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At least 541 records · Page 30Linked to original sources
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↗
PubMed2005

A tutorial on the use of ROC analysis for computer-aided diagnostic systems.

The application of the receiver operating characteristic (ROC) curve for computer-aided diagnostic systems is reviewed. A statistical framework is presented and different methods of evaluating the classification performance of computer-aided diagnostic systems, and, in particular, systems for ultrasonic tissue characterization, are derived. Most classifiers that are used today are dependent on a separation threshold, which can be chosen freely in many cases. The separation threshold separates the range of output values of the classification system into different target groups, thus conducting the actual classification process. In the first part of this paper, threshold specific performance measures, e.g., sensitivity and specificity, are presented. In the second part, a threshold-independent performance measure, the area under the ROC curve, is reviewed. Only the use of separation threshold-independent performance measures provides classification results that are overall representative for computer-aided diagnostic systems. The following text was motivated by the lack of a complete and definite discussion of the underlying subject in available textbooks, references and publications. Most manuscripts published so far address the theme of performance evaluation using ROC analysis in a manner too general to be practical for everyday use in the development of computer-aided diagnostic systems. Nowadays, the user of computer-aided diagnostic systems typically handles huge amounts of numerical data, not always distributed normally. Many assumptions made in more or less theoretical works on ROC analysis are no longer valid for real-life data. The paper aims at closing the gap between theoretical works and real-life data. The review provides the interested scientist with information needed to conduct ROC analysis and to integrate algorithms performing ROC analysis into classification systems while understanding the basic principles of classification.

Diagnosis, Computer-Assisted↗
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↗
PubMed2005

A conceptual framework for modeling aggregate and cumulative exposures to chemicals.

Computer simulation programs have been identified as useful tools for characterizing uncertainty and variability in longitudinal exposures to multiple sources by multiple routes of exposures. This paper provides a conceptual framework for such programs that separates and appropriately models the processes that determine uncertainty, inter- and intraindividual variability, as well as the processes that determine the relationships between the individuals and sources of exposure. The framework is based on a series of four nested loops. These are: the exposure event loop that models the route-specific doses to a person from one or more sources at one point in time; the time step loop that moves a person through time updating the sources and the person's characteristics, the interindividual variation loop that determines the initial characteristics of each person modeled, and finally the uncertainty loop that characterizes the uncertainty from model and parameter uncertainties. This framework provides a flexible and internally consistent approach for the design of simulation software.

Computer Simulation↗
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↗
PubMed2005

Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab.

Dimerization is essential for activity of human epidermal growth factor receptors (HER1/EGFR, HER2/ErbB2, HER3/ErbB3, and ErbB4) and mediates intracellular signaling events leading to cancer cell proliferation, survival, and resistance to therapy. HER2 is the preferred dimerization partner. Activation of HER signaling pathways may be blocked by inhibition of dimer formation using a monoclonal antibody (MAb) directed against the dimerization domain of HER2. The murine MAb 2C4 that specifically binds the HER2 dimerization domain was cloned as a chimeric antibody, humanized using a computer-generated model to guide framework substitutions, and variants were tested as Fabs. Pharmacokinetics and toxicology were evaluated in rodents and cynomolgus monkeys. Cloning the variable domains of MAb 2C4 into a vector containing human kappa and CH1 domains allowed construction of a mouse-human chimeric Fab. DNA sequencing of the chimeric clone permitted identification of CDR residues. The full-length IgG1 of variant F-10 was equivalent in binding to chimeric IgG1 and was designated pertuzumab (rhuMAb 2C4; Omnitarg). Pertuzumab pharmacokinetics was best described by a two-compartment model with a distribution phase of <1 day, terminal half-life of approximately 10 days, and volume of distribution of approximately 40 mL/kg that approximates serum volume. With the exception of diarrhea, pertuzumab was generally well tolerated in cynomolgus monkeys. Pertuzumab, a recombinant humanized IgG1 MAb, is the first of a new class of agents known as HER dimerization inhibitors. Inhibition of HER dimerization may be an effective anticancer strategy in tumors with either normal or elevated expression of HER2.

Animals↗
PubMed2004

Eye movements in reading isolated words: evidence for strong biases towards the center of the screen.

Three experiments were conducted that compared the eye movement pattern to a peripheral word or letter string as a function of the position of an initial fixation stimulus relative to the center of the screen and the straight-ahead position. Results revealed a strong bias of the eye behavior towards the center of the screen, but not towards the straight-ahead position. Saccades were greater in length, and landed closer to the center of words/strings when launched from a position left of center than when launched from either center or right part of the screen. In addition, the initial saccade launch site was deviated to the right, or to the left of the initial fixation stimulus depending on where relative to the center of the screen the fixation stimulus was displayed. Data were interpreted with the assumption that saccades are programmed in a visual reference framework, with saccade amplitude being computed in relative coordinates. Further research will determine whether the observed bias generalizes to text reading.

Adult↗
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↗
PubMed2006

Cortico-basal ganglia circuit mechanism for a decision threshold in reaction time tasks.

Growing evidence from primate neurophysiology and modeling indicates that in reaction time tasks, a perceptual choice is made when the firing rate of a selective cortical neural population reaches a threshold. This raises two questions: what is the neural substrate of the threshold and how can it be adaptively tuned according to behavioral demands? Using a biophysically based network model of spiking neurons, we show that local dynamics in the superior colliculus gives rise to an all-or-none burst response that signals threshold crossing in upstream cortical neurons. Furthermore, the threshold level depends only weakly on the efficacy of the cortico-collicular pathway. In contrast, the threshold and the rate of reward harvest are sensitive to, and hence can be optimally tuned by, the strength of cortico-striatal synapses, which are known to be modifiable by dopamine-dependent plasticity. Our model provides a framework to describe the main computational steps in a reaction time task and suggests that separate brain pathways are critical to the detection and adjustment of a decision threshold.

Action Potentials↗
PubMed2005

A first-principle study of the adsorption of 1-amino-3-cyclopentene on the (100) silicon surface.

The adsorption of 1-amino-3-cyclopentene on the (100) silicon surface has been studied by methods rooted in the density-functional theory using both delocalized (plane waves, PWs) and localized (Gaussian-type orbitals, GTOs) basis functions. The results obtained by modeling the surface by silicon clusters of different sizes are quite similar, thus confirming that the reaction is quite localized. Furthermore, PW and GTO computations give comparable results, provided that the same density functional and carefully chosen computational parameters (contraction of GTO, pseudopotentials, etc.) are used. Slab computations performed in the PW framework show that the cluster results are retrieved when low-coverage adsorption on the surface is considered. On these grounds, we are quite confident that reaction parameters obtained by the more reliable hybrid density functional (PBE0) are essentially converged, our best estimates of reaction and activation free energies are thus -40 and 6 kcal/mol, respectively.

Journal Article↗