Hierarchically-coupled hidden Markov models for learning kinetic rates from single-molecule data

We address the problem of analyzing sets of noisy time-varying signals that all report on the same process but confound straightforward analyses due to complex inter-signal heterogeneities and measurement artifacts. In particular we consider single-molecule experiments which indirectly measure the distinct steps in a biomolecular process via observations of noisy time-dependent signals such as a fluorescence intensity or bead position. Straightforward hidden Markov model (HMM) analyses attempt to characterize such processes in terms of a set of conformational states, the transitions that can occur between these states, and the associated rates at which those transitions occur; but require ad-hoc post-processing steps to combine multiple signals. Here we develop a hierarchically coupled HMM that allows experimentalists to deal with inter-signal variability in a principled and automatic way. Our approach is a generalized expectation maximization hyperparameter point estimation procedure with variational Bayes at the level of individual time series that learns an single interpretable representation of the overall data generating process.Comment: 9 pages, 5 figure

Distributed Services with Foreseen and Unforeseen Tasks: The Mobile Re-allocation Problem

In this paper we deal with a common problem found in the operations of security and preventive/corrective maintenance services: that of routing a number of mobile resources to serve foreseen and unforeseen tasks during a shift. We define the (Mobile Re-Allocation Problem) MRAP as the problem of devising a routing strategy to maximize the expected weighted number of tasks served on time. For obtaining a solution to the MRAP, we propose to solve successively a multi-objective optimization problem called the stochastic Team Orienteering Problem with Multiple Time Windows (s-TOP-MTW) so as to consider information about known tasks and the arrival process of new unforeseen tasks. Solving successively the s-TOP-MTW we find that considering information about the arrival process of new unforeseen tasks may aid in maximizing the expected proportion of tasks accomplished on time.location;reliability;routing;distributed services

Isotropic Dynamic Hierarchical Clustering

We face a need of discovering a pattern in locations of a great number of points in a high-dimensional space. Goal is to group the close points together. We are interested in a hierarchical structure, like a B-tree. B-Trees are hierarchical, balanced, and they can be constructed dynamically. B-Tree approach allows to determine the structure without any supervised learning or a priori knowlwdge. The space is Euclidean and isotropic. Unfortunately, there are no B-Tree implementations processing indices in a symmetrical and isotropical way. Some implementations are based on constructing compound asymmetrical indices from point coordinates; and the others split the nodes along the coordinate hyper-planes. We need to process tens of millions of points in a thousand-dimensional space. The application has to be scalable. Ideally, a cluster should be an ellipsoid, but it would require to store O(n2) ellipse axes. So, we are using multi-dimensional balls defined by the centers and radii. Calculation of statistical values like the mean and the average deviation, can be done in an incremental way. While adding a point to a tree, the statistical values for nodes recalculated in O(1) time. We support both, brute force O(2n) and greedy O(n2) split algorithms. Statistical and aggregated node information also allows to manipulate (to search, to delete) aggregated sets of closely located points. Hierarchical information retrieval. When searching, the user is provided with the highest appropriate nodes in the tree hierarchy, with the most important clusters emerging in the hierarchy automatically. Then, if interested, the user may navigate down the tree to more specific points. The system is implemented as a library of Java classes representing Points, Sets of points with aggregated statistical information, B-tree, and Nodes with a support of serialization and storage in a MySQL database.Comment: 6 pages with 3 example

Experience-driven formation of parts-based representations in a model of layered visual memory

Growing neuropsychological and neurophysiological evidence suggests that the visual cortex uses parts-based representations to encode, store and retrieve relevant objects. In such a scheme, objects are represented as a set of spatially distributed local features, or parts, arranged in stereotypical fashion. To encode the local appearance and to represent the relations between the constituent parts, there has to be an appropriate memory structure formed by previous experience with visual objects. Here, we propose a model how a hierarchical memory structure supporting efficient storage and rapid recall of parts-based representations can be established by an experience-driven process of self-organization. The process is based on the collaboration of slow bidirectional synaptic plasticity and homeostatic unit activity regulation, both running at the top of fast activity dynamics with winner-take-all character modulated by an oscillatory rhythm. These neural mechanisms lay down the basis for cooperation and competition between the distributed units and their synaptic connections. Choosing human face recognition as a test task, we show that, under the condition of open-ended, unsupervised incremental learning, the system is able to form memory traces for individual faces in a parts-based fashion. On a lower memory layer the synaptic structure is developed to represent local facial features and their interrelations, while the identities of different persons are captured explicitly on a higher layer. An additional property of the resulting representations is the sparseness of both the activity during the recall and the synaptic patterns comprising the memory traces.Comment: 34 pages, 12 Figures, 1 Table, published in Frontiers in Computational Neuroscience (Special Issue on Complex Systems Science and Brain Dynamics), http://www.frontiersin.org/neuroscience/computationalneuroscience/paper/10.3389/neuro.10/015.2009

Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Developmental changes in the temporal and spatial regulation of gene expression drive the emergence of normal mature brain function, while disruptions in these processes underlie many neurodevelopmental abnormalities. To solidify our foundational knowledge of such changes in a primate brain with an extended period of postnatal maturation like in human, we investigated the whole-genome transcriptional profiles of rhesus monkey brains from birth to adulthood. We found that gene expression dynamics are largest from birth through infancy, after which gene expression profiles transition to a relatively stable state by young adulthood. Biological pathway enrichment analysis revealed that genes more highly expressed at birth are associated with cell adhesion and neuron differentiation, while genes more highly expressed in juveniles and adults are associated with cell death. Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex. Using network analysis, we identified 27 co-expression modules containing genes with highly correlated expression patterns that are associated with specific brain regions, ages or both. In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes. This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD

Marriage and the City

Do people move to cities because of marriage market considerations? In cities singles can meet more potential partners than in rural areas. Singles are therefore prepared to pay a premium in terms of higher housing prices. Once married, the marriage market benefits disappear while the housing premium remains. We extend the model of Burdett and Coles (1997) with a distinction between efficient (cities) and less efficient (non-cities) search markets. One implication of the model is that singles are more likely to move from rural areas to cities while married couples are more likely to make the reverse movement. A second prediction of the model is that attractive singles benefit most from a dense market (i.e. from being choosy). Those predictions are tested with a unique Danish dataset.marriage, search, mobility, city

The evolutionary origins of volition

It appears to be a straightforward implication of distributed cognition principles that there is no integrated executive control system (e.g. Brooks 1991, Clark 1997). If distributed cognition is taken as a credible paradigm for cognitive science this in turn presents a challenge to volition because the concept of volition assumes integrated information processing and action control. For instance the process of forming a goal should integrate information about the available action options. If the goal is acted upon these processes should control motor behavior. If there were no executive system then it would seem that processes of action selection and performance couldn’t be functionally integrated in the right way. The apparently centralized decision and action control processes of volition would be an illusion arising from the competitive and cooperative interaction of many relatively simple cognitive systems. Here I will make a case that this conclusion is not well-founded. Prima facie it is not clear that distributed organization can achieve coherent functional activity when there are many complex interacting systems, there is high potential for interference between systems, and there is a need for focus. Resolving conflict and providing focus are key reasons why executive systems have been proposed (Baddeley 1986, Norman and Shallice 1986, Posner and Raichle 1994). This chapter develops an extended theoretical argument based on this idea, according to which selective pressures operating in the evolution of cognition favor high order control organization with a ‘highest-order’ control system that performs executive functions