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2011


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Combined whole-body PET/MR imaging: MR contrast agents do not affect the quantitative accuracy of PET following attenuation correction

Lois, C., Kupferschläger, J., Bezrukov, I., Schmidt, H., Werner, M., Mannheim, J., Pichler, B., Schwenzer, N., Beyer, T.

(SST15-05 ), 97th Scientific Assemble and Annual Meeting of the Radiological Society of North America (RSNA), December 2011 (talk)

Abstract
PURPOSE Combined PET/MR imaging entails the use of MR contrast agents (MRCA) as part of integrated protocols. We assess additional attenuation of the PET emission signals in the presence of oral and intraveneous (iv) MRCA made up of iron oxide and Gd-chelates, respectively. METHOD AND MATERIALS Phantom scans were performed on a clinical PET/CT (Biograph HiRez16, Siemens) and integrated whole-body PET/MR (Biograph mMR, Siemens) using oral (Lumirem) and intraveneous (Gadovist) MRCA. Reference PET attenuation values were determined on a small-animal PET (Inveon, Siemens) using standard PET transmission imaging (TX). Seven syringes of 5mL were filled with (a) Water, (b) Lumirem_100 (100% conc.), (c) Gadovist_100 (100%), (d) Gadovist_18 (18%), (e) Gadovist_02 (0.2%), (f) Imeron-400 CT iv-contrast (100%) and (g) Imeron-400 (2.4%). The same set of syringes was scanned on CT (Sensation16, Siemens) at 120kVp and 160mAs. The effect of MRCA on the attenuation of PET emission data was evaluated using a 20cm cylinder filled uniformly with [18F]-FDG (FDG) in water (BGD). Three 4.5cm diameter cylinders were inserted into the phantom: (C1) Teflon, (C2) Water+FDG (2:1) and (C3) Lumirem_100+FDG (2:1). Two 50mL syringes filled with Gadovist_02+FDG (Sy1) and water+FDG (Sy2) were attached to the sides of (C1) to mimick the effects of iv-contrast in vessels near bone. Syringe-to-background activity ratio was 4-to-1. PET emission data were acquired for 10min each using the PET/CT and the PET/MR. Images were reconstructed using CT- and MR-based attenuation correction. RESULTS Mean linear PET attenuation (cm-1) on TX was (a) 0.098, (b) 0.098, (c) 0.300, (d) 0.134, (e) 0.095, (f) 0.397 and (g) 0.105. Corresponding CT attenuation (HU) was: (a) 5, (b) 14, (c) 3070, (d) 1040, (e) 13, (f) 3070 and (g) 347. Lumirem had little effect on PET attenuation with (C3) being 13% and 10% higher than (C2) on PET/CT and PET/MR, respectively. Gadovist_02 had even smaller effects with (Sy1) being 2.5% lower than (Sy2) on PET/CT and 1.2% higher than (Sy2) on PET/MR. CONCLUSION MRCA in high and clinically relevant concentrations have attenuation values similar to that of CT contrast and water, respectively. In clinical PET/MR scenarios MRCA are not expected to lead to significant attenuation of the PET emission signals.

ei

Web [BibTex]

2011


Web [BibTex]


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Causal Inference on Discrete Data using Additive Noise Models

Peters, J., Janzing, D., Schölkopf, B.

IEEE Transactions on Pattern Analysis and Machine Intelligence, 33(12):2436-2450, December 2011 (article)

Abstract
Inferring the causal structure of a set of random variables from a finite sample of the joint distribution is an important problem in science. The case of two random variables is particularly challenging since no (conditional) independences can be exploited. Recent methods that are based on additive noise models suggest the following principle: Whenever the joint distribution {\bf P}^{(X,Y)} admits such a model in one direction, e.g., Y=f(X)+N, N \perp\kern-6pt \perp X, but does not admit the reversed model X=g(Y)+\tilde{N}, \tilde{N} \perp\kern-6pt \perp Y, one infers the former direction to be causal (i.e., X\rightarrow Y). Up to now, these approaches only dealt with continuous variables. In many situations, however, the variables of interest are discrete or even have only finitely many states. In this work, we extend the notion of additive noise models to these cases. We prove that it almost never occurs that additive noise models can be fit in both directions. We further propose an efficient algorithm that is able to perform this way of causal inference on finite samples of discrete variables. We show that the algorithm works on both synthetic and real data sets.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Spontaneous epigenetic variation in the Arabidopsis thaliana methylome

Becker, C., Hagmann, J., Müller, J., Koenig, D., Stegle, O., Borgwardt, K., Weigel, D.

Nature, 480(7376):245-249, December 2011 (article)

Abstract
Heritable epigenetic polymorphisms, such as differential cytosine methylation, can underlie phenotypic variation1, 2. Moreover, wild strains of the plant Arabidopsis thaliana differ in many epialleles3, 4, and these can influence the expression of nearby genes1, 2. However, to understand their role in evolution5, it is imperative to ascertain the emergence rate and stability of epialleles, including those that are not due to structural variation. We have compared genome-wide DNA methylation among 10 A. thaliana lines, derived 30 generations ago from a common ancestor6. Epimutations at individual positions were easily detected, and close to 30,000 cytosines in each strain were differentially methylated. In contrast, larger regions of contiguous methylation were much more stable, and the frequency of changes was in the same low range as that of DNA mutations7. Like individual positions, the same regions were often affected by differential methylation in independent lines, with evidence for recurrent cycles of forward and reverse mutations. Transposable elements and short interfering RNAs have been causally linked to DNA methylation8. In agreement, differentially methylated sites were farther from transposable elements and showed less association with short interfering RNA expression than invariant positions. The biased distribution and frequent reversion of epimutations have important implications for the potential contribution of sequence-independent epialleles to plant evolution.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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HHfrag: HMM-based fragment detection using HHpred

Kalev, I., Habeck, M.

Bioinformatics, 27(22):3110-3116, November 2011 (article)

Abstract
Motivation: Over the last decade, both static and dynamic fragment libraries for protein structure prediction have been introduced. The former are built from clusters in either sequence or structure space and aim to extract a universal structural alphabet. The latter are tailored for a particular query protein sequence and aim to provide local structural templates that need to be assembled in order to build the full-length structure. Results: Here, we introduce HHfrag, a dynamic HMM-based fragment search method built on the profile–profile comparison tool HHpred. We show that HHfrag provides advantages over existing fragment assignment methods in that it: (i) improves the precision of the fragments at the expense of a minor loss in sequence coverage; (ii) detects fragments of variable length (6–21 amino acid residues); (iii) allows for gapped fragments and (iv) does not assign fragments to regions where there is no clear sequence conservation. We illustrate the usefulness of fragments detected by HHfrag on targets from most recent CASP.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Reward-Weighted Regression with Sample Reuse for Direct Policy Search in Reinforcement Learning

Hachiya, H., Peters, J., Sugiyama, M.

Neural Computation, 23(11):2798-2832, November 2011 (article)

Abstract
Direct policy search is a promising reinforcement learning framework, in particular for controlling continuous, high-dimensional systems. Policy search often requires a large number of samples for obtaining a stable policy update estimator, and this is prohibitive when the sampling cost is expensive. In this letter, we extend an expectation-maximization-based policy search method so that previously collected samples can be efficiently reused. The usefulness of the proposed method, reward-weighted regression with sample reuse (R), is demonstrated through robot learning experiments.

ei

Web DOI [BibTex]


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Model Learning in Robotics: a Survey

Nguyen-Tuong, D., Peters, J.

Cognitive Processing, 12(4):319-340, November 2011 (article)

Abstract
Models are among the most essential tools in robotics, such as kinematics and dynamics models of the robot's own body and controllable external objects. It is widely believed that intelligent mammals also rely on internal models in order to generate their actions. However, while classical robotics relies on manually generated models that are based on human insights into physics, future autonomous, cognitive robots need to be able to automatically generate models that are based on information which is extracted from the data streams accessible to the robot. In this paper, we survey the progress in model learning with a strong focus on robot control on a kinematic as well as dynamical level. Here, a model describes essential information about the behavior of the environment and the in uence of an agent on this environment. In the context of model based learning control, we view the model from three di fferent perspectives. First, we need to study the di erent possible model learning architectures for robotics. Second, we discuss what kind of problems these architecture and the domain of robotics imply for the applicable learning methods. From this discussion, we deduce future directions of real-time learning algorithms. Third, we show where these scenarios have been used successfully in several case studies.

ei

PDF [BibTex]

PDF [BibTex]


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Cooperative Cuts: a new use of submodularity in image segmentation

Jegelka, S.

Second I.S.T. Austria Symposium on Computer Vision and Machine Learning, October 2011 (talk)

ei

Web [BibTex]

Web [BibTex]


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Effect of MR Contrast Agents on Quantitative Accuracy of PET in Combined Whole-Body PET/MR Imaging

Lois, C., Bezrukov, I., Schmidt, H., Schwenzer, N., Werner, M., Pichler, B., Kupferschläger, J., Beyer, T.

2011(MIC3-3), 2011 IEEE Nuclear Science Symposium, Medical Imaging Conference (NSS-MIC), October 2011 (talk)

Abstract
Combined whole-body PET/MR systems are being tested in clinical practice today. Integrated imaging protocols entail the use of MR contrast agents (MRCA) that could bias PET attenuation correction. In this work, we assess the effect of MRCA in PET/MR imaging. We analyze the effect of oral and intravenous MRCA on PET activity after attenuation correction. We conclude that in clinical scenarios, MRCA are not expected to lead to significant attenuation of PET signals, and that attenuation maps are not biased after the ingestion of adequate oral contrasts.

ei

Web [BibTex]

Web [BibTex]


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First Results on Patients and Phantoms of a Fully Integrated Clinical Whole-Body PET/MRI

Schmidt, H., Schwenzer, N., Bezrukov, I., Kolb, A., Mantlik, F., Kupferschläger, J., Lois, C., Sauter, A., Brendle, C., Pfannenberg, C., Pichler, B.

2011(J2-8), 2011 IEEE Nuclear Science Symposium, Medical Imaging Conference (NSS-MIC), October 2011 (talk)

Abstract
First clinical fully integrated whole-body PET/MR scanners are just entering the field. Here, we present studies toward quantification accuracy and variation within the PET field of view of small lesions from our BrainPET/MRI, a dedicated clinical brain scanner which was installed three years ago in Tbingen. Also, we present first results for patient and phantom scans of a fully integral whole-body PET/MRI, which was installed two months ago at our department. The quantification accuracy and homogeneity of the BrainPET-Insert (Siemens Medical Solutions, Germany) installed inside the magnet bore of a clinical 3T MRI scanner (Magnetom TIM Trio, Siemens Medical Solutions, Germany) was evaluated by using eight hollow spheres with inner diameters from 3.95 to 7.86 mm placed at different positions inside a homogeneous cylinder phantom with an 9:1 and 6:1 sphere to background ratio. The quantification accuracy for small lesions at different positions in the PET FoV shows a standard deviation of up to 11% and is acceptable for quantitative brain studies where the homogeneity of quantification on the entire FoV is essental. Image quality and resolution of the new Siemens whole-body PET/MR system (Biograph mMR, Siemens Medical Solutions, Germany) was evaluated according to the NEMA NU2 2007 protocol using a body phantom containing six spheres with inner diameter from 10 to 37 mm at sphere to background ratios of 8:1 and 4:1 and the F-18 point sources located at different positions inside the PET FoV, respectively. The evaluation of the whole-body PET/MR system reveals a good PET image quality and resolution comparable to state-of-the-art clinical PET/CT scanners. First images of patient studies carried out at the whole-body PET/MR are presented highlighting the potency of combined PET/MR imaging.

ei

Web [BibTex]

Web [BibTex]


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FaST linear mixed models for genome-wide association studies

Lippert, C., Listgarten, J., Liu, Y., Kadie, CM., Davidson, RI., Heckerman, D.

Nature Methods, 8(10):833–835, October 2011 (article)

Abstract
We describe factored spectrally transformed linear mixed models (FaST-LMM), an algorithm for genome-wide association studies (GWAS) that scales linearly with cohort size in both run time and memory use. On Wellcome Trust data for 15,000 individuals, FaST-LMM ran an order of magnitude faster than current efficient algorithms. Our algorithm can analyze data for 120,000 individuals in just a few hours, whereas current algorithms fail on data for even 20,000 individuals (http://mscompbio.codeplex.com/).

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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The effect of noise correlations in populations of diversely tuned neurons

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

Journal of Neuroscience, 31(40):14272-14283, October 2011 (article)

Abstract
The amount of information encoded by networks of neurons critically depends on the correlation structure of their activity. Neurons with similar stimulus preferences tend to have higher noise correlations than others. In homogeneous populations of neurons, this limited range correlation structure is highly detrimental to the accuracy of a population code. Therefore, reduced spike count correlations under attention, after adaptation, or after learning have been interpreted as evidence for a more efficient population code. Here, we analyze the role of limited range correlations in more realistic, heterogeneous population models. We use Fisher information and maximum-likelihood decoding to show that reduced correlations do not necessarily improve encoding accuracy. In fact, in populations with more than a few hundred neurons, increasing the level of limited range correlations can substantially improve encoding accuracy. We found that this improvement results from a decrease in noise entropy that is associated with increasing correlations if the marginal distributions are unchanged. Surprisingly, for constant noise entropy and in the limit of large populations, the encoding accuracy is independent of both structure and magnitude of noise correlations.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging

Lois, C., Kupferschläger, J., Bezrukov, I., Schmidt, H., Werner, M., Mannheim, J., Pichler, B., Schwenzer, N., Beyer, T.

(OP314), Annual Congress of the European Association of Nuclear Medicine (EANM), October 2011 (talk)

Abstract
PURPOSE:Combined PET/MR imaging entails the use of MR contrast agents (MRCA) as part of integrated protocols. MRCA are made up of iron oxide and Gd-chelates for oral and intravenous (iv) application, respectively. We assess additional attenuation of the PET emission signals in the presence of oral and iv MRCA.MATERIALS AND METHODS:Phantom scans were performed on a clinical PET/CT (Biograph HiRez16, Siemens) and an integrated whole-body PET/MR (Biograph mMR, Siemens). Two common MRCA were evaluated: Lumirem (oral) and Gadovist (iv).Reference PET attenuation values were determined on a dedicated small-animal PET (Inveon, Siemens) using equivalent standard PET transmission source imaging (TX). Seven syringes of 5mL were filled with (a) Water, (b) Lumirem_100 (100% concentration), (c) Gadovist_100 (100%), (d) Gadovist_18 (18%), (e) Gadovist_02 (0.2%), (f) Imeron-400 CT iv-contrast (100%) and (g) Imeron-400 (2.4%). The same set of syringes was scanned on CT (Sensation16, Siemens) at 120kVp and 160mAs.The effect of MRCA on the attenuation of PET emission data was evaluated using a 20cm cylinder filled uniformly with [18F]-FDG (FDG) in water (BGD). Three 4.5cm diameter cylinders were inserted into the phantom: (C1) Teflon, (C2) Water+FDG (2:1) and (C3) Lumirem_100+FDG (2:1). Two 50mL syringes filled with Gadovist_02+FDG (Sy1) and water+FDG (Sy2) were attached to the sides of (C1) to mimick the effects of iv-contrast in vessels near bone. Syringe-to-background activity ratio was 4-to-1.PET emission data were acquired for 10min each using the PET/CT and the PET/MR. Images were reconstructed using CT- and MR-based attenuation correction (AC). Since Teflon is not correctly identified on MR, PET(/MR) data were reconstructed using MR-AC and CT-AC.RESULTS:Mean linear PET attenuation (cm-1) on TX was (a) 0.098, (b) 0.098, (c) 0.300, (d) 0.134, (e) 0.095, (f) 0.397 and (g) 0.105. Corresponding CT attenuation (HU) was: (a) 5, (b) 14, (c) 3070, (d) 1040, (e) 13, (f) 3070 and (g) 347.Lumirem had little effect on PET attenuation with (C3) being 13%, 10% and 11% higher than (C2) on PET/CT, PET/MR with MR-AC, and PET/MR with CT-AC, respectively. Gadovist_02 had even smaller effects with (Sy1) being 2.5% lower, 1.2% higher, and 3.5% lower than (Sy2) on PET/CT, PET/MR with MR-AC and PET/MR with CT-AC, respectively.CONCLUSION:MRCA in high and clinically relevant concentrations have attenuation values similar to that of CT contrast and water, respectively. In clinical PET/MR scenarios MRCA are not expected to lead to significant attenuation of the PET emission signals.

ei

Web [BibTex]

Web [BibTex]


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Analysis of Fixed-Point and Coordinate Descent Algorithms for Regularized Kernel Methods

Dinuzzo, F.

IEEE Transactions on Neural Networks, 22(10):1576-1587, October 2011 (article)

Abstract
In this paper, we analyze the convergence of two general classes of optimization algorithms for regularized kernel methods with convex loss function and quadratic norm regularization. The first methodology is a new class of algorithms based on fixed-point iterations that are well-suited for a parallel implementation and can be used with any convex loss function. The second methodology is based on coordinate descent, and generalizes some techniques previously proposed for linear support vector machines. It exploits the structure of additively separable loss functions to compute solutions of line searches in closed form. The two methodologies are both very easy to implement. In this paper, we also show how to remove non-differentiability of the objective functional by exactly reformulating a convex regularization problem as an unconstrained differentiable stabilization problem.

ei

Web DOI Project Page [BibTex]

Web DOI Project Page [BibTex]


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A biomimetic approach to robot table tennis

Mülling, K., Kober, J., Peters, J.

Adaptive Behavior , 19(5):359-376 , October 2011 (article)

Abstract
Playing table tennis is a difficult motor task that requires fast movements, accurate control and adaptation to task parameters. Although human beings see and move slower than most robot systems, they significantly outperform all table tennis robots. One important reason for this higher performance is the human movement generation. In this paper, we study human movements during table tennis and present a robot system that mimics human striking behavior. Our focus lies on generating hitting motions capable of adapting to variations in environmental conditions, such as changes in ball speed and position. Therefore, we model the human movements involved in hitting a table tennis ball using discrete movement stages and the virtual hitting point hypothesis. The resulting model was evaluated both in a physically realistic simulation and on a real anthropomorphic seven degrees of freedom Barrett WAM™ robot arm.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Whole-genome sequencing of multiple Arabidopsis thaliana populations

Cao, J., Schneeberger, K., Ossowski, S., Günther, T., Bender, S., Fitz, J., Koenig, D., Lanz, C., Stegle, O., Lippert, C., Wang, X., Ott, F., Müller, J., Alonso-Blanco, C., Borgwardt, K., Schmid, K., Weigel, D.

Nature Genetics, 43(10):956–963, October 2011 (article)

Abstract
The plant Arabidopsis thaliana occurs naturally in many different habitats throughout Eurasia. As a foundation for identifying genetic variation contributing to adaptation to diverse environments, a 1001 Genomes Project to sequence geographically diverse A. thaliana strains has been initiated. Here we present the first phase of this project, based on population-scale sequencing of 80 strains drawn from eight regions throughout the species' native range. We describe the majority of common small-scale polymorphisms as well as many larger insertions and deletions in the A. thaliana pan-genome, their effects on gene function, and the patterns of local and global linkage among these variants. The action of processes other than spontaneous mutation is identified by comparing the spectrum of mutations that have accumulated since A. thaliana diverged from its closest relative 10 million years ago with the spectrum observed in the laboratory. Recent species-wide selective sweeps are rare, and potentially deleterious mutations are more common in marginal populations.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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What are the Causes of Performance Variation in Brain-Computer Interfacing?

Grosse-Wentrup, M.

International Journal of Bioelectromagnetism, 13(3):115-116, September 2011 (article)

Abstract
While research on brain-computer interfacing (BCI) has seen tremendous progress in recent years, performance still varies substantially between as well as within subjects, with roughly 10 - 20% of subjects being incapable of successfully operating a BCI system. In this short report, I argue that this variation in performance constitutes one of the major obstacles that impedes a successful commercialization of BCI systems. I review the current state of research on the neuro-physiological causes of performance variation in BCI, discuss recent progress and open problems, and delineate potential research programs for addressing this issue.

ei

PDF Web [BibTex]

PDF Web [BibTex]


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Multiple reference genomes and transcriptomes for Arabidopsis thaliana

Gan, X., Stegle, O., Behr, J., Steffen, J., Drewe, P., Hildebrand, K., Lyngsoe, R., Schultheiss, S., Osborne, E., Sreedharan, V., Kahles, A., Bohnert, R., Jean, G., Derwent, P., Kersey, P., Belfield, E., Harberd, N., Kemen, E., Toomajian, C., Kover, P., Clark, R., Rätsch, G., Mott, R.

Nature, 477(7365):419–423, September 2011 (article)

Abstract
Genetic differences between Arabidopsis thaliana accessions underlie the plant’s extensive phenotypic variation, and until now these have been interpreted largely in the context of the annotated reference accession Col-0. Here we report the sequencing, assembly and annotation of the genomes of 18 natural A. thaliana accessions, and their transcriptomes. When assessed on the basis of the reference annotation, one-third of protein-coding genes are predicted to be disrupted in at least one accession. However, re-annotation of each genome revealed that alternative gene models often restore coding potential. Gene expression in seedlings differed for nearly half of expressed genes and was frequently associated with cis variants within 5 kilobases, as were intron retention alternative splicing events. Sequence and expression variation is most pronounced in genes that respond to the biotic environment. Our data further promote evolutionary and functional studies in A. thaliana, especially the MAGIC genetic reference population descended from these accessions.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Weisfeiler-Lehman Graph Kernels

Shervashidze, N., Schweitzer, P., van Leeuwen, E., Mehlhorn, K., Borgwardt, M.

Journal of Machine Learning Research, 12, pages: 2539-2561, September 2011 (article)

Abstract
In this article, we propose a family of efficient kernels for large graphs with discrete node labels. Key to our method is a rapid feature extraction scheme based on the Weisfeiler-Lehman test of isomorphism on graphs. It maps the original graph to a sequence of graphs, whose node attributes capture topological and label information. A family of kernels can be defined based on this Weisfeiler-Lehman sequence of graphs, including a highly efficient kernel comparing subtree-like patterns. Its runtime scales only linearly in the number of edges of the graphs and the length of the Weisfeiler-Lehman graph sequence. In our experimental evaluation, our kernels outperform state-of-the-art graph kernels on several graph classification benchmark data sets in terms of accuracy and runtime. Our kernels open the door to large-scale applications of graph kernels in various disciplines such as computational biology and social network analysis.

ei

PDF Web [BibTex]

PDF Web [BibTex]


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Gravitational Lensing Accuracy Testing 2010 (GREAT10) Challenge Handbook

Kitching, T., Amara, A., Gill, M., Harmeling, S., Heymans, C., Massey, R., Rowe, B., Schrabback, T., Voigt, L., Balan, S., Bernstein, G., Bethge, M., Bridle, S., Courbin, F., Gentile, M., Heavens, A., Hirsch, M., Hosseini, R., Kiessling, A., Kirk, D., Kuijken, K., Mandelbaum, R., Moghaddam, B., Nurbaeva, G., Paulin-Henriksson, S., Rassat, A., Rhodes, J., Schölkopf, B., Shawe-Taylor, J., Shmakova, M., Taylor, A., Velander, M., van Waerbeke, L., Witherick, D., Wittman, D.

Annals of Applied Statistics, 5(3):2231-2263, September 2011 (article)

Abstract
GRavitational lEnsing Accuracy Testing 2010 (GREAT10) is a public image analysis challenge aimed at the development of algorithms to analyze astronomical images. Specifically, the challenge is to measure varying image distortions in the presence of a variable convolution kernel, pixelization and noise. This is the second in a series of challenges set to the astronomy, computer science and statistics communities, providing a structured environment in which methods can be improved and tested in preparation for planned astronomical surveys. GREAT10 extends upon previous work by introducing variable fields into the challenge. The “Galaxy Challenge” involves the precise measurement of galaxy shape distortions, quantified locally by two parameters called shear, in the presence of a known convolution kernel. Crucially, the convolution kernel and the simulated gravitational lensing shape distortion both now vary as a function of position within the images, as is the case for real data. In addition, we introduce the “Star Challenge” that concerns the reconstruction of a variable convolution kernel, similar to that in a typical astronomical observation. This document details the GREAT10 Challenge for potential participants. Continually updated information is also available from www.greatchallenges.info.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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MRI-Based Attenuation Correction for Whole-Body PET/MRI: Quantitative Evaluation of Segmentation- and Atlas-Based Methods

Hofmann, M., Bezrukov, I., Mantlik, F., Aschoff, P., Steinke, F., Beyer, T., Pichler, B., Schölkopf, B.

Journal of Nuclear Medicine, 52(9):1392-1399, September 2011 (article)

Abstract
PET/MRI is an emerging dual-modality imaging technology that requires new approaches to PET attenuation correction (AC). We assessed 2 algorithms for whole-body MRI-based AC (MRAC): a basic MR image segmentation algorithm and a method based on atlas registration and pattern recognition (AT&PR). METHODS: Eleven patients each underwent a whole-body PET/CT study and a separate multibed whole-body MRI study. The MR image segmentation algorithm uses a combination of image thresholds, Dixon fat-water segmentation, and component analysis to detect the lungs. MR images are segmented into 5 tissue classes (not including bone), and each class is assigned a default linear attenuation value. The AT&PR algorithm uses a database of previously aligned pairs of MRI/CT image volumes. For each patient, these pairs are registered to the patient MRI volume, and machine-learning techniques are used to predict attenuation values on a continuous scale. MRAC methods are compared via the quantitative analysis of AC PET images using volumes of interest in normal organs and on lesions. We assume the PET/CT values after CT-based AC to be the reference standard. RESULTS: In regions of normal physiologic uptake, the average error of the mean standardized uptake value was 14.1% ± 10.2% and 7.7% ± 8.4% for the segmentation and the AT&PR methods, respectively. Lesion-based errors were 7.5% ± 7.9% for the segmentation method and 5.7% ± 4.7% for the AT&PR method. CONCLUSION: The MRAC method using AT&PR provided better overall PET quantification accuracy than the basic MR image segmentation approach. This better quantification was due to the significantly reduced volume of errors made regarding volumes of interest within or near bones and the slightly reduced volume of errors made regarding areas outside the lungs.

ei

Web DOI Project Page [BibTex]


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Multi-parametric Tumor Characterization and Therapy Monitoring using Simultaneous PET/MRI: initial results for Lung Cancer and GvHD

Sauter, A., Schmidt, H., Gueckel, B., Brendle, C., Bezrukov, I., Mantlik, F., Kolb, A., Mueller, M., Reimold, M., Federmann, B., Hetzel, J., Claussen, C., Pfannenberg, C., Horger, M., Pichler, B., Schwenzer, N.

(T110), 2011 World Molecular Imaging Congress (WMIC), September 2011 (talk)

Abstract
Hybrid imaging modalities such as [18F]FDG-PET/CT are superior in staging of e.g. lung cancer disease compared with stand-alone modalities. Clinical PET/MRI systems are about to enter the field of hybrid imaging and offer potential advantages. One added value could be a deeper insight into the tumor metabolism and tumorigenesis due to the combination of PET and dedicated MR methods such as MRS and DWI. Additionally, therapy monitoring of diffucult to diagnose disease such as chronic sclerodermic GvHD (csGvHD) can potentially be improved by this combination. We have applied PET/MRI in 3 patients with lung cancer and 4 patients with csGvHD before and during therapy. All 3 patients had lung cancer confirmed by histology (2 adenocarcinoma, 1 carcinoid). First, a [18F]FDG-PET/CT was performed with the following parameters: injected dose 351.7±25.1 MBq, uptake time 59.0±2.6 min, 3 min/bed. Subsequently, patients were brought to the PET/MRI imaging facility. The whole-body PET/MRI Biograph mMR system comprises 56 detector cassettes with a 59.4 cm transaxial and 25.8 cm axial FoV. The MRI is a modified Verio system with a magnet bore of 60 cm. The following parameters for PET acquisition were applied: uptake time 121.3±2.3 min, 3 bed positions, 6 min/bed. T1w, T2w, and DWI MR images were recorded simultaneously for each bed. Acquired PET data were reconstructed with an iterative 3D OSEM algorithm using 3 iterations and 21 subsets, Gaussian filter of 3 mm. The 4 patients with GvHD were brought to the brainPET/MRI imaging facility 2:10h-2:28h after tracer injection. A 9 min brainPET-acquisition with simultaneous MRI of the lower extremities was accomplished. MRI examination included T1-weighted (pre and post gadolinium) and T2-weighted sequences. Attenuation correction was calculated based on manual bone segmentation and thresholds for soft tissue, fat and air. Soleus muscle (m), crural fascia (f1) and posterior crural intermuscular septum fascia (f2) were surrounded with ROIs based on the pre-treatment T1-weighted images and coregistered using IRW (Siemens). Fascia-to-muscle ratios for PET (f/m), T1 contrast uptake (T1_post-contrast_f-pre-contrast_f/post-contrast_m-pre-contrast_m) and T2 (T2_f/m) were calculated. Both patients with adenocarcinoma show a lower ADC value compared with the carcinoid patient suggesting a higher cellularity. This is also reflected in FDG-PET with higher SUV values. Our initial results reveal that PET/MRI can provide complementary information for a profound tumor characterization and therapy monitoring. The high soft tissue contrast provided by MRI is valuable for the assessment of the fascial inflammation. While in the first patient FDG and contrast uptake as well as edema, represented by T2 signals, decreased with ongoing therapy, all parameters remained comparatively stable in the second patient. Contrary to expectations, an increase in FDG uptake of patient 3 and 4 was accompanied by an increase of the T2 signals, but a decrease in contrast uptake. These initial results suggest that PET/MRI provides complementary information of the complex disease mechanisms in fibrosing disorders.

ei

Web [BibTex]

Web [BibTex]


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Semi-supervised kernel canonical correlation analysis with application to human fMRI

Blaschko, M., Shelton, J., Bartels, A., Lampert, C., Gretton, A.

Pattern Recognition Letters, 32(11):1572-1583 , August 2011 (article)

Abstract
Kernel canonical correlation analysis (KCCA) is a general technique for subspace learning that incorporates principal components analysis (PCA) and Fisher linear discriminant analysis (LDA) as special cases. By finding directions that maximize correlation, KCCA learns representations that are more closely tied to the underlying process that generates the data and can ignore high-variance noise directions. However, for data where acquisition in one or more modalities is expensive or otherwise limited, KCCA may suffer from small sample effects. We propose to use semi-supervised Laplacian regularization to utilize data that are present in only one modality. This approach is able to find highly correlated directions that also lie along the data manifold, resulting in a more robust estimate of correlated subspaces. Functional magnetic resonance imaging (fMRI) acquired data are naturally amenable to subspace techniques as data are well aligned. fMRI data of the human brain are a particularly interesting candidate. In this study we implemented various supervised and semi-supervised versions of KCCA on human fMRI data, with regression to single and multi-variate labels (corresponding to video content subjects viewed during the image acquisition). In each variate condition, the semi-supervised variants of KCCA performed better than the supervised variants, including a supervised variant with Laplacian regularization. We additionally analyze the weights learned by the regression in order to infer brain regions that are important to different types of visual processing.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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Statistical Image Analysis and Percolation Theory

Langovoy, M., Habeck, M., Schölkopf, B.

2011 Joint Statistical Meetings (JSM), August 2011 (talk)

Abstract
We develop a novel method for detection of signals and reconstruction of images in the presence of random noise. The method uses results from percolation theory. We specifically address the problem of detection of multiple objects of unknown shapes in the case of nonparametric noise. The noise density is unknown and can be heavy-tailed. The objects of interest have unknown varying intensities. No boundary shape constraints are imposed on the objects, only a set of weak bulk conditions is required. We view the object detection problem as hypothesis testing for discrete statistical inverse problems. We present an algorithm that allows to detect greyscale objects of various shapes in noisy images. We prove results on consistency and algorithmic complexity of our procedures. Applications to cryo-electron microscopy are presented.

ei

Web [BibTex]

Web [BibTex]


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Multi-subject learning for common spatial patterns in motor-imagery BCI

Devlaminck, D., Wyns, B., Grosse-Wentrup, M., Otte, G., Santens, P.

Computational Intelligence and Neuroscience, 2011(217987):1-9, August 2011 (article)

Abstract
Motor-imagery-based brain-computer interfaces (BCIs) commonly use the common spatial pattern filter (CSP) as preprocessing step before feature extraction and classification. The CSP method is a supervised algorithm and therefore needs subject-specific training data for calibration, which is very time consuming to collect. In order to reduce the amount of calibration data that is needed for a new subject, one can apply multitask (from now on called multisubject) machine learning techniques to the preprocessing phase. Here, the goal of multisubject learning is to learn a spatial filter for a new subject based on its own data and that of other subjects. This paper outlines the details of the multitask CSP algorithm and shows results on two data sets. In certain subjects a clear improvement can be seen, especially when the number of training trials is relatively low.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Policy Search for Motor Primitives in Robotics

Kober, J., Peters, J.

Machine Learning, 84(1-2):171-203, July 2011 (article)

Abstract
Many motor skills in humanoid robotics can be learned using parametrized motor primitives. While successful applications to date have been achieved with imitation learning, most of the interesting motor learning problems are high-dimensional reinforcement learning problems. These problems are often beyond the reach of current reinforcement learning methods. In this paper, we study parametrized policy search methods and apply these to benchmark problems of motor primitive learning in robotics. We show that many well-known parametrized policy search methods can be derived from a general, common framework. This framework yields both policy gradient methods and expectation-maximization (EM) inspired algorithms. We introduce a novel EM-inspired algorithm for policy learning that is particularly well-suited for dynamical system motor primitives. We compare this algorithm, both in simulation and on a real robot, to several well-known parametrized policy search methods such as episodic REINFORCE, ‘Vanilla’ Policy Gradients with optimal baselines, episodic Natural Actor Critic, and episodic Reward-Weighted Regression. We show that the proposed method out-performs them on an empirical benchmark of learning dynamical system motor primitives both in simulation and on a real robot. We apply it in the context of motor learning and show that it can learn a complex Ball-in-a-Cup task on a real Barrett WAM™ robot arm.

ei

PDF PDF DOI Project Page [BibTex]

PDF PDF DOI Project Page [BibTex]


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ccSVM: correcting Support Vector Machines for confounding factors in biological data classification

Li, L., Rakitsch, B., Borgwardt, K.

Bioinformatics, 27(13: ISMB/ECCB 2011):i342-i348, July 2011 (article)

Abstract
Motivation: Classifying biological data into different groups is a central task of bioinformatics: for instance, to predict the function of a gene or protein, the disease state of a patient or the phenotype of an individual based on its genotype. Support Vector Machines are a wide spread approach for classifying biological data, due to their high accuracy, their ability to deal with structured data such as strings, and the ease to integrate various types of data. However, it is unclear how to correct for confounding factors such as population structure, age or gender or experimental conditions in Support Vector Machine classification. Results: In this article, we present a Support Vector Machine classifier that can correct the prediction for observed confounding factors. This is achieved by minimizing the statistical dependence between the classifier and the confounding factors. We prove that this formulation can be transformed into a standard Support Vector Machine with rescaled input data. In our experiments, our confounder correcting SVM (ccSVM) improves tumor diagnosis based on samples from different labs, tuberculosis diagnosis in patients of varying age, ethnicity and gender, and phenotype prediction in the presence of population structure and outperforms state-of-the-art methods in terms of prediction accuracy.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Epistasis detection on quantitative phenotypes by exhaustive enumeration using GPUs

Kam-Thong, T., Pütz, B., Karbalai, N., Müller-Myhsok, B., Borgwardt, K.

Bioinformatics, 27(13: ISMB/ECCB 2011):i214-i221, July 2011 (article)

Abstract
Motivation: In recent years, numerous genome-wide association studies have been conducted to identify genetic makeup that explains phenotypic differences observed in human population. Analytical tests on single loci are readily available and embedded in common genome analysis software toolset. The search for significant epistasis (gene–gene interactions) still poses as a computational challenge for modern day computing systems, due to the large number of hypotheses that have to be tested. Results: In this article, we present an approach to epistasis detection by exhaustive testing of all possible SNP pairs. The search strategy based on the Hilbert–Schmidt Independence Criterion can help delineate various forms of statistical dependence between the genetic markers and the phenotype. The actual implementation of this search is done on the highly parallelized architecture available on graphics processing units rendering the completion of the full search feasible within a day.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Empirical Inference

Schölkopf, B.

International Journal of Materials Research, 2011(7):809-814, July 2011 (article)

Abstract
Empirical Inference is the process of drawing conclusions from observational data. For instance, the data can be measurements from an experiment, which are used by a researcher to infer a scientific law. Another kind of empirical inference is performed by living beings, continuously recording data from their environment and carrying out appropriate actions. Do these problems have anything in common, and are there underlying principles governing the extraction of regularities from data? What characterizes hard inference problems, and how can we solve them? Such questions are studied by a community of scientists from various fields, engaged in machine learning research. This short paper, which is based on the author’s lecture to the scientific council of the Max Planck Society in February 2010, will attempt to describe some of the main ideas and problems of machine learning. It will provide illustrative examples of real world machine learning applications, including the use of machine learning towards the design of intelligent systems.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Online Multi-frame Blind Deconvolution with Super-resolution and Saturation Correction

Hirsch, M., Harmeling, S., Sra, S., Schölkopf, B.

Astronomy & Astrophysics, 531(A9):11, July 2011 (article)

Abstract
Astronomical images taken by ground-based telescopes suffer degradation due to atmospheric turbulence. This degradation can be tackled by costly hardware-based approaches such as adaptive optics, or by sophisticated software-based methods such as lucky imaging, speckle imaging, or multi-frame deconvolution. Software-based methods process a sequence of images to reconstruct a deblurred high-quality image. However, existing approaches are limited in one or several aspects: (i) they process all images in batch mode, which for thousands of images is prohibitive; (ii) they do not reconstruct a super-resolved image, even though an image sequence often contains enough information; (iii) they are unable to deal with saturated pixels; and (iv) they are usually non-blind, i.e., they assume the blur kernels to be known. In this paper we present a new method for multi-frame deconvolution called online blind deconvolution (OBD) that overcomes all these limitations simultaneously. Encouraging results on simulated and real astronomical images demonstrate that OBD yields deblurred images of comparable and often better quality than existing approaches.

ei

PDF DOI [BibTex]


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Closing the sensorimotor loop: haptic feedback facilitates decoding of motor imagery

Gomez Rodriguez, M., Peters, J., Hill, J., Schölkopf, B., Gharabaghi, A., Grosse-Wentrup, M.

Journal of Neural Engineering, 8(3):1-12, June 2011 (article)

Abstract
The combination of brain–computer interfaces (BCIs) with robot-assisted physical therapy constitutes a promising approach to neurorehabilitation of patients with severe hemiparetic syndromes caused by cerebrovascular brain damage (e.g. stroke) and other neurological conditions. In such a scenario, a key aspect is how to reestablish the disrupted sensorimotor feedback loop. However, to date it is an open question how artificially closing the sensorimotor feedback loop influences the decoding performance of a BCI. In this paper, we answer this issue by studying six healthy subjects and two stroke patients. We present empirical evidence that haptic feedback, provided by a seven degrees of freedom robotic arm, facilitates online decoding of arm movement intention. The results support the feasibility of future rehabilitative treatments based on the combination of robot-assisted physical therapy with BCIs.

ei

PDF PDF DOI [BibTex]


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Greedy Learning of Binary Latent Trees

Harmeling, S., Williams, C.

IEEE Transactions on Pattern Analysis and Machine Intelligence, 33(6):1087-1097, June 2011 (article)

Abstract
Inferring latent structures from observations helps to model and possibly also understand underlying data generating processes. A rich class of latent structures are hierarchical latent class (HLC) models. Zhang (2004) proposed a search algorithm for learning such models that can find good solutions but is often computationally expensive. As an alternative we investigate two greedy procedures: the BIN-G algorithm determines both the structure of the tree and the cardinality of the latent variables in a bottom-up fashion. The BIN-A algorithm first determines the tree structure using agglomerative hierarchical clustering, and then determines the cardinality of the latent variables as for BIN-G. We show that even with restricting ourselves to binary trees we obtain HLC models of comparable quality to Zhang‘s solutions, while being faster to compute. This claim is validated by a comprehensive comparison on several datasets. Furthermore, we demonstrate that our methods are able to estimate int erpretable latent structures on real-world data with a large number of variables. By applying our method to a restricted version of the 20 newsgroups data these models turn out to be related to topic models, and on data from the PASCAL Visual Object Classes (VOC) 2007 challenge we show how such tree-structured models help us understand how objects co-occur in images.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Learning Dynamic Tactile Sensing with Robust Vision-based Training

Kroemer, O., Lampert, C., Peters, J.

IEEE Transactions on Robotics, 27(3):545-557 , June 2011 (article)

Abstract
Dynamic tactile sensing is a fundamental ability to recognize materials and objects. However, while humans are born with partially developed dynamic tactile sensing and quickly master this skill, today's robots remain in their infancy. The development of such a sense requires not only better sensors but the right algorithms to deal with these sensors' data as well. For example, when classifying a material based on touch, the data are noisy, high-dimensional, and contain irrelevant signals as well as essential ones. Few classification methods from machine learning can deal with such problems. In this paper, we propose an efficient approach to infer suitable lower dimensional representations of the tactile data. In order to classify materials based on only the sense of touch, these representations are autonomously discovered using visual information of the surfaces during training. However, accurately pairing vision and tactile samples in real-robot applications is a difficult problem. The proposed approach, therefore, works with weak pairings between the modalities. Experiments show that the resulting approach is very robust and yields significantly higher classification performance based on only dynamic tactile sensing.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Algebraic polynomials and moments of stochastic integrals

Langovoy, M.

Statistics & Probability Letters, 81(6):627-631, June 2011 (article)

Abstract
We propose an algebraic method for proving estimates on moments of stochastic integrals. The method uses qualitative properties of roots of algebraic polynomials from certain general classes. As an application, we give a new proof of a variation of the Burkholder–Davis–Gundy inequality for the case of stochastic integrals with respect to real locally square integrable martingales. Further possible applications and extensions of the method are outlined.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Inference for psychometric functions in the presence of nonstationary behavior

Fründ, I., Haenel, N., Wichmann, F.

Journal of Vision, 11(6):1-19, May 2011 (article)

Abstract
Measuring sensitivity is at the heart of psychophysics. Often, sensitivity is derived from estimates of the psychometric function. This function relates response probability to stimulus intensity. In estimating these response probabilities, most studies assume stationary observers: Responses are expected to be dependent only on the intensity of a presented stimulus and not on other factors such as stimulus sequence, duration of the experiment, or the responses on previous trials. Unfortunately, a number of factors such as learning, fatigue, or fluctuations in attention and motivation will typically result in violations of this assumption. The severity of these violations is yet unknown. We use Monte Carlo simulations to show that violations of these assumptions can result in underestimation of confidence intervals for parameters of the psychometric function. Even worse, collecting more trials does not eliminate this misestimation of confidence intervals. We present a simple adjustment of the confidence intervals that corrects for the underestimation almost independently of the number of trials and the particular type of violation.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Transition from the locked in to the completely locked-in state: A physiological analysis

Ramos Murguialday, A., Hill, J., Bensch, M., Martens, S., Halder, S., Nijboer, F., Schölkopf, B., Birbaumer, N., Gharabaghi, A.

Clinical Neurophysiology, 122(5):925-933 , May 2011 (article)

Abstract
Objective To clarify the physiological and behavioral boundaries between locked-in (LIS) and the completely locked-in state (CLIS) (no voluntary eye movements, no communication possible) through electrophysiological data and to secure brain–computer-interface (BCI) communication. Methods Electromyography from facial muscles, external anal sphincter (EAS), electrooculography and electrocorticographic data during different psychophysiological tests were acquired to define electrophysiological differences in an amyotrophic lateral sclerosis (ALS) patient with an intracranially implanted grid of 112 electrodes for nine months while the patient passed from the LIS to the CLIS. Results At the very end of the LIS there was no facial muscle activity, nor external anal sphincter but eye control. Eye movements were slow and lasted for short periods only. During CLIS event related brain potentials (ERP) to passive limb movements and auditory stimuli were recorded, vibrotactile stimulation of different body parts resulted in no ERP response. Conclusions The results presented contradict the commonly accepted assumption that the EAS is the last remaining muscle under voluntary control and demonstrate complete loss of eye movements in CLIS. The eye muscle was shown to be the last muscle group under voluntary control. The findings suggest ALS as a multisystem disorder, even affecting afferent sensory pathways. Significance Auditory and proprioceptive brain–computer-interface (BCI) systems are the only remaining communication channels in CLIS.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Incremental online sparsification for model learning in real-time robot control

Nguyen-Tuong, D., Peters, J.

Neurocomputing, 74(11):1859-1867, May 2011 (article)

Abstract
For many applications such as compliant, accurate robot tracking control, dynamics models learned from data can help to achieve both compliant control performance as well as high tracking quality. Online learning of these dynamics models allows the robot controller to adapt itself to changes in the dynamics (e.g., due to time-variant nonlinearities or unforeseen loads). However, online learning in real-time applications -- as required in control -- cannot be realized by straightforward usage of off-the-shelf machine learning methods such as Gaussian process regression or support vector regression. In this paper, we propose a framework for online, incremental sparsification with a fixed budget designed for fast real-time model learning. The proposed approach employs a sparsification method based on an independence measure. In combination with an incremental learning approach such as incremental Gaussian process regression, we obtain a model approximation method which is applicable in real-time online learning. It exhibits competitive learning accuracy when compared with standard regression techniques. Implementation on a real Barrett WAM robot demonstrates the applicability of the approach in real-time online model learning for real world systems.

ei

PDF DOI [BibTex]


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Causal Influence of Gamma Oscillations on the Sensorimotor Rhythm

Grosse-Wentrup, M., Schölkopf, B., Hill, J.

NeuroImage, 56(2):837-842, May 2011 (article)

Abstract
Gamma oscillations of the electromagnetic field of the brain are known to be involved in a variety of cognitive processes, and are believed to be fundamental for information processing within the brain. While gamma oscillations have been shown to be correlated with brain rhythms at different frequencies, to date no empirical evidence has been presented that supports a causal influence of gamma oscillations on other brain rhythms. In this work, we study the relation of gamma oscillations and the sensorimotor rhythm (SMR) in healthy human subjects using electroencephalography. We first demonstrate that modulation of the SMR, induced by motor imagery of either the left or right hand, is positively correlated with the power of frontal and occipital gamma oscillations, and negatively correlated with the power of centro-parietal gamma oscillations. We then demonstrate that the most simple causal structure, capable of explaining the observed correlation of gamma oscillations and the SMR, entails a causal influence of gamma oscillations on the SMR. This finding supports the fundamental role attributed to gamma oscillations for information processing within the brain, and is of particular importance for brain–computer interfaces (BCIs). As modulation of the SMR is typically used in BCIs to infer a subject's intention, our findings entail that gamma oscillations have a causal influence on a subject's capability to utilize a BCI for means of communication.

ei

PDF DOI Project Page [BibTex]


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The effect of patient positioning aids on PET quantification in PET/MR imaging

Mantlik, F., Hofmann, M., Werner, M., Sauter, A., Kupferschläger, J., Schölkopf, B., Pichler, B., Beyer, T.

European Journal of Nuclear Medicine and Molecular Imaging, 38(5):920-929, May 2011 (article)

Abstract
Objectives Clinical PET/MR requires the use of patient positioning aids to immobilize and support patients for the duration of the combined examination. Ancillary immobilization devices contribute to overall attenuation of the PET signal, but are not detected with conventional MR sequences and, hence, are ignored in standard MR-based attenuation correction (MR-AC). We report on the quantitative effect of not accounting for the attenuation of patient positioning aids in combined PET/MR imaging. Methods We used phantom and patient data acquired with positioning aids on a PET/CT scanner (Biograph 16, HI-REZ) to mimic PET/MR imaging conditions. Reference CT-based attenuation maps were generated from measured (original) CT transmission images (origCT-AC). We also created MR-like attenuation maps by following the same conversion procedure of the attenuation values except for the prior delineation and subtraction of the positioning aids from the CT images (modCT-AC). First, a uniform 68Ge cylinder was positioned centrally in the PET/CT scanner and fixed with a vacuum mattress (10 cm thick) and, in a repeat examination, with MR positioning foam pads. Second, 16 patient datasets were selected for subsequent processing. All patients were regionally immobilized with positioning aids: a vacuum mattress for head/neck imaging (nine patients) and a foam mattress for imaging of the lower extremities (seven patients). PET images were reconstructed following CT-based attenuation and scatter correction using the original and modified (MR-like) CT images: PETorigCT-AC and PETmodCT-AC, respectively. PET images following origCT-AC and modCT-AC were compared visually and in terms of mean differences of voxels with a standardized uptake value of at least 1.0. In addition, we report maximum activity concentration in lesions for selected patients. Results In the phantom study employing the vacuum mattress the average voxel activity in PETmodCT-AC was underestimated by 6.4% compared to PETorigCT-AC, with 3.4% of the PET voxels being underestimated by 10% or more. When the MR foam pads were not accounted for during AC, PETmodCT-AC was underestimated by 1.1% on average, with none of the PET voxels being underestimated by 10% or more. Evaluation of the head/neck patient data showed a decrease of 8.4% ([68Ga]DOTATOC) and 7.4% ([18F]FDG) when patient positioning aids were not accounted for during AC, while the corresponding decrease was insignificant for the lower extremities. Conclusion Depending on the size and density of the positioning aids used, a regionally variable underestimation of PET activity following AC is observed when positioning aids are not accounted for. This underestimation may become relevant in combined PET/MR imaging of patients with neuropsychiatric indications, but appears to be of no clinical relevance in imaging the extremities.

ei

PDF DOI Project Page [BibTex]

PDF DOI Project Page [BibTex]


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Loose-limbed People: Estimating 3D Human Pose and Motion Using Non-parametric Belief Propagation

Sigal, L., Isard, M., Haussecker, H., Black, M. J.

International Journal of Computer Vision, 98(1):15-48, Springer Netherlands, May 2011 (article)

Abstract
We formulate the problem of 3D human pose estimation and tracking as one of inference in a graphical model. Unlike traditional kinematic tree representations, our model of the body is a collection of loosely-connected body-parts. In particular, we model the body using an undirected graphical model in which nodes correspond to parts and edges to kinematic, penetration, and temporal constraints imposed by the joints and the world. These constraints are encoded using pair-wise statistical distributions, that are learned from motion-capture training data. Human pose and motion estimation is formulated as inference in this graphical model and is solved using Particle Message Passing (PaMPas). PaMPas is a form of non-parametric belief propagation that uses a variation of particle filtering that can be applied over a general graphical model with loops. The loose-limbed model and decentralized graph structure allow us to incorporate information from "bottom-up" visual cues, such as limb and head detectors, into the inference process. These detectors enable automatic initialization and aid recovery from transient tracking failures. We illustrate the method by automatically tracking people in multi-view imagery using a set of calibrated cameras and present quantitative evaluation using the HumanEva dataset.

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pdf publisher's site link (url) Project Page Project Page [BibTex]

pdf publisher's site link (url) Project Page Project Page [BibTex]


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Improving quantification of functional networks with EEG inverse problem: Evidence from a decoding point of view

Besserve, M., Martinerie, J., Garnero, L.

NeuroImage, 55(4):1536-1547, April 2011 (article)

Abstract
Decoding experimental conditions from single trial Electroencephalographic (EEG) signals is becoming a major challenge for the study of brain function and real-time applications such as Brain Computer Interface. EEG source reconstruction offers principled ways to estimate the cortical activities from EEG signals. But to what extent it can enhance informative brain signals in single trial has not been addressed in a general setting. We tested this using the minimum norm estimate solution (MNE) to estimate spectral power and coherence features at the cortical level. With a fast implementation, we computed a support vector machine (SVM) classifier output from these quantities in real-time, without prior on the relevant functional networks. We applied this approach to single trial decoding of ongoing mental imagery tasks using EEG data recorded in 5 subjects. Our results show that reconstructing the underlying cortical network dynamics significantly outperforms a usual electrode level approach in terms of information transfer and also reduces redundancy between coherence and power features, supporting a decrease of volume conduction effects. Additionally, the classifier coefficients reflect the most informative features of network activity, showing an important contribution of localized motor and sensory brain areas, and of coherence between areas up to 6 cm distance. This study provides a computationally efficient and interpretable strategy to extract information from functional networks at the cortical level in single trial. Moreover, this sets a general framework to evaluate the performance of EEG source reconstruction methods by their decoding abilities.

ei

Web DOI Project Page [BibTex]


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Using brain–computer interfaces to induce neural plasticity and restore function

Grosse-Wentrup, M., Mattia, D., Oweiss, K.

Journal of Neural Engineering, 8(2):1-5, April 2011 (article)

Abstract
Analyzing neural signals and providing feedback in real-time is one of the core characteristics of a brain-computer interface (BCI). As this feature may be employed to induce neural plasticity, utilizing BCI-technology for therapeutic purposes is increasingly gaining popularity in the BCI-community. In this review, we discuss the state-of-the-art of research on this topic, address the principles of and challenges in inducing neural plasticity by means of a BCI, and delineate the problems of study design and outcome evaluation arising in this context. The review concludes with a list of open questions and recommendations for future research in this field.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

Kam-Thong, T., Czamara, D., Tsuda, K., Borgwardt, K., Lewis, C., Erhardt-Lehmann, A., Hemmer, B., Rieckmann, P., Daake, M., Weber, F., Wolf, C., Ziegler, A., Pütz, B., Holsboer, F., Schölkopf, B., Müller-Myhsok, B.

European Journal of Human Genetics, 19(4):465-471, April 2011 (article)

Abstract
Detection of epistatic interaction between loci has been postulated to provide a more in-depth understanding of the complex biological and biochemical pathways underlying human diseases. Studying the interaction between two loci is the natural progression following traditional and well-established single locus analysis. However, the added costs and time duration required for the computation involved have thus far deterred researchers from pursuing a genome-wide analysis of epistasis. In this paper, we propose a method allowing such analysis to be conducted very rapidly. The method, dubbed EPIBLASTER, is applicable to case–control studies and consists of a two-step process in which the difference in Pearson‘s correlation coefficients is computed between controls and cases across all possible SNP pairs as an indication of significant interaction warranting further analysis. For the subset of interactions deemed potentially significant, a second-stage analysis is performed using the likelihood ratio test from the logistic regression to obtain the P-value for the estimated coefficients of the individual effects and the interaction term. The algorithm is implemented using the parallel computational capability of commercially available graphical processing units to greatly reduce the computation time involved. In the current setup and example data sets (211 cases, 222 controls, 299468 SNPs; and 601 cases, 825 controls, 291095 SNPs), this coefficient evaluation stage can be completed in roughly 1 day. Our method allows for exhaustive and rapid detection of significant SNP pair interactions without imposing significant marginal effects of the single loci involved in the pair.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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Model learning for robot control: a survey

Nguyen-Tuong, D., Peters, J.

Cognitive Processing, 12(4):319-340, April 2011 (article)

Abstract
Models are among the most essential tools in robotics, such as kinematics and dynamics models of the robot’s own body and controllable external objects. It is widely believed that intelligent mammals also rely on internal models in order to generate their actions. However, while classical robotics relies on manually generated models that are based on human insights into physics, future autonomous, cognitive robots need to be able to automatically generate models that are based on information which is extracted from the data streams accessible to the robot. In this paper, we survey the progress in model learning with a strong focus on robot control on a kinematic as well as dynamical level. Here, a model describes essential information about the behavior of the environment and the influence of an agent on this environment. In the context of model-based learning control, we view the model from three different perspectives. First, we need to study the different possible model learning architectures for robotics. Second, we discuss what kind of problems these architecture and the domain of robotics imply for the applicable learning methods. From this discussion, we deduce future directions of real-time learning algorithms. Third, we show where these scenarios have been used successfully in several case studies.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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Crowdsourcing for optimisation of deconvolution methods via an iPhone application

Lang, A.

Hochschule Reutlingen, Germany, April 2011 (mastersthesis)

ei

[BibTex]

[BibTex]


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Critical issues in state-of-the-art brain–computer interface signal processing

Krusienski, D., Grosse-Wentrup, M., Galan, F., Coyle, D., Miller, K., Forney, E., Anderson, C.

Journal of Neural Engineering, 8(2):1-8, April 2011 (article)

Abstract
This paper reviews several critical issues facing signal processing for brain–computer interfaces (BCIs) and suggests several recent approaches that should be further examined. The topics were selected based on discussions held during the 4th International BCI Meeting at a workshop organized to review and evaluate the current state of, and issues relevant to, feature extraction and translation of field potentials for BCIs. The topics presented in this paper include the relationship between electroencephalography and electrocorticography, novel features for performance prediction, time-embedded signal representations, phase information, signal non-stationarity, and unsupervised adaptation.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Point-and-Click Cursor Control With an Intracortical Neural Interface System by Humans With Tetraplegia

Kim, S., Simeral, J. D., Hochberg, L. R., Donoghue, J. P., Friehs, G. M., Black, M. J.

IEEE Transactions on Neural Systems and Rehabilitation Engineering, 19(2):193-203, April 2011 (article)

Abstract
We present a point-and-click intracortical neural interface system (NIS) that enables humans with tetraplegia to volitionally move a 2D computer cursor in any desired direction on a computer screen, hold it still and click on the area of interest. This direct brain-computer interface extracts both discrete (click) and continuous (cursor velocity) signals from a single small population of neurons in human motor cortex. A key component of this system is a multi-state probabilistic decoding algorithm that simultaneously decodes neural spiking activity and outputs either a click signal or the velocity of the cursor. The algorithm combines a linear classifier, which determines whether the user is intending to click or move the cursor, with a Kalman filter that translates the neural population activity into cursor velocity. We present a paradigm for training the multi-state decoding algorithm using neural activity observed during imagined actions. Two human participants with tetraplegia (paralysis of the four limbs) performed a closed-loop radial target acquisition task using the point-and-click NIS over multiple sessions. We quantified point-and-click performance using various human-computer interaction measurements for pointing devices. We found that participants were able to control the cursor motion accurately and click on specified targets with a small error rate (< 3% in one participant). This study suggests that signals from a small ensemble of motor cortical neurons (~40) can be used for natural point-and-click 2D cursor control of a personal computer.

ps

pdf publishers's site pub med link (url) Project Page [BibTex]

pdf publishers's site pub med link (url) Project Page [BibTex]


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Dynamics of excitable neural networks with heterogeneous connectivity

Chavez, M., Besserve, M., Le Van Quyen, M.

Progress in Biophysics and Molecular Biology, 105(1-2):29-33, March 2011 (article)

Abstract
A central issue of neuroscience is to understand how neural units integrates internal and external signals to create coherent states. Recently, it has been shown that the sensitivity and dynamic range of neural assemblies are optimal at a critical coupling among its elements. Complex architectures of connections seem to play a constructive role on the reliable coordination of neural units. Here we show that, the synchronizability and sensitivity of excitable neural networks can be tuned by diversity in the connections strengths. We illustrate our findings for weighted networks with regular, random and complex topologies. Additional comparisons of real brain networks support previous studies suggesting that heterogeneity in the connectivity may play a constructive role on information processing. These findings provide insights into the relationship between structure and function of neural circuits.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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A Blind Deconvolution Approach for Improving the Resolution of Cryo-EM Density Maps

Hirsch, M., Schölkopf, B., Habeck, M.

Journal of Computational Biology, 18(3):335-346, March 2011 (article)

Abstract
Cryo-electron microscopy (cryo-EM) plays an increasingly prominent role in structure elucidation of macromolecular assemblies. Advances in experimental instrumentation and computational power have spawned numerous cryo-EM studies of large biomolecular complexes resulting in the reconstruction of three-dimensional density maps at intermediate and low resolution. In this resolution range, identification and interpretation of structural elements and modeling of biomolecular structure with atomic detail becomes problematic. In this article, we present a novel algorithm that enhances the resolution of intermediate- and low-resolution density maps. Our underlying assumption is to model the low-resolution density map as a blurred and possibly noise-corrupted version of an unknown high-resolution map that we seek to recover by deconvolution. By exploiting the nonnegativity of both the high-resolution map and blur kernel, we derive multiplicative updates reminiscent of those used in nonnegative matrix factorization. Our framework allows for easy incorporation of additional prior knowledge such as smoothness and sparseness, on both the sharpened density map and the blur kernel. A probabilistic formulation enables us to derive updates for the hyperparameters; therefore, our approach has no parameter that needs adjustment. We apply the algorithm to simulated three-dimensional electron microscopic data. We show that our method provides better resolved density maps when compared with B-factor sharpening, especially in the presence of noise. Moreover, our method can use additional information provided by homologous structures, which helps to improve the resolution even further.

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Web DOI [BibTex]

Web DOI [BibTex]


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Combining computational modeling with sparse and low-resolution data

Habeck, M., Nilges, M.

Journal of Structural Biology, 173(3):419, March 2011 (article)

Abstract
Structural biology is moving into a new era by shifting its focus from static structures of single proteins and protein domains to large and often fragile multi-component complexes. Over the past decade, structural genomics initiatives aimed to fill the voids in fold space and to provide a census of all protein structures. Completion of such an atlas of protein structures is still ongoing, but not sufficient for a mechanistic understanding of how living cells function. One of the great challenges is to bridge the gap between atomic resolution detail and the more fuzzy description of the molecular complexes that govern cellular processes or host–pathogen interactions. We want to move from cartoon-like representations of multi-component complexes to atomic resolution structures. To characterize the structures of the increasingly large and often flexible complexes, high resolution structure determination (as was possible for example for the ribosome) will likely stay the exception. Rather, data from many different methods providing information on the shape (X-ray crystallography, electron microscopy, SAXS, AFM, etc.) or on contacts between components (mass spectrometry, co-purification, or spectroscopic methods) need to be integrated with prior structural knowledge to build a consistent model of the complex. A particular difficulty is that the ratio between the number of conformational degrees of freedom and the number of measurements becomes unfavorable as we work with large complexes: data become increasingly sparse. Structural characterization of large molecular assemblies often involves a loss in resolution as well as in number and quality of data. We are good at solving structures of single proteins, but classical high-resolution structure determination by X-ray crystallography and NMR spectroscopy is often facing its limits as we move to higher molecular mass and increased flexibility. Therefore, structural studies on large complexes rely on new experimental techniques that complement the classical high resolution methods. But also computational approaches are becoming more important when it comes to integrating and analyzing structural information of often heterogeneous nature. Cryoelectron microscopy may serve as an example of how experimental methods can benefit from computation. Low-resolution data from cryo-EM show their true power when combined with modeling and bioinformatics methods such rigid docking and secondary structure hunting. Even in high resolution structure determination, molecular modeling is always necessary to calculate structures from data, to complement the missing information and to evaluate and score the obtained structures. With sparse data, all these three aspects become increasingly difficult, and the quality of the modeling approach becomes more important. With data alone, algorithms may not converge any more; scoring against data becomes meaningless; and the potential energy function becomes central not only as a help in making algorithms converge but also to score and evaluate the structures. In addition to the sparsity of the data, hybrid approaches bring the additional difficulty that the different sources of data may have rather different quality, and may be in the extreme case incompatible with each other. In addition to scoring the structures, modeling should also score in some way the data going into the calculation. This special issue brings together some of the numerous efforts to solve the problems that come from sparsity of data and from integrating data from different sources in hybrid approaches. The methods range from predominantly force-field based to mostly data based. Systems of very different sizes, ranging from single domains to multi-component complexes, are treated. We hope that you will enjoy reading the issue and find it a useful and inspiring resource.

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PDF DOI [BibTex]

PDF DOI [BibTex]


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Statistical mechanics analysis of sparse data

Habeck, M.

Journal of Structural Biology, 173(3):541-548, March 2011 (article)

Abstract
Inferential structure determination uses Bayesian theory to combine experimental data with prior structural knowledge into a posterior probability distribution over protein conformational space. The posterior distribution encodes everything one can say objectively about the native structure in the light of the available data and additional prior assumptions and can be searched for structural representatives. Here an analogy is drawn between the posterior distribution and the canonical ensemble of statistical physics. A statistical mechanics analysis assesses the complexity of a structure calculation globally in terms of ensemble properties. Analogs of the free energy and density of states are introduced; partition functions evaluate the consistency of prior assumptions with data. Critical behavior is observed with dwindling restraint density, which impairs structure determination with too sparse data. However, prior distributions with improved realism ameliorate the situation by lowering the critical number of observations. An in-depth analysis of various experimentally accessible structural parameters and force field terms will facilitate a statistical approach to protein structure determination with sparse data that avoids bias as much as possible.

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PDF DOI [BibTex]

PDF DOI [BibTex]