorporation of additional tools. This flexibility is achieved by employing a three-tier distributed architecture and recent technologies including CORBA middleware, Java, JDBC, and JSP. A CORBA server permits transparent access to a workbench management database, which stores information about the users, their data, as well as the description of all bioinformatics applications that can be launched from the workbench. CONCLUSION: AnaBench is an efficient and intuitive interactive bioinformatics environment, which offers scientists application-driven, data-driven and protocol-driven analysis approaches. The prototype of AnaBench, managed by a team at the Université de Montréal, is accessible on-line at: http://malawimonas.bcm.umontreal.ca:8091/anabench. Please contact the authors for details about setting up a local-network AnaBench site elsewhere.

Computational Biology↗

PubMed1992

Crystal structure of the unique parvalbumin component from muscle of the leopard shark (Triakis semifasciata). The first X-ray study of an alpha-parvalbumin.

The three-dimensional structure of parvalbumin from leopard shark (Triakis semifasciata) with 109 amino acid residues (alpha-series) is described at 1.54 A resolution. Crystals were grown at 20 degrees C from 2.9 M-potassium/sodium phosphate solutions at pH 5.6. The space group is P3(1)21 and unit cell dimensions are a = b = 32.12 A and c = 149.0 A. The structure has been solved by the molecular replacement method using pike 4.10 parvalbumin as a model. The final structure refinement resulted in an R-factor of 17.3% for 11,363 independent reflections at 1.54 A resolution. The shark parvalbumin shows the main features of all parvalbumins: the folding of the chain including six alpha-helices, the salt bridge between Arg75 and Glu81, and the hydrophobic core. Compared to the structure of beta-parvalbumins from pike and carp, one main difference is observed: the chain is one residue longer and this additional residue, which extends the F helix, is involved through its C-terminal carboxylate group in a network of electrostatic contacts with two basic residues, His31 in the B helix and Lys36 in the BC segment. Furthermore, hydrogen bonds exist between the side-chains of Gln108 (F helix) and Tyr26 (B helix). There is therefore a "locking" of the tertiary structure through contacts between two sequentially distant regions in the protein and this is likely to contribute to making the stability of an alpha-parvalbumin higher in comparison to that of a beta-parvalbumin. The lengthening of the C-terminal F helix by one residue appears to be a major feature of alpha-parvalbumins in general, owing to the homologies of the amino acid sequences. Besides the lengthening of the C-terminal helix, the classification of the leopard shark parvalbumin in the alpha-series rests upon the observation of Lys13, Leu32, Glu61 and Val66. As this is the first crystal structure description of a parvalbumin from the alpha-phylogenetic lineage, it was hoped that it would clearly determine the presence or absence of a third cation binding site in parvalbumins belonging to the alpha-lineage. In beta-pike pI 4.10 parvalbumin, Asp61 participates as a direct ligand of a third site, the satellite of the CD site. In shark parvalbumin, as in nearly all alpha-parvalbumins, one finds Glu at position 61. Unfortunately, the conformation of the polar head of Glu61 cannot be inferred from the X-ray data.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMedDate not supplied

A comparative investigation on subspace dimension determination.

It is well-known that constrained Hebbian self-organization on multiple linear neural units leads to the same k-dimensional subspace spanned by the first k principal components. Not only the batch PCA algorithm has been widely applied in various fields since 1930s, but also a variety of adaptive algorithms have been proposed in the past two decades. However, most studies assume a known dimension k or determine it heuristically, though there exist a number of model selection criteria in the literature of statistics. Recently, criteria have also been obtained under the framework of Bayesian Ying-Yang (BYY) harmony learning. This paper further investigates the BYY criteria in comparison with existing typical criteria, including Akaike's information criterion (AIC), the consistent Akaike's information criterion (CAIC), the Bayesian inference criterion (BIC), and the cross-validation (CV) criterion. This comparative study is made via experiments not only on simulated data sets of different sample sizes, noise variances, data space dimensions, and subspace dimensions, but also on two real data sets from air pollution problem and sport track records, respectively. Experiments have shown that BIC outperforms AIC, CAIC, and CV while the BYY criteria are either comparable with or better than BIC. Therefore, BYY harmony learning is a more preferred tool for subspace dimension determination by further considering that the appropriate subspace dimension k can be automatically determined during implementing BYY harmony learning for the principal subspace while the selection of subspace dimension k by BIC, AIC, CAIC, and CV has to be made at the second stage based on a set of candidate subspaces with different dimensions which have to be obtained at the first stage of learning.

Air Pollution↗

PubMed2003

Basal ganglia network mediates the control of movement amplitude.

In the present study we address the hypothesis that the basal ganglia are specifically involved in the planning of movement amplitude (or related covariates). This prediction has often been put forward based on the observation that Parkinson's disease (PD) patients exhibit hypokinesia. A close examination of the literature shows, however, that this commonly reported clinical symptom is not consistently echoed by experimental observations. When required to point to visual targets in the absence of vision of the moving limb, PD subjects exhibit various patterns of inaccuracy, including hypometria, hypermetria, systematic direction bias, or direction-dependent errors. They have even been shown to be as accurate as healthy, age-matched subjects. The main aim of the current study is to address the origin of these inconsistencies. To this end, we required nine patients presenting with advanced PD and 15 age-matched control subjects to perform planar reaching movements to visual targets. Eight targets were presented in equally spaced directions around a circle centered on the hand's starting location. Based on a previously validated parsing procedure, end-point errors were segmented into localization and planning errors. Localization errors refer to the existence of systematic biases in the estimation of the initial hand location. These biases can potentially transform a simple pattern of pure amplitude errors into a complex pattern involving both amplitude and direction errors. Results indicated that localization errors were different in the PD patients and the control subjects. This is not surprising knowing both that proprioception is altered in PD patients and that the ability to locate the hand at rest relies mainly on the proprioceptive sense, even when vision is available. Unlike normal subjects, localization errors in PD were idiosyncratic, lacking a consistent pattern across subjects. When the confounding effect of initial hand localization errors was canceled, we found that end-point errors were only due to the implementation of an underscaled movement gain (15%), without direction bias. Interestingly, the level of undershoot was found to increase with the severity of the disease (inferred from the Unified Parkinson's Disease Rating Scale, UPDRS, motor score). We also observed that movement variability was amplified (32%), but only along the main movement axis (extent variability). Direction variability was not significantly different in the patient population and the control group. When considered together, these results support the idea that the basal ganglia are specifically involved in the control of movement amplitude (or of some covariates). We propose that this structure participates in extent planning by modulating cortical activity and/or the tuning of the spinal interneuronal circuits.

Aged↗

PubMed2006

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

Adolescent↗

PubMed2004

Combination of direct and indirect evidence in mixed treatment comparisons.

Mixed treatment comparison (MTC) meta-analysis is a generalization of standard pairwise meta-analysis for A vs B trials, to data structures that include, for example, A vs B, B vs C, and A vs C trials. There are two roles for MTC: one is to strengthen inference concerning the relative efficacy of two treatments, by including both 'direct' and 'indirect' comparisons. The other is to facilitate simultaneous inference regarding all treatments, in order for example to select the best treatment. In this paper, we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS. These are multivariate random effects models that allow for variation in true treatment effects across trials. We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models. We also compare models with fixed (unconstrained) baseline study effects with models with random baselines drawn from a common distribution. These models are applied to an illustrative data set and posterior parameter distributions are compared. We discuss model critique and model selection, illustrating the role of Bayesian deviance analysis, and node-based model criticism. The assumptions underlying the MTC models and their parameterization are also discussed.

Humans↗

PubMed2006

Comments on 'Is partial coherence a viable technique for identifying generators of neural oscillations?': Why the term 'Gersch Causality' is inappropriate: common neural structure inference pitfalls.

To aid prospective neural connectivity inference analysts and hoping to preclude misconception spread, we exploit the didatic value of some of the issues raised by Albo et al. (Biol Cybern 90: 318-326, 2004) who claim that signal-to-noise ratio (SNR) values can lead to mistakes in structural inference when using partial coherence in connection to Gersch's 1970 method for spotting signal sources (Gersch in Math Biosci 14: 177- 196, 1972). We show theoretically that Gersch's method is able only to spot which measurement of some common underlying factor has the least amount of additive noise and that this has nothing to do with any reasonable notion of 'causality' as suggested by Albo et al. (Biol Cybern 90: 318-326, 2004). We also show that despite the inherent structural ambiguity of the model used by Albo et al. (Biol Cybern 90: 318-326, 2004) to back their claim, its data can nonetheless furnish the correct time precedence hierarchy between the activities in its measured structures, both when simple (correlation) and more sophisticated methods are used (partial directed coherence) (Baccala and Sameshima in Biol Cybern 84:463-474, 2001a) in a true depiction of time series causality.

Animals↗

PubMed2006

TWNFI--a transductive neuro-fuzzy inference system with weighted data normalization for personalized modeling.

This paper introduces a novel transductive neuro-fuzzy inference model with weighted data normalization (TWNFI). In transductive systems a local model is developed for every new input vector, based on a certain number of data that are selected from the training data set and the closest to this vector. The weighted data normalization method (WDN) optimizes the data normalization ranges of the input variables for the model. A steepest descent algorithm is used for training the TWNFI models. The TWNFI is compared with some other widely used connectionist systems on two case study problems: Mackey-Glass time series prediction and a real medical decision support problem of estimating the level of renal function of a patient. The TWNFI method not only results in a "personalized" model with a better accuracy of prediction for a single new sample, but also depicts the most significant input variables (features) for the model that may be used for a personalized medicine.

Algorithms↗

PubMed2007

Neuro-fuzzy technology as a predictor of parathyroid hormone level in hemodialysis patients.

Measuring the plasma parathyroid hormone (PTH) concentration is crucial to evaluate renal bone disease in patients with renal failure. Although frequent measurement is needed to avoid inadequate prescription of phosphate binders and vitamin D preparations, artificial intelligence can repeatedly perform the forecasting tasks and may be a satisfactory substitute for laboratory tests. Neuro-fuzzy technology represents a promising forecasting application in clinical medicine. We therefore constructed a coactive neuro-fuzzy inference system (CANFIS) to predict plasma PTH concentrations in hemodialysis patients. The CANFIS was constructed with clinical parameters (patient age, plasma albumin, calcium, phosphorus, alkaline phosphatase, and calcium-phosphorus product) from a cohort of hemodialysis patients, and plasma PTH concentration measured by radioimmunoassay (RIA) was the supervised outcome. The accuracy of the CANFIS was prospectively compared with RIA in another hospital. Plasma PTH concentrations measured by RIA and predicted by CANFIS were 179.04 +/- 38.18 ng/l and 179.34 +/- 37.76 ng/l, respectively (p = 0.15). The CANFIS was able to precisely estimate plasma PTH concentrations in hemodialysis patients. These results suggest that the neuro-fuzzy technology, based on limited clinical parameters, is an excellent alternative to RIA for accurately predicting plasma PTH concentration in hemodialysis patients.

Aged↗

PubMed1996

Neural connectivity only accounts for a small part of neural correlation in auditory cortex.

In order to allow the relation of functional connectivity patterns (inferred from cross-correlograms) to structural connectivity (the anatomical substrate), we analyzed cross-correlogram peaks for spontaneous and stimulated activity in the auditory cortex. It was assumed that the broad correlograms, usually encountered, represent neural connectivity as well as secondary effects such as intrinsic firing patterns, global synchrony related to the ongoing electroencephalographic activity, and stimulus-related effects. Data were collected from 604 neuron pairs recorded under spontaneous conditions in primary auditory cortex of seven juvenile (30-70 days) and nine adult cats. Three hundred and six pairs (51%) had a peak cross-correlation coefficient significantly different from zero. For 113 neuron pairs out of this subgroup, correlations were calculated also for spike trains recorded during click stimulation. After a combined burst-correction and deconvolution procedure was carried out, the correlation peak strengths were not significantly changed for spontaneous activity, but peak width was narrower for single-electrode pairs than for dual-electrode pairs, suggesting a better synchronization for neighboring neurons. Under click stimulation conditions, overall peak synchronization strength was independent of interelectrode distance, whereas, after correction for secondary and stimulus effects, peak synchronization was significantly lower for dual-electrode pairs. However, the primary peak width for single-electrode pairs under stimulus conditions was no longer different from that of dual-electrode pairs. This implies that both under spontaneous and stimulus conditions secondary effects largely obscure any underlying correlation produced by anatomical connectivity. The secondary effects may be the result of intrinsic as well as network properties in auditory cortex and may functionally be more important than the weak primary effects resulting from anatomical connections. Cross-interval analysis suggests that the correlations in auditory cortex are dynamic and may show random switching between states of stronger and weaker synchronization.

Acoustic Stimulation↗

PubMed1999

A model of human pattern perception: association fields for adaptive spatial filters.

Visual neurons in the primary visual cortex 'look' at the retinal image through a four-dimensional array of spatial receptive fields (filter-elements): two spatial dimensions and, at each spatial location, two Fourier dimensions of spatial frequency and orientation. In general, visual objects activate filter-elements along each of these dimensions, suggesting a need for some kind of linking mechanism that determines whether two or more filter-elements are responding to the same or different contours or objects. In the spatial domain, a (spatial) association field between filter-elements, arranged to form first-order curves, has been inferred as a flexible method by which different parts of extended (luminance) contours become associated (Field et al., 1993). Linking has also been explored between filters selective for different regions in Fourier space (e.g. Georgeson and Meese, 1997). Perceived structure of stationary plaids suggests that spatial filtering is adaptive: synthetic filters can be created by the linear summation of basis-filters across orientation or spatial frequency in a stimulus-dependent way. For example, a plaid with a pair of sine-wave components at +/-45 deg looks like a blurred checkerboard; a structure that can be understood if features are derived after linear summation of spatial filters at different orientations. However, the addition of an oblique third-harmonic component causes the plaid to perceptually segment into overlapping oblique contours. This result can be understood if filters are summed across spatial frequency, but, in this case, treated independently across orientation. In the present paper, the architecture of an association field is proposed to permit linking and segmentation of filter-elements across spatial frequency and orientation. Three types of link are proposed: (1) A chain of constructive links around sites of common spatial frequency but different orientation, to promote binding of filters across orientation; (2) Constructive links between sites with common orientation but different spatial frequency, to promote binding of filters across spatial frequency; (3) Long-range links between sites of common spatial frequency but different orientation, whose activation and role are determined by activity in a higher spatial frequency band. A model employing the proposed network of links is consistent with at least six previously reported effects on the perception of briefly presented stationary plaids.

Computer Simulation↗

PubMed2001

Analyzing holistic parsers: implications for robust parsing and systematicity.

Holistic parsers offer a viable alternative to traditional algorithmic parsers. They have good generalization performance and are robust inherently. In a holistic parser, parsing is achieved by mapping the connectionist representation of the input sentence to the connectionist representation of the target parse tree directly. Little prior knowledge of the underlying parsing mechanism thus needs to be assumed. However, it also makes holistic parsing difficult to understand. In this article, an analysis is presented for studying the operations of the confluent preorder parser (CPP). In the analysis, the CPP is viewed as a dynamical system, and holistic parsing is perceived as a sequence of state transitions through its state-space. The seemingly one-shot parsing mechanism can thus be elucidated as a step-by-step inference process, with the intermediate parsing decisions being reflected by the states visited during parsing. The study serves two purposes. First, it improves our understanding of how grammatical errors are corrected by the CPP. The occurrence of an error in a sentence will cause the CPP to deviate from the normal track that is followed when the original sentence is parsed. But as the remaining terminals are read, the two trajectories will gradually converge until finally the correct parse tree is produced. Second, it reveals that having systematic parse tree representations alone cannot guarantee good generalization performance in holistic parsing. More important, they need to be distributed in certain useful locations of the representational space. Sentences with similar trailing terminals should have their corresponding parse tree representations mapped to nearby locations in the representational space. The study provides concrete evidence that encoding the linearized parse trees as obtained via preorder traversal can satisfy such a requirement.

Algorithms↗

PubMedDate not supplied

EON: a component-based approach to automation of protocol-directed therapy.

Provision of automated support for planning protocol-directed therapy requires a computer program to take as input clinical data stored in an electronic patient-record system and to generate as output recommendations for therapeutic interventions and laboratory testing that are defined by applicable protocols. This paper presents a synthesis of research carried out at Stanford University to model the therapy-planning task and to demonstrate a component-based architecture for building protocol-based decision-support systems. We have constructed general-purpose software components that (1) interpret abstract protocol specifications to construct appropriate patient-specific treatment plans; (2) infer from time-stamped patient data higher-level, interval-based, abstract concepts; (3) perform time-oriented queries on a time-oriented patient database; and (4) allow acquisition and maintenance of protocol knowledge in a manner that facilitates efficient processing both by humans and by computers. We have implemented these components in a computer system known as EON. Each of the components has been developed, evaluated, and reported independently. We have evaluated the integration of the components as a composite architecture by implementing T-HELPER, a computer-based patient-record system that uses EON to offer advice regarding the management of patients who are following clinical trial protocols for AIDS or HIV infection. A test of the reuse of the software components in a different clinical domain demonstrated rapid development of a prototype application to support protocol-based care of patients who have breast cancer.

Algorithms↗