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MOTIVATION Our goal is to construct a model for genetic regulatory networks such that the model class: (i) incorporates rule-based dependencies between genes; (ii) allows the systematic study of global network dynamics; (iii) is able to cope with uncertainty, both in the data and the model selection; and (iv) permits the quantification of the relative(More)
In recent years, several lines of evidence have supported the hypothesis that memory storage involves persistent, experience-dependent modulation of synaptic function. Synapses can be modified in many ways, but the function that has been investigated most assiduously has been SYNAPTIC STRENGTH. This alteration of synaptic strength typically takes the form(More)
AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors mediate fast excitatory synaptic transmission in the brain. These ion channels rapidly deactivate and desensitize, which determine the time course of synaptic transmission. Here, we find that the AMPA receptor interacting protein, stargazin, not only mediates AMPA receptor(More)
We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA(More)
MOTIVATION A major objective of gene regulatory network modeling, in addition to gaining a deeper understanding of genetic regulation and control, is the development of computational tools for the identification and discovery of potential targets for therapeutic intervention in diseases such as cancer. We consider the general question of the potential(More)
Mathematical and computational modeling of genetic regulatory networks promises to uncover the fundamental principles governing biological systems in an integrative and holistic manner. It also paves the way toward the development of systematic approaches for effective therapeutic intervention in disease. The central theme in this paper is the Boolean(More)
We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and(More)
MOTIVATION Most approaches to gene expression analysis use real-valued expression data, produced by high-throughput screening technologies, such as microarrays. Often, some measure of similarity must be computed in order to extract meaningful information from the observed data. The choice of this similarity measure frequently has a profound effect on the(More)
At most excitatory central synapses, glutamate is released from presynaptic terminals and binds to postsynaptic AMPA receptors, initiating a series of conformational changes that result in ion channel opening. Efficient transmission at these synapses requires that glutamate binding to AMPA receptors results in rapid and near-synchronous opening of(More)
Several lines of evidence have indicated that the deep cerebellar nuclei (DCN) are a site of memory storage for certain forms of motor learning, most notably associative eyelid conditioning. In particular, these experiments, together with network models, have implicated the excitatory glutamatergic synapse between mossy fibers and DCN neurons in this memory(More)