A critical need still remains for effective delivery of RNA interference (RNAi) therapeutics to target tissues and cells. Self-assembled lipid- and polymer-based systems have been most extensively explored for transfection with small interfering RNA (siRNA) in liver and cancer therapies. Safety and compatibility of materials implemented in delivery systems must be ensured to maximize therapeutic indices. Hydrogel nanoparticles of defined dimensions and compositions, prepared via a particle molding process that is a unique off-shoot of soft lithography known as PRINT (Particle Replication in Non-wetting Templates), were explored in these studies as delivery vectors. Initially, siRNA was encapsulated in particles through electrostatic association and physical entrapment. Dose-dependent gene silencing was elicited by PEGylated hydrogels at low siRNA doses without cytotoxicity. To prevent disassociation of cargo from particles after systemic administration or during post-fabrication processing for surface functionalization, a polymerizable siRNA pro-drug conjugate with a degradable, disulfide linkage was prepared. Triggered release of siRNA from the prodrug hydrogels was observed under a reducing environment while cargo retention and integrity were maintained under physiological conditions. Gene silencing efficiency and cytocompatibility were optimized by screening the amine content of the particles. When appropriate control siRNA cargos were loaded into hydrogels, gene knockdown was only encountered for hydrogels containing releasable, target-specific siRNAs, accompanied by minimal cell death. Further investigation into shape, size, and surface decoration of siRNA-conjugated hydrogels should enable efficacious targeted in vivo RNAi therapies.
The complex [MnII(R,R-mcp)(CF3SO3)2] is an efficient and practical catalyst for the epoxidation of electron-deficient olefins. This catalyst is capable of epoxidizing olefins with as little as 0.1 mol % catalyst in under 5 min using 1.2 equiv of peracetic acid as the terminal oxidant. A wide scope of substrates are epoxidized including terminal, tertiary, cis and trans internal, enones, and methacrylates with >85% isolated yields.
[reaction: see text] A mu-oxo-iron(III) dimer, [((phen)(2)(H(2)O)Fe(III))(2)(mu-O)](ClO(4))(4), is an efficient epoxidation catalyst for a wide range of alkenes, including terminal alkenes, using peracetic acid as the oxidant. Low catalyst loadings, in situ catalyst preparation from common reagents, fast reaction times (<5 min at 0 degrees C), and enhanced reaction performance at high substrate concentrations combine to create a temporally and synthetically efficient procedure for alkene epoxidation.
[reaction: see text] Nineteen Mn(II) complexes were screened for the catalytic epoxidation of terminal olefins using peracetic acid. Few of these complexes are efficient catalysts at pH < 2, but many are effective at 1 mol % catalyst loading at pH 4. With 0.1 mol % loading, four complexes epoxidize 1-octene in approximately 80% yield in 5 min. The relative reactivity of the catalysts toward different olefins was probed using a multicomponent intermolecular competition reaction.
The demand for low-dissipation nanoscale memory devices is as strong as ever. As Moore's Law is staggering, and the demand for a low-power-consuming supercomputer is high, the goal of making information processing circuits out of superconductors is one of the central goals of modern technology and physics. So far, digital superconducting circuits could not demonstrate their immense potential. One important reason for this is that a dense superconducting memory technology is not yet available. Miniaturization of traditional superconducting quantum interference devices is difficult below a few micrometers because their operation relies on the geometric inductance of the superconducting loop. Magnetic memories do allow nanometer-scale miniaturization, but they are not purely superconducting [1]. Our approach is to make nanometer scale memory cells based on the kinetic inductance (and not geometric inductance) of superconducting nanowire loops, which have already shown many fascinating properties [2,3]. This allows much smaller devices and naturally eliminates magnetic-field cross-talk. We demonstrate that the vorticity, i.e., the winding number of the order parameter, of a closed superconducting loop can be used for realizing a nanoscale nonvolatile memory device. We demonstrate how to alter the vorticity in a controlled fashion by applying calibrated current pulses. A reliable read-out of the memory is also demonstrated. We present arguments that such memory can be developed to operate without energy dissipation.Power management and cooling demands of high performance processors have become one of the main obstacles to further progress of the computing devices. Thus development of the 1
Atomically precise donor-based quantum devices are a promising candidate for solid-state quantum computing and analog quantum simulations. However, critical challenges in atomically precise fabrication have meant systematic, atomic scale control of the tunneling rates and tunnel coupling has not been demonstrated. Here using a room temperature grown locking layer and precise control over the entire fabrication process, we reduce unintentional dopant movement while achieving high quality epitaxy in scanning tunnelling microscope (STM)-patterned devices. Using the Si(100)2 × 1 surface reconstruction as an atomically-precise ruler to characterize the tunnel gap in precision-patterned single electron transistors, we demonstrate the exponential scaling of the tunneling resistance on the tunnel gap as it is varied from 7 dimer rows to 16 dimer rows. We demonstrate the capability to reproducibly pattern devices with atomic precision and a donor-based fabrication process where atomic scale changes in the patterned tunnel gap result in the expected changes in the tunneling rates.
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