Structural characterization of intrinsically disordered proteins by NMR spectroscopy.

Recent advances in NMR methodology and techniques allow the structural investigation of biomolecules of increasing size with atomic resolution. NMR spectroscopy is especially well-suited for the study of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) which are in general highly flexible and do not have a well-defined secondary or tertiary structure under functional conditions. In the last decade, the important role of IDPs in many essential cellular processes has become more evident as the lack of a stable tertiary structure of many protagonists in signal transduction, transcription regulation and cell-cycle regulation has been discovered. The growing demand for structural data of IDPs required the development and adaption of methods such as 13C-direct detected experiments, paramagnetic relaxation enhancements (PREs) or residual dipolar couplings (RDCs) for the study of 'unstructured' molecules in vitro and in-cell. The information obtained by NMR can be processed with novel computational tools to generate conformational ensembles that visualize the conformations IDPs sample under functional conditions. Here, we address NMR experiments and strategies that enable the generation of detailed structural models of IDPs

Hiding Satisfying Assignments: Two are Better than One

The evaluation of incomplete satisfiability solvers depends critically on the availability of hard satisfiable instances. A plausible source of such instances consists of random k-SAT formulas whose clauses are chosen uniformly from among all clauses satisfying some randomly chosen truth assignment A. Unfortunately, instances generated in this manner tend to be relatively easy and can be solved efficiently by practical heuristics. Roughly speaking, as the formula's density increases, for a number of different algorithms, A acts as a stronger and stronger attractor. Motivated by recent results on the geometry of the space of satisfying truth assignments of random k-SAT and NAE-k-SAT formulas, we introduce a simple twist on this basic model, which appears to dramatically increase its hardness. Namely, in addition to forbidding the clauses violated by the hidden assignment A, we also forbid the clauses violated by its complement, so that both A and complement of A are satisfying. It appears that under this "symmetrization'' the effects of the two attractors largely cancel out, making it much harder for algorithms to find any truth assignment. We give theoretical and experimental evidence supporting this assertion.Comment: Preliminary version appeared in AAAI 200

Cortical Learning of Recognition Categories: A Resolution of the Exemplar Vs. Prototype Debate

Do humans and animals learn exemplars or prototypes when they categorize objects and events in the world? How are different degrees of abstraction realized through learning by neurons in inferotemporal and prefrontal cortex? How do top-down expectations influence the course of learning? Thirty related human cognitive experiments (the 5-4 category structure) have been used to test competing views in the prototype-exemplar debate. In these experiments, during the test phase, subjects unlearn in a characteristic way items that they had learned to categorize perfectly in the training phase. Many cognitive models do not describe how an individual learns or forgets such categories through time. Adaptive Resonance Theory (ART) neural models provide such a description, and also clarify both psychological and neurobiological data. Matching of bottom-up signals with learned top-down expectations plays a key role in ART model learning. Here, an ART model is used to learn incrementally in response to 5-4 category structure stimuli. Simulation results agree with experimental data, achieving perfect categorization in training and a good match to the pattern of errors exhibited by human subjects in the testing phase. These results show how the model learns both prototypes and certain exemplars in the training phase. ART prototypes are, however, unlike the ones posited in the traditional prototype-exemplar debate. Rather, they are critical patterns of features to which a subject learns to pay attention based on past predictive success and the order in which exemplars are experienced. Perturbations of old memories by newly arriving test items generate a performance curve that closely matches the performance pattern of human subjects. The model also clarifies exemplar-based accounts of data concerning amnesia.Defense Advanced Projects Research Agency SyNaPSE program (Hewlett-Packard Company, DARPA HR0011-09-3-0001; HRL Laboratories LLC #801881-BS under HR0011-09-C-0011); Science of Learning Centers program of the National Science Foundation (NSF SBE-0354378

The effect of functional roles on group efficiency

The usefulness of ‘roles’ as a pedagogical approach to support small group performance can be often read, however, their effect is rarely empirically assessed. Roles promote cohesion and responsibility and decrease so-called ‘process losses’ caused by coordination demands. In addition, roles can increase awareness of intra-group interaction. In this article, the effect of functional roles on group performance, efficiency and collaboration during computer-supported collaborative learning (CSCL) was investigated with questionnaires and quantitative content analysis of e-mail communication. A comparison of thirty-three questionnaire observations, distributed over ten groups in two research conditions: role (n = 5, N = 14) and non-role (n = 5, N = 19), revealed no main effect for performance (grade). A latent variable was interpreted as ‘perceived group efficiency’ (PGE). Multilevel modelling (MLM) yielded a positive marginal effect of PGE. Groups in the role condition appear to be more aware of their efficiency, compared to groups in the ‘non-role’ condition, regardless whether the group performs well or poor. Content analysis reveals that students in the role condition contribute more ‘task content’ focussed statements. This is, however, not as hypothesised due to the premise that roles decrease coordination and thus increase content focused statements; in fact, roles appear to stimulate coordination and simultaneously the amount of ‘task content’ focussed statements increases

Learning scalable and transferable multi-robot/machine sequential assignment planning via graph embedding

Can the success of reinforcement learning methods for simple combinatorial optimization problems be extended to multi-robot sequential assignment planning? In addition to the challenge of achieving near-optimal performance in large problems, transferability to an unseen number of robots and tasks is another key challenge for real-world applications. In this paper, we suggest a method that achieves the first success in both challenges for robot/machine scheduling problems. Our method comprises of three components. First, we show a robot scheduling problem can be expressed as a random probabilistic graphical model (PGM). We develop a mean-field inference method for random PGM and use it for Q-function inference. Second, we show that transferability can be achieved by carefully designing two-step sequential encoding of problem state. Third, we resolve the computational scalability issue of fitted Q-iteration by suggesting a heuristic auction-based Q-iteration fitting method enabled by transferability we achieved. We apply our method to discrete-time, discrete space problems (Multi-Robot Reward Collection (MRRC)) and scalably achieve 97% optimality with transferability. This optimality is maintained under stochastic contexts. By extending our method to continuous time, continuous space formulation, we claim to be the first learning-based method with scalable performance among multi-machine scheduling problems; our method scalability achieves comparable performance to popular metaheuristics in Identical parallel machine scheduling (IPMS) problems

Making and breaking power laws in evolutionary algorithm population dynamics

Deepening our understanding of the characteristics and behaviors of population-based search algorithms remains an important ongoing challenge in Evolutionary Computation. To date however, most studies of Evolutionary Algorithms have only been able to take place within tightly restricted experimental conditions. For instance, many analytical methods can only be applied to canonical algorithmic forms or can only evaluate evolution over simple test functions. Analysis of EA behavior under more complex conditions is needed to broaden our understanding of this population-based search process. This paper presents an approach to analyzing EA behavior that can be applied to a diverse range of algorithm designs and environmental conditions. The approach is based on evaluating an individual’s impact on population dynamics using metrics derived from genealogical graphs.\ud From experiments conducted over a broad range of conditions, some important conclusions are drawn in this study. First, it is determined that very few individuals in an EA population have a significant influence on future population dynamics with the impact size fitting a power law distribution. The power law distribution indicates there is a non-negligible probability that single individuals will dominate the entire population, irrespective of population size. Two EA design features are however found to cause strong changes to this aspect of EA behavior: i) the population topology and ii) the introduction of completely new individuals. If the EA population topology has a long path length or if new (i.e. historically uncoupled) individuals are continually inserted into the population, then power law deviations are observed for large impact sizes. It is concluded that such EA designs can not be dominated by a small number of individuals and hence should theoretically be capable of exhibiting higher degrees of parallel search behavior