<i>Ab Initio</i> Molecular Dynamics Using Recursive, Spatially Separated, Overlapping Model Subsystems Mixed within an ONIOM-Based Fragmentation Energy Extrapolation Technique

Here, we demonstrate the application of fragment-based electronic structure calculations in (a) <i>ab initio</i> molecular dynamics (AIMD) and (b) reduced dimensional potential calculations, for medium- and large-sized protonated water clusters. The specific fragmentation algorithm used here is derived from ONIOM, but includes multiple, overlapping “model” systems. The interaction between the various overlapping model systems is (a) approximated by invoking the principle of inclusion-exclusion at the chosen higher level of theory and (b) within a real calculation performed at the chosen lower level of theory. The fragmentation algorithm itself is written using bit-manipulation arithmetic, which will prove to be advantageous, since the number of fragments in such methods has the propensity to grow exponentially with system size. Benchmark calculations are performed for three different protonated water clusters: H₉O₄⁺, H₁₃O₆⁺ and H­(H₂O)₂₁⁺. For potential energy surface benchmarks, we sample the normal coordinates and compare our surface energies with full MP2 and CCSD­(T) calculations. The mean absolute error for the fragment-based algorithm is <0.05 kcal/mol, when compared with MP2 calculations, and <0.07 kcal/mol, when compared with CCSD­(T) calculations over 693 different geometries for the H₉O₄⁺ system. For the larger H­(H₂O)₂₁⁺ water cluster, the mean absolute error is on the order of a 0.1 kcal/mol, when compared with full MP2 calculations for 84 different geometries, at a fraction of the computational cost. <i>Ab initio</i> dynamics calculations were performed for H₉O₄⁺ and H₁₃O₆⁺, and the energy conservation was found to be of the order of 0.01 kcal/mol for short trajectories (on the order of a picosecond). The trajectories were kept short because our algorithm does not currently include dynamical fragmentation, which will be considered in future publications. Nevertheless, the velocity autocorrelation functions and their Fourier transforms computed from the fragment-based AIMD approaches were found to be in excellent agreement with those computed using the respective higher level of theory from the chosen hybrid calculation

Direct Atomic-Scale Observation of Intermediate Pathways of Melting and Crystallization in Supported Bi Nanoparticles

Uncovering the evolutional pathways of melting and crystallization atomically is critical to understanding complex microscopic mechanism of first-order phase transformation. We conduct in situ atomic-scale observations of melting and crystallization in supported Bi nanoparticles under heating and cooling within an aberration-corrected TEM. We provide direct evidence of the multiple intermediate state events in melting and crystallization. The melting of the supported nanocrystal involves the formation and migration of domain boundaries and dislocations due to the atomic rearrangement under heating, which occurs through a size-dependent multiple intermediate state. A critical size, which is key to inducing the transition pathway in melting from two to four barriers, is identified for the nanocrystal. In contrast, crystallization of a Bi droplet involves three stages. These findings demonstrate that the phase transformations cannot be viewed as a simple single barrier-crossing event but as a complex multiple intermediate state phenomenon, highlighting the importance of nonlocal behaviors

Efficient, “On-the-Fly”, Born–Oppenheimer and Car–Parrinello-type Dynamics with Coupled Cluster Accuracy through Fragment Based Electronic Structure

We recently developed two fragment based <i>ab initio</i> molecular dynamics methods, and in this publication we have demonstrated both approaches by constructing efficient classical trajectories in agreement with trajectories obtained from “on-the-fly” CCSD. The dynamics trajectories are obtained using both Born–Oppenheimer and extended Lagrangian (Car–Parrinello-style) options, and hence, here, for the first time, we present Car–Parrinello-like AIMD trajectories that are accurate to the CCSD level of post-Hartree–Fock theory. The specific extended Lagrangian implementation used here is a generalization to atom-centered density matrix propagation (ADMP) that provides post-Hartree–Fock accuracy, and hence the new method is abbreviated as ADMP-pHF; whereas the Born–Oppenheimer version is called frag-BOMD. The fragmentation methodology is based on a set-theoretic, inclusion-exclusion principle based generalization of the well-known ONIOM method. Thus, the fragmentation scheme contains multiple overlapping “model” systems, and overcounting is compensated through the inclusion-exclusion principle. The energy functional thus obtained is used to construct Born–Oppenheimer forces (frag-BOMD) and is also embedded within an extended Lagrangian (ADMP-pHF). The dynamics is tested by computing structural and vibrational properties for protonated water clusters. The frag-BOMD trajectories yield structural and vibrational properties in excellent agreement with full CCSD-based “on-the-fly” BOMD trajectories, at a small fraction of the cost. The asymptotic (large system) computational scaling of both frag-BOMD and ADMP-pHF is inferred as O(N3.5), for on-the-fly CCSD accuracy. The extended Lagrangian implementation, ADMP-pHF, also provides structural features in excellent agreement with full “on-the-fly” CCSD calculations, but the dynamical frequencies are slightly red-shifted. Furthermore, we study the behavior of ADMP-pHF as a function of the electronic inertia tensor and find a monotonic improvement in the red-shift as we reduce the electronic inertia. In all cases a uniform spectral scaling factor, that in our preliminary studies appears to be independent of system and independent of level of theory (same scaling factor for both MP2 and CCSD implementations ADMP-pHF and for ADMP DFT), improves on agreement between ADMP-pHF and full CCSD calculations. Hence, we believe both frag-BOMD and ADMP-pHF will find significant utility in modeling complex systems. The computational power of frag-BOMD and ADMP-pHF is demonstrated through preliminary studies on a much larger protonated 21-water cluster, for which AIMD trajectories with “on-the-fly” CCSD are not feasible

Endosomal-Escape Polymers Based on Multicomponent Reaction-Synthesized Monomers Integrating Alkyl and Imidazolyl Moieties for Efficient Gene Delivery

As one of the toughest tasks in the course of intracellular therapeutics delivery, endosomal escape must be effectively achieved, particularly for intracellular gene transport. In this report, novel endosomal-escape polymers were designed and synthesized from monomers by integrating alkyl and imidazolyl via Passerini reaction and reversible addition–fragmentation chain transfer polymerization (RAFT). After introducing the endosomal-escape polymers with proper degrees of polymerization (DPs) into poly­(2-dimethylaminoethyl methacrylate) (PDMAEMA) as the gene delivery vectors, the block copolymers exhibited significantly enhanced hemolytic activity at endosomal pH, and the plasmid DNA (pDNA)-loaded polyplexes showed efficient endosomal escape compared with PDMAEMA, ultimately achieving dramatically increased gene transfection efficacy. These results suggest that the polymers that integrate alkyl and imidazolyl moieties for efficient endosomal escape have wide potential applications for intracellular gene delivery

<i>In Situ</i> Atomic-Scale Observation of Droplet Coalescence Driven Nucleation and Growth at Liquid/Solid Interfaces

Unraveling dynamical processes of liquid droplets at liquid/solid interfaces and the interfacial ordering is critical to understanding solidification, liquid-phase epitaxial growth, wetting, liquid-phase joining, crystal growth, and lubrication processes, all of which are linked to different important applications in material science. In this work, we observe direct <i>in situ</i> atomic-scale behavior of Bi droplets segregated on SrBi₂Ta₂O₉ by using aberration-corrected transmission electron microscopy and demonstrate ordered interface and surface structures for the droplets on the oxide at the atomic scale and unravel a nucleation mechanism involving droplet coalescence at the liquid/solid interface. We identify a critical diameter of the formed nanocrystal in stabilizing the crystalline phase and reveal lattice-induced fast crystallization of the droplet at the initial stage of the coalescence of the nanocrystal with the droplet. Further sequential observations show the stepped coalescence and growth mechanism of the nanocrystals at the atomic scale. These results offer insights into the dynamic process at liquid/solid interfaces, which may have implications for many functionalities of materials and their applications

Direct Atomic-Scale Observation of Intermediate Pathways of Melting and Crystallization in Supported Bi Nanoparticles

Uncovering the evolutional pathways of melting and crystallization atomically is critical to understanding complex microscopic mechanism of first-order phase transformation. We conduct in situ atomic-scale observations of melting and crystallization in supported Bi nanoparticles under heating and cooling within an aberration-corrected TEM. We provide direct evidence of the multiple intermediate state events in melting and crystallization. The melting of the supported nanocrystal involves the formation and migration of domain boundaries and dislocations due to the atomic rearrangement under heating, which occurs through a size-dependent multiple intermediate state. A critical size, which is key to inducing the transition pathway in melting from two to four barriers, is identified for the nanocrystal. In contrast, crystallization of a Bi droplet involves three stages. These findings demonstrate that the phase transformations cannot be viewed as a simple single barrier-crossing event but as a complex multiple intermediate state phenomenon, highlighting the importance of nonlocal behaviors

Estimated continuous annual BCSM rates and hazard ratio of BCSM in certain subpopulations.

<p>(A) Patients were age<40 with ER negative and node positive diseases. (B) Patients were age≥60 with ER positive and node negative diseases.</p

Estimated continuous annual BCSM rates and hazard ratio of BCSM.

<p>A, B & C show estimated continuous annual BCSM rates. The solid line represents patients in cohort 1; the dashed line represents patients in cohort 2.D, E & F show differences of BCSM between patients in the two cohorts. Patients in C1 as reference, the absolute number of decreased BCSM rate (C2 minus C1).G, H & I show hazard ratio of BCSM (Cohort 1 versus cohort 2). Light grey shadows represent 95% CI of survival. HRs with 95% CIs were estimated from the flexible parametric survival models. Curves cut off at 0.5 yrs from diagnosis because of sparse data. Total population: A, D & G; ER negative: B, E & H; ER positive: C, F & I. Notes: Rates were reported per 1000 persons per year; y-axis scales were different in different analyses.</p

Annual BCSM rates and hazard ratio of BCSM in the total population and different subgroups.

<p>Annual BCSM rates and hazard ratio of BCSM in the total population and different subgroups.</p

Real-Time Dynamical Observation of Lattice Induced Nucleation and Growth in Interfacial Solid–Solid Phase Transitions

Uncovering dynamical processes of lattice induced epitaxial growth of nanocrystal on the support is critical to understanding crystallization, solid-phase epitaxial growth, Oswald ripening process, and advanced nanofabrication, all of which are linked to different important applications in the materials field. Here, we conduct direct <i>in situ</i> atomic-scale dynamical observation of segregated Bi layers on SrBi₂Ta₂O₉ support under low dose electron irradiation to explore the nucleation and growth from an initial disordered solid state to a stable faceted crystal by using aberration-corrected transmission electron microscopy. We provide, for the first time, atomic-scale insights into the initial prenucleation stage of lattice induced interfacial nucleation, size-dependent crystalline fluctuation, and stepped-growth stage of the formed nanocrystal on the oxide support at the atomic scale. We identify a critical diameter in forming a stable faceted configuration and find interestingly that the stable nanocrystal presents a size-dependent coalescence mechanism. These results offer an atomic-scale view into the dynamic process at solid/solid interfaces, which has implications for thin film growth and advanced nanofabrication