Roles of Electrostatics and Conformation in Protein-Crystal Interactions

In vitro studies have shown that the phosphoprotein osteopontin (OPN) inhibits the nucleation and growth of hydroxyapatite (HA) and other biominerals. In vivo, OPN is believed to prevent the calcification of soft tissues. However, the nature of the interaction between OPN and HA is not understood. In the computational part of the present study, we used molecular dynamics simulations to predict the adsorption of 19 peptides, each 16 amino acids long and collectively covering the entire sequence of OPN, to the {100} face of HA. This analysis showed that there is an inverse relationship between predicted strength of adsorption and peptide isoelectric point (P<0.0001). Analysis of the OPN sequence by PONDR (Predictor of Naturally Disordered Regions) indicated that OPN sequences predicted to adsorb well to HA are highly disordered. In the experimental part of the study, we synthesized phosphorylated and non-phosphorylated peptides corresponding to OPN sequences 65–80 (pSHDHMDDDDDDDDDGD) and 220–235 (pSHEpSTEQSDAIDpSAEK). In agreement with the PONDR analysis, these were shown by circular dichroism spectroscopy to be largely disordered. A constant-composition/seeded growth assay was used to assess the HA-inhibiting potencies of the synthetic peptides. The phosphorylated versions of OPN65-80 (IC50 = 1.93 µg/ml) and OPN220-235 (IC50 = 1.48 µg/ml) are potent inhibitors of HA growth, as is the nonphosphorylated version of OPN65-80 (IC50 = 2.97 µg/ml); the nonphosphorylated version of OPN220-235 has no measurable inhibitory activity. These findings suggest that the adsorption of acidic proteins to Ca2+-rich crystal faces of biominerals is governed by electrostatics and is facilitated by conformational flexibility of the polypeptide chain

Hybrid supervisory utilization control of real-time systems

Feedback control real-time scheduling (FCS) aims at satisfying performance specifications of real-time systems based on adaptive resource management. Existing FCS algorithms often rely on the existence of continuous control variables in real-time systems. A number of real-time systems, however, support only a finite set of discrete configurations that limit the adaptation mechanisms. This paper presents Hybrid Supervisory Utilization CONtrol (HySUCON) for scheduling such real-time systems. HySUCON enforces processor utilization bounds by managing the switchings between the discrete configurations. Our approach is based on a best-first-search algorithm that is invoked only if reconfiguration is necessary. Theoretical analysis and simulations demonstrate that the approach leads to robust utilization bounds for varying execution times. Experimental results demonstrate the algorithm performance for a representative application scenario. 1

Distributed Diagnosis for Qualitative Systems

In this paper we propose a novel automaton-based architecture to build a diagnoser, based on which an efficient distributed diagnostic method consisting of local computation and communication is presented. The method proposed here is highly scalable and robust to partial failures of the overall diagnoser

Programmable Timed Petri Nets in the Analysis and Design of Hybrid Control Systems ∗

In this paper, a class of timed Petri nets, named programmable timed Petri nets is used to model and study switched hybrid systems. Supervisory control of a hybrid system in which the continuous state is transfered to a region of the state space in a way that respects safety specifications on the plant’s discrete and continuous dynamics is examined. The approach is illustrated using a power system example.

Runtime Verification with Particle Filtering

Abstract. We introduce Runtime Verification with Particle Filtering (RVPF), a powerful and versatile method for controlling the tradeoff between uncertainty and overhead in runtime verification. Overhead and accuracy are controlled by adjusting the frequency and duration of observation gaps, during which program events are not monitored, and by adjusting the number of particles used in the RVPF algorithm. We succinctly represent the program model, the program monitor, their interaction, and their observations as a dynamic Bayesian network (DBN). Our formulation of RVPF in terms of DBNs is essential for a proper formalization of peek events: low-cost observations of parts of the program state, which are performed probabilistically at the end of observation gaps. Peek events provide information that our algorithm uses to reduce the uncertainty in the monitor state after gaps. We estimate the internal state of the DBN using particle filtering (PF) with sequential importance resampling (SIR). PF uses a collection of conceptual particles (random samples) to estimate the probability distribution for the system’s current state: the probability of a state is given by the sum of the importance weights of the particles in that state. After an observed event, each particle chooses a state transition to execute by sampling the DBN’s joint transition probability distribution; particles are then redistributed among the states that best predicted the current observation. SIR exploits the DBN structure and the current observation to reduce the variance of the PF and increase its performance. We experimentally compare the overhead and accuracy of our RVPF algorithm with two previous approaches to runtime verification with state estimation: an exact algorithm based on the forward algorithm for HMMs, and an approximate version of that algorithm, which uses precomputation to reduce runtime overhead. Our results confim RVPF’s versatility, showing how it can be used to control the tradeoff between execution time and memory usage while, at the same time, being the most accurate of the three algorithms.