Incorporating Nuclear Quantum Effects in Molecular Dynamics with a Constrained Minimized Energy Surface

The accurate incorporation of nuclear quantum effects in large-scale molecular dynamics (MD) simulations remains a significant challenge. Recently, we combined constrained nuclear-electronic orbital (CNEO) theory with classical MD and obtained a new approach (CNEO-MD) that can accurately and efficiently incorporate nuclear quantum effects into classical simulations. In this Letter, we provide the theoretical foundation for CNEO-MD by developing an alternative formulation of the equations of motion for MD. In this new formulation, the expectation values of quantum nuclear positions evolve classically on an effective energy surface that is obtained from a constrained energy minimization procedure when solving for the quantum nuclear wave function, thus enabling the incorporation of nuclear quantum effects in classical MD simulations. For comparison with other existing approaches, we examined a series of model systems and found that this new MD approach is significantly more accurate than the conventional way of performing classical MD and generally outperforms centroid MD and ring-polymer MD in describing vibrations in these model systems

Incorporating Nuclear Quantum Effects in Molecular Dynamics with a Constrained Minimized Energy Surface

The accurate incorporation of nuclear quantum effects in large-scale molecular dynamics (MD) simulations remains a significant challenge. Recently, we combined constrained nuclear-electronic orbital (CNEO) theory with classical MD and obtained a new approach (CNEO-MD) that can accurately and efficiently incorporate nuclear quantum effects into classical simulations. In this Letter, we provide the theoretical foundation for CNEO-MD by developing an alternative formulation of the equations of motion for MD. In this new formulation, the expectation values of quantum nuclear positions evolve classically on an effective energy surface that is obtained from a constrained energy minimization procedure when solving for the quantum nuclear wave function, thus enabling the incorporation of nuclear quantum effects in classical MD simulations. For comparison with other existing approaches, we examined a series of model systems and found that this new MD approach is significantly more accurate than the conventional way of performing classical MD and generally outperforms centroid MD and ring-polymer MD in describing vibrations in these model systems

Defects in Halide Perovskites: Does It Help to Switch from 3D to 2D?

Two-dimensional (2D) organic–inorganic hybrid iodide perovskites have been put forward in recent years as stable alternatives to their three-dimensional (3D) counterparts. Using first-principles calculations, we demonstrate that equilibrium concentrations of point defects in the 2D perovskites PEA2PbI4, BA2PbI4, and PEA2SnI4 (PEA, phenethylammonium; BA, butylammonium) are much lower than in comparable 3D perovskites. Bonding disruptions by defects are more destructive in 2D than in 3D networks, making defect formation energetically more costly. The stability of 2D Sn iodide perovskites can be further enhanced by alloying with Pb. Should, however, point defects emerge in sizable concentrations as a result of nonequilibrium growth conditions, for instance, then those defects likely hamper the optoelectronic performance of the 2D perovskites, as they introduce deep traps. We suggest that trap levels are responsible for the broad sub-bandgap emission in 2D perovskites observed in experiments

Generalized Optimized Effective Potential for Orbital Functionals and Self-Consistent Calculation of Random Phase Approximations

A new self-consistent procedure for calculating the total energy with an orbital-dependent density functional approximation (DFA), the generalized optimized effective potential (GOEP), is developed in the present work. The GOEP is a nonlocal Hermitian potential that delivers the sets of occupied and virtual orbitals and minimizes the total energy. The GOEP optimization leads to the same minimum as does the orbital optimization. The GOEP method is promising as an effective optimization approach for orbital-dependent functionals, as demonstrated for the self-consistent calculations of the random phase approximation (RPA) to the correlation functionals in the particle–hole (ph) and particle–particle (pp) channels. The results show that the accuracy in describing the weakly interacting van der Waals systems is significantly improved in the self-consistent calculations. In particular, the important single excitations contribution in non-self-consistent RPA calculations can be captured self-consistently through the GOEP optimization, leading to orbital renormalization, without using the single excitations in the energy functional

Multireference Density Functional Theory with Generalized Auxiliary Systems for Ground and Excited States

To describe static correlation, we develop a new approach to density functional theory (DFT), which uses a generalized auxiliary system that is of a different symmetry, such as particle number or spin, from that of the physical system. The total energy of the physical system consists of two parts: the energy of the auxiliary system, which is determined with a chosen density functional approximation (DFA), and the excitation energy from an approximate linear response theory that restores the symmetry to that of the physical system, thus rigorously leading to a multideterminant description of the physical system. The electron density of the physical system is different from that of the auxiliary system and is uniquely determined from the functional derivative of the total energy with respect to the external potential. Our energy functional is thus an implicit functional of the physical system density, but an explicit functional of the auxiliary system density. We show that the total energy minimum and stationary states, describing the ground and excited states of the physical system, can be obtained by a self-consistent optimization with respect to the explicit variable, the generalized Kohn–Sham noninteracting density matrix. We have developed the generalized optimized effective potential method for the self-consistent optimization. Among options of the auxiliary system and the associated linear response theory, reformulated versions of the particle–particle random phase approximation (pp-RPA) and the spin-flip time-dependent density functional theory (SF-TDDFT) are selected for illustration of principle. Numerical results show that our multireference DFT successfully describes static correlation in bond dissociation and double bond rotation

Ultrastretchable, Highly Conductive, Rapid Self-Recovery, and Antiswelling Hydrogels as Multifunctional Wearable Electronic Devices

The development of wearable electronic devices requires stretchable, highly conductive, self-recovery, and ideally environmentally resistant sensors. Hydrogels are ideal candidates for fabricating flexible sensors due to their stretchability and unique ionic conduction pathways. However, the intrinsic incompatibility of the conductive and elastic networks in hydrogels and the high hydrophilicity of the hydrogel network led to difficulties in obtaining hydrogels with strong mechanical properties, high conductivity, rapid self-recovery ability, and antiswelling properties. Based on the single-core multidentate coordination strategy, single-core multidentate coordinated chitosan/poly(acrylic acid)/Al3+ (CPAL) hydrogels were prepared with Al3+ as a metal coordination center and the amino group of chitosan (CS) and the carboxyl group of poly(acrylic acid) (PAA) as coordination atoms. The obtained hydrogels exhibit excellent tensile stress/strain: 1.11 ± 0.04 MPa/2472.79 ± 99.27%, rapid self-recovery capability (mechanical properties were fully recovered in 10 min), antifatigue property, good conductivity (1.09 ± 0.02 S/m), and antiswelling property. Furthermore, flexible sensors based on CPAL hydrogels demonstrated multiplex mode sensing. It was worth noting that the flexible devices based on CPAL hydrogel could not only use Morse code table to realize mechanical-information visualization but also detect the human condition in multiple dimensions, including temperature, electromyographic (EMG), and electrocardiogram (ECG). In this work, we reported a single-core multidentate coordination strategy that provided a pathway for fabricating the ideal hydrogel-based flexible sensors, showing great potential for wearable electronic devices

Additional file 1: Figure S1. of Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

Fluorescence-activated cell sorting of c-kit+/SSEA1− cells. C-kit+/SSEA1− cells were isolated in vitro illustrated by flow cytometry. (PNG 810 kb

DataSheet1_Asymmetries and relationships between muscle strength, proprioception, biomechanics, and postural stability in patients with unilateral knee osteoarthritis.docx

Background: The pathological mechanism of knee osteoarthritis (KOA) is unknown. KOA degeneration may be associated with changes in muscle strength, proprioception, biomechanics, and postural stability.Objective: This study aimed to assess asymmetries in muscle strength, proprioception, biomechanics, and postural stability of bilateral lower limbs in patients with unilateral KOA and healthy controls and analyze correlations between KOA and these parameters.Methods: A total of 50 patients with unilateral KOA (age range: 50-70) and 50 healthy subjects were recruited as study participants (age range: 50-70). Muscle strength, proprioception, femorotibial angle (FTA), femoral condylar–tibial plateau angle (FCTP), average trajectory error (ATE), and center of pressure (COP) sways areas were accessed in study participants, and the correlation between these variables was investigated.Results: In patients with unilateral KOA, lower limb muscle strength was significantly lower on the symptomatic side than on the asymptomatic side (p 0.05). Patients with unilateral KOA had lower muscle strength than healthy controls (p 0.05).Conclusion: In patients with unilateral KOA, muscle strength, proprioception, biomechanics, and postural stability of bilateral limbs are asymmetrical in unilateral KOA patients. Muscle strength, proprioception, and postural stability are significantly associated variables, and changes in these variables should be considered in KOA prevention and rehabilitation.</p

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen <i>Blastomyces</i> and Close Relative <i>Emmonsia</i>

<div><p>Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, <i>Blastomyces</i>, and two species of the related genus <i>Emmonsia</i>, typically pathogens of small mammals. Compared to related species, <i>Blastomyces</i> genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for <i>gypsy</i> elements, are variable in total size between isolates, and are least expanded in the avirulent <i>B</i>. <i>dermatitidis</i> strain ER-3 as compared with the virulent <i>B</i>. <i>gilchristii</i> strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the <i>Blastomyces</i> lineage. While gene content is highly conserved between <i>Blastomyces</i> and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of <i>B</i>. <i>dermatitidis</i> during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in <i>Blastomyces</i>, and upregulation of dioxygenases <i>in vivo</i> suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively <i>in vivo</i>, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in <i>in vitro</i> studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of <i>Blastomyces</i> to its host environment. These results reveal the dynamics of genome evolution and of factors contributing to virulence in <i>Blastomyces</i>.</p></div

Correspondence of GC content and synteny for <i>Blastomyces</i>.

<p>Comparison of GC content (top panel) and genome synteny (lower panel) for a 5.2 Mb region of <i>B</i>. <i>dermatitidis</i> strain ER-3 (scaffold (sc) 1, coordinates from 4.5 to 9.7 Mb) and corresponding syntenic regions of <i>B</i>. <i>gilchristii</i> strain SLH14081 and <i>Histoplasma capsulatum</i> strain WU24. Location of genes (blue boxes) and gypsy elements (green boxes) are depicted across each genomic region. Orthologs between genomes are connected in pink, which are organized into syntenic regions that are disrupted by GC-poor regions in both <i>Blastomyces</i> genomes.</p