7,286 research outputs found
Local Tomography of Large Networks under the Low-Observability Regime
This article studies the problem of reconstructing the topology of a network
of interacting agents via observations of the state-evolution of the agents. We
focus on the large-scale network setting with the additional constraint of
observations, where only a small fraction of the agents can be
feasibly observed. The goal is to infer the underlying subnetwork of
interactions and we refer to this problem as . In order to
study the large-scale setting, we adopt a proper stochastic formulation where
the unobserved part of the network is modeled as an Erd\"{o}s-R\'enyi random
graph, while the observable subnetwork is left arbitrary. The main result of
this work is establishing that, under this setting, local tomography is
actually possible with high probability, provided that certain conditions on
the network model are met (such as stability and symmetry of the network
combination matrix). Remarkably, such conclusion is established under the
- , where the cardinality of the observable
subnetwork is fixed, while the size of the overall network scales to infinity.Comment: To appear in IEEE Transactions on Information Theor
Preface to the 10th anniversary issue of the Journal on Ambient Intelligence and Smart Environments
The Editors in Chief of the JAISE journal reflect on the evolution of the technical area and the scientific community the publication has been serving for a decade
Regulation of arginine transport by GCN2 eIF2 kinase is important for replication of the intracellular parasite Toxoplasma gondii
Toxoplasma gondii is a prevalent protozoan parasite that can infect any nucleated cell but cannot replicate outside of its host cell. Toxoplasma is auxotrophic for several nutrients including arginine, tryptophan, and purines, which it must acquire from its host cell. The demands of parasite replication rapidly deplete the host cell of these essential nutrients, yet Toxoplasma successfully manages to proliferate until it lyses the host cell. In eukaryotic cells, nutrient starvation can induce the integrated stress response (ISR) through phosphorylation of an essential translation factor eIF2. Phosphorylation of eIF2 lowers global protein synthesis coincident with preferential translation of gene transcripts involved in stress adaptation, such as that encoding the transcription factor ATF4 (CREB2), which activates genes that modulate amino acid metabolism and uptake. Here, we discovered that the ISR is induced in host cells infected with Toxoplasma. Our results show that as Toxoplasma depletes host cell arginine, the host cell phosphorylates eIF2 via protein kinase GCN2 (EIF2AK4), leading to induced ATF4. Increased ATF4 then enhances expression of the cationic amino acid transporter CAT1 (SLC7A1), resulting in increased uptake of arginine in Toxoplasma-infected cells. Deletion of host GCN2, or its downstream effectors ATF4 and CAT1, lowers arginine levels in the host, impairing proliferation of the parasite. Our findings establish that Toxoplasma usurps the host cell ISR to help secure nutrients that it needs for parasite replication
From Zn to Mn: the study of novel manganese-binding groups in the search for new drugs against tuberculosis.
In most eubacteria, apicomplexans, and most plants, including the causal agents for diseases such as malaria, leprosy, and tuberculosis, the methylerythritol phosphate pathway is the route for the biosynthesis of the C(5) precursors to the essential isoprenoid class of compounds. Owing to their absence in humans, the enzymes of the methylerythritol phosphate pathway have become attractive targets for drug discovery. This work investigates a new class of inhibitors against the second enzyme of the pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase. Inhibition of this enzyme may involve the chelation of a crucial active site Mn ion, and the metal-chelating moieties studied here have previously been shown to be successful in application to the zinc-dependent metalloproteinases. Quantum mechanics and docking calculations presented in this work suggest the transferability of these metal-chelating compounds to Mn-containing 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme, as a promising starting point to the development of potent inhibitors
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