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A full interionic potential for Na(1+x)Zr(2)Si(x)P(3-x)O(12) superionic conductors.

Most inorganic solids are made up of octahedral and tetrahedral units interconnected to give an infinite framework. Use of computer simulation to study these materials has not been as prevalent as in the organic or biomolecules. Na(1+x)Zr(2)Si(x)P(3-x)O(12) is a typical inorganic solid with ZrO(6) octahedra and (Si/P)O(4) tetrahedra which are shown along with a few Na(+) sites marked M1, M2, and M3. We report here a full interionic potential which reproduces the structure and conductivity of these solids. This augurs well for the study of other inorganic solids.

Journal Article↗

Kinetics of salt-induced J-aggregation of cyanine dyes.

The addition of monovalent, divalent, and trivalent metal ions to three anionic ethyl meso-thiacarbocyanine dyes, an ethyl meso-oxacarbocyanine, and an imidacarbocyanine in aqueous solution at room temperature results in the production of J-aggregates within the range of tens to hundreds of seconds. The rate of formation of J-aggregates correlates with the rate of decay of dimers or monomers and is dependent on the type of metal ion, dye structure, and temperature. The rate of formation of J-aggregates increases as the temperature decreases and the dye and salt concentrations increase, and the rate is highest for trivalent ions and smallest for monovalent ions, independent of the type of anion. The time course of formation of J-aggregates is described in most cases by a sigmoidal curve, and the kinetics and mechanism are discussed within the framework of autocatalysis. Computer simulations reveal that the sigmoidal time dependence is transferred to an exponential-like curve by substantially increasing the rate constant for the noncatalytic step. The reaction pathway into J-aggregates can be switched from dimeric ion pairs as the reactant to monomeric ion pairs, when the rate constant for the catalytic step via the monomer becomes larger with respect to that via the dimer.

Carbocyanines↗

Conjunctive representations in learning and memory: principles of cortical and hippocampal function.

The authors present a theoretical framework for understanding the roles of the hippocampus and neocortex in learning and memory. This framework incorporates a theme found in many theories of hippocampal function: that the hippocampus is responsible for developing conjunctive representations binding together stimulus elements into a unitary representation that can later be recalled from partial input cues. This idea is contradicted by the fact that hippocampally lesioned rats can learn nonlinear discrimination problems that require conjunctive representations. The authors' framework accommodates this finding by establishing a principled division of labor, where the cortex is responsible for slow learning that integrates over multiple experiences to extract generalities whereas the hippocampus performs rapid learning of the arbitrary contents of individual experiences. This framework suggests that tasks involving rapid, incidental conjunctive learning are better tests of hippocampal function. The authors implement this framework in a computational neural network model and show that it can account for a wide range of data in animal learning.

Animals↗

Molecular systematics of the Eastern Fence Lizard (Sceloporus undulatus): a comparison of Parsimony, Likelihood, and Bayesian approaches.

Phylogenetic analysis of large datasets using complex nucleotide substitution models under a maximum likelihood framework can be computationally infeasible, especially when attempting to infer confidence values by way of nonparametric bootstrapping. Recent developments in phylogenetics suggest the computational burden can be reduced by using Bayesian methods of phylogenetic inference. However, few empirical phylogenetic studies exist that explore the efficiency of Bayesian analysis of large datasets. To this end, we conducted an extensive phylogenetic analysis of the wide-ranging and geographically variable Eastern Fence Lizard (Sceloporus undulatus). Maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses were performed on a combined mitochondrial DNA dataset (12S and 16S rRNA, ND1 protein-coding gene, and associated tRNA; 3,688 bp total) for 56 populations of S. undulatus (78 total terminals including other S. undulatus group species and outgroups). Maximum parsimony analysis resulted in numerous equally parsimonious trees (82,646 from equally weighted parsimony and 335 from weighted parsimony). The majority rule consensus tree derived from the Bayesian analysis was topologically identical to the single best phylogeny inferred from the maximum likelihood analysis, but required approximately 80% less computational time. The mtDNA data provide strong support for the monophyly of the S. undulatus group and the paraphyly of "S. undulatus" with respect to S. belli, S. cautus, and S. woodi. Parallel evolution of ecomorphs within "S. undulatus" has masked the actual number of species within this group. This evidence, along with convincing patterns of phylogeographic differentiation suggests "S. undulatus" represents at least four lineages that should be recognized as evolutionary species.

Animals↗

Maximizing phylogenetic diversity in biodiversity conservation: Greedy solutions to the Noah's Ark problem.

The Noah's Ark Problem (NAP) is a comprehensive cost-effectiveness methodology for biodiversity conservation that was introduced by Weitzman (1998) and utilizes the phylogenetic tree containing the taxa of interest to assess biodiversity. Given a set of taxa, each of which has a particular survival probability that can be increased at some cost, the NAP seeks to allocate limited funds to conserving these taxa so that the future expected biodiversity is maximized. Finding optimal solutions using this framework is a computationally difficult problem to which a simple and efficient "greedy" algorithm has been proposed in the literature and applied to conservation problems. We show that, although algorithms of this type cannot produce optimal solutions for the general NAP, there are two restricted scenarios of the NAP for which a greedy algorithm is guaranteed to produce optimal solutions. The first scenario requires the taxa to have equal conservation cost; the second scenario requires an ultrametric tree. The NAP assumes a linear relationship between the funding allocated to conservation of a taxon and the increased survival probability of that taxon. This relationship is briefly investigated and one variation is suggested that can also be solved using a greedy algorithm.

Algorithms↗

A divide-and-conquer approach to fragment assembly.

MOTIVATION: One of the major problems in DNA sequencing is assembling the fragments obtained by shotgun sequencing. Most existing fragment assembly techniques follow the overlap-layout-consensus approach. This framework requires extensive computation in each phase and becomes inefficient with increasing number of fragments. RESULTS: We propose a new algorithm which solves the overlap, layout, and consensus phases simultaneously. The fragments are clustered with respect to their Average Mutual Information (AMI) profiles using the k-means algorithm. This removes the unnecessary burden of considering the collection of fragments as a whole. Instead, the orientation and overlap detection are solved efficiently, within the clusters. The algorithm has successfully reconstructed both artificial and real data. AVAILABILITY: Available on request from the authors.

Algorithms↗

Scaling linear-model breeding values to the liability scale: an application to pig binary traits.

In commercial pig production, many important traits are recorded as binary phenotypes. For such traits, threshold models offer an appropriate framework but are computationally intensive. Thus, linear models are widely used to obtain genomic estimated breeding values (GEBV); however, these are on the observed scale (phenotypic). This creates the need for a robust method to approximate GEBV from linear models to the liability scale. A recently proposed approximation showed good concordance for low-prevalence traits (<5%) but has not yet been tested for a wider range of prevalence values and for models with more than one random effect. We aimed to evaluate the performance of this approximation for pig binary traits with prevalences ranging from <5% to >86%, in both animal and maternal animal models. Data were available for five fitness traits (FT1-FT5), with up to 233k animals with phenotypes, of which 204k animals were genotyped with a 25k SNP array. Variance component estimates were obtained using threshold models. Classical animal models were used for FT1-FT3, and maternal animal models for FT4 and FT5. Variance components on the observed scale were then obtained by multiplying estimates from a threshold model by the square of the height of the standard normal density evaluated at the threshold. GEBV were predicted using single-step genomic best linear unbiased prediction under both linear and threshold models. The approximation tested involved scaling the GEBV using the height of the ordinate of the standard normal distribution evaluated at the threshold as a scaling factor. The agreement between GEBV from the scaled linear model and the threshold model on the probability scale was evaluated using Pearson and Spearman correlations, mean squared error (MSE), regression parameters, overlapping coefficient (OVL), distribution overlap, and classification accuracy (CACC). Correlations between linear and threshold GEBV ranged from 0.94 (low-prevalence traits) to 0.99 (high-prevalence traits) for the direct GEBV and were 0.99 for the maternal GEBV. MSE were close to zero. The OVL exceeded 0.83 for all traits. CACC ranged from 95.10% to 98.33% for the direct GEBV and from 92.54% to 97.42% for the maternal GEBV. Regardless of model and trait prevalence, this approximation yielded GEBV that are highly consistent with threshold model GEBV, providing a reliable, practical approach for large-scale pig genetic evaluations for binary traits using linear models.

Animals↗

Pulmonary airways: 3-D reconstruction from multislice CT and clinical investigation.

In the framework of computer-aided diagnosis, this paper proposes a novel functionality for the computerized tomography (CT)-based investigation of the pulmonary airways. It relies on an energy-based three-dimensional (3-D) reconstruction of the bronchial tree from multislice CT acquisitions, up to the sixth- to seventh-order subdivisions. Global and local analysis of the reconstructed airways is possible by means of specific visualization modalities, respectively, the CT bronchography and the virtual bronchoscopy. The originality of the 3-D reconstruction approach consists in combining axial and radial propagation potentials to control the growth of a subset of low-order airways extracted from the CT volume by means of a robust mathematical morphology operator-the selective marking and depth constrained (SMDC) connection cost. The proposed approach proved to be robust with respect to a large spectrum of airway pathologies, including even severe stenosis (bronchial lumen obstruction/collapse). Validated by expert radiologists, examples of airway 3-D reconstructions are presented and discussed for both normal and pathological cases. They highlight the interest in considering CT bronchography and virtual bronchoscopy as complementary tools for clinical diagnosis and follow-up of airway diseases.

Algorithms↗

The use of visual search to assess attention.

BACKGROUND: Under some conditions, the time required for a visual search increases with the number of elements to be searched. It has been suggested that the overall search time reflects the duration that attention is devoted to each element multiplied by the number of elements. On this basis, it has been proposed that visual search time can be used as a measure of attention capability in dyslexic readers. However, there is evidence to suggest that the search time reflects task difficulty rather than attentional factors. Many dyslexic readers suffer from various sensory deficits. These deficits would effectively increase task difficulty for these readers. Here we use computer simulations to investigate the potential effects of sensory deficits on visual search. METHOD: Visual search was modelled on a computer within the framework of signal detection theory as a matter of detecting a noisy signal from a series of noisy distractors. Sensory deficits were modelled as decreased discriminability. RESULTS: Consistent with previous observations, we find that discriminability, which decreases with the number of distractors, may have a substantial effect on the search time. With regard to the effects of sensory deficits, we find that under low discriminability conditions, small sensory deficits may cause pronounced increases in search time. CONCLUSION: The finding that small sensory deficits may cause pronounced increases in search time makes it specifically problematic to use visual search to test attention in individuals who suffer from sensory deficits. This applies particularly to dyslexic individuals, many of whom have been shown to suffer from visual deficiencies.

Attention↗

Self-organized modularization in evolutionary algorithms.

The principle of modularization has proven to be extremely successful in the field of technical applications and particularly for Software Engineering purposes. The question to be answered within the present article is whether mechanisms can also be identified within the framework of Evolutionary Computation that cause a modularization of solutions. We will concentrate on processes, where modularization results only from the typical evolutionary operators, i.e. selection and variation by recombination and mutation (and not, e.g., from special modularization operators). This is what we call Self-Organized Modularization. Based on a combination of two formalizations by Radcliffe and Altenberg, some quantitative measures of modularity are introduced. Particularly, we distinguish Built-in Modularity as an inherent property of a genotype and Effective Modularity, which depends on the rest of the population. These measures can easily be applied to a wide range of present Evolutionary Computation models. It will be shown, both theoretically and by simulation, that under certain conditions, Effective Modularity (as defined within this paper) can be a selection factor. This causes Self-Organized Modularization to take place. The experimental observations emphasize the importance of Effective Modularity in comparison with Built-in Modularity. Although the experimental results have been obtained using a minimalist toy model, they can lead to a number of consequences for existing models as well as for future approaches. Furthermore, the results suggest a complex self-amplification of highly modular equivalence classes in the case of respected relations. Since the well-known Holland schemata are just the equivalence classes of respected relations in most Simple Genetic Algorithms, this observation emphasizes the role of schemata as Building Blocks (in comparison with arbitrary subsets of the search space).

Algorithms↗

Estimating genomic coexpression networks using first-order conditional independence.

We describe a computationally efficient statistical framework for estimating networks of coexpressed genes. This framework exploits first-order conditional independence relationships among gene-expression measurements to estimate patterns of association. We use this approach to estimate a coexpression network from microarray gene-expression measurements from Saccharomyces cerevisiae. We demonstrate the biological utility of this approach by showing that a large number of metabolic pathways are coherently represented in the estimated network. We describe a complementary unsupervised graph search algorithm for discovering locally distinct subgraphs of a large weighted graph. We apply this algorithm to our coexpression network model and show that subgraphs found using this approach correspond to particular biological processes or contain representatives of distinct gene families.

Algorithms↗

The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord.

Spontaneous episodic activity occurs throughout the developing nervous system because immature circuits are hyperexcitable. It is not fully understood how the temporal pattern of this activity is regulated. Here, we study the role of activity-dependent depression of network excitability in the generation and regulation of spontaneous activity in the embryonic chick spinal cord. We demonstrate that the duration of an episode of activity depends on the network excitability at the beginning of the episode. We found a positive correlation between episode duration and the preceding inter-episode interval, but not with the following interval, suggesting that episode onset is stochastic whereas episode termination occurs deterministically, when network excitability falls to a fixed level. This is true over a wide range of developmental stages and under blockade of glutamatergic or GABAergic/glycinergic synapses. We also demonstrate that during glutamatergic blockade the remaining part of the network becomes more excitable, compensating for the loss of glutamatergic synapses and allowing spontaneous activity to recover. This compensatory increase in the excitability of the remaining network reflects the progressive increase in synaptic efficacy that occurs in the absence of activity. Therefore, the mechanism responsible for the episodic nature of the activity automatically renders this activity robust to network disruptions. The results are presented using the framework of our computational model of spontaneous activity in the developing cord. Specifically, we show how they follow logically from a bistable network with a slow activity-dependent depression switching periodically between the active and inactive states.

Animals↗

Cohort parity analysis: statistical estimates of the extent of fertility control.

Cohort parity analysis (CPA) is a method for indirect measurement of the extent and timing of the adoption of fertility control within marriage. It uses information on the parity distribution of a cohort of women of specified marriage ages and durations. A multinomial model of parity provides a convenient framework for the computation of distributional parameters describing the extent to which marital fertility control has been accepted and characterizing the way control has been used within specific durations of marriage. This leads to a pair of easily implemented formulas for upper- and lower-bound estimates of the expected proportion of the population ever controlling and the distribution of controllers by parity. The power of CPA is illustrated, using census data for currently married couples in Dublin, Belfast, and other county boroughs of Ireland in 1911.

Adult↗

CT of the nasopharyngeal region. Normal and pathologic anatomy.

The soft tissue anatomy of the nasopharynx is presented in terms of deglutitional and masticatory muscle layers. Within this framework of analysis, computed tomography can detect relatively early soft tissue changes of nasopharyngeal carcinoma.

Deglutition↗

Digital archives and communication highways in health care require a second look at the legal framework of the seventies.

The present state of the art and the state of practice regarding legal aspects of medical informatics are reported. Examples are taken from networking, archiving, and virtual reality. It is derived that the data protection concepts of the seventies are covering only some legal aspects of the application scene today and in the future. Thus a far wider legal approach is necessary. It can only be mastered if engineers and lawyers discuss future trends and derive together a new legal framework for medical computer systems in the late nineties. As computers will be everywhere from childhood to death the key issue is not to just protect an individual but to positively frame an information society.

Computer Communication Networks↗

The receptor revolution--multiplicity of G-protein-coupled receptors.

The superfamily of G-protein-coupled receptors (GPCR) is probably the largest protein-encoding gene family in our genome. It is already known to include hundreds of members and many more are expected to emerge as the molecular cloning revolution proceeds. By definition the GPCR respond to ligands by interacting with intracellular G-proteins and thereby transduce external signals to the interior of the cell. A large body of evidence suggests that the GPCR are organized in the cell membrane like bacteriorhodopsin (BR). All GPCR possess seven hydrophobic membrane-spanning segments which seem to form a characteristic BR-like barrel structure. Thus, the three-dimensional structure of BR may be used as a framework for computer-aided structural modelling of GPCR. The ligands which activate the various members of the GPCR family include an enormous variety of molecules such as amines, amino acids and peptides as well as several small hydrophobic molecules. Many ligands bind to multiple distinct GPCR, e.g. neuropeptide Y (NPY). We have isolated molecular clones encoding a human NPY receptor whose binding properties conform to those of the Y1 subtype. This clone will be a useful tool in our efforts to unravel the molecular mechanisms of the many physiological functions of neuropeptide Y.

Amino Acid Sequence↗

Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration.

In bone tissue engineering using a biodegradable scaffold, geometry of the porous scaffold microstructure is a key factor for controlling mechanical function of the bone-scaffold system in the regeneration process as well as after the regeneration. In this study, we propose a framework for the optimal design of the porous scaffold microstructure by three-dimensional computational simulation of bone tissue regeneration that consists of scaffold degradation and new bone formation. The rate of scaffold degradation due to hydrolysis, that leads to decrease in mechanical properties, was simply assumed to relate to the water content diffused from the surface to the bulk material. For the new bone formation on both bone and scaffold surfaces, the rate equation of trabecular surface remodeling driven by mechanical stimulation was applied. Solving these two phenomena in the same time frame, the bone regeneration process in the bone-scaffold system was predicted by computational simulation using a voxel finite element method. The change in the mechanical function of the bone-scaffold system during the regeneration process was quantitatively evaluated by measuring the change in total strain energy, and this was used for the evaluation function to optimize the scaffold microstructure that provides the desired mechanical function during and after the bone regeneration process. A case study conducted for the scaffold with a simple microstructure demonstrated that the proposed simulation method could be applied to the design of a porous scaffold microstructure. In addition, the regeneration process was found to be very complex even though the simple rate equations for scaffold regeneration and new bone formation were used because of the coupling effects of these phenomena.

Animals↗

Adaptive algorithms for first principal eigenvector computation.

The paper presents a unified framework to derive and analyze 10 different adaptive algorithms, some well-known, to compute the first principal eigenvector of the correlation matrix of a random vector sequence. Since adaptive principal eigenvector algorithms have originated from a diverse set of disciplines, including ad hoc methods, it is necessary to examine them in a unified framework. In a common framework consisting of five steps, we analyze the derivation, convergence, and rate results for many well-known algorithms as well as two new adaptive algorithms. In the process, we offer fresh perspectives on the known algorithms, and derive new results for others. The common framework also allows us to comparatively study the 10 algorithms. Finally, we show experimental results to support our analyses.

Algorithms↗