Self-organising satellite constellation in geostationary Earth orbit

This paper presents a novel solution to the problem of autonomous task allocation for a self-organizing satellite constellation in Earth orbit. The method allows satellites to cluster themselves above targets on the Earth’s surface. This is achieved using Coupled Selection Equations (CSE) - a dynamical systems approach to combinatorial optimization whose solution tends asymptotically towards a Boolean matrix describing the pairings of satellites and targets which solves the relevant assignment problems. Satellite manoeuvers are actuated by an Artificial Potential Field method which incorporates the CSE output. Three demonstrations of the method’s efficacy are given - first with equal numbers of satellites and targets, then with a satellite surplus, including agent failures, and finally with a fractionated constellation. Finally, a large constellation of 100 satellites is simulated to demonstrate the utility of the method in future swarm mission scenarios. The method provides efficient solutions with quick convergence, is robust to satellite failures, and hence appears suitable for distributed, on-board autonomy

Autonomous satellite constellation for enhanced Earth coverage using coupled selection equations

This paper presents a novel solution to the problem of autonomous task allocation for a self-organising constellation of small satellites in Earth orbit. The method allows the constellation members to plan manoeuvres to cluster themselves above particular target longitudes on the Earth’s surface. This is enabled through the use of Coupled Selection Equations, which represent a dynamical systems approach to combinatorial optimisation problems, and whose solution tends towards a Boolean matrix which describes pairings of the satellites and targets which solves the relevant assignment problems. Satellite manoeuvres are actuated using a simple control law which incorporates the results of the Coupled Selection Equations. Three demonstrations of the efficacy of the method are given in order of increasing complexity - first with an equal number of satellites and targets, then with a surplus of satellites, including agent failure events, and finally with a constellation of two different satellite types. The method is shown to provide efficient solutions, whilst being computationally non-intensive, quick to converge and robust to satellite failures. Proposals to extend the method for on-board processing on a distributed architecture are discussed

The chaperone TRAP1 as a modulator of the mitochondrial adaptations in cancer cells

Mitochondria can receive, integrate, and transmit a variety of signals to shape many biochemical activities of the cell. In the process of tumor onset and growth, mitochondria contribute to the capability of cells of escaping death insults, handling changes in ROS levels, rewiring metabolism, and reprograming gene expression. Therefore, mitochondria can tune the bioenergetic and anabolic needs of neoplastic cells in a rapid and flexible way, and these adaptations are required for cell survival and proliferation in the fluctuating environment of a rapidly growing tumor mass. The molecular bases of pro-neoplastic mitochondrial adaptations are complex and only partially understood. Recently, the mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor associated protein 1) was identified as a key regulator of mitochondrial bioenergetics in tumor cells, with a profound impact on neoplastic growth. In this review, we analyze these findings and discuss the possibility that targeting TRAP1 constitutes a new antitumor approach

Japan as a Victim of Comparative Law

Article published in the Michigan State International Law Review

Similar folds with different stabilization mechanisms: the cases of prion and doppel proteins

BACKGROUND: Protein misfolding is the main cause of a group of fatal neurodegenerative diseases in humans and animals. In particular, in Prion-related diseases the normal cellular form of the Prion Protein PrP (PrP(C)) is converted into the infectious PrP(Sc )through a conformational process during which it acquires a high β-sheet content. Doppel is a protein that shares a similar native fold, but lacks the scrapie isoform. Understanding the molecular determinants of these different behaviours is important both for biomedical and biophysical research. RESULTS: In this paper, the dynamical and energetic properties of the two proteins in solution is comparatively analyzed by means of long time scale explicit solvent, all-atom molecular dynamics in different temperature conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach (Tiana et al, Prot. Sci. 2004) aimed at identifying the key residues for the stabilization and folding of the protein. Our analysis shows that Prion and Doppel have two different cores stabilizing the native state and that the relative contribution of the nucleus to the global stability of the protein for Doppel is sensitively higher than for PrP. Moreover, under misfolding conditions the Doppel core is conserved, while the energy stabilization network of PrP is disrupted. CONCLUSION: These observations suggest that different sequences can share similar native topology with different stabilizing interactions and that the sequences of the Prion and Doppel proteins may have diverged under different evolutionary constraints resulting in different folding and stabilization mechanisms

A decoy set for the thermostable subdomain from chicken villin headpiece, comparison of different free energy estimators

BACKGROUND: Estimators of free energies are routinely used to judge the quality of protein structural models. As these estimators still present inaccuracies, they are frequently evaluated by discriminating native or native-like conformations from large ensembles of so-called decoy structures. RESULTS: A decoy set is obtained from snapshots taken from 5 long (100 ns) molecular dynamics (MD) simulations of the thermostable subdomain from chicken villin headpiece. An evaluation of the energy of the decoys is given using: i) a residue based contact potential supplemented by a term for the quality of dihedral angles; ii) a recently introduced combination of four statistical scoring functions for model quality estimation (FRST); iii) molecular mechanics with solvation energy estimated either according to the generalized Born surface area (GBSA) or iv) the Poisson-Boltzmann surface area (PBSA) method. CONCLUSION: The decoy set presented here has the following features which make it attractive for testing energy scoring functions: 1) it covers a broad range of RMSD values (from less than 2.0 Å to more than 12 Å); 2) it has been obtained from molecular dynamics trajectories, starting from different non-native-like conformations which have diverse behaviour, with secondary structure elements correctly or incorrectly formed, and in one case folding to a native-like structure. This allows not only for scoring of static structures, but also for studying, using free energy estimators, the kinetics of folding; 3) all structures have been obtained from accurate MD simulations in explicit solvent and after molecular mechanics (MM) energy minimization using an implicit solvent method. The quality of the covalent structure therefore does not suffer from steric or covalent problems. The statistical and physical effective energy functions tested on the set behave differently when native simulation snapshots are included or not in the set and when averaging over the trajectory is performed

Targeting tumor angiogenesis with TSP-1-based compounds: rational design of antiangiogenic mimetics of endogenous inhibitors

Inhibitors of angiogenesis are an important addition to conventional chemotherapy. Among different “druggable” angiogenic factors, fibroblast growth factor-2 (FGF-2) is an attractive target for novel therapies because of its intricated involvement in tumor neovascularization, tumor cell proliferation and migration, and the acquisition of resistance to antiangiogenic therapies. FGF-2 bioavailability and activity is affected by several natural ligands, including the endogenous inhibitor of angiogenesis thrombospondin-1 (TSP-1). We hypothesized that the FGF-2-binding sequence of TSP-1 might serve as a template for the development of non-peptide inhibitors of angiogenesis. Computational biology and nuclear magnetic resonance spectroscopy approaches, major investigative tools in the characterizations of protein-protein interaction (PPI), were used to map the residues at the TSP-1/FGF-2 interface. The translation of this three-dimensional information into a pharmacophore model allowed screening a small molecule databases, identifying three FGF-2-binding, antiangiogenic small molecules, mimetic of TSP-1. Pharmacophore-based approaches are thus feasible tools to exploit naturally occurring PPI, by generating a set of lead compounds mimetic of endogenous proteins, as a starting point for the development of novel therapeutic agents