917 research outputs found
Network Plasticity as Bayesian Inference
General results from statistical learning theory suggest to understand not
only brain computations, but also brain plasticity as probabilistic inference.
But a model for that has been missing. We propose that inherently stochastic
features of synaptic plasticity and spine motility enable cortical networks of
neurons to carry out probabilistic inference by sampling from a posterior
distribution of network configurations. This model provides a viable
alternative to existing models that propose convergence of parameters to
maximum likelihood values. It explains how priors on weight distributions and
connection probabilities can be merged optimally with learned experience, how
cortical networks can generalize learned information so well to novel
experiences, and how they can compensate continuously for unforeseen
disturbances of the network. The resulting new theory of network plasticity
explains from a functional perspective a number of experimental data on
stochastic aspects of synaptic plasticity that previously appeared to be quite
puzzling.Comment: 33 pages, 5 figures, the supplement is available on the author's web
page http://www.igi.tugraz.at/kappe
Communities in Networks
We survey some of the concepts, methods, and applications of community
detection, which has become an increasingly important area of network science.
To help ease newcomers into the field, we provide a guide to available
methodology and open problems, and discuss why scientists from diverse
backgrounds are interested in these problems. As a running theme, we emphasize
the connections of community detection to problems in statistical physics and
computational optimization.Comment: survey/review article on community structure in networks; published
version is available at
http://people.maths.ox.ac.uk/~porterm/papers/comnotices.pd
Adaptive learning in a compartmental model of visual cortex—how feedback enables stable category learning and refinement
The categorization of real world objects is often reflected in the similarity of their visual appearances. Such categories of objects do not necessarily form disjunct sets of objects, neither semantically nor visually. The relationship between categories can often be described in terms of a hierarchical structure. For instance, tigers and leopards build two separate mammalian categories, but both belong to the category of felines. In other words, tigers and leopards are subcategories of the category Felidae. In the last decades, the unsupervised learning of categories of visual input stimuli has been addressed by numerous approaches in machine learning as well as in the computational neurosciences. However, the question of what kind of mechanisms might be involved in the process of subcategory learning, or category refinement, remains a topic of active investigation. We propose a recurrent computational network architecture for the unsupervised learning of categorial and subcategorial visual input representations. During learning, the connection strengths of bottom-up weights from input to higher-level category representations are adapted according to the input activity distribution. In a similar manner, top-down weights learn to encode the characteristics of a specific stimulus category. Feedforward and feedback learning in combination realize an associative memory mechanism, enabling the selective top-down propagation of a category's feedback weight distribution. We suggest that the difference between the expected input encoded in the projective field of a category node and the current input pattern controls the amplification of feedforward-driven representations. Large enough differences trigger the recruitment of new representational resources and the establishment of (sub-) category representations. We demonstrate the temporal evolution of such learning and show how the approach successully establishes category and subcategory representations
Bioinformatics Techniques for Studying Drug Resistance In HIV and Staphylococcus Aureus
The worldwide HIV/AIDS pandemic has been partly controlled and treated by antivirals targeting HIV protease, integrase and reverse transcriptase, however, drug resistance has become a serious problem. HIV-1 drug resistance to protease inhibitors evolves by mutations in the PR gene. The resistance mutations can alter protease catalytic activity, inhibitor binding, and stability.
Different machine learning algorithms (restricted boltzmann machines, clustering, etc.) have been shown to be effective machine learning tools for classification of genomic and resistance data. Application of restricted boltzmann machine produced highly accurate and robust classification of HIV protease resistance. They can also be used to compare resistance profiles of different protease inhibitors.
HIV drug resistance has also been studied by enzyme kinetics and X-ray crystallography. Triple mutant HIV-1 protease with resistance mutations V32I, I47V and V82I has been used as a model for the active site of HIV-2 protease. The effects of four investigational antiviral inhibitors was measured for Triple mutant. The tested compounds had significantly worse inhibition of triple mutant with Ki values of 17-40 nM compared to 2-10 pM for wild type protease. The crystal structure of triple mutant in complex with GRL01111 was solved and showed few changes in protease interactions with inhibitor. These new inhibitors are not expected to be effective for HIV-2 protease or HIV-1 protease with changes V32I, I47V and V82I.
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that causes hospital and community-acquired infections. Antibiotic resistance occurs because of newly acquired low-affinity penicillin-binding protein (PBP2a). Transcriptome analysis was performed to determine how MuM (mutated PBP2 gene) responds to spermine and how Mu50 (wild type) responds to spermine and spermine–β-lactam synergy. Exogenous spermine and oxacillin were found to alter some significant gene expression patterns with major biochemical pathways (iron, sigB regulon) in MRSA with mutant PBP2 protein
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