Survivable network design under optimal and heuristic interdiction scenarios

We examine the problem of building or fortifying a network to defend against enemy attacks in various scenarios. In particular, we examine the case in which an enemy can destroy any portion of any arc that a designer constructs on the network, subject to some interdiction budget. This problem takes the form of a three-level, two-player game, in which the designer acts first to construct a network and transmit an initial set of flows through the network. The enemy acts next to destroy a set of constructed arcs in the designer’s network, and the designer acts last to transmit a final set of flows in the network. Most studies of this nature assume that the enemy will act optimally; however, in real-world scenarios one cannot necessarily assume rationality on the part of the enemy. Hence, we prescribe optimal network design algorithms for three different profiles of enemy action: an enemy destroying arcs based on capacities, based on initial flows, or acting optimally to minimize our maximum profits obtained from transmitting flows.     

A hexacyclic ent-trachylobane diterpenoid possessing an oxetane ring from Mitrephora glabra

[chemical reaction: see text]. Three new ent-trachylobane diterpenoids (1-3) were isolated and structures elucidated from Mitrephora glabra Scheff. (Annonaceae). Mitrephorone A (1) possesses a hexacyclic ring system with adjacent ketone moieties and an oxetane ring, both of which are unprecedented among trachylobanes. All compounds were evaluated for cytotoxicity against a panel of cancer cells, where 1 displayed the most potent and broadest activity, and against a battery of antimicrobial assays, where all compounds were approximately equipotent.     

Fibrin network adaptation to cell-generated forces

Fibrin promotes wound healing by serving as provisional extracellular matrix for fibroblasts that realign and degrade fibrin fibers, and sense and respond to surrounding substrate in a mechanical-feedback loop. We aimed to study mechanical adaptation of fibrin networks due to cell-generated forces at the micron-scale. Fibroblasts were elongated-shaped in networks with ≤?2 mg/ml fibrinogen, or cobblestone-shaped with 3 mg/ml fibrinogen at 24 h. At frequencies f?<?10² Hz, G′ of fibroblast-seeded fibrin networks with ≥?1 mg/ml fibrinogen increased compared to that of fibrin networks. At frequencies f?>?10³ Hz, G″ of fibrin networks decreased with increasing concentration following the power-law in frequency with exponents ranging from 0.75?±?0.03 to 0.43?±?0.03 at 3 h, and of fibroblast-seeded fibrin networks with exponents ranging from 0.56?±?0.08 to 0.28?±?0.06. In conclusion, fibroblasts actively contributed to a change in viscoelastic properties of fibrin networks at the micron-scale, suggesting that the cells and fibrin network mechanically interact. This provides better understanding of, e.g., cellular migration in wound healing.

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Multiprotein Dynamic Combinatorial Chemistry: A Strategy for the Simultaneous Discovery of Subfamily‐Selective Inhibitors for Nucleic Acid Demethylases FTO and ALKBH3

Dynamic combinatorial chemistry (DCC) is a powerful supramolecular approach for discovering ligands for biomolecules. To date, most, if not all, biologically templated DCC systems employ only a single biomolecule to direct the self‐assembly process. To expand the scope of DCC, herein, a novel multiprotein DCC strategy has been developed that combines the discriminatory power of a zwitterionic “thermal tag” with the sensitivity of differential scanning fluorimetry. This strategy is highly sensitive and could differentiate the binding of ligands to structurally similar subfamily members. Through this strategy, it was possible to simultaneously identify subfamily‐selective probes against two clinically important epigenetic enzymes: FTO ( 7 ; IC₅₀=2.6 μm ) and ALKBH3 ( 8 ; IC₅₀=3.7 μm ). To date, this is the first report of a subfamily‐selective ALKBH3 inhibitor. The developed strategy could, in principle, be adapted to a broad range of proteins; thus it is of broad scientific interest.     

Design of crashworthy attenuator structures as a part of vehicle safety against impact: Application of waste aluminum can-based material

The impact attenuator is an essential system in both race cars and urban vehicles. The structure of an impact attenuator serves as a safety barrier between the impacted surface and the driver in an accident.Attenuator materials tend to have a high price; thus, alternative materials were explored in the current work, i.e., used cans from food and beverage containers. The study deployed a nonlinear finite element algorithm to calculate a series of impacts on the attenuator structures. The thickness of the cans and velocity of the impact were considered as the main parameters. Analysis results concluded that the attenuator's average energy was 160 0 0 J for a can thickness of 1 mm. This value is more than two times the0.5 mm thick used cans. The attenuator's new design was then matched with an attenuator regulation,and the results surpassed the standard value of 7350 J.