Student-Led Webinar to Support LGBTQ+ Students Applying to Medical School During the COVID-19 Pandemic.

Lesbian, gay, bisexual, transgender, queer, intersex, asexual, non-binary, two-spirit, and other (LGBTQ+) students are a diverse group with unique and frequently overlooked needs in medical training. The present study was designed to understand the concerns of LGBTQ+ applicants to medical school and examine the effectiveness of a webinar in alleviating concerns. Sixty participants joined webinars discussing the medical school application process with particular attention to concerns pertinent to the LGBTQ+ population. Pre and post surveys were administered to examine webinar effectiveness and participant concerns. Results were analyzed using quantitative and qualitative methods. Pre-medical students reported that the webinar format was helpful for their application process. Specifically, pre- and post-test analyses revealed that the webinar increased both students' preparedness as well as their confidence in disclosing their LGBTQ+ identity or being "out" when applying to medical school. Student-led, online webinars increase LGBTQ+ students' confidence and help address SGM students' concerns about applying to medical school.

Electrochemically Triggered Release of Reagent to the Proximal Leaflet of a Microcavity Supported Lipid Bilayer.

A novel and versatile approach to electrichemically triggering the release of a reagent, ß-cyclodextrin (ß-CD), selectively to the proximal leaflet of a supported lipid bilayer is described. Selective delivery is achieved by creating a spanning lipid bilayer across a microcavity array and exploiting the irreversible redox disassembly of the host-guest complex formed between thiolated ferrocene (Fc) and ß-cyclodextrin (ß-CD) in the presence of chloride. Self-assembled monolayers of the ferrocene-alkanethiols were formed regioselectively on the interior surface of highly ordered 2.8 µm cavities while the exterior top surface of the array was blocked with a monolayer of mercaptoethanol. The Fc monolayers were complexed with ß-CD or ß-CD-conjugated to streptavidin (ß-CD-SA). Phospholipid bilayers were then assembled across the array via combined Langmuir-Blodgett/vesicle fusion leading to a spanning bilayer suspended across the aqueous filled microcavities. Upon application of a positive potential, ferrocene is oxidized to ferrocinium cation, disrupting the inclusion complex and leading to the release of the ß-CD into the microcavity solution where it diffuses to the lower leaflet of the suspended bilayer. Disassembly of the supramolecular complex within the cavities and binding of the ß-CD-SA to a biotinylated bilayer was followed by voltammetry and impedance spectroscopy where it caused a large increase in membrane resistance. For unmodified ß-CD, the extraction of cholesterol from a cholesterol containing bilayer was evident in a decrease in the bilayer resistance. For the first time, this direct approach to targeted delivery of a reagent to the proximal layer of a lipid bilayer offers the potential to build models of bidirectional signaling (inside-out vs outside-in) in cell membrane model systems.

Magnetic and noble metal nanocomposites for separation and optical detection of biological species.

Nanoalloys and nanocomposites are widely studied classes of nanomaterials within the context of biological systems. They are of immense interest because of the possibility of tuning the optical, magnetic, electronic and chemical properties through particle composition and internal architecture. In principle these properties can therefore be optimized for application in biological detections such as of DNA sequences, bacteria, viruses, antibodies, antigens, and cancer cells. This article presents an overview of methods currently used for nanoalloy and nanocomposite synthesis and characterisation, focusing on Au-Ag and FexOy@Au structures as primary components in detection platforms for plasmonic and magnetically enabled plasmonic bio-sensing.

The application of water soluble, mega-Stokes-shifted BODIPY fluorophores to cell and tissue imaging.

BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophores are widely used in bioimaging to label proteins, lipids and nucleotides, but in spite of their attractive optical properties they tend to be prone to self-quenching because of their notably small Stokes shift. Herein, we compare two BODIPY compounds from a recently developed family of naphthyridine substituted BODIPY derivatives, one a visible emitting derivative (BODIPY-VIS) and one a near-infrared emitting fluorophore with a Stokes shift of approximately 165 nm as contrast reagents for live mammalian cells and murine brain tissue. The compounds were rendered water soluble by their conjugation to polyethylene glycol (PEG). Both PEGylated compounds exhibited good cell uptake compared with their parent compounds and confocal fluorescence microscopy revealed all dyes explored to be nuclear excluding, localizing predominantly within the lipophilic organelles; the endoplasmic reticulum and mitochondria. Cytotoxicity studies revealed that these BODIPY derivatives are modestly cytotoxic at concentrations exceeding 10 µM where they induce apoptosis and necrosis. Although the quantum yield of emission of the visible emitting fluorophore was over an order of magnitude greater than the Mega-Stokes shifted probe, the latter showed considerably reduced tendency to self quench and less interference from autofluorescence. The near-infrared probe also showed good penetrability and staining in live tissue samples. In the latter case similar tendency to exclude the nucleus and to localize in the mitochondria and endoplasmic reticulum was observed as in live cells. This to our knowledge is the first demonstration of such a Mega-Stokes BODIPY probe applied to cell and tissue imaging.

Synthesis, tailoring and characterization of silica nanoparticles containing a highly stable ruthenium complex.

This paper describes the synthesis and characterization of sol-gel silica nanoparticles (NPs) derived from tetraethoxysilane (TEOS) and from tetraethoxysilane and methyltriethoxysilane (TEOS-MTEOS) in which is encapsulated, an in-house synthesized, stable oxygen-sensitive ruthenium complex, ruthenium (II) (bis-2,2-bipyridyl)-2(4-carboxylphenyl) imidazo[4,5-f][1,10]phenanthroline. These NPs were characterized using dynamic light scattering, transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and Brunauer-Emmett-Teller analysis. The spherical, stable and monodispersed NPs have been prepared using the Stöber method. It was found that the addition of prehydrolyzed MTEOS-based sol prepared in an acidic environment to the reaction mixture containing TEOS NPs synthesized for 6 h produced material with increased porosity when compared to pure silica NPs. Oxygen sensitivity, stability, photobleaching and leaching have been characterized. The hybrid NPs exhibit enhanced O2 sensitivity but a high degree of leaching when compared to pure silica NPs, which have minimum O2 sensitivity and no leaching.

The proton momentum distribution in strongly H-bonded phases of water: a critical test of electrostatic models.

Water is often viewed as a collection of monomers interacting electrostatically with each other. We compare the water proton momentum distributions from recent neutron scattering data with those calculated from two electronic structure-based models. We find that below 500 K these electrostatic models, one based on a multipole expansion, which includes the polarizability of the monomers, are not able to even qualitatively account for the sizable vibrational zero-point contribution to the enthalpy of vaporization. This discrepancy is evidence that the change in the proton well upon solvation cannot be entirely explained by electrostatic effects alone, but requires correlations of the electronic states on the molecules involved in the hydrogen bonds to produce the observed softening of the well.

Proteins fold by subdiffusion of the order parameter.

It is shown that the folding of a C(alpha) model of chymotyprsin inhibitor (CI2) protein cannot be described by either diffusion (Smoluchowski equation, SE) or a normal-diffusion continuous time random walk of a single order parameter under the influence of the thermodynamic force. The reason for these failures is that the order parameter follows subdiffusion. A theory is proposed based on the idea that an ordinary SE holds along a contour representative of the folding pathways, and that displacements along the contour obey a fractal relationship to, and are longer than, those along the reaction coordinate defined by the order parameter. With a new, constraint-free method to determine the order-parameter-dependent diffusion constant, and statistical temperature molecular dynamics (STMD) enhanced sampling of the free energy, the fractal SE theory is completely characterized by short-time simulations, and its predictions are in quantitative agreement with simulated long-time folding dynamics. Thus, the fractal SE may serve as an accelerated algorithm to study the folding of proteins too slow to be simulated directly.

Chemical and photoluminescence properties of purified poly(2-methoxyaniline-5-sulfonic acid) and oligomer.

Both the chemical and the electrochemical synthesis of poly(2-methoxyaniline-5-sulfonate) (PMAS) in aqueous media have been found to give two distinct polymer fractions with molecular weights of approximately 8-10 and 2 kDa, respectively. It is now possible to isolate the pure high molecular weight (HMWT) PMAS and low molecular weight (LMWT) PMAS oligomer and to study their individual and combined photochemistry and redox chemistry. The HMWT PMAS fraction was confirmed to be an emeraldine salt by its characteristic redox and pH switching behavior, in contrast to the oligomeric LMWT PMAS, which was inert under the same conditions. Mixtures of these two fractions exhibit photoluminescence arising from the oligomeric LMWT PMAS fraction. The observed LMWT PMAS emission was modulated by the presence of the conducting HMWT PMAS emeraldine salt via a static resonant energy transfer arising from quenching at 460 nm when excited at 355 nm. The nonlinear fluorophore-quencher behavior suggests that the two PMAS fractions are strongly associated. The behavior fitted the static Perrin quenching model in which the oligomeric LMWT PMAS fluorophore is diffusionally restricted by the presence of HMWT PMAS quencher.

Time correlation function and finite field approaches to the calculation of the fifth order Raman response in liquid xenon.

The fifth order, two-dimensional Raman response in liquid xenon is calculated via a time correlation function (TCF) theory and the numerically exact finite field method. Both employ classical molecular dynamics simulations. The results are shown to be in excellent agreement, suggesting the efficacy of the TCF approach, in which the response function is written approximately in terms of a single classical multitime TCF.

Theoretical investigation of the temperature dependence of the fifth-order Raman response function of fluid and liquid xenon.

The temperature dependence of the fifth-order Raman response function, R(5)(t1,t2), is calculated for fluid xenon by employing a recently developed time-correlation function (TCF) theory. The TCF theory expresses the two-dimensional (2D) Raman quantum response function in terms of a two-time, computationally tractable, classical TCF. The theory was shown to be in excellent agreement with existing exact classical MD calculations for liquid xenon as well as reproducing line shape characteristics predicted by earlier theoretical work. It is applied here to investigate the temperature dependence of the fifth-order Raman response function in fluid xenon. In general, the characteristic line shapes are preserved over the temperature range investigated (for the reduced temperature points T* = 0.5, 1.0, and 2.0); differences in the signal decay times and a large decline in intensity with decreasing temperature (and associated anharmonicity) are observed. In addition, there are some signature features that were not observed in earlier results for T* = 1. The most dramatic difference in line shape is observed for the polarization condition, xxzzxx, that shows a vibrational echo peak. In contrast, the fully polarized signal changes mainly in magnitude.

Applications of a time correlation function theory for the fifth-order Raman response function I: atomic liquids.

Multidimensional spectroscopy has the ability to provide great insight into the complex dynamics and time-resolved structure of liquids. Theoretically describing these experiments requires calculating the nonlinear-response function, which is a combination of quantum-mechanical time correlation functions R5(t1,t2) was expressed with a two-time, computationally tractable, classical TCF. Writing the response function in terms of classical TCFs brings the full power of atomistically detailed molecular dynamics to the problem. In this paper, the new TCF theory is employed to calculate the fifth-order Raman response function for liquid xenon and investigate several of the polarization conditions for which experiments can be performed on an isotropic system. The theory is shown to reproduce line-shape characteristics predicted by earlier theoretical work.

Qualitative features of the two-dimensional Raman spectrum in liquids.

The theory presented earlier [J. Kim and T. Keyes, Phys. Rev. E 66, 051110 (2002)] is analyzed to determine the information available from the two-dimensional Raman spectrum R((5))(t(2),t(1)) in liquids. The known spectra are well represented by the sum of two products of ordinary time correlations predicted by the theory. The shape of R((5)) is related in general to the values of simple same-time averages and concepts amenable to physical intuition. Using standard models for the time correlations entering the theory, specific analytic expressions for the spectrum are obtained depending on two parameters and a time scale, and the behavior of the spectrum is mapped out in the parameter space.

On the breakdown of the Stokes-Einstein law in supercooled liquids.

The wavevector-dependent shear viscosity, eta(k), is evaluated for a range of temperatures in a supercooled binary Lennard-Jones liquid. The mode coupling theory of Keyes and Oppenheim (Phys. Rev. A 1973, 8, 937) expresses the self-diffusion constant, D, in terms of eta(k). Replacing eta(k) with the usual viscosity, eta identical with eta(k = 0), yields the Stokes-Einstein law. It is found that the breakdown of the SE law in this system is well described by keeping the simulated k-dependence. Simply put, bath processes on all length scales (wavevectors) contribute to D, the system is much less viscous at finite k, and thus D exceeds the SE estimate based upon eta. The functional form of eta(k) allows for the estimation of a correlation length that grows with decreasing T.

Tractable theory of nonlinear response and multidimensional nonlinear spectroscopy.

Nonlinear spectroscopy provides insights into dynamics, but the response functions required for its interpretation pose a challenge to theorists. We proposed an approach in which the fifth-order response function [R5( t1, t2)] was expressed as a two-time classical time correlation function (TCF). Here, we present TCF theory results for R5( t1, t2) in liquid xenon. Using a first-order dipole-induced dipole polarizability model, the result is compared to an exact numerical calculation showing remarkable agreement. In addition, R5( t1, t2) is calculated using the exactly solved polarizability model, yielding different results and predicting an echo signal.

On the mechanism of reorientational and structural relaxation in supercooled liquids: the role of border dynamics and cooperativity.

Molecular dynamics simulation and analysis based upon the many-body potential energy landscape (PEL) are employed to characterize single molecule reorientation and structural relaxation, and their interrelation, in deeply supercooled liquid CS(2). The rotational mechanism changes from small-step Debye diffusion to sudden large angle reorientation (SLAR) as the temperature falls below the mode-coupling temperature T(c). The onset of SLAR is explained in terms of the PEL; it is an essential feature of low-T rotational dynamics, along with the related phenomena of dynamic heterogeneity and the bifurcation of slow and fast relaxation processes. A long trajectory in which the system is initially trapped in a low energy local minimum, and eventually escapes, is followed in detail, both on the PEL and in real space. During the trapped period, "return" dynamics occurs, always leading back to the trap. Structural relaxation is identified with irreversible escape to a new trap. These processes lead to weak and strong SLAR, respectively; strong SLAR is a clear signal of structural relaxation. Return dynamics involves small groups of two to four molecules, while a string-like structure composed of all the active groups participates in the escape. It is proposed that, rather than simple, nearly instantaneous, one-dimensional barrier crossings, relaxation involves activation of the system to the complex, multidimensional region on the borders of the basins of attraction of the minima for an extended period.

A time correlation function theory of two-dimensional infrared spectroscopy with applications to liquid water.

A theory describing the third-order response function R((3))(t(1),t(2),t(3)), which is associated with two-dimensional infrared (2DIR) spectroscopy, has been developed. R((3)) can be written as sums and differences of four distinct quantum mechanical dipole (multi)time correlation functions (TCF's), each with the same classical limit; the combination of TCF's has a leading contribution of order variant Planck's over 2pi (3) and thus there is no obvious classical limit that can be written in terms of a TCF. In order to calculate the response function in a form amenable to classical mechanical simulation techniques, it is rewritten approximately in terms of a single classical TCF, B(R)(t(1),t(2),t(3))=micro(j)(t(2)+t(1))micro(i)(t(3)+t(2)+t(1))micro(k)(t(1))micro(l)(0), where the subscripts denote the Cartesian dipole directions. The response function is then given, in the frequency domain, as the Fourier transform of a classical TCF multiplied by frequency factors. This classical expression can then further be quantum corrected to approximate the true response function, although for low frequency spectroscopy no correction is needed. In the classical limit, R((3)) becomes the sum of multidimensional time derivatives of B(R)(t(1),t(2),t(3)). To construct the theory, the response function's four TCF's are rewritten in terms of a single TCF: first, two TCF's are eliminated from R((3)) using frequency domain detailed balance relationships, and next, two more are removed by relating the remaining TCF's to each other within a harmonic oscillator approximation; the theory invokes a harmonic approximation only in relating the TCF's and applications of theory involve fully anharmonic, atomistically detailed molecular dynamics (MD). Writing the response function as a single TCF thus yields a form amenable to calculation using classical MD methods along with a suitable spectroscopic model. To demonstrate the theory, the response function is obtained for liquid water with emphasis on the OH stretching portion of the spectrum. This approach to evaluating R((3)) can easily be applied to chemically interesting systems currently being explored experimentally by 2DIR and to help understand the information content of the emerging multidimensional spectroscopy.

Potential-energy-landscape-based extended van der Waals equation.

The inherent structures (IS) are the local minima of the 3N-dimensional potential energy surface, or landscape, of an N-atom system. Stillinger has given an exact IS formulation of thermodynamics. Here the implications for the equation of state are investigated. It is shown that the van der Waals (vdW) equation, with density-dependent a and b coefficients, holds if the averaged IS energy is close to its high-temperature plateau value. The density-dependence alone significantly enriches the equation of state. Furthermore, an additional "landscape" contribution to the pressure is found at lower T. The resulting extended vdW equation is capable of yielding a waterlike density anomaly, flat isotherms in the coexistence region vs vdW loops, and several other desirable features. The plateau IS energy, the width of the distribution of IS, and T(TOL), the "top of the landscape" temperature at which the plateau is reached, are simulated over a broad reduced density range, 2.0>or=rho>or=0.20, in the Lennard-Jones fluid. Fits to the data yield an explicit equation of state, which is argued to be plausible at high density. Nevertheless, a(rho(c)) and b(rho(c)), where rho(c) is the critical density, are in excellent agreement with the standard values obtained by fitting the vdW equation at the critical point.

Probes of heterogeneity in rotational dynamics: application to supercooled liquid CS2.

The distribution of individual molecular contributions to the second-rank rotational correlation function is introduced and used to construct probes of heterogeneity in rotational dynamics. The ideas are tested in a molecular dynamics simulation of supercooled liquid CS2. Both the quantity of heterogeneity and its lifetime or exchange time tau(ex) increase as the temperature is lowered through the supercooled state, and increase strongly as the mode-coupling temperature T(c) is approached. Crossover from Arrhenius to super-Arrhenius behavior of the rotational relaxation times tau(1) and tau(2) is observed, direct evidence of fragility in CS2. The T dependence of tau(ex) is stronger than that of the rotational times, and it may approach them from below at T(c), although the simulation is then very difficult. A detailed characterization of other aspects of the dynamical crossover is obtained, and the general implications of rotational heterogeneity for supercooled dynamics are discussed.

Generalized Langevin equation approach to higher-order classical response: second-order-response time-resolved Raman experiment in CS2.

A simple, systematic generalized Langevin equation approach for calculating classical nonlinear response functions is formulated and discussed. The two-time Poisson brackets appearing at second and higher order are rendered tractable by a physically motivated approximation. The method is used to calculate the fifth order (second order response) Raman response of liquid CS2. Agreement with simulation is good, but the simplicity of the theoretical expression suggests that the path to obtaining qualitatively new information about liquids with the fifth order experiment is uncertain. Further applications of the basic approach are suggested.

Potential energy landscape and mechanisms of diffusion in liquids.

The mechanism of diffusion in supercooled liquids is investigated from the potential energy landscape point of view, with emphasis on the crossover from high- to low-T dynamics over the range T(A) > or =T > or =T(c). Molecular dynamics simulations with a time dependent mapping to the associated local minimum or inherent structure (IS) are performed on unit-density Lennard-Jones. Dynamical quantities introduced include r2(is)(t), the mean-square displacement (MSD) within a basin of attraction of an IS, R2(t), the MSD of the IS itself, and g(t), the distribution of IS waiting times. The configuration space is treated as a composite of the contributions of cooperative local regions, and a method is given to obtain the physically meaningful g(loc)(t) and mean waiting time tau(loc) from g(t). An understanding of the crossover is obtained in terms of r2(is)(t) and tau(loc). At intermediate T, r2(is)(t) possesses an interval of linear t dependence allowing calculation of an intrabasin diffusion constant D(is). Near T(c), where intrabasin diffusion is well established for t