Dynamic signatures of electronically nonadiabatic coupling in sodium hydride: a rigorous test for the symmetric quasi-classical model applied to realistic, ab initio electronic states in the adiabatic representation.

Sodium hydride (NaH) in the gas phase presents a seemingly simple electronic structure making it a potentially tractable system for the detailed investigation of nonadiabatic molecular dynamics from both computational and experimental standpoints. The single vibrational degree of freedom, as well as the strong nonadiabatic coupling that arises from the excited electronic states taking on considerable ionic character, provides a realistic chemical system to test the accuracy of quasi-classical methods to model population dynamics where the results are directly comparable against quantum mechanical benchmarks. Using a simulated pump-probe type experiment, this work presents computational predictions of population transfer through the avoided crossings of NaH via symmetric quasi-classical Meyer-Miller (SQC/MM), Ehrenfest, and exact quantum dynamics on realistic, ab initio potential energy surfaces. The main driving force for population transfer arises from the ground vibrational level of the D1Σ+ adiabatic state that is embedded in the manifold of near-dissociation C1Σ+ vibrational states. When coupled through a sharply localized first-order derivative coupling most of the population transfers between t = 15 and t = 30 fs depending on the initially excited vibronic wavepacket. While quantum mechanical effects are expected due to the reduced mass of NaH, predictions of the population dynamics from both the SQC/MM and Ehrenfest models perform remarkably well against the quantum dynamics benchmark. Additionally, an analysis of the vibronic structure in the nonadiabatically coupled regime is presented using a variational eigensolver methodology.

Trajectory-adjusted electronic zero point energy in classical Meyer-Miller vibronic dynamics: Symmetrical quasiclassical application to photodissociation.

An electronic zero-point energy (ZPE) adjustment protocol is presented within the context of the symmetrical quasiclassical (SQC) quantization of the electronic oscillator degrees of freedom (DOF) in classical Meyer-Miller (MM) vibronic dynamics for the molecular dynamics treatment of electronically nonadiabatic processes. The "adjustment" procedure maintains the same initial and final distributions of coordinates and momenta in the electronic oscillator DOF as previously given by the SQC windowing protocol but modifies the ZPE parameter in the MM Hamiltonian, on a per trajectory basis, so that the initial nuclear forces are precisely those corresponding to the initial electronic quantum state. Examples demonstrate that this slight modification to the standard SQC/MM approach significantly improves treatment of the multistate nonadiabatic dynamics following a Franck-Condon type vertical excitation onto a highly repulsive potential energy surface as is typical in the photodissociation context.

A symmetrical quasi-classical windowing model for the molecular dynamics treatment of non-adiabatic processes involving many electronic states.

In the previous work of Cotton and Miller [J. Chem. Phys. 145, 144108 (2016)], an improved symmetrical quasi-classical (SQC) windowing model for the molecular dynamics treatment of electronically non-adiabatic processes was developed in order to extend the original SQC approach to the regime of weak-coupling between the electronic states. The improved SQC model-based on triangular-shaped window functions-handled the weak-coupling limit as intended and, as a bonus, was shown to be universally superior to the original square/histogram SQC windowing model over all coupling regimes, but only for treating systems of two electronic states, as no higher-dimensional generalization was evident. This paper, therefore, provides a generalized version for treating an arbitrary number of electronic states. By construction, the benefits of the two-state triangle model-seamless treatment of weak-coupling and improved accuracy in all coupling regimes-carry over to the generalized version. Far more significant, however, is that the new model provides vastly improved windowing statistics in higher dimensions, enabling the SQC simulation of electronically non-adiabatic processes involving many more relevant electronic states than was previously practical. Capabilities are demonstrated with respect to a 24 pigment trimer model of the Fenna-Matthews-Olson light-harvesting complex, as well as treating similar 48- and 96-electronic state model problems, illustrating the scaling properties of the new method.

External ear cytological results and resident flora of clinically normal alpacas (Vicugna pacos).

BACKGROUND: Otitis is common in alpacas. Suppurative otitis media/interna can be an extension from the external ear canal or from a respiratory infection. Cytological evaluation provides rapid and inexpensive information to assist in therapeutic decision; to date, there is no published information regarding the normal cytological results and flora of the alpaca external ear canal. HYPOTHESIS/OBJECTIVES: To describe normal resident cytological findings and flora and possible variation over time, we sampled clinically normal alpaca external ear canals during two different seasons. ANIMALS: Fifty privately owned, healthy alpacas of different ages and sexes in two northeastern United States flocks. METHODS AND MATERIALS: One ear per alpaca had both cytological swabs (ectoparasites, inflammatory and epithelial cells, bacteria and yeast) and sterile swabs (bacterial and fungal cultures) taken. This was done in August 2017 and repeated in January 2018. RESULTS: Yeast organisms were noted cytologically in 2-4% of the samples. Prevalence of total yeast genera was 6% in August and 30% in January. Cytologically, rod-shaped bacteria [maximum 4-10/high power field (HPF); median 0-0.5/HPF] were seen in 50% of alpacas in August and 26% in January. Coccal bacteria (maximum 6-10/HPF; median 0/HPF) were seen in 32% of alpacas in August and 16% in January. No statistically significant findings were noted between sampling months. Common bacterial genera isolated in August were Bacillus (44%), Arthrobacter (40%) and nonhaemolytic Staphylococcus (26%), and in January were Bacillus (42%) and Pantoea (38%). CONCLUSIONS AND CLINICAL IMPORTANCE: This information may be useful when evaluating alpaca external ear canal samples, which subsequently may help dictate empirical therapy.

EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.

In eukaryotes, post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and is involved in repressing gene expression through methylation of histone H3 on lysine 27 (H3K27). EZH2 overexpression is implicated in tumorigenesis and correlates with poor prognosis in several tumour types. Additionally, somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 occur in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. The Y641 residue is the most frequently mutated residue, with up to 22% of germinal centre B-cell DLBCL and follicular lymphoma harbouring mutations at this site. These lymphomas have increased H3K27 tri-methylation (H3K27me3) owing to altered substrate preferences of the mutant enzymes. However, it is unknown whether specific, direct inhibition of EZH2 methyltransferase activity will be effective in treating EZH2 mutant lymphomas. Here we demonstrate that GSK126, a potent, highly selective, S-adenosyl-methionine-competitive, small-molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

The symmetrical quasi-classical approach to electronically nonadiabatic dynamics applied to ultrafast exciton migration processes in semiconducting polymers.

In the last several years, a symmetrical quasi-classical (SQC) windowing model applied to the classical Meyer-Miller (MM) vibronic Hamiltonian has been shown to be a simple, efficient, general, and quite-accurate method for treating electronically nonadiabatic processes at the totally classical level. Here, the SQC/MM methodology is applied to ultrafast exciton dynamics in a Frenkel/site-exciton model of oligothiophene (OT) as a model of organic semiconductor polymers. In order to keep the electronic representation as compact and efficient as possible, the adiabatic version of the MM Hamiltonian was employed, with dynamical calculations carried out in the recently developed "kinematic momentum" representation, from which site/monomer-specific (diabatic) excitation probabilities were extracted using a new procedure developed in this work. The SQC/MM simulation results are seen to describe coherent exciton transport driven by planarization of a central torsion defect in the OT oligomer as well as to capture exciton self-trapping effects in good agreement with benchmark quantum calculations using the multi-layer multiconfiguration time-dependent Hartree approach. The SQC/MM calculations are also seen to significantly outperform the standard Ehrenfest approach, which shows serious discrepancies. These results are encouraging, not only because they illustrate a significant further application of the SQC/MM approach and its utility, but because they strongly suggest that classical mechanical simulations (with the potential for linear scaling efficiency) can be used to capture, quantitatively, important dynamical features of electronic excitation energy transfer in semiconducting polymers.

On the adiabatic representation of Meyer-Miller electronic-nuclear dynamics.

The Meyer-Miller (MM) classical vibronic (electronic + nuclear) Hamiltonian for electronically non-adiabatic dynamics-as used, for example, with the recently developed symmetrical quasiclassical (SQC) windowing model-can be written in either a diabatic or an adiabatic representation of the electronic degrees of freedom, the two being a canonical transformation of each other, thus giving the same dynamics. Although most recent applications of this SQC/MM approach have been carried out in the diabatic representation-because most of the benchmark model problems that have exact quantum results available for comparison are typically defined in a diabatic representation-it will typically be much more convenient to work in the adiabatic representation, e.g., when using Born-Oppenheimer potential energy surfaces (PESs) and derivative couplings that come from electronic structure calculations. The canonical equations of motion (EOMs) (i.e., Hamilton's equations) that come from the adiabatic MM Hamiltonian, however, in addition to the common first-derivative couplings, also involve second-derivative non-adiabatic coupling terms (as does the quantum Schrödinger equation), and the latter are considerably more difficult to calculate. This paper thus revisits the adiabatic version of the MM Hamiltonian and describes a modification of the classical adiabatic EOMs that are entirely equivalent to Hamilton's equations but that do not involve the second-derivative couplings. The second-derivative coupling terms have not been neglected; they simply do not appear in these modified adiabatic EOMs. This means that SQC/MM calculations can be carried out in the adiabatic representation, without approximation, needing only the PESs and the first-derivative coupling elements. The results of example SQC/MM calculations are presented, which illustrate this point, and also the fact that simply neglecting the second-derivative couplings in Hamilton's equations (and presumably also in the Schrödinger equation) can cause very significant errors.

Classical molecular dynamics simulation of electronically non-adiabatic processes.

Both classical and quantum mechanics (as well as hybrids thereof, i.e., semiclassical approaches) find widespread use in simulating dynamical processes in molecular systems. For large chemical systems, however, which involve potential energy surfaces (PES) of general/arbitrary form, it is usually the case that only classical molecular dynamics (MD) approaches are feasible, and their use is thus ubiquitous nowadays, at least for chemical processes involving dynamics on a single PES (i.e., within a single Born-Oppenheimer electronic state). This paper reviews recent developments in an approach which extends standard classical MD methods to the treatment of electronically non-adiabatic processes, i.e., those that involve transitions between different electronic states. The approach treats nuclear and electronic degrees of freedom (DOF) equivalently (i.e., by classical mechanics, thereby retaining the simplicity of standard MD), and provides "quantization" of the electronic states through a symmetrical quasi-classical (SQC) windowing model. The approach is seen to be capable of treating extreme regimes of strong and weak coupling between the electronic states, as well as accurately describing coherence effects in the electronic DOF (including the de-coherence of such effects caused by coupling to the nuclear DOF). A survey of recent applications is presented to illustrate the performance of the approach. Also described is a newly developed variation on the original SQC model (found universally superior to the original) and a general extension of the SQC model to obtain the full electronic density matrix (at no additional cost/complexity).

A new symmetrical quasi-classical model for electronically non-adiabatic processes: Application to the case of weak non-adiabatic coupling.

Previous work has shown how a symmetrical quasi-classical (SQC) windowing procedure can be used to quantize the initial and final electronic degrees of freedom in the Meyer-Miller (MM) classical vibronic (i.e, nuclear + electronic) Hamiltonian, and that the approach provides a very good description of electronically non-adiabatic processes within a standard classical molecular dynamics framework for a number of benchmark problems. This paper explores application of the SQC/MM approach to the case of very weak non-adiabatic coupling between the electronic states, showing (as anticipated) how the standard SQC/MM approach used to date fails in this limit, and then devises a new SQC windowing scheme to deal with it. Application of this new SQC model to a variety of realistic benchmark systems shows that the new model not only treats the weak coupling case extremely well, but it is also seen to describe the "normal" regime (of electronic transition probabilities ≳ 0.1) even more accurately than the previous "standard" model.

Communication: Wigner functions in action-angle variables, Bohr-Sommerfeld quantization, the Heisenberg correspondence principle, and a symmetrical quasi-classical approach to the full electronic density matrix.

It is pointed out that the classical phase space distribution in action-angle (a-a) variables obtained from a Wigner function depends on how the calculation is carried out: if one computes the standard Wigner function in Cartesian variables (p, x), and then replaces p and x by their expressions in terms of a-a variables, one obtains a different result than if the Wigner function is computed directly in terms of the a-a variables. Furthermore, the latter procedure gives a result more consistent with classical and semiclassical theory-e.g., by incorporating the Bohr-Sommerfeld quantization condition (quantum states defined by integer values of the action variable) as well as the Heisenberg correspondence principle for matrix elements of an operator between such states-and has also been shown to be more accurate when applied to electronically non-adiabatic applications as implemented within the recently developed symmetrical quasi-classical (SQC) Meyer-Miller (MM) approach. Moreover, use of the Wigner function (obtained directly) in a-a variables shows how our standard SQC/MM approach can be used to obtain off-diagonal elements of the electronic density matrix by processing in a different way the same set of trajectories already used (in the SQC/MM methodology) to obtain the diagonal elements.

An alternative to the Sandmeyer approach to aryl iodides.

Iodoarenes are important synthons for a wide range of organic transformations. Here we report a general strategy to prepare singly iodinated electron-rich aromatic compounds through the intermediacy of diaryliodonium salts. This process, which incorporates a phase separation that greatly simplifies product purification, is an attractive replacement for the Sandmeyer approach to iodoarenes that are otherwise difficult to access.

A journey through chemical dynamics.

The charge with the invitation to write this autobiographical article was to describe what led me to a career in science and to choose the specific topics and scientific directions I have pursued. This is thus a very personal story and by no means a scientific review of the work that is mentioned. As will be clear, this journey was not an orderly, well-thought-out plan, but just "happened," one step after the other.

A Symmetrical Quasi-Classical Spin-Mapping Model for the Electronic Degrees of Freedom in Non-Adiabatic Processes.

A recent series of papers has shown that a symmetrical quasi-classical (SQC) windowing procedure applied to the Meyer-Miller (MM) classical vibronic Hamiltonian provides a very good treatment of electronically nonadiabatic processes in a variety of benchmark model systems, including systems that exhibit strong quantum coherence effects and some which other approximate approaches have difficulty in describing correctly. In this paper, a different classical electronic Hamiltonian for the treatment of electronically nonadiabatic processes is proposed (and "quantized" via the SQC windowing approach), which maps the dynamics of F coupled electronic states to a set of F spin-(1)/2 degrees of freedom (DOF), similar to the Fermionic spin model described by Miller and White (J. Chem. Phys. 1986, 84, 5059). It is noted that this spin-mapping (SM) Hamiltonian is an exact Hamiltonian if treated as a quantum mechanical (QM) operator-and thus QM'ly equivalent to the MM Hamiltonian-but that an analytically distinct classical analogue is obtained by replacing the QM spin-operators with their classical counterparts. Due to their analytic differences, a practical comparison is then made between the MM and SM Hamiltonians (when quantized with the SQC technique) by applying the latter to many of the same benchmark test problems successfully treated in our recent work with the SQC/MM model. We find that for every benchmark problem the MM model provides (slightly) better agreement with the correct quantum nonadiabatic transition probabilities than does the new SM model. This is despite the fact that one might expect, a priori, a more natural description of electronic state populations (occupied versus unoccupied) to be provided by DOF with only two states, i.e., spin-(1)/2 DOF, rather than by harmonic oscillator DOF which have an infinite manifold of states (though only two of these are ever occupied).

Communication: Note on detailed balance in symmetrical quasi-classical models for electronically non-adiabatic dynamics.

It is noted that the recently developed symmetrical quasi-classical (SQC) treatment of the Meyer-Miller (MM) model for the simulation of electronically non-adiabatic dynamics provides a good description of detailed balance, even though the dynamics which results from the classical MM Hamiltonian is "Ehrenfest dynamics" (i.e., the force on the nuclei is an instantaneous coherent average over all electronic states). This is seen to be a consequence of the SQC windowing methodology for "processing" the results of the trajectory calculation. For a particularly simple model discussed here, this is shown to be true regardless of the choice of windowing function employed in the SQC model, and for a more realistic full classical molecular dynamics simulation, it is seen to be maintained correctly for very long time.

Symmetrical windowing for quantum states in quasi-classical trajectory simulations: application to electron transfer.

It has recently been shown [S. J. Cotton and W. H. Miller, J. Chem. Phys. 139, 234112 (2013)] that a symmetrical windowing quasi-classical (SQC) approach [S. J. Cotton and W. H. Miller, J. Phys. Chem. A 117, 7190 (2013)] applied to the Meyer-Miller model [H.-D. Meyer and W. H. Miller, J. Chem. Phys. 70, 3214 (1979)] for the electronic degrees of freedom in electronically non-adiabatic dynamics is capable of quantitatively reproducing quantum mechanical results for a variety of test applications, including cases where "quantum" coherence effects are significant. Here we apply this same SQC methodology, within a flux-side correlation function framework, to calculate thermal rate constants corresponding to several proposed models of electron transfer processes [P. Huo, T. F. Miller III, and D. F. Coker, J. Chem. Phys. 139, 151103 (2013); A. R. Menzeleev, N. Ananth, and T. F. Miller III, J. Chem. Phys. 135, 074106 (2011)]. Good quantitative agreement with Marcus Theory is obtained over several orders of magnitude variation in non-adiabatic coupling. Moreover, the "inverted regime" in thermal rate constants (with increasing bias) known from Marcus Theory is also reproduced with good accuracy by this very simple classical approach. The SQC treatment is also applied to a recent model of photoinduced proton coupled electron transfer [C. Venkataraman, A. V. Soudackov, and S. Hammes-Schiffer, J. Chem. Phys. 131, 154502 (2009)] and population decay of the photoexcited donor state is found to be in reasonable agreement with results calculated via reduced density matrix theory.

A quasi-classical mapping approach to vibrationally coupled electron transport in molecular junctions.

We develop a classical mapping approach suitable to describe vibrationally coupled charge transport in molecular junctions based on the Cartesian mapping for many-electron systems [B. Li and W. H. Miller, J. Chem. Phys. 137, 154107 (2012)]. To properly describe vibrational quantum effects in the transport characteristics, we introduce a simple transformation rewriting the Hamiltonian in terms of occupation numbers and use a binning function to facilitate quantization. The approach provides accurate results for the nonequilibrium Holstein model for a range of bias voltages, vibrational frequencies, and temperatures. It also captures the hallmarks of vibrational quantum effects apparent in step-like structure in the current-voltage characteristics at low temperatures as well as the phenomenon of Franck-Condon blockade.

Classical mapping for Hubbard operators: application to the double-Anderson model.

A classical Cartesian mapping for Hubbard operators is developed to describe the nonequilibrium transport of an open quantum system with many electrons. The mapping of the Hubbard operators representing the many-body Hamiltonian is derived by using analogies from classical mappings of boson creation and annihilation operators vis-à-vis a coherent state representation. The approach provides qualitative results for a double quantum dot array (double Anderson impurity model) coupled to fermionic leads for a range of bias voltages, Coulomb couplings, and hopping terms. While the width and height of the conduction peaks show deviations from the master equation approach considered to be accurate in the limit of weak system-leads couplings and high temperatures, the Hubbard mapping captures all transport channels involving transition between many electron states, some of which are not captured by approximate nonequilibrium Green function closures.

Scaling dermatosis in three dogs associated with abnormal sebaceous gland differentiation.

BACKGROUND: Abnormal sebaceous gland differentiation, so-called 'sebaceous gland dysplasia', is a rare condition described in the dog and the cat. Although little is known about this condition, it is thought that a genetic defect causes abnormal sebaceous gland development. Clinically, this condition occurs in young cats and dogs and is characterized by variable degrees of adherent scale, hair casts, poor coat quality and hypotrichosis. HYPOTHESIS/OBJECTIVE: Here, we describe the clinical presentation and treatment of three adult dogs with abnormal sebaceous gland differentiation. ANIMALS: Three adult dogs presented with a keratinization defect characterized by progressive scaling, hair casts, dull, dry, brittle hair coat and hypotrichosis beginning in puppyhood to early adulthood. METHODS: Multiple 6 mm punch skin biopsy samples were obtained from each dog. Treatments included various topical keratomodulatory agents, oral essential fatty acids and oral vitamin A. RESULTS: Histologically, all sebaceous glands were small and composed of a mixture of irregularly clustered basal reserve cells and mature sebocytes. With therapy, two of the dogs showed moderate to marked clinical improvement in scaling, hair casts and hair coat quality. CONCLUSIONS AND CLINICAL IMPORTANCE: Although rare, 'sebaceous gland dysplasia' should be considered in cases where a primary keratinization defect is suspected. Given that abnormal sebaceous differentiation is a structural defect of the skin, treatment must be maintained and is aimed at ameliorating the clinical signs rather than curing the disease.

Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes.

The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H(2)O(2) and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ(10) significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with CAD alone. Elevated mtROS production in the endothelium of patients with CAD and T2D increases AMPK activation, supporting a role for the kinase in defence against oxidative stress. Further investigation is required to determine whether pharmacological activators of AMPK will prove beneficial in the attenuation of endothelial dysfunction in patients with CAD and T2D.

Symmetrical windowing for quantum states in quasi-classical trajectory simulations.

A microscopically reversible approach toward computing reaction probabilities via classical trajectory simulation has been developed that bins trajectories symmetrically on the basis of their initial and final classical actions. The symmetrical quasi-classical (SQC) approach involves defining a classical action window function centered at integer quantum values of the action, choosing a width parameter that is less than unit quantum width, and applying the window function to both initial reactant and final product vibrational states. Calculations were performed using flat histogram windows and Gaussian windows over a range of width parameters. Use of the Wigner distribution function was also investigated as a possible choice. It was demonstrated for collinear H + H2 reactive scattering on the BKMP2 potential energy surface that reaction probabilities computed via the SQC methodology using a Gaussian window function of 1/2 unit width produces good agreement with quantum mechanical results over the 0.4-0.6 eV energy range relevant to the ground vibrational state to the ground vibrational state reactive transition.