Ruthenium-caged antisense morpholinos for regulating gene expression in zebrafish embryos

Photochemical approaches afford high spatiotemporal control over molecular structure and function, for broad applications in materials and biological science. Here, we present the first example of a visible light responsive ruthenium-based photolinker, Ru(bipyridine)₂(3-ethynylpyridine)₂ (RuBEP), which was reacted stoichiometrically with a 25mer DNA or morpholino (MO) oligonucleotide functionalized with 3′ and 5′ terminal azides, via Cu(i)-mediated [3+2] Huisgen cycloaddition reactions. RuBEP-caged circular morpholinos (Ru-MOs) targeting two early developmental zebrafish genes, chordin and notail, were synthesized and tested in vivo. One-cell-stage zebrafish embryos microinjected with Ru-MO and incubated in the dark for 24 h developed normally, consistent with caging, whereas irradiation at 450 nm dissociated one 3-ethynylpyridine ligand (Φ = 0.33) and uncaged the MO to achieve gene knockdown. As demonstrated, Ru photolinkers provide a versatile method for controlling structure and function of biopolymers.     

Copper-catalyzed hydroamination of propargyl imidates

Propargyl imidates derived from aromatic and aliphatic nitriles cyclize at room temperature in high yields when treated with a catalytic amount of copper (I) iodide. This 5-exo-dig process affords dihydrooxazoles which do not aromatize under the reaction conditions, and which are isolated without chromatography. Investigations of the reaction scope, subsequent functionalization of the reaction products, and preliminary mechanistic data are presented.     

Heterogeneous surface-to-air missile defense battery location: a game theoretic approach

In the context of an air defense missile-and-interceptor engagement, a challenge for the defender is that surface-to-air missile batteries often must be located to protect high-value targets dispersed over a vast area, subject to which an attacker may observe the disposition of batteries and subsequently develop and implement an attack plan. To model this scenario, we formulate a two-player, extensive form, three-stage, perfect information, zero-sum game that accounts for, respectively, a defender’s location of batteries, an attacker’s launch of missiles against targets, and a defender’s assignment of interceptor missiles from batteries to incoming attacker missiles. The resulting trilevel math programming formulation cannot be solved via direct optimization, and it is not suitable to solve via full enumeration for realistically-sized instances. We instead adapt the game tree search technique Double Oracle, within which we embed either of two alternative heuristics to solve an important subproblem for the attacker. We test and compare these solution methods to solve a designed set of 52 instances having parametric variations, from which we derive insights regarding the nature of the underlying problem. Enhancing the solution methods with alternative initialization strategies, our superlative methodology attains the optimal solution for over 75% of the instances tested and solutions within 3% of optimal, on average, for the remaining 25% of the instances, and it is promising for realistically-sized instances, scaling well with regard to computational effort.     

Cryogenic Properties of a Polyurethane Adhesive*

Abstract

Differential thermal analysis (DTA), rebound resilience, and tensile proerties of a polyurethane adhesive were measured at cryogenic temperatures. The experimental methods are described, and test results which aid in evaluating the polyurethane for use at low temperatures are discussed. The DTA thermogram reveals that the glass transition temperature (T_g) is 235°K. The resilience profile indicates a resilience minimum (T_r) at 270°K and a frequency of 3800 Hz, which is consistent with the T_g measured by DTA. The low resilience below T_r, caused by secondary low-temperature transitions, shows the high energy absorption capabilities of the polyurethane. Considerable plastic flow at 195°K (40°K below T_g) is evidenced in the results of the tensile tests. The results of the three tests indicate that the polyurethane adhesive will perform well at low temperatures. The test methods should also be useful for evaluating the low-temperature performance of new polymers.