Polymer–Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs

Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β‐amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To expand this potential utility to include systemic delivery of mRNA, hybrid polymer–lipid nanoformulations for systemic delivery to the lungs were developed. Through coformulation of PBAEs with lipid–polyethylene glycol (PEG), mRNA formulations were developed with increased serum stability and increased in vitro potency. The formulations were capable of functional delivery of mRNA to the lungs after intravenous administration in mice. To our knowledge, this is the first report of the systemic administration of mRNA for delivery to the lungs using degradable polymer–lipid nanoparticles.     

Teleportation via decay

We present a rare example of a decay mechanism playing a constructive role in quantum information processing. We show how the state of an atom trapped in a cavity can be teleported to a second atom trapped in a distant cavity by the joint detection of photon leakage from the cavities. The scheme, which is probabilistic, requires only a single three level atom in a cavity. We also show how this scheme can be modified to a teleportation with insurance.     

A Convenient Synthesis of Thiophen-Derived Polyamine Macrocycles

The facile preparation of novel polyamine macrocycles by an in situ reduction, using NaBH₄/borax, of the reaction mixture (thiophen-2,5-dicarbaldehyde and 1,n-alkanediamine) producing the precursor tetra-imine macrocycle is reported.     

过渡金属掺杂铈中晶格氧的活化

采用密度泛函理论计算研究了在铈表面掺杂的过渡金属(TM)离子对表面晶格氧原子活化的影响.为此,测定了经TM离子修饰的CeO2最稳定(111)表面终端的结构和稳定性.除了保持八面体氧配位的锆和铂掺杂剂外, TM掺杂剂在取代表面Ce离子时更倾向于正方形平面配位.除了Pt(1.14 eV)和Zr(正方形平面配位不稳定)外,所有TM掺杂剂的表面结构从八面体到正方形平面都很容易.通常,四价TM阳离子的离子半径比Ce^4+的小得多,从而导致了显著的拉伸应变晶格,并解释了氧空位形成能量的降低.除Zr外,当产生一个氧空位时,优先形成正方形平面结构.热力学分析表明, TM掺杂CeO2表面在典型环境催化条件下存在氧缺陷.一个具有实际意义的例子是锆掺杂CeO2(111)中的晶格氧容易活化,从而有利于CO氧化.研究结果强调了晶格氧活化的本质和TM掺杂剂在TM-铈固溶催化剂中的优选位置.     

Phragmén-Lindelöf theorems

Results of Phragmén-Lindelöf type are obtained for subharmonic functions in sectorial domains of bounded angular extent.

     

Catalytic Lewis acid phosphorylation with pyrophosphates

We report a method for the Lewis acid catalyzed phosphorylation of alcohols with pyrophosphates. Ti(O^tBu)₄ was found to be the most effective catalyst in the phosphorylation of both primary and secondary alcohols with tetrabenzylpyrophosphate, providing conversions between 54% and >98% and isolated yields between 50% and 97%. Other pyrophosphates with orthogonal protecting groups were synthesized and screened to validate the generality of the approach. This study will describe how benzyl, methyl, ethyl, allyl, and o-nitrobenzyl pyrophosphates are all effective phosphorylating agents under Lewis acid catalysis.     

Contribution of the Purkinje network to wave propagation in the canine ventricle: insights from a combined electrophysiological-anatomical model

The heart includes a specialized conduction system that ensures the necessary activation sequence and timing of the ventricles to produce an effective contraction. The role of this system, called the Purkinje network, during ventricular tachyarrhythmias remains unclear. To understand how the Purkinje network interacts with ventricular muscle, we develop the first combined electrophysiology-structural model of the canine Purkinje network based on microelectrode recordings and a digitized reconstruction of the Purkinje system. For the Purkinje electrophysiology model, we construct a new model of canine Purkinje electrophysiology based on action potentials recorded from canine tissue and designed to reproduce the important phenomenon of alternans. In addition, we use digital photographs of canine ventricular endocardium stained with Lugol’s solution to develop a structural model of the Purkinje network. We combine these electrophysiological and anatomical models of the Purkinje system with a model of canine ventricular electrophysiology to study how the Purkinje network can interact with the ventricular muscle during arrhythmias. Using our combined model, we find that two different results can occur: The long-range connections provided by the Purkinje network can depolarize the tissue more quickly, thereby promoting arrhythmia termination, but if termination does not occur, the Purkinje system can increase the dispersion of refractoriness in the tissue, thereby sustaining the arrhythmia. The different behaviors result from the two competing effects contributed by the Purkinje network: effective reduction in tissue size and increased spatial heterogeneity.     

Homogenization of geomaterials containing voids by random fields and finite elements

The paper describes the use of random fields and finite elements to assess the influence of porosity and void size on the effective elastic stiffness of geomaterials. A finite element model is developed involving “tied freedoms” that allows analysis of an ideal block of materials leading to direct evaluation of the effective Young’s modulus and Poisson’s ratio. The influence of block size and representative volume elements (RVE) are discussed. The use of random fields and Monte-Carlo simulations deliver a mean and standard deviation of the elastic parameters that lead naturally to a probabilistic interpretation. The methodology is extended to a foundation problem involving a footing on an elastic foundation containing voids. The approach enables estimates to be made of the probability of excessive settlement.