X-ray crystallography is currently the most common way protein structures are elucidated. One of the most time-consuming steps in the crystallographic process is interpretation of the electron density map, a task that involves finding patterns in a three-dimensional picture of a protein. This paper describes DEFT (DEFormable Template), an algorithm using pictorial structures to build a flexible protein model from the protein's amino-acid sequence. Matching this pictorial structure into the density map is a way of automating density-map interpretation. Also described are several extensions to the pictorial structure matching algorithm necessary for this automated interpretation. DEFT is tested on a set of density maps ranging from 2 to 4Å resolution, producing rootmean-squared errors ranging from 1.38 to 1.84Å.

We propose a new interpretation of spiking neurons as Bayesian integrators accumulating evidence over time about events in the external world or the body, and communicating to other neurons their certainties about these events. In this model, spikes signal the occurrence of new information, i.e. what cannot be predicted from the past activity. As a result, firing statistics are close to Poisson, albeit providing a deterministic representation of probabilities. We proceed to develop a theory of Bayesian inference in spiking neural networks, recurrent interactions implementing a variant of belief propagation. Many perceptual and motor tasks performed by the central nervous system are probabilistic, and can be described in a Bayesian framework [4, 3].

Theories of access consciousness address how it is that some mental states but not others are available for evaluation, choice behavior, and verbal report. Farah, O'Reilly, and Vecera (1994) argue that quality of representation is critical; Dehaene, Sergent, and Changeux (2003) argue that the ability to communicate representations is critical. We present a probabilistic information transmission or PIT model that suggests both of these conditions are essential for access consciousness. Having successfully modeled data from the repetition priming literature in the past, we use the PIT model to account for data from two experiments on subliminal priming, showing that the model produces priming even in the absence of accessibility and reportability of internal states. The model provides a mechanistic basis for understanding the dissociation of priming and awareness. Philosophy has made many attempts to identify distinct aspects of consciousness. Perhaps the most famous effort is Block's (1995) delineation of phenomenal and access consciousness. Phenomenal consciousness has to do with "what it is like" to experience chocolate or a pin prick. Access consciousness refers to internal states whose content is "(1) inferentially promiscuous, i.e., poised to be used as a premise in reasoning, (2) poised for control of action, and (3) poised for rational control of speech."

An analog system-on-chip for kernel-based pattern classification and sequence estimation is presented. State transition probabilities conditioned on input data are generated by an integrated support vector machine. Dot product based kernels and support vector coefficients are implemented in analog programmable floating gate translinear circuits, and probabilities are propagated and normalized using sub-threshold current-mode circuits. A 14-input, 24-state, and 720-support vector forward decoding kernel machine is integrated on a 3mm 3mm chip in 0.5µm CMOS technology. Experiments with the processor trained for speaker verification and phoneme sequence estimation demonstrate real-time recognition accuracy at par with floating-point software, at sub-microwatt power.

Many machine learning algorithms for clustering or dimensionality reduction take as input a cloud of points in Euclidean space, and construct a graph with the input data points as vertices. This graph is then partitioned (clustering) or used to redefine metric information (dimensionality reduction). There has been much recent work on new methods for graph-based clustering and dimensionality reduction, but not much on constructing the graph itself. Graphs typically used include the fullyconnected graph, a local fixed-grid graph (for image segmentation) or a nearest-neighbor graph. We suggest that the graph should adapt locally to the structure of the data. This can be achieved by a graph ensemble that combines multiple minimum spanning trees, each fit to a perturbed version of the data set. We show that such a graph ensemble usually produces a better representation of the data manifold than standard methods; and that it provides robustness to a subsequent clustering or dimensionality reduction algorithm based on the graph.

Learning in a multiagent system is a challenging problem due to two key factors. First, if other agents are simultaneously learning then the environment is no longer stationary, thus undermining convergence guarantees. Second, learning is often susceptible to deception, where the other agents may be able to exploit a learner's particular dynamics. In the worst case, this could result in poorer performance than if the agent was not learning at all. These challenges are identifiable in the two most common evaluation criteria for multiagent learning algorithms: convergence and regret.

Many sequential prediction tasks involve locating instances of patterns in sequences. Generative probabilistic language models, such as hidden Markov models (HMMs), have been successfully applied to many of these tasks. A limitation of these models however, is that they cannot naturally handle cases in which pattern instances overlap in arbitrary ways. We present an alternative approach, based on conditional Markov networks, that can naturally represent arbitrarily overlapping elements. We show how to efficiently train and perform inference with these models. Experimental results from a genomics domain show that our models are more accurate at locating instances of overlapping patterns than are baseline models based on HMMs.

Motor control depends on sensory feedback in multiple modalities with different latencies. In this paper we consider within the framework of reinforcement learning how different sensory modalities can be combined and selected for real-time, optimal movement control. We propose an actor-critic architecture with multiple modules, whose output are combined using a softmax function. We tested our architecture in a simulation of a sequential reaching task. Reaching was initially guided by visual feedback with a long latency. Our learning scheme allowed the agent to utilize the somatosensory feedback with shorter latency when the hand is near the experienced trajectory. In simulations with different latencies for visual and somatosensory feedback, we found that the agent depended more on feedback with shorter latency.

We claim and present arguments to the effect that a large class of manifold learning algorithms that are essentially local and can be framed as kernel learning algorithms will suffer from the curse of dimensionality, at the dimension of the true underlying manifold. This observation suggests to explore non-local manifold learning algorithms which attempt to discover shared structure in the tangent planes at different positions. A criterion for such an algorithm is proposed and experiments estimating a tangent plane prediction function are presented, showing its advantages with respect to local manifold learning algorithms: it is able to generalize very far from training data (on learning handwritten character image rotations), where a local nonparametric method fails.

The formation of disulphide bridges among cysteines is an important feature of protein structures. Here we develop new methods for the prediction of disulphide bond connectivity. We first build a large curated data set of proteins containing disulphide bridges and then use 2-Dimensional Recursive Neural Networks to predict bonding probabilities between cysteine pairs. These probabilities in turn lead to a weighted graph matching problem that can be addressed efficiently. We show how the method consistently achieves better results than previous approaches on the same validation data. In addition, the method can easily cope with chains with arbitrary numbers of bonded cysteines. Therefore, it overcomes one of the major limitations of previous approaches restricting predictions to chains containing no more than 10 oxidized cysteines. The method can be applied both to situations where the bonded state of each cysteine is known or unknown, in which case bonded state can be predicted with 85% precision and 90% recall. The method also yields an estimate for the total number of disulphide bridges in each chain.