A triple farnesoid X receptor and peroxisome proliferator-activated receptor α/δ activator reverses hepatic fibrosis in diet-induced NASH in mice

Non-alcoholic steatohepatitis (NASH) - a hepatic manifestation of the metabolic syndrome - is a multifactorial disease with alarming global prevalence. It involves steatosis, inflammation and fibrosis in the liver, thus demanding multiple modes of action for robust therapeutic efficacy. Aiming to fuse complementary validated anti-NASH strategies in a single molecule, we have designed and systematically optimized a scaffold for triple activation of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR) α and PPARδ. Pilot profiling of the resulting triple modulator demonstrated target engagement in native cellular settings and in mice, rendering it a suitable tool to probe the triple modulator concept in vivo. In DIO NASH in mice, the triple agonist counteracted hepatic inflammation and reversed hepatic fibrosis highlighting the potential of designed polypharmacology in NASH.

Analysis of Economic Indicators of Oligopolistic Markets under Cyberthreats

The article is devoted to dynamic economic analysis of optimal Nash strategies of oligopolists under cyber-attacks on critical infrastructure. Oligopolists maximize their NPV taking into account that attackers try to minimize this criterion. Different scenarios of evolution of some abstract ologopolistic market experienced cyber-attacks are considered.

Hierarchical exact controllability of semilinear parabolic equations with distributed and boundary controls

We present some exact controllability results for parabolic equations in the context of hierarchic control using Stackelberg–Nash strategies. We analyze two cases: in the first one, the main control (the leader) acts in the interior of the domain and the secondary controls (the followers) act on small parts of the boundary; in the second one, we consider a leader acting on the boundary while the followers are of the distributed kind. In both cases, for each leader, an associated Nash equilibrium pair is found; then, we obtain a leader that leads the system exactly to a prescribed (but arbitrary) trajectory. We consider linear and semilinear problems.

PERIODIC STRATEGIES: A NEW SOLUTION CONCEPT AND AN ALGORITHM FOR NONTRIVIAL STRATEGIC FORM GAMES

We introduce a new solution concept, called periodicity, for selecting optimal strategies in strategic form games. This periodicity solution concept yields new insight into nontrivial games. In mixed strategy strategic form games, periodic solutions yield values for the utility function of each player that are equal to the Nash equilibrium ones. In contrast to the Nash strategies, here the payoffs of each player are robust against what the opponent plays. Sometimes, periodicity strategies yield higher utilities, and sometimes the Nash strategies do, but often the utilities of these two strategies coincide. We formally define and study periodic strategies in two player perfect information strategic form games with pure strategies and we prove that every nontrivial finite game has at least one periodic strategy, with nontrivial meaning nondegenerate payoffs. In some classes of games where mixed strategies are used, we identify quantitative features. Particularly interesting are the implications for collective action games, since there the collective action strategy can be incorporated in a purely noncooperative context. Moreover, we address the periodicity issue when the players have a continuum set of strategies available.

Linear Quadratic Nash Game of Stochastic Singular Time-Delay Systems with Multiple Decision Makers

This paper discusses linear quadratic Nash game of stochastic singular time-delay systems governed by Itô’s differential equation. Sufficient condition for the existence of Nash strategies is given by means of linear matrix inequality for the first time. Moreover, in order to demonstrate the usefulness of the proposed theory, stochastic H2∕H∞control with multiple decision makers is discussed as an immediate application.

On the Strategic Choice of Union-Oligopoly Bargaining Agenda: Further Results

This paper revisits the strategic selection of the bargaining agenda in a unionized industry with potential entry and decentralized negotiations for different competition modes. The incumbent chooses Right-to-Manage (RTM) or Efficient Bargaining (EB) considering two scenarios: (1) the agenda is imposed to the (potential) entrant (committed bargaining) and (2) the entrant can flexibly choose the agenda (flexible bargaining). In the mixed duopoly, the timing of the game is as follows: at stage 1, the EB firm bargains over wage and employment with its union, while the RTM firm bargains over the wage; at stage 2, the RTM firm chooses employment. This paper shows that the strategic selection of the agenda strongly depends on the interaction between the degree of market competition, the union’s power, and the convergence or divergence between parties on the agenda’s choice. This complex interaction leads to a very rich set of equilibrium outcomes, including multiple and even (as regards the union’s preferences on the agenda) asymmetric equilibria. Compared with alternative timings in the literature, this specification leads to substantial differences with flexible bargaining: EB emerges as equilibrium in Nash strategies for a noticeably increased set of cases.