External and internal electrostatic potentials of cholinesterase models

The electrostatic potentials for the three-dimensional structures of cholinesterases from various species were calculated, using the Delphi algorithm, on the basis of the Poisson–Boltzmann equation. We used structures for Torpedo californica and mouse acetylcholinesterase, and built homology models of the human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and human butyrylcholinesterase. All these structures reveal a negative external surface potential, in the area around the entrance to the active-site gorge, that becomes more negative as the rim of the gorge is approached. Moreover, in all cases, the potential becomes increasingly more negative along the central axis running down the gorge, and is largest at the base of the gorge, near the active site. Ten key acidic residues conserved in the sequence alignments of AChE from various species, both in the surface area near the entrance of the active-site gorge and at its base, appear to be primarily responsible for these potentials. The potentials are highly correlated among the structures examined, down to sequence identities as low as 35%. This indicates that they are a conserved property of the cholinesterase family, could serve to attract the positively charged substrate into and down the gorge to the active site, and may play other roles important for cholinesterase function.     

A New Approach to Abstract Syntax with Variable Binding

The permutation model of set theory with atoms (FM-sets), devised by Fraenkel and Mostowski in the 1930s, supports notions of ‘name-abstraction’ and ‘fresh name’ that provide a new way to represent, compute with, and reason about the syntax of formal systems involving variable-binding operations. Inductively defined FM-sets involving the name-abstraction set former (together with Cartesian product and disjoint union) can correctly encode syntax modulo renaming of bound variables. In this way, the standard theory of algebraic data types can be extended to encompass signatures involving binding operators. In particular, there is an associated notion of structural recursion for defining syntax-manipulating functions (such as capture avoiding substitution, set of free variables, etc.) and a notion of proof by structural induction, both of which remain pleasingly close to informal practice in computer science. Received October 2000 / Accepted in revised form April 2001     

Roles of word frequency and age of acquisition in word naming and lexical decision.

Six experiments are reported that contrasted the effects of frequency and age of acquisition on written word recognition. Age of acquisition affected word-naming speed when frequency was controlled (Experiment 1), but there was no effect of frequency when age of acquisition was controlled (Experiment 2). Experiments 3 and 4 found an effect of age of acquisition upon immediate but not delayed naming speed, but no frequency effect on either immediate or delayed naming once age of acquisition was controlled. Independent effects of frequency and age of acquisition were observed in the lexical decision task (Experiments 5 and 6). Implications for theoretical accounts of word recognition and the possible roles of age of acquisition and frequency in word recognition are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynex: multiplex ELISA technology

Conventional enzyme-linked immunosorbent assay (ELISA) is a gold standard for screening antibodies and testing for protein or antigen presence. A significant limitation of this assay resides in the fact that only one analyte can be assessed per microplate well. Here, we describe and investigate a new technology consisting of an automated ELISA system in which up to 10 analytes can be measured within one single well, thus improving productivity, accuracy, and repeatability by reducing the amount of human labor required. Another strength of the platform is that a user can load any necessary sets/subsets of beads to perform required assays, with improved flexibility compared to manufactured-loaded arrays for multiplex analysis. We also demonstrate that this system can be used to determine the pathogenicity (i.e., presence of Shiga toxins) and serotype (i.e., Escherichia coli O157) of E. coli isolates.     

Probabilistic heuristic estimates

Though they constitute the major knowledge source in problem-solving systems, no unified theory of heuristics has emerged. Pearl [15] defines heuristics as criteria, methods, or principles for deciding which among several alternative courses of action promises to be the most effective in order to achieve some goal. The absence of a more precise definition has impeded our efforts to understand, utilize, and discover heuristics. Another consequence is that problem-solving techniques which rely on heuristic knowledge cannot be relied upon to act rationally — in the sense of the normative theory of rationality.To provide a sound basis for BPS, the Bayesian Problem-Solver, we have developed a simple formal theory of heuristics, which is general enough to subsume traditional heuristic functions as well as other forms of problem-solving knowledge, and to straddle disparate problem domains. Probabilistic heuristic estimates represent a probabilistic association of sensations with prior experience — specifically, a mapping from observations directly to subjective probabilities which enables the use of theoretically principled mechanisms for coherent inference and decision making during problem-solving. This paper discusses some of the implications of this theory, and describes its successful application in BPS.This research was made possible by support from Heuristicrats, the National Aeronautics and Space Administration, and the Rand Corporation.     

Gaze tutor: A gaze-reactive intelligent tutoring system

We developed an intelligent tutoring system (ITS) that aims to promote engagement and learning by dynamically detecting and responding to students' boredom and disengagement. The tutor uses a commercial eye tracker to monitor a student's gaze patterns and identify when the student is bored, disengaged, or is zoning out. The tutor then attempts to reengage the student with dialog moves that direct the student to reorient his or her attentional patterns towards the animated pedagogical agent embodying the tutor. We evaluated the efficacy of the gaze-reactive tutor in promoting learning, motivation, and engagement in a controlled experiment where 48 students were tutored on four biology topics with both gaze-reactive and non-gaze-reactive (control condition) versions of the tutor. The results indicated that: (a) gaze-sensitive dialogs were successful in dynamically reorienting students’ attentional patterns to the important areas of the interface, (b) gaze-reactivity was effective in promoting learning gains for questions that required deep reasoning, (c) gaze-reactivity had minimal impact on students’ state motivation and on self-reported engagement, and (d) individual differences in scholastic aptitude moderated the impact of gaze-reactivity on overall learning gains. We discuss the implications of our findings, limitations, future work, and consider the possibility of using gaze-reactive ITSs in classrooms.     

Types and associated type families for hardware simulation and synthesis

In this article we overview the design and implementation of the second generation of Kansas Lava. Driven by the needs and experiences of implementing telemetry decoders and other circuits, we have made a number of improvements to both the external API and the internal representations used. We have retained our dual shallow/deep representation of signals in general, but now have a number of externally visible abstractions for combinatorial and sequential circuits, and enabled signals. We introduce these abstractions, as well as our abstractions for reading and writing memory. Internally, we found the need to represent unknown values inside our circuits, so we made aggressive use of associated type families to lift our values to allow unknowns, in a principled and regular way. We discuss this design decision, how it unfortunately complicates the internals of Kansas Lava, and how we mitigate this complexity. Finally, when connecting Kansas Lava to the real world, the standardized idiom of using named input and output ports is provided by Kansas Lava using a new monad, called Fabric. We present the design of this Fabric monad, and illustrate its use in a small but complete example.     

Environmental-aware virtual data center network

Cloud computing services have recently become a ubiquitous service delivery model, covering a wide range of applications from personal file sharing to being an enterprise data warehouse. Building green data center networks providing cloud computing services is an emerging trend in the Information and Communication Technology (ICT) industry, because of Global Warming and the potential GHG emissions resulting from cloud services. As one of the first worldwide initiatives provisioning ICT services entirely based on renewable energy such as solar, wind and hydroelectricity across Canada and around the world, the GreenStar Network (GSN) was developed to dynamically transport user services to be processed in data centers built in proximity to green energy sources, reducing Greenhouse Gas (GHG) emissions of ICT equipments. Regarding the current approach, which focuses mainly in reducing energy consumption at the micro-level through energy efficiency improvements, the overall energy consumption will eventually increase due to the growing demand from new services and users, resulting in an increase in GHG emissions. Based on the cooperation between Mantychore FP7 and the GSN, our approach is, therefore, much broader and more appropriate because it focuses on GHG emission reductions at the macro-level. This article presents some outcomes of our implementation of such a network model, which spans multiple green nodes in Canada, Europe and the USA. The network provides cloud computing services based on dynamic provision of network slices through relocation of virtual data centers.