Weak Singular Hybrid Automata

The framework of Hybrid automata, introduced by Alur, Courcourbetis, Henzinger, and Ho, provides a formal modeling and analysis environment to analyze the interaction between the discrete and the continuous parts of cyber-physical systems. Hybrid automata can be considered as generalizations of finite state automata augmented with a finite set of real-valued variables whose dynamics in each state is governed by a system of ordinary differential equations. Moreover, the discrete transitions of hybrid automata are guarded by constraints over the values of these real-valued variables, and enable discontinuous jumps in the evolution of these variables. Singular hybrid automata are a subclass of hybrid automata where dynamics is specified by state-dependent constant vectors. Henzinger, Kopke, Puri, and Varaiya showed that for even very restricted subclasses of singular hybrid automata, the fundamental verification questions, like reachability and schedulability, are undecidable. In this paper we present \emph{weak singular hybrid automata} (WSHA), a previously unexplored subclass of singular hybrid automata, and show the decidability (and the exact complexity) of various verification questions for this class including reachability (NP-Complete) and LTL model-checking (PSPACE-Complete). We further show that extending WSHA with a single unrestricted clock or extending WSHA with unrestricted variable updates lead to undecidability of reachability problem

A push to cycling - Exploring the e-bike’s role in overcoming barriers to bicycle use with a survey and an intervention study

In Norway, as in many countries, there is a political goal to increase bicycle use. The electric bicycle (e-bike) is a promising tool for achieving this goal, given the hilliness of the country. However, little is yet known about the deterrents of cycling in Norway in general, and in particular how the purchase of an e-bike could be stimulated. In the current study, 5500 respondents from a convenience sample among car owners were asked about their perceptions of bicycling in general, and of e-bikes in particular as well as their willingness to pay for an e-bike. Randomly selected participants (N=66) were given access to an e-bike for a limited time (2 or 4 weeks). A second questionnaire captured the same perceptions and willingness to pay post-intervention. Results were compared with a control group (N=214). The results showed that those who cycle the least were most interested in buying an e-bike and that prior knowledge of the e-bike corresponded with a higher desire to buy one. Pro-environmental values did not predict interest in e-bikes, neither did norms and attitudes towards cycling. The willingness to pay for an e-bike increased after having experienced the benefits for those who used an e-bike compared to those who did not. Price reduction of the e-bike (e.g. VAT exemption), spread of knowledge among the wider population, and actions to offer an e-bike experience may therefore be effective strategies for further expansion of the e-bike in the transport system and thereby to increase bicycle use in Norway

The Electronic and Superconducting Properties of Oxygen-Ordered MgB2 compounds of the form Mg2B3Ox

Possible candidates for the Mg2B3Ox nanostructures observed in bulk of polycrystalline MgB2 (Ref.1) have been studied using a combination of Z-contrast imaging, electron energy loss spectroscopy (EELS) and first-principles calculations. The electronic structures, phonon modes, and electron phonon coupling parameters are calculated for two oxygen-ordered MgB2 compounds of composition Mg2B3O and Mg2B3O2, and compared with those of MgB2. We find that the density of states for both Mg2B3Ox structures show very good agreement with EELS, indicating that they are excellent candidates to explain the observed coherent oxygen precipitates. Incorporation of oxygen reduces the transition temperature and gives calculated TC values of 18.3 K and 1.6 K for Mg2B3O and Mg2B3O2, respectively.Comment: Submitted to PR

Post-translational modifications near the quinone binding site of mammalian complex I.

Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, the primary acceptor of electrons flavin mononucleotide (FMN), and a chain of seven iron-sulfur clusters that carries the electrons one at a time from FMN to a coenzyme Q molecule bound in the vicinity of the junction between the two arms. In the structure of the closely related bacterial enzyme from Thermus thermophilus, the quinone is thought to bind in a tunnel that spans the interface between the two arms, with the quinone head group close to the terminal iron-sulfur cluster, N2. The tail of the bound quinone is thought to extend from the tunnel into the lipid bilayer. In the mammalian enzyme, it is likely that this tunnel involves three of the subunits of the complex, ND1, PSST, and the 49-kDa subunit. An arginine residue in the 49-kDa subunit is symmetrically dimethylated on the ω-N(G) and ω-N(G') nitrogen atoms of the guanidino group and is likely to be close to cluster N2 and to influence its properties. Another arginine residue in the PSST subunit is hydroxylated and probably lies near to the quinone. Both modifications are conserved in mammalian enzymes, and the former is additionally conserved in Pichia pastoris and Paracoccus denitrificans, suggesting that they are functionally significant

Bayesian optimisation of restriction zones for bluetongue control.

We investigate the restriction of animal movements as a method to control the spread of bluetongue, an infectious disease of livestock that is becoming increasingly prevalent due to the onset of climate change. We derive control policies for the UK that minimise the number of infected farms during an outbreak using Bayesian optimisation and a simulation-based model of BT. Two cases are presented: first, where the region of introduction is randomly selected from England and Wales to find a generalised strategy. This "national" model is shown to be just as effective at subduing the spread of bluetongue as the current strategy of the UK government. Our proposed controls are simpler to implement, affect fewer farms in the process and, in so doing, minimise the potential economic implications. Second, we consider policies that are tailored to the specific region in which the first infection was detected. Seven different regions in the UK were explored and improvements in efficiency from the use of specialised policies presented. As a consequence of the increasing temperatures associated with climate change, efficient control measures for vector-borne diseases such as this are expected to become increasingly important. Our work demonstrates the potential value of using Bayesian optimisation in developing cost-effective disease management strategies

NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I.

Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 subunits. One arm is embedded in the inner membrane with the other protruding ∼100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH and the primary electron acceptor FMN, and it provides a scaffold for seven iron-sulfur clusters that form an electron pathway linking FMN to the terminal electron acceptor, ubiquinone, which is bound in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, probably energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Complex I is put together from preassembled subcomplexes. Their compositions have been characterized partially, and at least 12 extrinsic assembly factor proteins are required for the assembly of the complex. One such factor, NDUFAF7, is predicted to belong to the family of S-adenosylmethionine-dependent methyltransferases characterized by the presence in their structures of a seven-β-strand protein fold. In the present study, the presence of NDUFAF7 in the mitochondrial matrix has been confirmed, and it has been demonstrated that it is a protein methylase that symmetrically dimethylates the ω-N(G),N(G') atoms of residue Arg-85 in the NDUFS2 subunit of complex I. This methylation step occurs early in the assembly of complex I and probably stabilizes a 400-kDa subcomplex that forms the initial nucleus of the peripheral arm and its juncture with the membrane arm

Complementary DNA sequences of two 14.5 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria Completion of the primary structure of the complex?

AbstractThe amino acid sequences of two nuclear-encoded subunits of complex I from bovine heart mitochondria have been determined. Both proteins have an apparent molecular weight of 14.5 kDa and their N-α-amino groups are acetylated. They are known as subunits B14.5a and B14.5b. Neither protein is evidently related to any known protein and their functions are obscure. A total of 34 nuclear-encoded subunits of bovine complex 1 have now been sequenced and it is thought that the primary structure of the complex is now complete, although with such a complicated structure it is difficult to be certain that there are no other subunits remaining to be sequenced. Seven additional hydrophobic subunits of the enzyme are encoded in mitochondrial DNA, and therefore bovine heart complex I is an assembly of about 41 different proteins. If it is assumed that there is one copy of each protein in the assembly, these polypeptides contain 7,955 amino acids in their sequences, more than are found in the Escherichia coli ribosome, which contains 7,336 amino acids in its 32 polypeptides

Identification in Saccharomyces cerevisiae of two isoforms of a novel mitochondrial transporter for 2-oxoadipate and 2-oxoglutarate.

The nuclear genome of Saccharomyces cerevisiae encodes 35 members of a family of membrane proteins. Known members transport substrates and products across the inner membranes of mitochondria. We have localized two hitherto unidentified family members, Odc1p and Odc2p, to the inner membranes of mitochondria. They are isoforms with 61% sequence identity, and we have shown in reconstituted liposomes that they transport the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a strict counter exchange mechanism. Intraliposomal adipate and glutarate and to a lesser extent malate and citrate supported [14C]oxoglutarate uptake. The expression of Odc1p, the more abundant isoform, made in the presence of nonfermentable carbon sources, is repressed by glucose. The main physiological roles of Odc1p and Odc2p are probably to supply 2-oxoadipate and 2-oxoglutarate from the mitochondrial matrix to the cytosol where they are used in the biosynthesis of lysine and glutamate, respectively, and in lysine catabolism