Protein Docking by the Underestimation of Free Energy Funnels in the Space of Encounter Complexes

Similarly to protein folding, the association of two proteins is driven by a free energy funnel, determined by favorable interactions in some neighborhood of the native state. We describe a docking method based on stochastic global minimization of funnel-shaped energy functions in the space of rigid body motions (SE(3)) while accounting for flexibility of the interface side chains. The method, called semi-definite programming-based underestimation (SDU), employs a general quadratic function to underestimate a set of local energy minima and uses the resulting underestimator to bias further sampling. While SDU effectively minimizes functions with funnel-shaped basins, its application to docking in the rotational and translational space SE(3) is not straightforward due to the geometry of that space. We introduce a strategy that uses separate independent variables for side-chain optimization, center-to-center distance of the two proteins, and five angular descriptors of the relative orientations of the molecules. The removal of the center-to-center distance turns out to vastly improve the efficiency of the search, because the five-dimensional space now exhibits a well-behaved energy surface suitable for underestimation. This algorithm explores the free energy surface spanned by encounter complexes that correspond to local free energy minima and shows similarity to the model of macromolecular association that proceeds through a series of collisions. Results for standard protein docking benchmarks establish that in this space the free energy landscape is a funnel in a reasonably broad neighborhood of the native state and that the SDU strategy can generate docking predictions with less than 5 � ligand interface Ca root-mean-square deviation while achieving an approximately 20-fold efficiency gain compared to Monte Carlo methods.

Skin Color-Based Video Segmentation under Time-Varying Illumination

A novel approach for real-time skin segmentation in video sequences is described. The approach enables reliable skin segmentation despite wide variation in illumination during tracking. An explicit second order Markov model is used to predict evolution of the skin-color (HSV) histogram over time. Histograms are dynamically updated based on feedback from the current segmentation and predictions of the Markov model. The evolution of the skin-color distribution at each frame is parameterized by translation, scaling and rotation in color space. Consequent changes in geometric parameterization of the distribution are propagated by warping and resampling the histogram. The parameters of the discrete-time dynamic Markov model are estimated using Maximum Likelihood Estimation, and also evolve over time. The accuracy of the new dynamic skin color segmentation algorithm is compared to that obtained via a static color model. Segmentation accuracy is evaluated using labeled ground-truth video sequences taken from staged experiments and popular movies. An overall increase in segmentation accuracy of up to 24% is observed in 17 out of 21 test sequences. In all but one case the skin-color classification rates for our system were higher, with background classification rates comparable to those of the static segmentation.

Specialized Mappings Architecture with Applications to Vision-based Estimation of Articulated Body Pose

A fundamental task of vision systems is to infer the state of the world given some form of visual observations. From a computational perspective, this often involves facing an ill-posed problem; e.g., information is lost via projection of the 3D world into a 2D image. Solution of an ill-posed problem requires additional information, usually provided as a model of the underlying process. It is important that the model be both computationally feasible as well as theoretically well-founded. In this thesis, a probabilistic, nonlinear supervised computational learning model is proposed: the Specialized Mappings Architecture (SMA). The SMA framework is demonstrated in a computer vision system that can estimate the articulated pose parameters of a human body or human hands, given images obtained via one or more uncalibrated cameras. The SMA consists of several specialized forward mapping functions that are estimated automatically from training data, and a possibly known feedback function. Each specialized function maps certain domains of the input space (e.g., image features) onto the output space (e.g., articulated body parameters). A probabilistic model for the architecture is first formalized. Solutions to key algorithmic problems are then derived: simultaneous learning of the specialized domains along with the mapping functions, as well as performing inference given inputs and a feedback function. The SMA employs a variant of the Expectation-Maximization algorithm and approximate inference. The approach allows the use of alternative conditional independence assumptions for learning and inference, which are derived from a forward model and a feedback model. Experimental validation of the proposed approach is conducted in the task of estimating articulated body pose from image silhouettes. Accuracy and stability of the SMA framework is tested using artificial data sets, as well as synthetic and real video sequences of human bodies and hands.

Detour-Based Mobility Coordination in DTNs

Commonly, research work in routing for delay tolerant networks (DTN) assumes that node encounters are predestined, in the sense that they are the result of unknown, exogenous processes that control the mobility of these nodes. In this paper, we argue that for many applications such an assumption is too restrictive: while the spatio-temporal coordinates of the start and end points of a node's journey are determined by exogenous processes, the specific path that a node may take in space-time, and hence the set of nodes it may encounter could be controlled in such a way so as to improve the performance of DTN routing. To that end, we consider a setting in which each mobile node is governed by a schedule consisting of a ist of locations that the node must visit at particular times. Typically, such schedules exhibit some level of slack, which could be leveraged for DTN message delivery purposes. We define the Mobility Coordination Problem (MCP) for DTNs as follows: Given a set of nodes, each with its own schedule, and a set of messages to be exchanged between these nodes, devise a set of node encounters that minimize message delivery delays while satisfying all node schedules. The MCP for DTNs is general enough that it allows us to model and evaluate some of the existing DTN schemes, including data mules and message ferries. In this paper, we show that MCP for DTNs is NP-hard and propose two detour-based approaches to solve the problem. The first (DMD) is a centralized heuristic that leverages knowledge of the message workload to suggest specific detours to optimize message delivery. The second (DNE) is a distributed heuristic that is oblivious to the message workload, and which selects detours so as to maximize node encounters. We evaluate the performance of these detour-based approaches using extensive simulations based on synthetic workloads as well as real schedules obtained from taxi logs in a major metropolitan area. Our evaluation shows that our centralized, workload-aware DMD approach yields the best performance, in terms of message delay and delivery success ratio, and that our distributed, workload-oblivious DNE approach yields favorable performance when compared to approaches that require the use of data mules and message ferries.

Combining Textual and Visual Cues for Content-based Image Retrieval on the World Wide Web

Some WWW image engines allow the user to form a query in terms of text keywords. To build the image index, keywords are extracted heuristically from HTML documents containing each image, and/or from the image URL and file headers. Unfortunately, text-based image engines have merely retro-fitted standard SQL database query methods, and it is difficult to include images cues within such a framework. On the other hand, visual statistics (e.g., color histograms) are often insufficient for helping users find desired images in a vast WWW index. By truly unifying textual and visual statistics, one would expect to get better results than either used separately. In this paper, we propose an approach that allows the combination of visual statistics with textual statistics in the vector space representation commonly used in query by image content systems. Text statistics are captured in vector form using latent semantic indexing (LSI). The LSI index for an HTML document is then associated with each of the images contained therein. Visual statistics (e.g., color, orientedness) are also computed for each image. The LSI and visual statistic vectors are then combined into a single index vector that can be used for content-based search of the resulting image database. By using an integrated approach, we are able to take advantage of possible statistical couplings between the topic of the document (latent semantic content) and the contents of images (visual statistics). This allows improved performance in conducting content-based search. This approach has been implemented in a WWW image search engine prototype.

Search Space Reduction in QoS Routing

To provide real-time service or engineer constrained-based paths, networks require the underlying routing algorithm to be able to find low-cost paths that satisfy given Quality-of-Service (QoS) constraints. However, the problem of constrained shortest (least-cost) path routing is known to be NP-hard, and some heuristics have been proposed to find a near-optimal solution. However, these heuristics either impose relationships among the link metrics to reduce the complexity of the problem which may limit the general applicability of the heuristic, or are too costly in terms of execution time to be applicable to large networks. In this paper, we focus on solving the delay-constrained minimum-cost path problem, and present a fast algorithm to find a near-optimal solution. This algorithm, called DCCR (for Delay-Cost-Constrained Routing), is a variant of the k-shortest path algorithm. DCCR uses a new adaptive path weight function together with an additional constraint imposed on the path cost, to restrict the search space. Thus, DCCR can return a near-optimal solution in a very short time. Furthermore, we use the method proposed by Blokh and Gutin to further reduce the search space by using a tighter bound on path cost. This makes our algorithm more accurate and even faster. We call this improved algorithm SSR+DCCR (for Search Space Reduction+DCCR). Through extensive simulations, we confirm that SSR+DCCR performs very well compared to the optimal but very expensive solution.

Articulated Pose Estimation in a Learned Smooth Space of Feasible Solutions

A learning based framework is proposed for estimating human body pose from a single image. Given a differentiable function that maps from pose space to image feature space, the goal is to invert the process: estimate the pose given only image features. The inversion is an ill-posed problem as the inverse mapping is a one to many process. Hence multiple solutions exist, and it is desirable to restrict the solution space to a smaller subset of feasible solutions. For example, not all human body poses are feasible due to anthropometric constraints. Since the space of feasible solutions may not admit a closed form description, the proposed framework seeks to exploit machine learning techniques to learn an approximation that is smoothly parameterized over such a space. One such technique is Gaussian Process Latent Variable Modelling. Scaled conjugate gradient is then used find the best matching pose in the space of feasible solutions when given an input image. The formulation allows easy incorporation of various constraints, e.g. temporal consistency and anthropometric constraints. The performance of the proposed approach is evaluated in the task of upper-body pose estimation from silhouettes and compared with the Specialized Mapping Architecture. The estimation accuracy of the Specialized Mapping Architecture is at least one standard deviation worse than the proposed approach in the experiments with synthetic data. In experiments with real video of humans performing gestures, the proposed approach produces qualitatively better estimation results.