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2009


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An algebraic characterization of the optimum of regularized kernel methods

Dinuzzo, F., De Nicolao, G.

Machine Learning, 74(3):315-345, March 2009 (article)

Abstract
The representer theorem for kernel methods states that the solution of the associated variational problem can be expressed as the linear combination of a finite number of kernel functions. However, for non-smooth loss functions, the analytic characterization of the coefficients poses nontrivial problems. Standard approaches resort to constrained optimization reformulations which, in general, lack a closed-form solution. Herein, by a proper change of variable, it is shown that, for any convex loss function, the coefficients satisfy a system of algebraic equations in a fixed-point form, which may be directly obtained from the primal formulation. The algebraic characterization is specialized to regression and classification methods and the fixed-point equations are explicitly characterized for many loss functions of practical interest. The consequences of the main result are then investigated along two directions. First, the existence of an unconstrained smooth reformulation of the original non-smooth problem is proven. Second, in the context of SURE (Stein’s Unbiased Risk Estimation), a general formula for the degrees of freedom of kernel regression methods is derived.

ei

PDF DOI [BibTex]

2009


PDF DOI [BibTex]


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Towards quantitative PET/MRI: a review of MR-based attenuation correction techniques

Hofmann, M., Pichler, B., Schölkopf, B., Beyer, T.

European Journal of Nuclear Medicine and Molecular Imaging, 36(Supplement 1):93-104, March 2009 (article)

Abstract
Introduction Positron emission tomography (PET) is a fully quantitative technology for imaging metabolic pathways and dynamic processes in vivo. Attenuation correction of raw PET data is a prerequisite for quantification and is typically based on separate transmission measurements. In PET/CT attenuation correction, however, is performed routinely based on the available CT transmission data. Objective Recently, combined PET/magnetic resonance (MR) has been proposed as a viable alternative to PET/CT. Current concepts of PET/MRI do not include CT-like transmission sources and, therefore, alternative methods of PET attenuation correction must be found. This article reviews existing approaches to MR-based attenuation correction (MR-AC). Most groups have proposed MR-AC algorithms for brain PET studies and more recently also for torso PET/MR imaging. Most MR-AC strategies require the use of complementary MR and transmission images, or morphology templates generated from transmission images. We review and discuss these algorithms and point out challenges for using MR-AC in clinical routine. Discussion MR-AC is work-in-progress with potentially promising results from a template-based approach applicable to both brain and torso imaging. While efforts are ongoing in making clinically viable MR-AC fully automatic, further studies are required to realize the potential benefits of MR-based motion compensation and partial volume correction of the PET data.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Generating Spike Trains with Specified Correlation Coefficients

Macke, J., Berens, P., Ecker, A., Tolias, A., Bethge, M.

Neural Computation, 21(2):397-423, February 2009 (article)

Abstract
Spike trains recorded from populations of neurons can exhibit substantial pairwise correlations between neurons and rich temporal structure. Thus, for the realistic simulation and analysis of neural systems, it is essential to have efficient methods for generating artificial spike trains with specified correlation structure. Here we show how correlated binary spike trains can be simulated by means of a latent multivariate gaussian model. Sampling from the model is computationally very efficient and, in particular, feasible even for large populations of neurons. The entropy of the model is close to the theoretical maximum for a wide range of parameters. In addition, this framework naturally extends to correlations over time and offers an elegant way to model correlated neural spike counts with arbitrary marginal distributions.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Automatic detection of preclinical neurodegeneration: Presymptomatic Huntington disease

Klöppel, S., Chu, C., Tan, G., Draganski, B., Johnson, H., Paulsen, J., Kienzle, W., Tabrizi, S., Ashburner, J., Frackowiak, R.

Neurology, 72(5):426-431, February 2009 (article)

Abstract
Background: Treatment of neurodegenerative diseases is likely to be most beneficial in the very early, possibly preclinical stages of degeneration. We explored the usefulness of fully automatic structural MRI classification methods for detecting subtle degenerative change. The availability of a definitive genetic test for Huntington disease (HD) provides an excellent metric for judging the performance of such methods in gene mutation carriers who are free of symptoms. Methods: Using the gray matter segment of MRI scans, this study explored the usefulness of a multivariate support vector machine to automatically identify presymptomatic HD gene mutation carriers (PSCs) in the absence of any a priori information. A multicenter data set of 96 PSCs and 95 age- and sex-matched controls was studied. The PSC group was subclassified into three groups based on time from predicted clinical onset, an estimate that is a function of DNA mutation size and age. Results: Subjects with at least a 33% chance of developing unequivocal signs of HD in 5 years were correctly assigned to the PSC group 69% of the time. Accuracy improved to 83% when regions affected by the disease were selected a priori for analysis. Performance was at chance when the probability of developing symptoms in 5 years was less than 10%. Conclusions: Presymptomatic Huntington disease gene mutation carriers close to estimated diagnostic onset were successfully separated from controls on the basis of single anatomic scans, without additional a priori information. Prior information is required to allow separation when degenerative changes are either subtle or variable.

ei

Web [BibTex]

Web [BibTex]


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Enumeration of condition-dependent dense modules in protein interaction networks

Georgii, E., Dietmann, S., Uno, T., Pagel, P., Tsuda, K.

Bioinformatics, 25(7):933-940, February 2009 (article)

Abstract
Motivation: Modern systems biology aims at understanding how the different molecular components of a biological cell interact. Often, cellular functions are performed by complexes consisting of many different proteins. The composition of these complexes may change according to the cellular environment, and one protein may be involved in several different processes. The automatic discovery of functional complexes from protein interaction data is challenging. While previous approaches use approximations to extract dense modules, our approach exactly solves the problem of dense module enumeration. Furthermore, constraints from additional information sources such as gene expression and phenotype data can be integrated, so we can systematically mine for dense modules with interesting profiles. Results: Given a weighted protein interaction network, our method discovers all protein sets that satisfy a user-defined minimum density threshold. We employ a reverse search strategy, which allows us to exploit the density criterion in an efficient way. Our experiments show that the novel approach is feasible and produces biologically meaningful results. In comparative validation studies using yeast data, the method achieved the best overall prediction performance with respect to confirmed complexes. Moreover, by enhancing the yeast network with phenotypic and phylogenetic profiles and the human network with tissue-specific expression data, we identified condition-dependent complex variants.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Prototype Classification: Insights from Machine Learning

Graf, A., Bousquet, O., Rätsch, G., Schölkopf, B.

Neural Computation, 21(1):272-300, January 2009 (article)

Abstract
We shed light on the discrimination between patterns belonging to two different classes by casting this decoding problem into a generalized prototype framework. The discrimination process is then separated into two stages: a projection stage that reduces the dimensionality of the data by projecting it on a line and a threshold stage where the distributions of the projected patterns of both classes are separated. For this, we extend the popular mean-of-class prototype classification using algorithms from machine learning that satisfy a set of invariance properties. We report a simple yet general approach to express different types of linear classification algorithms in an identical and easy-to-visualize formal framework using generalized prototypes where these prototypes are used to express the normal vector and offset of the hyperplane. We investigate nonmargin classifiers such as the classical prototype classifier, the Fisher classifier, and the relevance vector machine. We then study hard and soft margin cl assifiers such as the support vector machine and a boosted version of the prototype classifier. Subsequently, we relate mean-of-class prototype classification to other classification algorithms by showing that the prototype classifier is a limit of any soft margin classifier and that boosting a prototype classifier yields the support vector machine. While giving novel insights into classification per se by presenting a common and unified formalism, our generalized prototype framework also provides an efficient visualization and a principled comparison of machine learning classification.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Automatic classification of brain resting states using fMRI temporal signals

Soldati, N., Robinson, S., Persello, C., Jovicich, J., Bruzzone, L.

Electronics Letters, 45(1):19-21, January 2009 (article)

Abstract
A novel technique is presented for the automatic discrimination between networks of dasiaresting statesdasia of the human brain and physiological fluctuations in functional magnetic resonance imaging (fMRI). The method is based on features identified via a statistical approach to group independent component analysis time courses, which may be extracted from fMRI data. This technique is entirely automatic and, unlike other approaches, uses temporal rather than spatial information. The method achieves 83% accuracy in the identification of resting state networks.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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The DICS repository: module-assisted analysis of disease-related gene lists

Dietmann, S., Georgii, E., Antonov, A., Tsuda, K., Mewes, H.

Bioinformatics, 25(6):830-831, January 2009 (article)

Abstract
The DICS database is a dynamic web repository of computationally predicted functional modules from the human protein–protein interaction network. It provides references to the CORUM, DrugBank, KEGG and Reactome pathway databases. DICS can be accessed for retrieving sets of overlapping modules and protein complexes that are significantly enriched in a gene list, thereby providing valuable information about the functional context.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Motor Control and Learning in Table Tennis

Mülling, K.

Eberhard Karls Universität Tübingen, Gerrmany, 2009 (diplomathesis)

ei

[BibTex]

[BibTex]


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Hierarchical Clustering and Density Estimation Based on k-nearest-neighbor graphs

Drewe, P.

Eberhard Karls Universität Tübingen, Germany, 2009 (diplomathesis)

ei

[BibTex]

[BibTex]


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mGene: accurate SVM-based gene finding with an application to nematode genomes

Schweikert, G., Zien, A., Zeller, G., Behr, J., Dieterich, C., Ong, C., Philips, P., De Bona, F., Hartmann, L., Bohlen, A., Krüger, N., Sonnenburg, S., Rätsch, G.

Genome Research, 19(11):2133-43, 2009 (article)

Abstract
We present a highly accurate gene-prediction system for eukaryotic genomes, called mGene. It combines in an unprecedented manner the flexibility of generalized hidden Markov models (gHMMs) with the predictive power of modern machine learning methods, such as Support Vector Machines (SVMs). Its excellent performance was proved in an objective competition based on the genome of the nematode Caenorhabditis elegans. Considering the average of sensitivity and specificity, the developmental version of mGene exhibited the best prediction performance on nucleotide, exon, and transcript level for ab initio and multiple-genome gene-prediction tasks. The fully developed version shows superior performance in 10 out of 12 evaluation criteria compared with the other participating gene finders, including Fgenesh++ and Augustus. An in-depth analysis of mGene's genome-wide predictions revealed that approximately 2200 predicted genes were not contained in the current genome annotation. Testing a subset of 57 of these genes by RT-PCR and sequencing, we confirmed expression for 24 (42%) of them. mGene missed 300 annotated genes, out of which 205 were unconfirmed. RT-PCR testing of 24 of these genes resulted in a success rate of merely 8%. These findings suggest that even the gene catalog of a well-studied organism such as C. elegans can be substantially improved by mGene's predictions. We also provide gene predictions for the four nematodes C. briggsae, C. brenneri, C. japonica, and C. remanei. Comparing the resulting proteomes among these organisms and to the known protein universe, we identified many species-specific gene inventions. In a quality assessment of several available annotations for these genomes, we find that mGene's predictions are most accurate.

ei

DOI [BibTex]

DOI [BibTex]


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Learning with Structured Data: Applications to Computer Vision

Nowozin, S.

Technische Universität Berlin, Germany, 2009 (phdthesis)

ei

PDF [BibTex]

PDF [BibTex]


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Structure and activity of the N-terminal substrate recognition domains in proteasomal ATPases

Djuranovic, S., Hartmann, MD., Habeck, M., Ursinus, A., Zwickl, P., Martin, J., Lupas, AN., Zeth, K.

Molecular Cell, 34(5):580-590, 2009 (article)

Abstract
The proteasome forms the core of the protein quality control system in archaea and eukaryotes and also occurs in one bacterial lineage, the Actinobacteria. Access to its proteolytic compartment is controlled by AAA ATPases, whose N-terminal domains (N domains) are thought to mediate substrate recognition. The N domains of an archaeal proteasomal ATPase, Archaeoglobus fulgidus PAN, and of its actinobacterial homolog, Rhodococcus erythropolis ARC, form hexameric rings, whose subunits consist of an N-terminal coiled coil and a C-terminal OB domain. In ARC-N, the OB domains are duplicated and form separate rings. PAN-N and ARC-N can act as chaperones, preventing the aggregation of heterologous proteins in vitro, and this activity is preserved in various chimeras, even when these include coiled coils and OB domains from unrelated proteins. The structures suggest a molecular mechanism for substrate processing based on concerted radial motions of the coiled coils relative to the OB rings.

ei

DOI [BibTex]

DOI [BibTex]


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Discussion of: Brownian Distance Covariance

Gretton, A., Fukumizu, K., Sriperumbudur, B.

The Annals of Applied Statistics, 3(4):1285-1294, 2009 (article)

ei

[BibTex]

[BibTex]


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Efficient factor GARCH models and factor-DCC models

Zhang, K., Chan, L.

Quantitative Finance, 9(1):71-91, 2009 (article)

Abstract
We report that, in the estimation of univariate GARCH or multivariate generalized orthogonal GARCH (GO-GARCH) models, maximizing the likelihood is equivalent to making the standardized residuals as independent as possible. Based on this, we propose three factor GARCH models in the framework of GO-GARCH: independent-factor GARCH exploits factors that are statistically as independent as possible; factors in best-factor GARCH have the largest autocorrelation in their squared values such that their volatilities could be forecast well by univariate GARCH; and factors in conditional-decorrelation GARCH are conditionally as uncorrelated as possible. A convenient two-step method for estimating these models is introduced. Since the extracted factors may still have weak conditional correlations, we further propose factor-DCC models as an extension to the above factor GARCH models with dynamic conditional correlation (DCC) modelling the remaining conditional correlations between factors. Experimental results for the Hong Kong stock market show that conditional-decorrelation GARCH and independent-factor GARCH have better generalization performance than the original GO-GARCH, and that conditional-decorrelation GARCH (among factor GARCH models) and its extension with DCC embedded (among factor-DCC models) behave best.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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From Differential Equations to Differential Geometry: Aspects of Regularisation in Machine Learning

Steinke, F.

Universität des Saarlandes, Saarbrücken, Germany, 2009 (phdthesis)

ei

PDF [BibTex]


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Non-linear System Identification: Visual Saliency Inferred from Eye-Movement Data

Wichmann, F., Kienzle, W., Schölkopf, B., Franz, M.

Journal of Vision, 9(8):article 32, 2009 (article)

Abstract
For simple visual patterns under the experimenter's control we impose which information, or features, an observer can use to solve a given perceptual task. For natural vision tasks, however, there are typically a multitude of potential features in a given visual scene which the visual system may be exploiting when analyzing it: edges, corners, contours, etc. Here we describe a novel non-linear system identification technique based on modern machine learning methods that allows the critical features an observer uses to be inferred directly from the observer's data. The method neither requires stimuli to be embedded in noise nor is it limited to linear perceptive fields (classification images). We demonstrate our technique by deriving the critical image features observers fixate in natural scenes (bottom-up visual saliency). Unlike previous studies where the relevant structure is determined manually—e.g. by selecting Gabors as visual filters—we do not make any assumptions in this regard, but numerically infer number and properties them from the eye-movement data. We show that center-surround patterns emerge as the optimal solution for predicting saccade targets from local image structure. The resulting model, a one-layer feed-forward network with contrast gain-control, is surprisingly simple compared to previously suggested saliency models. Nevertheless, our model is equally predictive. Furthermore, our findings are consistent with neurophysiological hardware in the superior colliculus. Bottom-up visual saliency may thus not be computed cortically as has been thought previously.

ei

Web DOI [BibTex]


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mGene.web: a web service for accurate computational gene finding

Schweikert, G., Behr, J., Zien, A., Zeller, G., Ong, C., Sonnenburg, S., Rätsch, G.

Nucleic Acids Research, 37, pages: W312-6, 2009 (article)

Abstract
We describe mGene.web, a web service for the genome-wide prediction of protein coding genes from eukaryotic DNA sequences. It offers pre-trained models for the recognition of gene structures including untranslated regions in an increasing number of organisms. With mGene.web, users have the additional possibility to train the system with their own data for other organisms on the push of a button, a functionality that will greatly accelerate the annotation of newly sequenced genomes. The system is built in a highly modular way, such that individual components of the framework, like the promoter prediction tool or the splice site predictor, can be used autonomously. The underlying gene finding system mGene is based on discriminative machine learning techniques and its high accuracy has been demonstrated in an international competition on nematode genomes. mGene.web is available at http://www.mgene.org/web, it is free of charge and can be used for eukaryotic genomes of small to moderate size (several hundred Mbp).

ei

DOI [BibTex]

DOI [BibTex]

2008


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Modelling contrast discrimination data suggest both the pedestal effect and stochastic resonance to be caused by the same mechanism

Goris, R., Wagemans, J., Wichmann, F.

Journal of Vision, 8(15):1-21, November 2008 (article)

Abstract
Computational models of spatial vision typically make use of a (rectified) linear filter, a nonlinearity and dominant late noise to account for human contrast discrimination data. Linear–nonlinear cascade models predict an improvement in observers' contrast detection performance when low, subthreshold levels of external noise are added (i.e., stochastic resonance). Here, we address the issue whether a single contrast gain-control model of early spatial vision can account for both the pedestal effect, i.e., the improved detectability of a grating in the presence of a low-contrast masking grating, and stochastic resonance. We measured contrast discrimination performance without noise and in both weak and moderate levels of noise. Making use of a full quantitative description of our data with few parameters combined with comprehensive model selection assessments, we show the pedestal effect to be more reduced in the presence of weak noise than in moderate noise. This reduction rules out independent, additive sources of performance improvement and, together with a simulation study, supports the parsimonious explanation that a single mechanism underlies the pedestal effect and stochastic resonance in contrast perception.

ei

Web DOI [BibTex]


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The Effect of Mutual Information on Independent Component Analysis in EEG/MEG Analysis: A Simulation Study

Neumann, A., Grosse-Wentrup, M., Buss, M., Gramann, K.

International Journal of Neuroscience, 118(11):1534-1546, November 2008 (article)

Abstract
Objective: This study investigated the influence of mutual information (MI) on temporal and dipole reconstruction based on independent components (ICs) derived from independent component analysis (ICA). Method: Artificial electroencephalogram (EEG) datasets were created by means of a neural mass model simulating cortical activity of two neural sources within a four-shell spherical head model. Mutual information between neural sources was systematicallyvaried. Results: Increasing spatial error for reconstructed locations of ICs with increasing MI was observed. By contrast, the reconstruction error for the time course of source activity was largely independent of MI but varied systematically with Gaussianity of the sources. Conclusion: Independent component analysis is a viable tool for analyzing the temporal activity of EEG/MEG (magnetoencephalography) sources even if the underlying neural sources are mutually dependent. However, if ICA is used as a preprocessing algorithm for source localization, mutual information between sources introduces a bias in the reconstructed locations of the sources. Significance: Studies using ICA-algorithms based on MI have to be aware of possible errors in the spatial reconstruction of sources if these are coupled with other neural sources.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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gBoost: A Mathematical Programming Approach to Graph Classification and Regression

Saigo, H., Nowozin, S., Kadowaki, T., Kudo, T., Tsuda, K.

Machine Learning, 75(1):69-89, November 2008 (article)

Abstract
Graph mining methods enumerate frequently appearing subgraph patterns, which can be used as features for subsequent classification or regression. However, frequent patterns are not necessarily informative for the given learning problem. We propose a mathematical programming boosting method (gBoost) that progressively collects informative patterns. Compared to AdaBoost, gBoost can build the prediction rule with fewer iterations. To apply the boosting method to graph data, a branch-and-bound pattern search algorithm is developed based on the DFS code tree. The constructed search space is reused in later iterations to minimize the computation time. Our method can learn more efficiently than the simpler method based on frequent substructure mining, because the output labels are used as an extra information source for pruning the search space. Furthermore, by engineering the mathematical program, a wide range of machine learning problems can be solved without modifying the pattern search algorithm.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Variational Bayesian Model Selection in Linear Gaussian State-Space based Models

Chiappa, S.

International Workshop on Flexible Modelling: Smoothing and Robustness (FMSR 2008), 2008, pages: 1, November 2008 (poster)

ei

Web [BibTex]

Web [BibTex]


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Machine Learning for Motor Skills in Robotics

Peters, J.

K{\"u}nstliche Intelligenz, 2008(4):41-43, November 2008 (article)

Abstract
Autonomous robots that can adapt to novel situations has been a long standing vision of robotics, artificial intelligence, and the cognitive sciences. Early approaches to this goal during the heydays of artificial intelligence research in the late 1980s, however, made it clear that an approach purely based on reasoning or human insights would not be able to model all the perceptuomotor tasks of future robots. Instead, new hope was put in the growing wake of machine learning that promised fully adaptive control algorithms which learn both by observation and trial-and-error. However, to date, learning techniques have yet to fulfill this promise as only few methods manage to scale into the high-dimensional domains of manipulator and humanoid robotics and usually scaling was only achieved in precisely pre-structured domains. We have investigated the ingredients for a general approach to motor skill learning in order to get one step closer towards human-like performance. For doing so, we study two major components for such an approach, i.e., firstly, a theoretically well-founded general approach to representing the required control structures for task representation and execution and, secondly, appropriate learning algorithms which can be applied in this setting.

ei

PDF Web [BibTex]

PDF Web [BibTex]


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Kernels, Regularization and Differential Equations

Steinke, F., Schölkopf, B.

Pattern Recognition, 41(11):3271-3286, November 2008 (article)

Abstract
Many common machine learning methods such as Support Vector Machines or Gaussian process inference make use of positive definite kernels, reproducing kernel Hilbert spaces, Gaussian processes, and regularization operators. In this work these objects are presented in a general, unifying framework, and interrelations are highlighted. With this in mind we then show how linear stochastic differential equation models can be incorporated naturally into the kernel framework. And vice versa, many kernel machines can be interpreted in terms of differential equations. We focus especially on ordinary differential equations, also known as dynamical systems, and it is shown that standard kernel inference algorithms are equivalent to Kalman filter methods based on such models. In order not to cloud qualitative insights with heavy mathematical machinery, we restrict ourselves to finite domains, implying that differential equations are treated via their corresponding finite difference equations.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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The genome of the simian and human malaria parasite Plasmodium knowlesi

Pain, A., Böhme, U., Berry, A., Mungall, K., Finn, R., Jackson, A., Mourier, T., Mistry, J., Pasini, E., Aslett, M., Balasubrammaniam, S., Borgwardt, K., Brooks, K., Carret, C., Carver, T., Cherevach, I., Chillingworth, T., Clarke, T., Galinski, M., Hall, N., Harper, D., Harris, D., Hauser, H., Ivens, A., Janssen, C., Keane, T., Larke, N., Lapp, S., Marti, M., Moule, S., Meyer, I., Ormond, D., Peters, N., Sanders, M., Sanders, T., Sergeant, T., Simmonds, M., Smith, F., Squares, R., Thurston, S., Tivey, A., Walker, D., White, B., Zuiderwijk, E., Churcher, C., Quail, M., Cowman, A., Turner, C., Rajandream, M., Kocken, C., Thomas, A., Newbold, C., Barrell, B., Berriman, M.

Nature, 455(7214):799-803, October 2008 (article)

Abstract
Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia1, 2. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated3, and it has a close phylogenetic relationship to Plasmodium vivax 4, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone5) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome4 and other sequenced Plasmodium genomes6, 7, 8. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs9, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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A BOLD window into brain waves

Balduzzi, D., Riedner, B., Tononi, G.

Proceedings of the National Academy of Sciences of the United States of America, 105(41):15641-15642 , October 2008 (article)

Abstract
The brain is never inactive. Neurons fire at leisurely rates most of the time, even in sleep (1), although occasionally they fire more intensely, for example, when presented with certain stimuli. Coordinated changes in the activity and excitability of many neurons underlie spontaneous fluctuations in the electroencephalogram (EEG), first observed almost a century ago. These fluctuations can be very slow (infraslow oscillations, <0.1 Hz; slow oscillations, <1 Hz; and slow waves or delta waves, 1–4 Hz), intermediate (theta, 4–8 Hz; alpha, 8–12 Hz; and beta, 13–20 Hz), and fast (gamma, >30 Hz). Moreover, slower fluctuations appear to group and modulate faster ones (1, 2). The BOLD signal underlying functional magnetic resonance imaging (fMRI) also exhibits spontaneous fluctuations at the timescale of tens of seconds (infraslow, <0.1 Hz), which occurs at all times, during task-performance as well as during quiet wakefulness, rapid eye movement (REM) sleep, and non-REM sleep (NREM). Although the precise mechanism underlying the BOLD signal is still being investigated (3–5), it is becoming clear that spontaneous BOLD fluctuations are not just noise, but are tied to fluctuations in neural activity. In this issue of PNAS, He et al. (6) have been able to directly investigate the relationship between BOLD fluctuations and fluctuations in the brain's electrical activity in human subjects. He et al. (6) took advantage of the seminal observation by Biswal et al. (7) that spontaneous BOLD fluctuations in regions belonging to the same functional system are strongly correlated. As expected, He et al. saw that fMRI BOLD fluctuations were strongly correlated among regions within the sensorimotor system, but much less between sensorimotor regions and control regions (nonsensorimotor). The twist was that they did the fMRI recordings in subjects who had been implanted with intracranial electrocorticographic (ECoG) electrodes to record regional EEG signals (to localize epileptic foci). In a separate session, He et al. examined correlations in EEG signals between different regions. They found that, just like the BOLD fluctuations, infraslow and slow fluctuations in the EEG signal from sensorimotor-sensorimotor pairs of electrodes were positively correlated, whereas signals from sensorimotor-control pairs were not. Moreover, the correlation persisted across arousal states: in waking, NREM, and REM sleep. Finally, using several statistical approaches, they found a remarkable correspondence between regional correlations in the infraslow BOLD signal and regional correlations in the infraslow-slow EEG signal (<0.5 Hz or 1–4 Hz). Notably, another report has just appeared showing that mirror sites of auditory cortex across the two hemispheres, which show correlated BOLD activity, also show correlated infraslow EEG fluctuations recorded with ECoG electrodes (8). In this case, the correlated fluctuations reflected infraslow changes in EEG power in the gamma range [however, no significant correlations were found for slow ECoG frequencies (1–4 Hz)].

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Mixture Models for Protein Structure Ensembles

Hirsch, M., Habeck, M.

Bioinformatics, 24(19):2184-2192, October 2008 (article)

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Structure of the human voltage-dependent anion channel

Bayrhuber, M., Meins, T., Habeck, M., Becker, S., Giller, K., Villinger, S., Vonrhein, C., Griesinger, C., Zweckstetter, M., Zeth, K.

Proceedings of the National Academy of Sciences of the United States of America, 105(40):15370-15375, October 2008 (article)

Abstract
The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the channel known to guide the metabolic flux across the MOM and plays a key role in mitochondrially induced apoptosis. Here, we present the 3D structure of human VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography. Human VDAC1 (hVDAC1) adopts a &amp;#946;-barrel architecture composed of 19 &amp;#946;-strands with an &amp;#945;-helix located horizontally midway within the pore. Bioinformatic analysis indicates that this channel architecture is common to all VDAC proteins and is adopted by the general import pore TOM40 of mammals, which is also located in the MOM.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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MRI-Based Attenuation Correction for PET/MRI: A Novel Approach Combining Pattern Recognition and Atlas Registration

Hofmann, M., Steinke, F., Scheel, V., Charpiat, G., Farquhar, J., Aschoff, P., Brady, M., Schölkopf, B., Pichler, B.

Journal of Nuclear Medicine, 49(11):1875-1883, October 2008 (article)

Abstract
For quantitative PET information, correction of tissue photon attenuation is mandatory. Generally in conventional PET, the attenuation map is obtained from a transmission scan, which uses a rotating radionuclide source, or from the CT scan in a combined PET/CT scanner. In the case of PET/MRI scanners currently under development, insufficient space for the rotating source exists; the attenuation map can be calculated from the MR image instead. This task is challenging because MR intensities correlate with proton densities and tissue-relaxation properties, rather than with attenuation-related mass density. METHODS: We used a combination of local pattern recognition and atlas registration, which captures global variation of anatomy, to predict pseudo-CT images from a given MR image. These pseudo-CT images were then used for attenuation correction, as the process would be performed in a PET/CT scanner. RESULTS: For human brain scans, we show on a database of 17 MR/CT image pairs that our method reliably enables e stimation of a pseudo-CT image from the MR image alone. On additional datasets of MRI/PET/CT triplets of human brain scans, we compare MRI-based attenuation correction with CT-based correction. Our approach enables PET quantification with a mean error of 3.2% for predefined regions of interest, which we found to be clinically not significant. However, our method is not specific to brain imaging, and we show promising initial results on 1 whole-body animal dataset. CONCLUSION: This method allows reliable MRI-based attenuation correction for human brain scans. Further work is necessary to validate the method for whole-body imaging.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Support Vector Machines and Kernels for Computational Biology

Ben-Hur, A., Ong, C., Sonnenburg, S., Schölkopf, B., Rätsch, G.

PLoS Computational Biology, 4(10: e1000173):1-10, October 2008 (article)

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Approximations for Binary Gaussian Process Classification

Nickisch, H., Rasmussen, C.

Journal of Machine Learning Research, 9, pages: 2035-2078, October 2008 (article)

Abstract
We provide a comprehensive overview of many recent algorithms for approximate inference in Gaussian process models for probabilistic binary classification. The relationships between several approaches are elucidated theoretically, and the properties of the different algorithms are corroborated by experimental results. We examine both 1) the quality of the predictive distributions and 2) the suitability of the different marginal likelihood approximations for model selection (selecting hyperparameters) and compare to a gold standard based on MCMC. Interestingly, some methods produce good predictive distributions although their marginal likelihood approximations are poor. Strong conclusions are drawn about the methods: The Expectation Propagation algorithm is almost always the method of choice unless the computational budget is very tight. We also extend existing methods in various ways, and provide unifying code implementing all approaches.

ei

PDF PDF [BibTex]

PDF PDF [BibTex]


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Accurate NMR Structures Through Minimization of an Extended Hybrid Energy

Nilges, M., Bernard, A., Bardiaux, B., Malliavin, T., Habeck, M., Rieping, W.

Structure, 16(9):1305-1312, September 2008 (article)

Abstract
The use of generous distance bounds has been the hallmark of NMR structure determination. However, bounds necessitate the estimation of data quality before the calculation, reduce the information content, introduce human bias, and allow for major errors in the structures. Here, we propose a new rapid structure calculation scheme based on Bayesian analysis. The minimization of an extended energy function, including a new type of distance restraint and a term depending on the data quality, results in an estimation of the data quality in addition to coordinates. This allows for the determination of the optimal weight on the experimental information. The resulting structures are of better quality and closer to the X–ray crystal structure of the same molecule. With the new calculation approach, the analysis of discrepancies from the target distances becomes meaningful. The strategy may be useful in other applications—for example, in homology modeling.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Similarity, Kernels, and the Triangle Inequality

Jäkel, F., Schölkopf, B., Wichmann, F.

Journal of Mathematical Psychology, 52(5):297-303, September 2008 (article)

Abstract
Similarity is used as an explanatory construct throughout psychology and multidimensional scaling (MDS) is the most popular way to assess similarity. In MDS, similarity is intimately connected to the idea of a geometric representation of stimuli in a perceptual space. Whilst connecting similarity and closeness of stimuli in a geometric representation may be intuitively plausible, Tversky and Gati [Tversky, A., Gati, I. (1982). Similarity, separability, and the triangle inequality. Psychological Review, 89(2), 123–154] have reported data which are inconsistent with the usual geometric representations that are based on segmental additivity. We show that similarity measures based on Shepard’s universal law of generalization [Shepard, R. N. (1987). Toward a universal law of generalization for psychologica science. Science, 237(4820), 1317–1323] lead to an inner product representation in a reproducing kernel Hilbert space. In such a space stimuli are represented by their similarity to all other stimuli. This representation, based on Shepard’s law, has a natural metric that does not have additive segments whilst still retaining the intuitive notion of connecting similarity and distance between stimuli. Furthermore, this representation has the psychologically appealing property that the distance between stimuli is bounded.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Comparison of Pattern Recognition Methods in Classifying High-resolution BOLD Signals Obtained at High Magnetic Field in Monkeys

Ku, S., Gretton, A., Macke, J., Logothetis, N.

Magnetic Resonance Imaging, 26(7):1007-1014, September 2008 (article)

Abstract
Pattern recognition methods have shown that functional magnetic resonance imaging (fMRI) data can reveal significant information about brain activity. For example, in the debate of how object categories are represented in the brain, multivariate analysis has been used to provide evidence of a distributed encoding scheme [Science 293:5539 (2001) 2425–2430]. Many follow-up studies have employed different methods to analyze human fMRI data with varying degrees of success [Nature reviews 7:7 (2006) 523–534]. In this study, we compare four popular pattern recognition methods: correlation analysis, support-vector machines (SVM), linear discriminant analysis (LDA) and Gaussian naïve Bayes (GNB), using data collected at high field (7 Tesla) with higher resolution than usual fMRI studies. We investigate prediction performance on single trials and for averages across varying numbers of stimulus presentations. The performance of the various algorithms depends on the nature of the brain activity being categorized: for several tasks, many of the methods work well, whereas for others, no method performs above chance level. An important factor in overall classification performance is careful preprocessing of the data, including dimensionality reduction, voxel selection and outlier elimination.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Towards the neural basis of the flash-lag effect

Ecker, A., Berens, P., Hoenselaar, A., Subramaniyan, M., Tolias, A., Bethge, M.

International Workshop on Aspects of Adaptive Cortex Dynamics, 2008, pages: 1, September 2008 (poster)

ei

PDF [BibTex]

PDF [BibTex]


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A Single-shot Measurement of the Energy of Product States in a Translation Invariant Spin Chain Can Replace Any Quantum Computation

Janzing, D., Wocjan, P., Zhang, S.

New Journal of Physics, 10(093004):1-18, September 2008 (article)

Abstract
In measurement-based quantum computation, quantum algorithms are implemented via sequences of measurements. We describe a translationally invariant finite-range interaction on a one-dimensional qudit chain and prove that a single-shot measurement of the energy of an appropriate computational basis state with respect to this Hamiltonian provides the output of any quantum circuit. The required measurement accuracy scales inverse polynomially with the size of the simulated quantum circuit. This shows that the implementation of energy measurements on generic qudit chains is as hard as the realization of quantum computation. Here, a ‘measurement‘ is any procedure that samples from the spectral measurement induced by the observable and the state under consideration. As opposed to measurement-based quantum computation, the post-measurement state is irrelevant.

ei

PDF DOI [BibTex]


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Reinforcement Learning for Motor Primitives

Kober, J.

Biologische Kybernetik, University of Stuttgart, Stuttgart, Germany, August 2008 (diplomathesis)

ei

PDF [BibTex]

PDF [BibTex]


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Voluntary Brain Regulation and Communication with ECoG-Signals

Hinterberger, T., Widmann, G., Lal, T., Hill, J., Tangermann, M., Rosenstiel, W., Schölkopf, B., Elger, C., Birbaumer, N.

Epilepsy and Behavior, 13(2):300-306, August 2008 (article)

Abstract
Brain–computer interfaces (BCIs) can be used for communication in writing without muscular activity or for learning to control seizures by voluntary regulation of brain signals such as the electroencephalogram (EEG). Three of five patients with epilepsy were able to spell their names with electrocorticogram (ECoG) signals derived from motor-related areas within only one or two training sessions. Imagery of finger or tongue movements was classified with support-vector classification of autoregressive coefficients derived from the ECoG signals. After training of the classifier, binary classification responses were used to select letters from a computer-generated menu. Offline analysis showed increased theta activity in the unsuccessful patients, whereas the successful patients exhibited dominant sensorimotor rhythms that they could control. The high spatial resolution and increased signal-to-noise ratio in ECoG signals, combined with short training periods, may offer an alternative for communication in complete paralysis, locked-in syndrome, and motor restoration.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Asymmetries of Time Series under Inverting their Direction

Peters, J.

Biologische Kybernetik, University of Heidelberg, August 2008 (diplomathesis)

ei

PDF [BibTex]

PDF [BibTex]


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Predicting phenotypic effects of gene perturbations in C. elegans using an integrated network model

Borgwardt, K.

BioEssays, 30(8):707–710, August 2008 (article)

Abstract
Predicting the phenotype of an organism from its genotype is a central question in genetics. Most importantly, we would like to find out if the perturbation of a single gene may be the cause of a disease. However, our current ability to predict the phenotypic effects of perturbations of individual genes is limited. Network models of genes are one tool for tackling this problem. In a recent study, (Lee et al.) it has been shown that network models covering the majority of genes of an organism can be used for accurately predicting phenotypic effects of gene perturbations in multicellular organisms.

ei

Web DOI [BibTex]


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Multi-class Common Spatial Pattern and Information Theoretic Feature Extraction

Grosse-Wentrup, M., Buss, M.

IEEE Transactions on Biomedical Engineering, 55(8):1991-2000, August 2008 (article)

Abstract
We address two shortcomings of the common spatial patterns (CSP) algorithm for spatial filtering in the context of brain--computer interfaces (BCIs) based on electroencephalography/magnetoencephalography (EEG/MEG): First, the question of optimality of CSP in terms of the minimal achievable classification error remains unsolved. Second, CSP has been initially proposed for two-class paradigms. Extensions to multiclass paradigms have been suggested, but are based on heuristics. We address these shortcomings in the framework of information theoretic feature extraction (ITFE). We show that for two-class paradigms, CSP maximizes an approximation of mutual information of extracted EEG/MEG components and class labels. This establishes a link between CSP and the minimal classification error. For multiclass paradigms, we point out that CSP by joint approximate diagonalization (JAD) is equivalent to independent component analysis (ICA), and provide a method to choose those independent components (ICs) that approximately maximize mutual information of ICs and class labels. This eliminates the need for heuristics in multiclass CSP, and allows incorporating prior class probabilities. The proposed method is applied to the dataset IIIa of the third BCI competition, and is shown to increase the mean classification accuracy by 23.4% in comparison to multiclass CSP.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Learning an Interest Operator from Human Eye Movements

Kienzle, W.

Biologische Kybernetik, Eberhard-Karls-Universität Tübingen, Tübingen, Germany, July 2008 (phdthesis)

ei

[BibTex]

[BibTex]


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Policy Learning: A Unified Perspective With Applications In Robotics

Peters, J., Kober, J., Nguyen-Tuong, D.

8th European Workshop on Reinforcement Learning for Robotics (EWRL 2008), 8, pages: 10, July 2008 (poster)

Abstract
Policy Learning approaches are among the best suited methods for high-dimensional, continuous control systems such as anthropomorphic robot arms and humanoid robots. In this paper, we show two contributions: firstly, we show a unified perspective which allows us to derive several policy learning al- gorithms from a common point of view, i.e, policy gradient algorithms, natural- gradient algorithms and EM-like policy learning. Secondly, we present several applications to both robot motor primitive learning as well as to robot control in task space. Results both from simulation and several different real robots are shown.

ei

PDF [BibTex]

PDF [BibTex]


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At-TAX: A Whole Genome Tiling Array Resource for Developmental Expression Analysis and Transcript Identification in Arabidopsis thaliana

Laubinger, S., Zeller, G., Henz, S., Sachsenberg, T., Widmer, C., Naouar, N., Vuylsteke, M., Schölkopf, B., Rätsch, G., Weigel, D.

Genome Biology, 9(7: R112):1-16, July 2008 (article)

Abstract
Gene expression maps for model organisms, including Arabidopsis thaliana, have typically been created using gene-centric expression arrays. Here, we describe a comprehensive expression atlas, Arabidopsis thaliana Tiling Array Express (At-TAX), which is based on whole-genome tiling arrays. We demonstrate that tiling arrays are accurate tools for gene expression analysis and identified more than 1,000 unannotated transcribed regions. Visualizations of gene expression estimates, transcribed regions, and tiling probe measurements are accessible online at the At-TAX homepage.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Reinforcement Learning of Perceptual Coupling for Motor Primitives

Kober, J., Peters, J.

8th European Workshop on Reinforcement Learning for Robotics (EWRL 2008), 8, pages: 16, July 2008 (poster)

Abstract
Reinforcement learning is a natural choice for the learning of complex motor tasks by reward-related self-improvement. As the space of movements is high-dimensional and continuous, a policy parametrization is needed which can be used in this context. Traditional motor primitive approaches deal largely with open-loop policies which can only deal with small perturbations. In this paper, we present a new type of motor primitive policies which serve as closed-loop policies together with an appropriate learning algorithm. Our new motor primitives are an augmented version version of the dynamic systems motor primitives that incorporates perceptual coupling to external variables. We show that these motor primitives can perform complex tasks such a Ball-in-a-Cup or Kendama task even with large variances in the initial conditions where a human would hardly be able to learn this task. We initialize the open-loop policies by imitation learning and the perceptual coupling with a handcrafted solution. We first improve the open-loop policies and subsequently the perceptual coupling using a novel reinforcement learning method which is particularly well-suited for motor primitives.

ei

PDF [BibTex]

PDF [BibTex]


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Flexible Models for Population Spike Trains

Bethge, M., Macke, J., Berens, P., Ecker, A., Tolias, A.

AREADNE 2008: Research in Encoding and Decoding of Neural Ensembles, 2, pages: 52, June 2008 (poster)

ei

PDF [BibTex]

PDF [BibTex]


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Graphical Analysis of NMR Structural Quality and Interactive Contact Map of NOE Assignments in ARIA

Bardiaux, B., Bernard, A., Rieping, W., Habeck, M., Malliavin, T., Nilges, M.

BMC Structural Biology, 8(30):1-5, June 2008 (article)

Abstract
BACKGROUND: The Ambiguous Restraints for Iterative Assignment (ARIA) approach is widely used for NMR structure determination. It is based on simultaneously calculating structures and assigning NOE through an iterative protocol. The final solution consists of a set of conformers and a list of most probable assignments for the input NOE peak list. RESULTS: ARIA was extended with a series of graphical tools to facilitate a detailed analysis of the intermediate and final results of the ARIA protocol. These additional features provide (i) an interactive contact map, serving as a tool for the analysis of assignments, and (ii) graphical representations of structure quality scores and restraint statistics. The interactive contact map between residues can be clicked to obtain information about the restraints and their contributions. Profiles of quality scores are plotted along the protein sequence, and contact maps provide information of the agreement with the data on a residue pair level. CONCLUSIONS: The g raphical tools and outputs described here significantly extend the validation and analysis possibilities of NOE assignments given by ARIA as well as the analysis of the quality of the final structure ensemble. These tools are included in the latest version of ARIA, which is available at http://aria.pasteur.fr. The Web site also contains an installation guide, a user manual and example calculations.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Pairwise Correlations and Multineuronal Firing Patterns in the Primary Visual Cortex of the Awake, Behaving Macaque

Berens, P., Ecker, A., Subramaniyan, M., Macke, J., Hauck, P., Bethge, M., Tolias, A.

AREADNE 2008: Research in Encoding and Decoding of Neural Ensembles, 2, pages: 48, June 2008 (poster)

ei

PDF [BibTex]

PDF [BibTex]


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Operational Space Control: A Theoretical and Empirical Comparison

Nakanishi, J., Cory, R., Mistry, M., Peters, J., Schaal, S.

International Journal of Robotics Research, 27(6):737-757, June 2008 (article)

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Visual saliency re-visited: Center-surround patterns emerge as optimal predictors for human fixation targets

Wichmann, F., Kienzle, W., Schölkopf, B., Franz, M.

Journal of Vision, 8(6):635, 8th Annual Meeting of the Vision Sciences Society (VSS), June 2008 (poster)

Abstract
Humans perceives the world by directing the center of gaze from one location to another via rapid eye movements, called saccades. In the period between saccades the direction of gaze is held fixed for a few hundred milliseconds (fixations). It is primarily during fixations that information enters the visual system. Remarkably, however, after only a few fixations we perceive a coherent, high-resolution scene despite the visual acuity of the eye quickly decreasing away from the center of gaze: This suggests an effective strategy for selecting saccade targets. Top-down effects, such as the observer's task, thoughts, or intentions have an effect on saccadic selection. Equally well known is that bottom-up effects-local image structure-influence saccade targeting regardless of top-down effects. However, the question of what the most salient visual features are is still under debate. Here we model the relationship between spatial intensity patterns in natural images and the response of the saccadic system using tools from machine learning. This allows us to identify the most salient image patterns that guide the bottom-up component of the saccadic selection system, which we refer to as perceptive fields. We show that center-surround patterns emerge as the optimal solution to the problem of predicting saccade targets. Using a novel nonlinear system identification technique we reduce our learned classifier to a one-layer feed-forward network which is surprisingly simple compared to previously suggested models assuming more complex computations such as multi-scale processing, oriented filters and lateral inhibition. Nevertheless, our model is equally predictive and generalizes better to novel image sets. Furthermore, our findings are consistent with neurophysiological hardware in the superior colliculus. Bottom-up visual saliency may thus not be computed cortically as has been thought previously.

ei

Web DOI [BibTex]

Web DOI [BibTex]