Search

The automatic clustering of chemical compounds is an important branch of chemoinformatics. In this paper the Asymmetric Clustering Index (Aci) is proposed to assess how well an automatically created partition reflects the reference. The asymmetry allows for a distinction between the fixed reference and the numerically constructed partition. The introduced index is applied to evaluate the quality of hierarchical clustering procedures for 5-HT1A receptor ligands. We find that the most appropriate combination of parameters for the hierarchical clustering of compounds with a determined activity for this biological target is the Klekota Roth fingerprint combined with the complete linkage function and the Buser similarity metric. [ABSTRACT FROM AUTHOR]

Predicting the stock market has become an increasingly interesting research area for both researchers and investors, and many prediction models have been proposed. In these models, feature selection techniques are used to pre-process the raw data and remove noise. In this paper, a prediction model is constructed to forecast stock market behavior with the aid of independent component analysis, canonical correlation analysis, and a support vector machine. First, two types of features are extracted from the historical closing prices and 39 technical variables obtained by independent component analysis. Second, a canonical correlation analysis method is utilized to combine the two types of features and extract intrinsic features to improve the performance of the prediction model. Finally, a support vector machine is applied to forecast the next day's closing price. The proposed model is applied to the Shanghai stock market index and the Dow Jones index, and experimental results show that the proposed model performs better in the area of prediction than other two similar models. [ABSTRACT FROM AUTHOR]

Transient starch in leaves is synthesized by various biosynthetic enzymes in the chloroplasts during the light period. This paper presents the first mathematical model for the (bio)synthesis of the chain-length distribution (CLD) of transient starch to aid the understanding of this synthesis. The model expresses the rate of change of the CLD in terms of the actions of the enzymes involved. Using this to simulate the experimental CLD with different enzyme combinations is a new means to test for enzymes that are significant to the rate of change of the CLD during synthesis. Comparison between the simulated CLD from different enzyme combinations and the experimental CLD in the leaves of the model plant Arabidopsis thaliana indicate α-amylase, in addition to the core starch biosynthetic enzymes, is also involved in the modification of glucans for the synthesis of insoluble starch granules. The simulations suggest involvement of β-amylase, in the absence of α-amylase in mutants, slows the rate of attaining a crystalline-competent CLD for crystallization of glucans to form insoluble starch. This suggests a minor role of β-amylase in shaping normal starch synthesis. The model simulation predicts that debranching of glucans is an efficient mechanism for the attainment of crystalline-competent CLD; however, attaining this is still possible, albeit slower, through combinations of α- and β-amylase in the absence of isoamylase-type debranching enzyme. In Arabidopsis defective in one of the isoamylase-type debranching enzymes, the impact of α-amylase in starch synthesis is reduced, while β-amylase becomes significantly involved, slowing the rate of synthesis in this mutant. Modeling of transient starch CLD brings to light previously unrecognized but significant effects of α- and β-amylase on the rate of transient starch synthesis. [ABSTRACT FROM AUTHOR]

Background: Synthesizing and characterizing aptamers with high affinity and specificity have been extensively carried out for analytical and biomedical applications. Few publications can be found that describe structure–activity relationships (SARs) of candidate aptamer sequences. Methodology: This paper reports pattern recognition with support vector machine (SVM) classification techniques for the identification of streptavidin-binding aptamers as “low” or “high” affinity aptamers. The SVM parameters C and γ were optimized using genetic algorithms. Four descriptors, the topological descriptor PW4 (path/walk 4 - Randic shape index), the connectivity index X3A (average connectivity index chi-3), the topological charge index JGI2 (mean topological charge index of order 2), and the free energy E of the secondary structure, were used to describe the structures of candidate aptamer sequences from SELEX selection (Schütze et al. (2011) PLoS ONE (12):e29604). Conclusions: The predicted fractions of winning streptavidin-binding aptamers for ten rounds of SELEX conform to the aptamer evolutionary principles of SELEX-based screening. The feasibility of applying pattern recognition based on SVM and genetic algorithms for streptavidin-binding aptamers has been demonstrated. [ABSTRACT FROM AUTHOR]

Web services today are among the most widely used groups for Service Oriented Architecture (SOA). Service selection is one of the most significant current discussions in SOA, which evaluates discovered services and chooses the best candidate from them. Although a majority of service selection techniques apply Quality of Service (QoS), the behaviour of QoS-based service selection leads to service selection problems in Multi-Criteria Decision Making (MCDM). In the existing works, the confidence level of decision makers is neglected and does not consider their expertise in assessing Web services. In this paper, we employ the VIKOR (VIšekriterijumskoKOmpromisnoRangiranje) method, which is absent in the literature for service selection, but is well-known in other research. We propose a QoS-based approach that deals with service selection by applying VIKOR with improvement of features. This research determines the weights of criteria based on user preference and accounts for the confidence level of decision makers. The proposed approach is illustrated by an example in order to demonstrate and validate the model. The results of this research may facilitate service consumers to attain a more efficient decision when selecting the appropriate service. [ABSTRACT FROM AUTHOR]

Labeled graphs are widely used to model complex data in many domains, so subgraph querying has been attracting more and more attention from researchers around the world. Unfortunately, subgraph querying is very time consuming since it involves subgraph isomorphism testing that is known to be an NP-complete problem. In this paper, we propose a novel coding method for subgraph querying that is based on Laplacian spectrum and the number of walks. Our method follows the filtering-and-verification framework and works well on graph databases with frequent updates. We also propose novel two-step filtering conditions that can filter out most false positives and prove that the two-step filtering conditions satisfy the no-false-negative requirement (no dismissal in answers). Extensive experiments on both real and synthetic graphs show that, compared with six existing counterpart methods, our method can effectively improve the efficiency of subgraph querying. [ABSTRACT FROM AUTHOR]

An increasing number of genes have been experimentally confirmed in recent years as causative genes to various human diseases. The newly available knowledge can be exploited by machine learning methods to discover additional unknown genes that are likely to be associated with diseases. In particular, positive unlabeled learning (PU learning) methods, which require only a positive training set P (confirmed disease genes) and an unlabeled set U (the unknown candidate genes) instead of a negative training set N, have been shown to be effective in uncovering new disease genes in the current scenario. Using only a single source of data for prediction can be susceptible to bias due to incompleteness and noise in the genomic data and a single machine learning predictor prone to bias caused by inherent limitations of individual methods. In this paper, we propose an effective PU learning framework that integrates multiple biological data sources and an ensemble of powerful machine learning classifiers for disease gene identification. Our proposed method integrates data from multiple biological sources for training PU learning classifiers. A novel ensemble-based PU learning method EPU is then used to integrate multiple PU learning classifiers to achieve accurate and robust disease gene predictions. Our evaluation experiments across six disease groups showed that EPU achieved significantly better results compared with various state-of-the-art prediction methods as well as ensemble learning classifiers. Through integrating multiple biological data sources for training and the outputs of an ensemble of PU learning classifiers for prediction, we are able to minimize the potential bias and errors in individual data sources and machine learning algorithms to achieve more accurate and robust disease gene predictions. In the future, our EPU method provides an effective framework to integrate the additional biological and computational resources for better disease gene predictions. [ABSTRACT FROM AUTHOR]

Based on the necessity for enclosure protection of temperature and relative humidity sensors installed in a hostile environment, a wind tunnel was used to quantify the time that the sensors take to reach equilibrium in the environmental conditions to which they are exposed. Two treatments were used: (1) sensors with polyvinyl chloride (PVC) enclosure protection, and (2) sensors with no enclosure protection. The primary objective of this study was to develop and validate a 3-D computational fluid dynamics (CFD) model for analyzing the temperature and relative humidity distribution in a wind tunnel using sensors with PVC enclosure protection and sensors with no enclosure protection. A CFD simulation model was developed to describe the temperature distribution and the physics of mass transfer related to the airflow relative humidity. The first results demonstrate the applicability of the simulation. For verification, a sensor device was successfully assembled and tested in an environment that was optimized to ensure fast change conditions. The quantification setup presented in this paper is thus considered to be adequate for testing different materials and morphologies for enclosure protection. The results show that the boundary layer flow regime has a significant impact on the heat flux distribution. The results indicate that the CFD technique is a powerful tool which provides a detailed description of the flow and temperature fields as well as the time that the relative humidity takes to reach equilibrium with the environment in which the sensors are inserted. [ABSTRACT FROM AUTHOR]

There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm. [ABSTRACT FROM AUTHOR]

Collections of biological specimens are fundamental to scientific understanding and characterization of natural diversity—past, present and future. This paper presents a system for liberating useful information from physical collections by bringing specimens into the digital domain so they can be more readily shared, analyzed, annotated and compared. It focuses on insects and is strongly motivated by the desire to accelerate and augment current practices in insect taxonomy which predominantly use text, 2D diagrams and images to describe and characterize species. While these traditional kinds of descriptions are informative and useful, they cannot cover insect specimens “from all angles” and precious specimens are still exchanged between researchers and collections for this reason. Furthermore, insects can be complex in structure and pose many challenges to computer vision systems. We present a new prototype for a practical, cost-effective system of off-the-shelf components to acquire natural-colour 3D models of insects from around 3 mm to 30 mm in length. (“Natural-colour” is used to contrast with “false-colour”, i.e., colour generated from, or applied to, gray-scale data post-acquisition.) Colour images are captured from different angles and focal depths using a digital single lens reflex (DSLR) camera rig and two-axis turntable. These 2D images are processed into 3D reconstructions using software based on a visual hull algorithm. The resulting models are compact (around 10 megabytes), afford excellent optical resolution, and can be readily embedded into documents and web pages, as well as viewed on mobile devices. The system is portable, safe, relatively affordable, and complements the sort of volumetric data that can be acquired by computed tomography. This system provides a new way to augment the description and documentation of insect species holotypes, reducing the need to handle or ship specimens. It opens up new opportunities to collect data for research, education, art, entertainment, biodiversity assessment and biosecurity control. [ABSTRACT FROM AUTHOR]

In biological systems, the dynamic analysis method has gained increasing attention in the past decade. The Boolean network is the most common model of a genetic regulatory network. The interactions of activation and inhibition in the genetic regulatory network are modeled as a set of functions of the Boolean network, while the state transitions in the Boolean network reflect the dynamic property of a genetic regulatory network. A difficult problem for state transition analysis is the finding of attractors. In this paper, we modeled the genetic regulatory network as a Boolean network and proposed a solving algorithm to tackle the attractor finding problem. In the proposed algorithm, we partitioned the Boolean network into several blocks consisting of the strongly connected components according to their gradients, and defined the connection between blocks as decision node. Based on the solutions calculated on the decision nodes and using a satisfiability solving algorithm, we identified the attractors in the state transition graph of each block. The proposed algorithm is benchmarked on a variety of genetic regulatory networks. Compared with existing algorithms, it achieved similar performance on small test cases, and outperformed it on larger and more complex ones, which happens to be the trend of the modern genetic regulatory network. Furthermore, while the existing satisfiability-based algorithms cannot be parallelized due to their inherent algorithm design, the proposed algorithm exhibits a good scalability on parallel computing architectures. [ABSTRACT FROM AUTHOR]

Understanding the fire prediction capabilities of fuel models is vital to forest fire management. Various fuel models have been developed in the Great Xing'an Mountains in Northeast China. However, the performances of these fuel models have not been tested for historical occurrences of wildfires. Consequently, the applicability of these models requires further investigation. Thus, this paper aims to develop standard fuel models. Seven vegetation types were combined into three fuel models according to potential fire behaviors which were clustered using Euclidean distance algorithms. Fuel model parameter sensitivity was analyzed by the Morris screening method. Results showed that the fuel model parameters 1-hour time-lag loading, dead heat content, live heat content, 1-hour time-lag SAV(Surface Area-to-Volume), live shrub SAV, and fuel bed depth have high sensitivity. Two main sensitive fuel parameters: 1-hour time-lag loading and fuel bed depth, were determined as adjustment parameters because of their high spatio-temporal variability. The FARSITE model was then used to test the fire prediction capabilities of the combined fuel models (uncalibrated fuel models). FARSITE was shown to yield an unrealistic prediction of the historical fire. However, the calibrated fuel models significantly improved the capabilities of the fuel models to predict the actual fire with an accuracy of 89%. Validation results also showed that the model can estimate the actual fires with an accuracy exceeding 56% by using the calibrated fuel models. Therefore, these fuel models can be efficiently used to calculate fire behaviors, which can be helpful in forest fire management. [ABSTRACT FROM AUTHOR]

With the development of medical imaging modalities and image processing algorithms, there arises a need for methods of their comprehensive quantitative evaluation. In particular, this concerns the algorithms for vessel tracking and segmentation in magnetic resonance angiography images. The problem can be approached by using synthetic images, where true geometry of vessels is known. This paper presents a framework for computer modeling of MRA imaging and the results of its validation. A new model incorporates blood flow simulation within MR signal computation kernel. The proposed solution is unique, especially with respect to the interface between flow and image formation processes. Furthermore it utilizes the concept of particle tracing. The particles reflect the flow of fluid they are immersed in and they are assigned magnetization vectors with temporal evolution controlled by MR physics. Such an approach ensures flexibility as the designed simulator is able to reconstruct flow profiles of any type. The proposed model is validated in a series of experiments with physical and digital flow phantoms. The synthesized 3D images contain various features (including artifacts) characteristic for the time-of-flight protocol and exhibit remarkable correlation with the data acquired in a real MR scanner. The obtained results support the primary goal of the conducted research, i.e. establishing a reference technique for a quantified validation of MR angiography image processing algorithms. [ABSTRACT FROM AUTHOR]

Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational modeling to study the strategies of protein transport in the context of JNK (c-JUN NH2-terminal kinase) transport along microtubules to the terminals of neuronal cells. One such strategy for protein transport is for the proteins of the JNK signaling cascade to bind to scaffolds, and to have the whole protein-scaffold cargo transported by kinesin motors along microtubules. We show how this strategy outperforms protein transport by diffusion alone, using metrics such as signaling rate and signal amplification. We find that there exists a range of scaffold concentrations for which JNK transport is optimal. Increase in scaffold concentration increases signaling rate and signal amplification but an excess of scaffolds results in the dilution of reactants. Similarly, there exists a range of kinesin motor speeds for which JNK transport is optimal. Signaling rate and signal amplification increases with kinesin motor speed until the speed of motor translocation becomes faster than kinase/scaffold-motor binding. Finally, we suggest experiments that can be performed to validate whether, in physiological conditions, neuronal cells do indeed adopt such an optimal strategy. Understanding cytoskeletal-assisted protein transport is crucial since axonal and cell body accumulation of organelles and proteins is a histological feature in many human neurodegenerative diseases. In this paper, we have shown that axonal transport performance changes with altered transport component concentrations and transport speeds wherein these aspects can be modulated to improve axonal efficiency and prevent or slowdown axonal deterioration. [ABSTRACT FROM AUTHOR]

This paper proposes an efficient mixture model for establishing robust point correspondences between two sets of points under multi-layer motion. Our algorithm starts by creating a set of putative correspondences which can contain a number of false correspondences, or outliers, in addition to the true correspondences (inliers). Next we solve for correspondence by interpolating a set of spatial transformations on the putative correspondence set based on a mixture model, which involves estimating a consensus of inlier points whose matching follows a non-parametric geometrical constraint. We formulate this as a maximum a posteriori (MAP) estimation of a Bayesian model with hidden/latent variables indicating whether matches in the putative set are outliers or inliers. We impose non-parametric geometrical constraints on the correspondence, as a prior distribution, in a reproducing kernel Hilbert space (RKHS). MAP estimation is performed by the EM algorithm which by also estimating the variance of the prior model (initialized to a large value) is able to obtain good estimates very quickly (e.g., avoiding many of the local minima inherent in this formulation). We further provide a fast implementation based on sparse approximation which can achieve a significant speed-up without much performance degradation. We illustrate the proposed method on 2D and 3D real images for sparse feature correspondence, as well as a public available dataset for shape matching. The quantitative results demonstrate that our method is robust to non-rigid deformation and multi-layer/large discontinuous motion. [ABSTRACT FROM AUTHOR]

This paper focuses on real-time rotation estimation for model-based automated visual inspection. In the case of model-based inspection, spatial alignment is essential to distinguish visual defects from normal appearance variations. Defects are detected by comparing the inspected object with its spatially aligned ideal reference model. Rotation estimation is crucial for the inspection of rotationally symmetric objects where mechanical manipulation is unable to ensure the correct object rotation. We propose a novel method for in-plane rotation estimation. Rotation is estimated with an ensemble of nearest-neighbor estimators. Each estimator contains a spatially local representation of an object in a feature space for all rotation angles and is constructed with a semi-supervised self-training approach from a set of unlabeled training images. An individual representation in a feature space is obtained by calculating the Histograms of Oriented Gradients (HOG) over a spatially local region. Each estimator votes separately for the estimated angle; all votes are weighted and accumulated. The final estimation is the angle with the most votes. The method was evaluated on several datasets of pharmaceutical tablets varying in size, shape, and color. The results show that the proposed method is superior in robustness with comparable speed and accuracy to previously proposed methods for rotation estimation of pharmaceutical tablets. Furthermore, all evaluations were performed with the same set of parameters, which implies that the method requires minimal human intervention. Despite the evaluation focused on pharmaceutical tablets, we consider the method useful for any application that requires robust real-time in-plane rotation estimation. [ABSTRACT FROM AUTHOR]

Interleukin-12 is a pro-inflammatory cytokine which promotes Th1 and cytotoxic T lymphocyte activities, such as Interferon- secretion. For this reason Interleukin-12 could be a powerful therapeutic agent for cancer treatment. However, Interleukin-12 is also excessively toxic. Interleukin-27 is an immunoregulatory cytokine from the Interleukin-12 family, but it is not as toxic as Interleukin-12. In recent years, Interleukin-27 has been considered as a potential anti-tumor agent. Recent experiments in vitro and in vivo have shown that cancer cells transfected with IL-27 activate CD8+ T cells to promote the secretion of anti-tumor cytokines Interleukin-10, although, at the same time, IL-27 inhibits the secretion of Interferon- by CD8+ T cells. In the present paper we develop a mathematical model based on these experimental results. The model involves a dynamic network which includes tumor cells, CD8+ T cells and cytokines Interleukin-27, Interleukin-10 and Interferon-. Simulations of the model show how Interleukin-27 promotes CD8+ T cells to secrete Interleukin-10 to inhibit tumor growth. On the other hand Interleukin-27 inhibits the secretion of Interferon- by CD8+ T cells which somewhat diminishes the inhibition of tumor growth. Our numerical results are in qualitative agreement with experimental data. We use the model to design protocols of IL-27 injections for the treatment of cancer and find that, for some special types of cancer, with a fixed total amount of drug, within a certain range, continuous injection has better efficacy than intermittent injections in reducing the tumor load while the treatment is ongoing, although the decrease in tumor load is only temporary. [ABSTRACT FROM AUTHOR]

This paper describes osmotically-driven pressure generation in a membrane-bound compartment while taking into account volume expansion, solute dilution, surface area to volume ratio, membrane hydraulic permeability, and changes in osmotic gradient, bulk modulus, and degree of membrane fouling. The emphasis lies on the dynamics of pressure generation; these dynamics have not previously been described in detail. Experimental results are compared to and supported by numerical simulations, which we make accessible as an open source tool. This approach reveals unintuitive results about the quantitative dependence of the speed of pressure generation on the relevant and interdependent parameters that will be encountered in most osmotically-driven pressure generators. For instance, restricting the volume expansion of a compartment allows it to generate its first 5 kPa of pressure seven times faster than without a restraint. In addition, this dynamics study shows that plants are near-ideal osmotic pressure generators, as they are composed of many small compartments with large surface area to volume ratios and strong cell wall reinforcements. Finally, we demonstrate two applications of an osmosis-based pressure generator: actuation of a soft robot and continuous volume delivery over long periods of time. Both applications do not need an external power source but rather take advantage of the energy released upon watering the pressure generators. [ABSTRACT FROM AUTHOR]

In this paper, based on the gravity principle of classical physics, we propose a tunable gravity-based model, which considers tag usage pattern to weigh both the mass and distance of network nodes. We then apply this model in solving the problems of information filtering and network evolving. Experimental results on two real-world data sets, Del.icio.us and MovieLens, show that it can not only enhance the algorithmic performance, but can also better characterize the properties of real networks. This work may shed some light on the in-depth understanding of the effect of gravity model. [ABSTRACT FROM AUTHOR]

Time-course gene expression datasets, which record continuous biological processes of genes, have recently been used to predict gene function. However, only few positive genes can be obtained from annotation databases, such as gene ontology (GO). To obtain more useful information and effectively predict gene function, gene annotations are clustered together to form a learnable and effective learning system. In this paper, we propose a novel multi-instance hierarchical clustering (MIHC) method to establish a learning system by clustering GO and compare this method with other learning system establishment methods. Multi-label support vector machine classifier and multi-label K-nearest neighbor classifier are used to verify these methods in four yeast time-course gene expression datasets. The MIHC method shows good performance, which serves as a guide to annotators or refines the annotation in detail. [ABSTRACT FROM AUTHOR]

Hundreds of millions of figures are available in biomedical literature, representing important biomedical experimental evidence. This ever-increasing sheer volume has made it difficult for scientists to effectively and accurately access figures of their interest, the process of which is crucial for validating research facts and for formulating or testing novel research hypotheses. Current figure search applications can't fully meet this challenge as the “bag of figures” assumption doesn't take into account the relationship among figures. In our previous study, hundreds of biomedical researchers have annotated articles in which they serve as corresponding authors. They ranked each figure in their paper based on a figure's importance at their discretion, referred to as “figure ranking”. Using this collection of annotated data, we investigated computational approaches to automatically rank figures. We exploited and extended the state-of-the-art listwise learning-to-rank algorithms and developed a new supervised-learning model BioFigRank. The cross-validation results show that BioFigRank yielded the best performance compared with other state-of-the-art computational models, and the greedy feature selection can further boost the ranking performance significantly. Furthermore, we carry out the evaluation by comparing BioFigRank with three-level competitive domain-specific human experts: (1) First Author, (2) Non-Author-In-Domain-Expert who is not the author nor co-author of an article but who works in the same field of the corresponding author of the article, and (3) Non-Author-Out-Domain-Expert who is not the author nor co-author of an article and who may or may not work in the same field of the corresponding author of an article. Our results show that BioFigRank outperforms Non-Author-Out-Domain-Expert and performs as well as Non-Author-In-Domain-Expert. Although BioFigRank underperforms First Author, since most biomedical researchers are either in- or out-domain-experts for an article, we conclude that BioFigRank represents an artificial intelligence system that offers expert-level intelligence to help biomedical researchers to navigate increasingly proliferated big data efficiently. [ABSTRACT FROM AUTHOR]

The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol). The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca2+]i transients; changes in intracellular and transmembrane Ca2+ fluxes; and [Na+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca2+]i transients. In particular, the model includes two subpopulations of the L-type Ca2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of mathematical models for other species or for pathological conditions. [ABSTRACT FROM AUTHOR]

Multiple sequence alignment is a crucial task in a number of biological analyses like secondary structure prediction, domain searching, phylogeny, etc. MSAProbs is currently the most accurate alignment algorithm, but its effectiveness is obtained at the expense of computational time. In the paper we present QuickProbs, the variant of MSAProbs customised for graphics processors. We selected the two most time consuming stages of MSAProbs to be redesigned for GPU execution: the posterior matrices calculation and the consistency transformation. Experiments on three popular benchmarks (BAliBASE, PREFAB, OXBench-X) on quad-core PC equipped with high-end graphics card show QuickProbs to be 5.7 to 9.7 times faster than original CPU-parallel MSAProbs. Additional tests performed on several protein families from Pfam database give overall speed-up of 6.7. Compared to other algorithms like MAFFT, MUSCLE, or ClustalW, QuickProbs proved to be much more accurate at similar speed. Additionally we introduce a tuned variant of QuickProbs which is significantly more accurate on sets of distantly related sequences than MSAProbs without exceeding its computation time. The GPU part of QuickProbs was implemented in OpenCL, thus the package is suitable for graphics processors produced by all major vendors. [ABSTRACT FROM AUTHOR]

The clinical notes in a given patient record contain much redundancy, in large part due to clinicians’ documentation habit of copying from previous notes in the record and pasting into a new note. Previous work has shown that this redundancy has a negative impact on the quality of text mining and topic modeling in particular. In this paper we describe a novel variant of Latent Dirichlet Allocation (LDA) topic modeling, Red-LDA, which takes into account the inherent redundancy of patient records when modeling content of clinical notes. To assess the value of Red-LDA, we experiment with three baselines and our novel redundancy-aware topic modeling method: given a large collection of patient records, (i) apply vanilla LDA to all documents in all input records; (ii) identify and remove all redundancy by chosing a single representative document for each record as input to LDA; (iii) identify and remove all redundant paragraphs in each record, leaving partial, non-redundant documents as input to LDA; and (iv) apply Red-LDA to all documents in all input records. Both quantitative evaluation carried out through log-likelihood on held-out data and topic coherence of produced topics and qualitative assessement of topics carried out by physicians show that Red-LDA produces superior models to all three baseline strategies. This research contributes to the emerging field of understanding the characteristics of the electronic health record and how to account for them in the framework of data mining. The code for the two redundancy-elimination baselines and Red-LDA is made publicly available to the community. [ABSTRACT FROM AUTHOR]

: Prediction and classification techniques have been well studied by machine learning researchers and developed for several real-word problems. However, the level of acceptance and success of prediction models are still below expectation due to some difficulties such as the low performance of prediction models when they are applied in different environments. Such a problem has been addressed by many researchers, mainly from the machine learning community. A second problem, principally raised by model users in different communities, such as managers, economists, engineers, biologists, and medical practitioners, etc., is the prediction models’ interpretability. The latter is the ability of a model to explain its predictions and exhibit the causality relationships between the inputs and the outputs. In the case of classification, a successful way to alleviate the low performance is to use ensemble classiers. It is an intuitive strategy to activate collaboration between different classifiers towards a better performance than individual classier. Unfortunately, ensemble classifiers method do not take into account the interpretability of the final classification outcome. It even worsens the original interpretability of the individual classifiers. In this paper we propose a novel implementation of classifiers combination approach that does not only promote the overall performance but also preserves the interpretability of the resulting model. We propose a solution based on Ant Colony Optimization and tailored for the case of Bayesian classifiers. We validate our proposed solution with case studies from medical domain namely, heart disease and Cardiotography-based predictions, problems where interpretability is critical to make appropriate clinical decisions. Availability: The datasets, Prediction Models and software tool together with supplementary materials are available at http://faculty.uaeu.ac.ae/salahb/ACO4BC.htm. [ABSTRACT FROM AUTHOR]

Local changes in land use result from the decisions and actions of land-users within land systems, which are structured by local and global environmental, economic, political, and cultural contexts. Such cross-scale causation presents a major challenge for developing a general understanding of how local decision-making shapes land-use changes at the global scale. This paper implements a generalized agent-based model (ABM) as a virtual laboratory to explore how global and local processes influence the land-use and livelihood decisions of local land-users, operationalized as settlement-level agents, across the landscapes of six real-world test sites. Test sites were chosen in USA, Laos, and China to capture globally-significant variation in population density, market influence, and environmental conditions, with land systems ranging from swidden to commercial agriculture. Publicly available global data were integrated into the ABM to model cross-scale effects of economic globalization on local land-use decisions. A suite of statistics was developed to assess the accuracy of model-predicted land-use outcomes relative to observed and random (i.e. null model) landscapes. At four of six sites, where environmental and demographic forces were important constraints on land-use choices, modeled land-use outcomes were more similar to those observed across sites than the null model. At the two sites in which market forces significantly influenced land-use and livelihood decisions, the model was a poorer predictor of land-use outcomes than the null model. Model successes and failures in simulating real-world land-use patterns enabled the testing of hypotheses on land-use decision-making and yielded insights on the importance of missing mechanisms. The virtual laboratory approach provides a practical framework for systematic improvement of both theory and predictive skill in land change science based on a continual process of experimentation and model enhancement. [ABSTRACT FROM AUTHOR]

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the reliability of a crowd simulation model developed by the authors by reproducing Dyer et al.'s experiments (published in Philosophical Transactions in 2009) on human leadership and consensus decision making in a computer-based environment. The theoretical crowd model of the simulation environment is presented, and its results are compared and analysed against Dyer et al.'s original experiments. It is concluded that the simulation results are largely consistent with the experiments, which demonstrates the reliability of the crowd model. Furthermore, the simulation data also reveals several additional new findings, namely: 1) the phenomena of sacrificing accuracy to reach a quicker consensus decision found in ants colonies was also discovered in the simulation; 2) the ability of reaching consensus in groups has a direct impact on the time and accuracy of arriving at the target position; 3) the positions of the informed individuals or leaders in the crowd could have significant impact on the overall crowd movement; and 4) the simulation also confirmed Dyer et al.'s anecdotal evidence of the proportion of the leadership in large crowds and its effect on crowd movement. The potential applications of these findings are highlighted in the final discussion of this paper. [ABSTRACT FROM AUTHOR]

Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. [ABSTRACT FROM AUTHOR]

In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP) is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential application for examining STDP by measuring neural population activity in a cultured neural network. [ABSTRACT FROM AUTHOR]

Backgroud: Type III secretion systems (T3SSs) are central to the pathogenesis and specifically deliver their secreted substrates (type III secreted proteins, T3SPs) into host cells. Since T3SPs play a crucial role in pathogen-host interactions, identifying them is crucial to our understanding of the pathogenic mechanisms of T3SSs. This study reports a novel and effective method for identifying the distinctive residues which are conserved different from other SPs for T3SPs prediction. Moreover, the importance of several sequence features was evaluated and further, a promising prediction model was constructed. Results: Based on the conservation profiles constructed by a position-specific scoring matrix (PSSM), 52 distinctive residues were identified. To our knowledge, this is the first attempt to identify the distinct residues of T3SPs. Of the 52 distinct residues, the first 30 amino acid residues are all included, which is consistent with previous studies reporting that the secretion signal generally occurs within the first 30 residue positions. However, the remaining 22 positions span residues 30–100 were also proven by our method to contain important signal information for T3SP secretion because the translocation of many effectors also depends on the chaperone-binding residues that follow the secretion signal. For further feature optimisation and compression, permutation importance analysis was conducted to select 62 optimal sequence features. A prediction model across 16 species was developed using random forest to classify T3SPs and non-T3 SPs, with high receiver operating curve of 0.93 in the 10-fold cross validation and an accuracy of 94.29% for the test set. Moreover, when performing on a common independent dataset, the results demonstrate that our method outperforms all the others published to date. Finally, the novel, experimentally confirmed T3 effectors were used to further demonstrate the model’s correct application. The model and all data used in this paper are freely available at http://cic.scu.edu.cn/bioinformatics/T3SPs.zip. [ABSTRACT FROM AUTHOR]

In modern logistics operations, large-scale logistics companies, besides active participation in profit-seeking commercial business, also play an essential role during an emergency relief process by dispatching urgently-required materials to disaster-affected areas. Therefore, an issue has been widely addressed by logistics practitioners and caught researchers' more attention as to how the logistics companies achieve maximum commercial profit on condition that emergency tasks are effectively and performed satisfactorily. In this paper, two vehicle scheduling models are proposed to solve the problem. One is a prediction-related scheme, which predicts the amounts of disaster-relief materials and commercial business and then accepts the business that will generate maximum profits; the other is a priority-directed scheme, which, firstly groups commercial and emergency business according to priority grades and then schedules both types of business jointly and simultaneously by arriving at the maximum priority in total. Moreover, computer-based simulations are carried out to evaluate the performance of these two models by comparing them with two traditional disaster-relief tactics in China. The results testify the feasibility and effectiveness of the proposed models. [ABSTRACT FROM AUTHOR]

Quality assessment (QA) for predicted protein structural models is an important and challenging research problem in protein structure prediction. Consensus Global Distance Test (CGDT) methods assess each decoy (predicted structural model) based on its structural similarity to all others in a decoy set and has been proved to work well when good decoys are in a majority cluster. Scoring functions evaluate each single decoy based on its structural properties. Both methods have their merits and limitations. In this paper, we present a novel method called PWCom, which consists of two neural networks sequentially to combine CGDT and single model scoring methods such as RW, DDFire and OPUS-Ca. Specifically, for every pair of decoys, the difference of the corresponding feature vectors is input to the first neural network which enables one to predict whether the decoy-pair are significantly different in terms of their GDT scores to the native. If yes, the second neural network is used to decide which one of the two is closer to the native structure. The quality score for each decoy in the pool is based on the number of winning times during the pairwise comparisons. Test results on three benchmark datasets from different model generation methods showed that PWCom significantly improves over consensus GDT and single scoring methods. The QA server (MUFOLD-Server) applying this method in CASP 10 QA category was ranked the second place in terms of Pearson and Spearman correlation performance. [ABSTRACT FROM AUTHOR]

In some large-scale face recognition task, such as driver license identification and law enforcement, the training set only contains one image per person. This situation is referred to as one sample problem. Because many face recognition techniques implicitly assume that several (at least two) images per person are available for training, they cannot deal with the one sample problem. This paper investigates principal component analysis (PCA), Fisher linear discriminant analysis (LDA), and locality preserving projections (LPP) and shows why they cannot perform well in one sample problem. After that, this paper presents four reasons that make one sample problem itself difficult: the small sample size problem; the lack of representative samples; the underestimated intra-class variation; and the overestimated inter-class variation. Based on the analysis, this paper proposes to enlarge the training set based on the inter-class relationship. This paper also extends LDA and LPP to extract features from the enlarged training set. The experimental results show the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Background: The electronic laboratory notebook (ELN) has the potential to replace the paper notebook with a marked-up digital record that can be searched and shared. However, it is a challenge to achieve these benefits without losing the usability and flexibility of traditional paper notebooks. We investigate a blog-based platform that addresses the issues associated with the development of a flexible system for recording scientific research. Methodology/Principal Findings: We chose a blog-based approach with the journal characteristics of traditional notebooks in mind, recognizing the potential for linking together procedures, materials, samples, observations, data, and analysis reports. We implemented the LabTrove blog system as a server process written in PHP, using a MySQL database to persist posts and other research objects. We incorporated a metadata framework that is both extensible and flexible while promoting consistency and structure where appropriate. Our experience thus far is that LabTrove is capable of providing a successful electronic laboratory recording system. Conclusions/Significance: LabTrove implements a one-item one-post system, which enables us to uniquely identify each element of the research record, such as data, samples, and protocols. This unique association between a post and a research element affords advantages for monitoring the use of materials and samples and for inspecting research processes. The combination of the one-item one-post system, consistent metadata, and full-text search provides us with a much more effective record than a paper notebook. The LabTrove approach provides a route towards reconciling the tensions and challenges that lie ahead in working towards the long-term goals for ELNs. LabTrove, an electronic laboratory notebook (ELN) system from the Smart Research Framework, based on a blog-type framework with full access control, facilitates the scientific experimental recording requirements for reproducibility, reuse, repurposing, and redeployment. [ABSTRACT FROM AUTHOR]

Distributed hash tables (DHTs) are usually used in the open networking environment, where they are vulnerable to Sybil attacks. Pebble-Rotating Game (PRG) mixes the nodes of the honest and the adversarial randomly, and can resist the Sybil attack efficiently. However, the adversary may have some tricks to corrupt the rule of PRG. This paper proposes a set of mechanisms to make the rule of PRG be obliged to obey. A new joining node must ask the Certificate Authority (CA) for its signature and certificate, which records the complete process on how a node joins the network and obtains the legitimacy of the node. Then, to prevent the adversary from accumulating identifiers, any node can make use of the latest certificate to judge whether one identifier is expired with the help of the replacement property of RPG. This paper analyzes in details the number of expired certificates which are needed to store in every node, and gives asymptotic solution of this problem. The analysis and simulations show that the mean number of the certificates stored in each node are , where n is the size of the network. [ABSTRACT FROM AUTHOR]

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code’s difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step ‘serverification’ protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org. [ABSTRACT FROM AUTHOR]

Accurate incidence forecasting of infectious disease is critical for early prevention and for better government strategic planning. In this paper, we present a comprehensive study of different forecasting methods based on the monthly incidence of typhoid fever. The seasonal autoregressive integrated moving average (SARIMA) model and three different models inspired by neural networks, namely, back propagation neural networks (BPNN), radial basis function neural networks (RBFNN), and Elman recurrent neural networks (ERNN) were compared. The differences as well as the advantages and disadvantages, among the SARIMA model and the neural networks were summarized and discussed. The data obtained for 2005 to 2009 and for 2010 from the Chinese Center for Disease Control and Prevention were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The results showed that RBFNN obtained the smallest MAE, MAPE and MSE in both the modeling and forecasting processes. The performances of the four models ranked in descending order were: RBFNN, ERNN, BPNN and the SARIMA model. [ABSTRACT FROM AUTHOR]

The gene encoding an NAD+-dependent, 3-hydroxyisobutyrate dehydrogenase (3HIBDH-IV) from Pseudomonas denitrificans ATCC 13867 was cloned and expressed in Escherichia coli BL 21 (DE3) and characterized to understand its physiological relevance in the degradation of 3-hydroxypropionic acid (3-HP). The deduced amino acid sequence showed high similarity to other 3-hydroxyisobutyrate dehydrogenase isozymes (3HIBDHs) of P. denitrificans ATCC 13867. A comparison of 3HIBDH-IV with its relevant enzymes along with molecular docking studies suggested that Lys171, Asn175 and Gly123 are important for its catalytic function on 3-hydroxyacids. The recombinant 3HIBDH-IV was purified to homogeneity utilizing a Ni-NTA-HP resin column in high yield. 3HIBDH-IV was very specific to (S)-3-hydroxyisobutyrate, but also catalyzed the oxidation of 3-HP to malonate semialdehyde. The specific activity and half-saturation constant (Km) for 3-HP at 30°C and pH 9.0 were determined to be 17 U/mg protein and 1.0 mM, respectively. Heavy metals, such as Ag+ and Hg2+, completely inhibited the 3HIBDH-IV activity, whereas dithiothreitol, 2-mercaptoethanol and ethylenediaminetetraacetic acid increased its activity 1.5–1.8-fold. This paper reports the characteristics of 3HIBDH-IV as well as its probable role in 3-HP degradation. [ABSTRACT FROM AUTHOR]

Backgrounds: Despite continuing progress in X-ray crystallography and high-field NMR spectroscopy for determination of three-dimensional protein structures, the number of unsolved and newly discovered sequences grows much faster than that of determined structures. Protein modeling methods can possibly bridge this huge sequence-structure gap with the development of computational science. A grand challenging problem is to predict three-dimensional protein structure from its primary structure (residues sequence) alone. However, predicting residue contact maps is a crucial and promising intermediate step towards final three-dimensional structure prediction. Better predictions of local and non-local contacts between residues can transform protein sequence alignment to structure alignment, which can finally improve template based three-dimensional protein structure predictors greatly. Methods: CNNcon, an improved multiple neural networks based contact map predictor using six sub-networks and one final cascade-network, was developed in this paper. Both the sub-networks and the final cascade-network were trained and tested with their corresponding data sets. While for testing, the target protein was first coded and then input to its corresponding sub-networks for prediction. After that, the intermediate results were input to the cascade-network to finish the final prediction. Results: The CNNcon can accurately predict 58.86% in average of contacts at a distance cutoff of 8 Å for proteins with lengths ranging from 51 to 450. The comparison results show that the present method performs better than the compared state-of-the-art predictors. Particularly, the prediction accuracy keeps steady with the increase of protein sequence length. It indicates that the CNNcon overcomes the thin density problem, with which other current predictors have trouble. This advantage makes the method valuable to the prediction of long length proteins. As a result, the effective prediction of long length proteins could be possible by the CNNcon. [ABSTRACT FROM AUTHOR]

Despite numerous technology advances, bioreactors are still mostly utilized as functional black-boxes where trial and error eventually leads to the desirable cellular outcome. Investigators have applied various computational approaches to understand the impact the internal dynamics of such devices has on overall cell growth, but such models cannot provide a comprehensive perspective regarding the system dynamics, due to limitations inherent to the underlying approaches. In this study, a novel multi-paradigm modeling platform capable of simulating the dynamic bidirectional relationship between cells and their microenvironment is presented. Designing the modeling platform entailed combining and coupling fully an agent-based modeling platform with a transport phenomena computational modeling framework. To demonstrate capability, the platform was used to study the impact of bioreactor parameters on the overall cell population behavior and vice versa. In order to achieve this, virtual bioreactors were constructed and seeded. The virtual cells, guided by a set of rules involving the simulated mass transport inside the bioreactor, as well as cell-related probabilistic parameters, were capable of displaying an array of behaviors such as proliferation, migration, chemotaxis and apoptosis. In this way the platform was shown to capture not only the impact of bioreactor transport processes on cellular behavior but also the influence that cellular activity wields on that very same local mass transport, thereby influencing overall cell growth. The platform was validated by simulating cellular chemotaxis in a virtual direct visualization chamber and comparing the simulation with its experimental analogue. The results presented in this paper are in agreement with published models of similar flavor. The modeling platform can be used as a concept selection tool to optimize bioreactor design specifications. [ABSTRACT FROM AUTHOR]

Forest surveys provide critical information for many diverse interests. Data are often collected from samples, and from these samples, maps of resources and estimates of aerial totals or averages are required. In this paper, two approaches for mapping and estimating totals; the spatial linear model (SLM) and k-NN (k-Nearest Neighbor) are compared, theoretically, through simulations, and as applied to real forestry data. While both methods have desirable properties, a review shows that the SLM has prediction optimality properties, and can be quite robust. Simulations of artificial populations and resamplings of real forestry data show that the SLM has smaller empirical root-mean-squared prediction errors (RMSPE) for a wide variety of data types, with generally less bias and better interval coverage than k-NN. These patterns held for both point predictions and for population totals or averages, with the SLM reducing RMSPE from 9% to 67% over some popular k-NN methods, with SLM also more robust to spatially imbalanced sampling. Estimating prediction standard errors remains a problem for k-NN predictors, despite recent attempts using model-based methods. Our conclusions are that the SLM should generally be used rather than k-NN if the goal is accurate mapping or estimation of population totals or averages. [ABSTRACT FROM AUTHOR]

This paper studies the output-input signal-to-noise ratio (SNR) gain of an uncoupled parallel array of static, yet arbitrary, nonlinear elements for transmitting a weak periodic signal in additive white noise. In the small-signal limit, an explicit expression for the SNR gain is derived. It serves to prove that the SNR gain is always a monotonically increasing function of the array size for any given nonlinearity and noisy environment. It also determines the SNR gain maximized by the locally optimal nonlinearity as the upper bound of the SNR gain achieved by an array of static nonlinear elements. With locally optimal nonlinearity, it is demonstrated that stochastic resonance cannot occur, i.e. adding internal noise into the array never improves the SNR gain. However, in an array of suboptimal but easily implemented threshold nonlinearities, we show the feasibility of situations where stochastic resonance occurs, and also the possibility of the SNR gain exceeding unity for a wide range of input noise distributions. [ABSTRACT FROM AUTHOR]

To help understand how semantic information is represented in the human brain, a number of previous studies have explored how a linear mapping from corpus derived semantic representations to corresponding patterns of fMRI brain activations can be learned. They have demonstrated that such a mapping for concrete nouns is able to predict brain activations with accuracy levels significantly above chance, but the more recent elaborations have achieved relatively little performance improvement over the original study. In fact, the absolute accuracies of all these models are still currently rather limited, and it is not clear which aspects of the approach need improving in order to achieve performance levels that might lead to better accounts of human capabilities. This paper presents a systematic series of computational experiments designed to identify the limiting factors of the approach. Two distinct series of artificial brain activation vectors with varying levels of noise are introduced to characterize how the brain activation data restricts performance, and improved corpus based semantic vectors are developed to determine how the word set and model inputs affect the results. These experiments lead to the conclusion that the current state-of-the-art input semantic representations are already operating nearly perfectly (at least for non-ambiguous concrete nouns), and that it is primarily the quality of the fMRI data that is limiting what can be achieved with this approach. The results allow the study to end with empirically informed suggestions about the best directions for future research in this area. [ABSTRACT FROM AUTHOR]

Neoclassical noncooperative game theory is based on a simple, yet powerful synthesis of mathematical and logical concepts: unconditional and immutable preference orderings and individual rationality. Although this structure has proven useful for characterizing competitive multi-player behavior, its applicability to scenarios involving complex social relationships is problematic. In this paper we directly address this limitation by the introduction of a conditional preference structure that permits players to modulate their preference orderings as functions of the preferences of other players. Embedding this expanded preference structure in a formal and graphical framework provides a systematic approach for characterizing a complex society. The result is an influence network that allows conditional preferences to propagate through the community, resulting in an emergent social model which characterizes all of the social relationships that exist and which leads to solution concepts that account for both group and individual interests. The Ultimatum game is presented as an example of how social influence can be modeled with conditional preferences. [ABSTRACT FROM AUTHOR]

The analysis of biological information from protein sequences is important for the study of cellular functions and interactions, and protein fold recognition plays a key role in the prediction of protein structures. Unfortunately, the prediction of protein fold patterns is challenging due to the existence of compound protein structures. Here, we processed the latest release of the Structural Classification of Proteins (SCOP, version 1.75) database and exploited novel techniques to impressively increase the accuracy of protein fold classification. The techniques proposed in this paper include ensemble classifying and a hierarchical framework, in the first layer of which similar or redundant sequences were deleted in two manners; a set of base classifiers, fused by various selection strategies, divides the input into seven classes; in the second layer of which, an analogous ensemble method is adopted to predict all protein folds. To our knowledge, it is the first time all protein folds can be intelligently detected hierarchically. Compared with prior studies, our experimental results demonstrated the efficiency and effectiveness of our proposed method, which achieved a success rate of 74.21%, which is much higher than results obtained with previous methods (ranging from 45.6% to 70.5%). When applied to the second layer of classification, the prediction accuracy was in the range between 23.13% and 46.05%. This value, which may not be remarkably high, is scientifically admirable and encouraging as compared to the relatively low counts of proteins from most fold recognition programs. The web server Hierarchical Protein Fold Prediction (HPFP) is available at http://datamining.xmu.edu.cn/software/hpfp. [ABSTRACT FROM AUTHOR]

In this paper I investigate the evolution of cooperation in the prisoner's dilemma when individuals change their strategies subject to performance evaluation of their neighbours over variable time horizons. In the monochrome setting, in which all agents per default share the same performance evaluation rule, weighing past events strongly dramatically enhances the prevalence of cooperators. For co-evolutionary models, in which evaluation time horizons and strategies can co-evolve, I demonstrate that cooperation naturally associates with long-term evaluation of others while defection is typically paired with very short time horizons. Moreover, considering the continuous spectrum in between enhanced and discounted weights of past performance, cooperation is optimally supported when cooperators neither give enhanced weight to past nor more recent events, but simply average payoffs. Payoff averaging is also found to emerge as the dominant strategy for cooperators in co-evolutionary models, thus proposing a natural route to the evolution of cooperation in viscous populations. [ABSTRACT FROM AUTHOR]

We present a novel formulation for biochemical reaction networks in the context of protein signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of “source” species, which are interpreted as input signals. Signals are transmitted to all other species in the system (the “target” species) with a specific delay and with a specific transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and even recalled to build dynamical models on the basis of state changes. By separating the temporal and the magnitudinal domain we can greatly simplify the computational model, circumventing typical problems of complex dynamical systems. The transfer function transformation of biochemical reaction systems can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant novel insights while remaining a fully testable and executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modularizations that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. Remarkably, we found that overall interconnectedness depends on the magnitude of inputs, with higher connectivity at low input concentrations and significant modularization at moderate to high input concentrations. This general result, which directly follows from the properties of individual transfer functions, contradicts notions of ubiquitous complexity by showing input-dependent signal transmission inactivation. [ABSTRACT FROM AUTHOR]

The one-sample-per-person problem has become an active research topic for face recognition in recent years because of its challenges and significance for real-world applications. However, achieving relatively higher recognition accuracy is still a difficult problem due to, usually, too few training samples being available and variations of illumination and expression. To alleviate the negative effects caused by these unfavorable factors, in this paper we propose a more accurate spectral feature image-based 2DLDA (two-dimensional linear discriminant analysis) ensemble algorithm for face recognition, with one sample image per person. In our algorithm, multi-resolution spectral feature images are constructed to represent the face images; this can greatly enlarge the training set. The proposed method is inspired by our finding that, among these spectral feature images, features extracted from some orientations and scales using 2DLDA are not sensitive to variations of illumination and expression. In order to maintain the positive characteristics of these filters and to make correct category assignments, the strategy of classifier committee learning (CCL) is designed to combine the results obtained from different spectral feature images. Using the above strategies, the negative effects caused by those unfavorable factors can be alleviated efficiently in face recognition. Experimental results on the standard databases demonstrate the feasibility and efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

Allelic richness (number of alleles) is a measure of genetic diversity indicative of a population's long-term potential for adaptability and persistence. It is used less commonly than heterozygosity as a genetic diversity measure, partially because it is more mathematically difficult to take into account the stochastic process of genetic drift for allelic richness. This paper presents a stochastic model for the allelic richness of a newly founded population experiencing genetic drift and gene flow. The model follows the dynamics of alleles lost during the founder event and simulates the effect of gene flow on maintenance and recovery of allelic richness. The probability of an allele's presence in the population was identified as the relevant statistical property for a meaningful interpretation of allelic richness. A method is discussed that combines the probability of allele presence with a population's allele frequency spectrum to provide predictions for allele recovery. The model's analysis provides insights into the dynamics of allelic richness following a founder event, taking into account gene flow and the allele frequency spectrum. Furthermore, the model indicates that the “One Migrant per Generation” rule, a commonly used conservation guideline related to heterozygosity, may be inadequate for addressing preservation of diversity at the allelic level. This highlights the importance of distinguishing between heterozygosity and allelic richness as measures of genetic diversity, since focusing merely on the preservation of heterozygosity might not be enough to adequately preserve allelic richness, which is crucial for species persistence and evolution. [ABSTRACT FROM AUTHOR]