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PubMed2003

A software tool for specifying voxel models for dosimetry estimation.

Many dose estimation problems can be conveniently formulated in terms of finding the energy emitted and absorbed by a set of homogeneous volume elements (voxels) arranged in a rectilinear grid. The solution of these problems requires an accurate model of the source and target geometry to be established, whereupon conventional Monte Carlo simulation of radiation transport can be employed to determine energy deposition. A software application ("MrVoxel") has been developed to assist in the specification of the source and target models. This application includes tools for image segmentation and image registration (2D and 3D, intra- and inter-modality, interactive, and automatic). It employs a plug-in architecture to facilitate customization and future expansion: plug-ins can be written to perform image import and export as well as to implement specialized image processing routines. Using plug-ins, the package can, for example, import DICOM 3.10 files and export input files for a voxel-based Monte Carlo package. Standard dosimetric tools such as the geometric mean method, transmission based attenuation correction, and MIRD-style voxel dose kernel convolution are also implemented as plug-ins. MrVoxel was implemented on a Macintosh computer using a commercial software framework to produce a conventional document-centric application. Hence it includes useful features such as the ability to undo an operation or to save a processed image set at any point. This latter feature enables the production of a processing trail, to allow post-hoc auditing of the analysis process. This paper describes the MrVoxel application and its role in the analysis of a particular dosimetry problem.

Algorithms↗

PubMedDate not supplied

Attitudes of Australian nurses toward the implementation of a clinical information system.

A computerized clinical information system (CIS) used for the majority of patient charting and medical records was installed in six of 15 beds in the intensive care unit (ICU) of a large Australian hospital in November 1993. Staff acceptance was identified as integral to the success of the system. A survey was issued to all nursing staff of the ICU to identify factors that affected attitude toward computers in the critical care environment. Factors resulting in negative attitudes then could be targeted through training and support for users. The factors considered that potentially could influence attitudes were age, nursing experience, intensive care nursing experience, and education. The study showed that nursing experience had a statistically significant effect on motivation to use computers. A strong relation was evident between the concepts of beliefs, attitudes, and motivation. A less apparent association was present between knowledge and the other concepts. Orientation and in-service education programs should provide appropriate and applied information to optimize the motivation, beliefs, and computer literacy of nurses using CIS frameworks.

Adult↗

PubMed2026

Endothelial cell-specific DNA methylation alterations in breast cancer.

DNA methylation alterations are well-established contributors to carcinogenesis, yet, in the tumor microenvironment (TME), patterns of lineage and cell-specific methylation alterations are not well understood. Single-cell DNA methylation profiling in the TME is limited by technical challenges and high costs. Here, we use bulk DNA methylation, cell type deconvolution (HiTIMED), and an interaction testing framework (CellDMC) to identify reproducible, computationally inferred lineage-specific epigenetic alterations in the TME supported by orthogonal data sources. Tumor endothelial cells (TECs), critical regulators of angiogenesis, vascular permeability, and immune cell trafficking, acquire structural and functional abnormalities that promote tumor growth. We hypothesize that TECs have altered DNA methylation compared with endothelial cells in non-tumor tissues. In genome-scale methylation data from discovery and validation datasets (tumor n = 1071; non-tumor n = 415), we identify and validate >4500 TEC-specific CpGs with altered methylation, many mapping to genes involved in angiogenesis and endothelial function. Integration with gene expression data indicates that TEC-specific methylation alterations may reprogram transcriptional networks controlling angiogenesis. High-resolution, cell lineage-specific epigenetic landscapes can be inferred from bulk methylation data, implicating TEC-specific DNA methylation alterations as potential drivers of cancer angiogenesis and vascular dysfunction and providing a framework for future mechanistic and translational studies of the tumor vasculature.

DNA Methylation↗

PubMed2000

Shape analysis of hippocampal surface structure in patients with unilateral mesial temporal sclerosis.

Structural hippocampal magnetic resonance (MR) imaging-based analysis is helpful in the diagnosis and treatment of mesial temporal epileptic seizures. Computational anatomic techniques provide a framework for objective assessment of three-dimensional hippocampal structure. We applied a previously validated technique of deformation-based hippocampal segmentations in 20 subjects with documented unilateral mesial temporal sclerosis (MTS) and temporal lobe epilepsy. Using composite images, we then measured shape differences between the epileptogenic, smaller hippocampus, and contralateral hippocampus. Final shape differences were projected on the contralateral "normal" side. We calculated results for the left MTS group (10 patients) and right MTS group (10 patients) separately. Both groups showed similar regions of maximal inward deformation in the affected hippocampus, which were the medial and lateral aspect of the head, and posterior aspect of the tail. These results suggest that there are specific three-dimensional patterns of volume loss in patients with mesial temporal epilepsy.

Dominance, Cerebral↗

PubMed1992

A computational model of the amplitude and implicit time of the b-wave of the human ERG.

To improve the usefulness of the ERG in identifying the sites and mechanisms of adaptation, development, and disease processes, a theoretical framework based upon Granit's analysis of the ERG was evaluated. The framework assumes that the ERG is the sum of two potentials, one, P3, generated by the receptors and the other, P2, generated by the cells of the INL. Hood and Birch (1990a, b) demonstrated that the leading edge of the a-wave can be quantitatively described by a model used to describe the response from single rod receptors. This model provides P3(t), a theoretical receptor response as a function of time, for any given flash intensity. The ERGs from normal observers and patients with retinal diseases were analyzed in this framework, first by deriving P2 by computer subtracting the predicted P3(t) responses. This analysis was successful and a computational model of the ERG was then derived. The model of P2(t) was constructed with linear filters and a static nonlinearity and using P3(t) as the input. The ERG for any given flash intensity is then P3(t) + P2(t). The model describes (1) the change both in implicit times and in trough-to-peak b-wave amplitudes with flash intensity for the normal, dark-adapted observers; and (2) the changes in b-wave implicit times and amplitudes for three patients with retinal diseases. Among the implications drawn from these analyses were as follows: (1) The fits of the Naka-Rushton equation to trough-to-peak b-wave amplitudes must be interpreted with great care. (2) When the INL is affected by retinal disease, the b-wave may be a very poor reflection of INL activity. (3) The implicit time of the b-wave can provide a measure of receptor sensitivity.

Adult↗

PubMed2003

Entropy-based dual-portal-to-3-DCT registration incorporating pixel correlation.

For patient setup verification in external beam radiotherapy (EBRT) of prostate cancer, we developed an information theoretic registration framework, called the minimax entropy registration framework, to simultaneously and iteratively segment portal images and register them to three-dimensional (3-D) computed tomography (CT) image data. The registration framework has two steps, the max step and the min step, and evaluates appropriate entropies to estimate segmentations of the portal images and to find the transformation parameters. In the initial version of the algorithm (Bansal et al. 1999), we assumed image pixels to be independently distributed, an assumption not true in general. Thus, to better segment the portal images and to improve the accuracy of the estimated registration parameters, in this initial formulation of the problem, the correlation among pixel intensities is modeled using a one-dimensional Markov random process. Line processes are incorporated into the model to improve the estimation of segmentation of the portal images. In the max step, the principle of maximum entropy is invoked to estimate the probability distribution on the segmentations. The estimated distribution is then incorporated into the min step to estimate the registration parameters. Performance of the proposed framework is evaluated and compared to that of a mutual information-based registration algorithm using both simulated and real patient data. In the proposed registration framework, registration of the 3-D CT image and the portal images is guided by an estimated segmentation of the pelvic bone. However, as the prostate can move with respect to the pelvic structure, further localization of the prostate using ultrasound image data is required, an issue to be further explored in future.

Algorithms↗

PubMed2003

A novel complexity measure for comparative analysis of protein sequences from complete genomes.

Analysis of sequence complexities of proteins is an important step in the characterization and classification of new genomes. A new measure has been proposed to compute sequence complexity in protein sequences based on linguistic complexity. The algorithm requires a single parameter, is computationally simple and provides a framework for comparative genomic analysis. Protein sequences were classified into groups of high or low complexity based on a quantitative measure termed F(c), which is proportional to the fraction of low complexity sequence present in the protein. The algorithm was tested on sequences of 196 non-homologous proteins whose crystal structures are available at </=2.0 A resolution. Protein sequences of high complexity had 'globular' structures (95% agreement), whereas those of low complexity had non-globular structures (80% agreement). Application of this measure to proteins of unknown structure/function from different genomes revealed that the sequences of high complexity constitute the majority in all genomes (about 90% in Archaea, about 93% in Eubacteria, 89% in Saccharomyces cerevisiae and 90% in Caenorhabditis elegans). Aeropyrum pernix among Archaeae and Deinococcus radiodurans among Eubacteria have the lowest fraction of high complexity proteins (75% and 80% respectively). Further, it was observed that a few bacterial pathogens (Mycobacterium tuberculosis, Pseudomonas aeruginosa) have high fraction of low complexity proteins. The program ScanCom is available from the authors as a PERL script (UNIX system).

Algorithms↗

PubMed2000

Clinical experiences of CNC-milled titanium frameworks supported by implants in the edentulous jaw: 1-year prospective study.

BACKGROUND: A new type of titanium framework has been introduced, but so far no clinical reports have been made in this treatment modality. PURPOSE: The aim of this study was to report the clinical performance of implant-supported prostheses with computer numeric controlled (CNC)-milled titanium frameworks in the edentulous jaw and to compare the results with prostheses provided with conventional cast frameworks during the first year of function. MATERIAL AND METHODS: A consecutive group of 65 patients with 67 prostheses were provided with CNC-milled titanium frameworks in 23 upper and 44 lower jaws. During the same period, 61 consecutive patients were treated on a routine basis with 31 upper and 31 lower conventional gold alloy casting prostheses. Clinical and radiographic 1-year data were collected for both the test and control groups. RESULTS: A total of 14 of 729 inserted implants were lost during the follow-up period (1.9%). All prostheses were functioning after 1 year except a conventional prosthesis with a cast framework, which was replaced by an implant-supported over-denture due to implant loss. The 1-year cumulative survival rate (CSR) was 100% and 97.8% for CNC prostheses and implants, respectively. The corresponding CSR for the control group was 98.3% and 98.3%, respectively. Few problems were reported in both groups, and the clinical and the radiologic performances were similar for both groups. No mechanical complications except some resin veneer fractures (n = 6) were observed. The mean marginal bone loss for the test group during the first year in function was 0.4 mm (SD = 0.35) and 0.4 mm (SD = 0.33) in the upper and lower jaws, respectively. A similar pattern of bone reaction was also observed in the control group. CONCLUSION: CNC-milled titanium frameworks can be used as an alternative to conventional castings in the edentulous jaw, presenting similar clinical and radiologic performances as conventional cast frameworks during the first year of function.

Adult↗

PubMed1996

Dynamical computational properties of local cortical networks for visual and motor processing: a bayesian framework.

A major unsolved question concerns the interaction between the coding of information in the cortex and the collective neural operations (such as perceptual grouping, mental rotation) that can be performed on this information. A key property of the local networks in the cerebral cortex is to combine thalamocortical or feedforward information with horizontal cortico-cortical connections. Among different types of neural networks compatible with the known functional and architectural properties of the cortex, we show that there exist interesting bayesian solutions resulting in an optimal collective decision made by the neuronal population. We suggest that thalamo-cortical and cortico-cortical synaptic plasticity can be differentially modulated to optimize this collective bayesian decision process. We take two examples of cortical dynamics, one for perceptual grouping in MT, and the other one for mental rotation in M1. We show that a neural implementation of the bayesian principle is both computationally efficient to perform these tasks and consistent with the experimental data on the related neuronal activities. A major implication is that a similar collective decision mechanism should exist in different cortical regions due to the similarity of the cortical functional architecture.

Algorithms↗

PubMed1992

An approach to evaluating heuristics in abduction: a case study using RedSoar--an abductive system for red blood cell antibody identification.

Abduction, or inference to a best explanation, is a ubiquitous type of inference that is frequently used by humans in a wide range of tasks. However, many realistic domains have properties that make abduction computationally intractable (i.e., where the time to reach a solution increases exponentially with the number of possible explanations). We present a domain task analysis and performance evaluation of RedSoar, a plausible cognitive computational model of abduction, that accomplishes the antibody identification task in immunohematology. The task analysis reveals how a computationally intractable abductive problem, where one is seeking optimal solutions, can be reformulated to be a computationally tractable abductive problem, by seeking satisfactory rather then optimal solutions. From the satisfactory perspective, our evaluation framework of RedSoar's performance explores the computational benefits and costs of having directly available abstract hypothesis formation knowledge, and how a strong causal constraint between hypotheses and data reduces the combinatorial explosion of constructing a best explanation.

Antibodies↗

PubMed2003

Comparing the importance of disease rate versus practice style variations in explaining differences in small area hospitalization rates for two respiratory conditions.

Many studies have reported large variations in age- and sex-adjusted rates of hospitalizations across small geographic areas. These variations have often been attributed to differences in medical practice style which are not reflected in differences in health care outcomes. There is, however, another potentially important source of variation that has not been examined much in the literature: geographic differences in the age-sex adjusted size of the pool of patients who present with the disease and are candidates for hospitalization. Previous studies of small area variations in hospitalization rates have only used data on hospitalizations. Thus, it has not been possible to distinguish the extent to which differences in hospitalization rates are due to (i). differences in the chance that patients diagnosed with a disease are admitted to a hospital, which we refer to as the 'practice style effect,' versus (ii). geographic differences in the total amount of diagnosed disease, which we refer to as the 'disease effect.' Elementary methods for estimating the relative strength of the two effects directly from the data can be misleading, since equal amounts of variability in each effect result in unequal impacts on hospitalization rates. In this paper we describe a model-based approach for estimating the relative importance of the practice style effect and the disease effect in explaining variations in hospitalization rates. The key to our approach is the use of data on both inpatient and outpatient visits. We use 1997 Medicare data for two respiratory medical conditions across 71 small areas in Massachusetts: chronic bronchitis and emphysema, and bacterial pneumonia. Based on a Poisson model for the process generating hospitalizations and outpatient visits, we use a Bayesian framework and Gibbs sampling to compute and compare the correlation between the number of people hospitalized and each of these two sources of variation. Our results show that for the two conditions, disease rate variation explains at least as much of the variation in hospitalization rates as does practice style variation.

Aged↗

PubMed2003

Understanding clay minerals with fuzzy mathematics.

A long-existing geochemical problem is the lack of a means of chemically defining non-stoichiometric complex minerals such as clays, which have no distinct composition and no clear compositional boundaries. We propose here a novel approach for describing the chemical nature of clay minerals using fuzzy logic. This non-conventional mathematical approach allows us to quantify compositional vagueness in such systems. We show that a clay mineral can be described in terms of how compositionally representative it is, of its own type ("belonging-ness") and to what extent it resembles other types (compositional overlap). Many clay minerals are seen to be far from the ideal, and most minerals are also to a lesser (and sometimes greater) extent, close to types other than their own. This has provided a means of grading such minerals, evaluating how "good" a sample is, and defining the extent of transition to other phases. We have derived here the fundamental methodology for such computations, which could be a framework for the analysis of other complex chemical systems, especially in the fields of geology and metallurgy.

Journal Article↗

PubMed1998

Analysis of a 14-kb fragment containing a putative cell wall gene and a candidate for the ARA1, arabinose kinase, gene from chromosome IV of Arabidopsis thaliana.

An Arabidopsis thaliana genomic DNA fragment of 14kb has been characterized in the framework of the E.S.S.A. programme. Computational and molecular approaches identified three novel gene sequences coding, respectively, for a protein of unknown function, a putative membrane-anchored cell wall protein and an arabinose kinase gene corresponding to the locus ARA1. The latter two genes named AtSEB1 and AtISA1 have been characterized in detail. They are very different in their organization, codon usage and level of expression. Homologues of AtSEB1 and AtISA1 have been identified. Sequence comparisons showed that the former genes contained a long 5' extension coding for an N-terminal domain probably specifying subcellular localization. Cloning and sequencing of the cognate cDNA for the AtISA1 homologue in A. thaliana, named GAL1, indicate that it encodes for a galactokinase-like protein. Our results highlight the integrative outcome of a systematic sequencing project in which links between biochemically and genetically characterized mutants, ESTs and genomic sequence data are generated.

Amino Acid Sequence↗

PubMed2000

Perceptual organization of two-dimensional patterns.

The perceptual organization of image patterns is considered from 2 standpoints. First, a theoretical framework is presented from which computational models of perceptual organization can be constructed and tested. Second, a specific computational model for perceptual organization of line images is described. In this model, input images are first processed by a dense array of neurons that have properties consistent with recent analyses of single-neuron responses in primary visual cortex. Then, complex image structure is discovered by interleaved pattern-matching and grouping processes constrained by a generalized uniqueness principle. A series of 3-pattern grouping experiments was performed to test a restricted version of the model and to estimate critical parameters. Using the estimated parameters, an extended version of the model was tested by generating predictions for a series of "textbook" perceptual organization demonstrations.

Humans↗

PubMed2000

Computational principles of movement neuroscience.

Unifying principles of movement have emerged from the computational study of motor control. We review several of these principles and show how they apply to processes such as motor planning, control, estimation, prediction and learning. Our goal is to demonstrate how specific models emerging from the computational approach provide a theoretical framework for movement neuroscience.

Animals↗

PubMed1999

Stretching single-domain proteins: phase diagram and kinetics of force-induced unfolding.

Single-molecule force spectroscopy reveals unfolding of domains in titin on stretching. We provide a theoretical framework for these experiments by computing the phase diagrams for force-induced unfolding of single-domain proteins using lattice models. The results show that two-state folders (at zero force) unravel cooperatively, whereas stretching of non-two-state folders occurs through intermediates. The stretching rates of individual molecules show great variations reflecting the heterogeneity of force-induced unfolding pathways. The approach to the stretched state occurs in a stepwise "quantized" manner. Unfolding dynamics and forces required to stretch proteins depend sensitively on topology. The unfolding rates increase exponentially with force f till an optimum value, which is determined by the barrier to unfolding when f = 0. A mapping of these results to proteins shows qualitative agreement with force-induced unfolding of Ig-like domains in titin. We show that single-molecule force spectroscopy can be used to map the folding free energy landscape of proteins in the absence of denaturants.

Amino Acid Sequence↗

PubMed2025

Rethinking GWAS: how lessons from genetic screens and artificial intelligence could reveal biological mechanisms.

MOTIVATION: Modern single-cell omics data are key to unraveling the complex mechanisms underlying risk for complex diseases revealed by genome-wide association studies (GWAS). Phenotypic screens in model organisms have several important parallels to GWAS which the author explores in this essay. RESULTS: The author provides the historical context of such screens, comparing and contrasting similarities to association studies, and how these screens in model organisms can teach us what to look for. Then the author considers how the results of GWAS might be exhaustively interrogated to interpret the biological mechanisms underpinning disease processes. Finally, the author proposes a general framework for tackling this problem computationally, and explore the data, mechanisms, and technology (both existing and yet to be invented) that are necessary to complete the task. AVAILABILITY AND IMPLEMENTATION: There are no data or code associated with this article.

Genome-Wide Association Study↗

PubMed1999

Distributions of transition matrix elements in classically mixed quantum systems.

The quantitative contributions of a mixed phase space to the mean characterizing the distribution of diagonal transition matrix elements and to the variance characterizing the distributions of nondiagonal transition matrix elements are studied. It is shown that the mean can be expressed as the sum of suitably weighted classical averages along an ergodic trajectory and along the stable periodic orbits. Similarly, it is shown that the values of the variance are well reproduced by the sum of the suitably weighted Fourier transforms of classical autocorrelation functions along an ergodic trajectory and along the stable periodic orbits. The illustrative numerical computations are done in the framework of a hydrogen atom in a strong magnetic field, for three different values of the scaled energy.

Journal Article↗