Different glassy characteristics are related to either caging or dynamical heterogeneity.

Despite the enormous theoretical and application interests, a fundamental understanding of the glassy dynamics remains elusive. The static properties of glassy and ordinary liquids are similar, but their dynamics are dramatically different. What leads to this difference is the central puzzle of the field. Even the primary defining glassy characteristics, their implications, and if they are related to a single mechanism remain unclear. This lack of clarity is a severe hindrance to theoretical progress. Here, we combine analytical arguments and simulations of various systems in different dimensions and address these questions. Our results suggest that the myriad of glassy features are manifestations of two distinct mechanisms. Particle caging controls the mean, and coexisting slow- and fast-moving regions govern the distribution of particle displacements. All the other glassy characteristics are manifestations of these two mechanisms; thus, the Fickian yet non-Gaussian nature of glassy liquids is not surprising. We discover a crossover, from stretched exponential to a power law, in the behavior of the overlap function. This crossover is prominent in simulation data and forms the basis of our analyses. Our results have crucial implications on how the glassy dynamics data are analyzed, challenge some recent suggestions on the mechanisms governing glassy dynamics, and impose strict constraints that a correct theory of glasses must have.

Two-temperature activity induces liquid-crystal phases inaccessible in equilibrium.

In equilibrium hard-rod fluids, and in effective hard-rod descriptions of anisotropic soft-particle systems, the transition from the isotropic (I) phase to the nematic phase (N) is observed above the rod aspect ratio L/D=3.70 as predicted by Onsager. We examine the fate of this criterion in a molecular dynamics study of a system of soft repulsive spherocylinders rendered active by coupling half the particles to a heat bath at a higher temperature than that imposed on the other half. We show that the system phase-separates and self-organizes into various liquid-crystalline phases that are not observed in equilibrium for the respective aspect ratios. In particular, we find a nematic phase for L/D=3 and a smectic phase for L/D=2 above a critical activity.

Diameter Dependent Melting and Softening of dsDNA Under Cylindrical Confinement.

Carbon nanotubes (CNTs) are considered promising candidates for biomolecular confinement, including DNA encapsulation for gene delivery. Threshold values of diameters have been reported for double-stranded DNA (dsDNA) encapsulation inside CNTs. We have performed all-atom molecular dynamics (MD) simulations of dsDNAs confined inside single-walled CNTs (SWCNTs) at the physiologically relevant temperature of 300 K. We found that the dsDNA can be confined without being denatured only when the diameter of the SWCNT exceeds a threshold value. Below this threshold diameter, the dsDNA gets denatured and melts even at the temperature of 300 K. Our simulations using SWCNTs with chirality indices (20,20) to (30,30) at 300 K found the critical diameter to be 3.25 nm (corresponding to (24,24) chirality). Analyses of the hydrogen bonds (H-bonds), Van der Walls (VdW) energy, and other inter-base interactions show drastic reduction in the number of H-bonds, VdW energy, and electrostatic energies between the bases of dsDNA when it is confined in narrower SWCNTs (up to diameter of 3.12 nm). On the other hand, the higher interaction energy between the dsDNA and the SWCNT surface in narrower SWCNTs assists in the melting of the dsDNA. Electrostatic mapping and hydration status analyses show that the dsDNA is not adequately hydrated and the counter ion distribution is not uniform below the critical diameter of the SWCNT. As properly hydrated counter ions provide stability to the dsDNA, we infer that the inappropriate hydration of counter ions and their non-uniform distribution around the dsDNA cause the melting of the dsDNA inside SWCNTs of diameter below the critical value of 3.25 nm. For confined dsDNAs that do not get denatured, we computed their elastic properties. The persistence length of dsDNA was found to increase by a factor of about two and the torsional stiffness by a factor of 1.5 for confinement inside SWCNTs of diameters up to 3.79 nm, the stretch modulus also following nearly the same trend. Interestingly, for higher diameters of SWCNT, 3.79 nm and above, the dsDNA becomes more flexible, demonstrating that the mechanical properties of the dsDNA under cylindrical confinement depend non-monotonically on the confinement diameter.

Thermodynamics and its correlation with dynamics in a mean-field model and pinned systems: A comparative study using two different methods of entropy calculation.

A recent study introduced a novel mean-field model system where each particle over and above the interaction with its regular neighbors interacts with k extra pseudo-neighbors. Here, we present an extensive study of thermodynamics and its correlation with the dynamics of this system. We surprisingly find that the well-known thermodynamic integration (TI) method of calculating the entropy provides unphysical results. It predicts vanishing of the configurational entropy at temperatures close to the onset temperature of the system and negative values of the configurational entropy at lower temperatures. Interestingly, well below the temperature at which the configurational entropy vanishes, both the collective and the single-particle dynamics of the system show complete relaxation. Negative values of the configurational entropy are unphysical, and complete relaxation when the configurational entropy is zero violates the prediction of the random first-order transition theory (RFOT). However, the entropy calculated using the two-phase thermodynamics (2PT) method remains positive at all temperatures for which we can equilibrate the system, and its values are consistent with RFOT predictions. We find that with an increase in k, the difference in the entropy computed using the two methods increases. A similar effect is also observed for a system where a randomly selected fraction of the particles are pinned in their positions in the equilibrated liquid. We show that the difference in entropy calculated via the 2PT and TI methods increases with pinning density.

Heating leads to liquid-crystal and crystalline order in a two-temperature active fluid of rods.

We report phase separation and liquid-crystal ordering induced by scalar activity in a system of soft repulsive spherocylinders (SRSs) of shape anisotropy L/D=5 using molecular dynamics (MD) simulations. Activity is introduced by increasing the temperature of half of the SRSs (labeled hot) while maintaining the temperature of the other half constant at a lower value (labeled cold). The difference between the two temperatures scaled by the lower temperature provides a measure of the activity. Starting from different equilibrium initial phases, we find that activity leads to segregation of the hot and cold particles. Activity also drives the cold particles through a phase transition to a more ordered state and the hot particles to a state of less order compared to the initial equilibrium state. The cold components of a homogeneous isotropic structure acquire nematic and, at higher activity, crystalline order. Similarly, the cold zone of a nematic initial state undergoes smectic and crystal ordering above a critical value of activity while the hot component turns isotropic. We find that the hot particles occupy a larger volume and exert an extra kinetic pressure, confining, compressing, and provoking an ordering transition of the cold-particle domains.

Effect of carboplatin dose capping on survival in recurrent breast, ovary and head and neck cancers: a single institutional retrospective study.

INTRODUCTION: Carboplatin based regimens are an integral part of chemotherapy regimens for recurrent head and neck cancers (rHNC), triple negative breast cancers (rTNBC) and ovarian cancers (rOC). Dose reduction/capping of carboplatin remains a controversial aspect of such regimens in patients with moderate creatinine clearance (50 ml/min to 125 ml/min), especially in resource limited setting. The authors, therefore, looked into the magnitude of difference in outcome this makes in the above mentioned subsites. METHODS: This single institutional retrospective study was performed with a total of 120 patients divided equally into Group A (patients receiving capped dose) and Group B (patients receiving uncapped dose). Further matching was performed with respect to age, sex, body surface area, weight, and primary malignancy subsite and baseline creatinine clearance. Patients in Group A had received 450 mg (for AUC 6 regimens) and 150 mg (for AUC 2 regimens) of carboplatin while patients in Group B received the actual calculated dose of carboplatin determined by the Calvert formula. Median progression free survival (mPFS) and median overall survival (mOS) were the co-primary outcome measures. RESULTS: At a median follow-up of 24 months, compared to Group A, Group B had a higher mPFS and mOS by 4 months (p < .001) and 5.5 months (p < .001), respectively. Statistically significant difference in outcome favouring Group B extends to all primary tumour subsites, with mPFS difference being 3.1 months (rHNC), 5.1 months (rTNBC) and 4.5 months (rOC) and mOS difference being 4.2 months (rHNC), 3 months (rTNBC) and 5.6 months (rOC). It was also found that capping had a statistically significant detriment in distal failure (p = .042) compared to locoregional failure (p = .842). A higher proportion of hematotoxicity was found in Group B, however, it was not statistically significant and well manageable. CONCLUSIONS: Blatant dose capping of carboplatin should be avoided probably with more caution in patients with distant disease recurrence compared to their counterparts with locoregional failure.

Dielectric Profile and Electromelting of a Monolayer of Water Confined in Graphene Slit Pore.

A monolayer of water confined between two parallel graphene sheets exists in many different phases and exhibits fascinating dielectric properties that have been studied in experiments. In this work, we use molecular dynamics simulations to study how the dielectric properties of a confined monolayer of water is affected by its structure. We consider six of the popular nonpolarizable water models-SPC/E, SPC/Fw, TIP3P, TIP3P_M (modified), TIP4P-2005, and TIP4P-2005f-and find that the in-plane structure of the water molecules at ambient temperature and pressure is strongly dependent on the water model: all the 3-point water models considered here show square ice formation, whereas no such structural ordering is observed for the 4-point water models. This allows us to investigate the role of the in-plane structure of the water monolayer on its dielectric profile. Our simulations show an anomalous perpendicular dielectric constant compared to the bulk, and the models that do not exhibit ice formation show very different dielectric response along the channel width compared to models that exhibit square ice formation. We also demonstrate the occurrence of electromelting of the in-plane ordered water under the application of a perpendicular electric field and find that the critical field for electromelting strongly depends on the water model. Together, we have shown the dependence of confined water properties on the different water structures that it may take when sandwiched between bilayer graphene. These remarkable properties of confined water can be exploited in various nanofluidic devices, artificial ion channels, and molecular sieving.

Dimensionality dependence of the Kauzmann temperature: A case study using bulk and confined water.

The Kauzmann temperature (TK) of a supercooled liquid is defined as the temperature at which the liquid entropy becomes equal to that of the crystal. The excess entropy, the difference between liquid and crystal entropies, is routinely used as a measure of the configurational entropy, whose vanishing signals the thermodynamic glass transition. The existence of the thermodynamic glass transition is a widely studied subject, and of particular recent interest is the role of dimensionality in determining the presence of a glass transition at a finite temperature. The glass transition in water has been investigated intensely and is challenging as the experimental glass transition appears to occur at a temperature where the metastable liquid is strongly prone to crystallization and is not stable. To understand the dimensionality dependence of the Kauzmann temperature in water, we study computationally bulk water (three-dimensions), water confined in the slit pore of the graphene sheet (two-dimensions), and water confined in the pore of the carbon nanotube of chirality (11,11) having a diameter of 14.9 Å (one-dimension), which is the lowest diameter where amorphous water does not always crystallize into nanotube ice in the supercooled region. Using molecular dynamics simulations, we compute the entropy of water in bulk and under reduced dimensional nanoscale confinement to investigate the variation of the Kauzmann temperature with dimension. We obtain a value of TK (133 K) for bulk water in good agreement with experiments [136 K (C. A. Angell, Science 319, 582-587 (2008) and K. Amann-Winkel et al., Proc. Natl. Acad. Sci. U. S. A. 110, 17720-17725 (2013)]. However, for confined water, in two-dimensions and one-dimension, we find that there is no finite temperature Kauzmann point (in other words, the Kauzmann temperature is 0 K). Analysis of the fluidicity factor, a measure of anharmonicity in the oscillation of normal modes, reveals that the Kauzmann temperature can also be computed from the difference in the fluidicity factor between amorphous and ice phases.

Nonequilibrium phase transition in an Ising model without detailed balance.

We study a two-dimensional ferromagnetic Ising model in which spins are updated using modified versions of the Metropolis and Glauber algorithms. These update rules do not obey the detailed balance condition. The steady-state behavior of the model is studied using molecular field theory and Monte Carlo simulations. This model is found to exhibit a nonequilibrium phase transition from a "paramagnetic" state with zero magnetization to a "ferromagnetic" state with nonzero magnetization as the variable that plays the role of temperature in the spin updates is decreased. From detailed Monte Carlo simulations using the modified Metropolis algorithm, we demonstrate explicitly the nonequilibrium nature of the transition and show that it cannot be described as an equilibrium transition with an effective temperature different from the temperature used in the spin updates. The critical exponents that characterize the singular behavior near this continuous phase transition are calculated from finite size scaling of specific heat, magnetization, susceptibility, and correlation length. We find that the values of these exponents are the same (within error bars) as those of the equilibrium Ising model in two dimensions.

Efficacy of Chronomodulated Chemotherapy for Palliation of Hematemesis in Inoperable Gastric Cancer: A Single-Institutional Retrospective Study.

CONTEXT: Aside abdominal discomfort and pain, upper gastrointestinal bleeding (UGIB) significantly disgraces the quality of life (QoL), especially in inoperable gastric cancer patients. Although, in early stages, it is infrequent and often ignored, but in advanced stages, its aggressiveness often deteriorates patient's hemoglobin (Hb) level and performing status. AIM: The aim of this study is to correlate the change in (1) the frequency of episodes of UGIB, (2) its severity in terms of Common Terminology Criteria for Adverse Events (CTCAE) grade for UGIB, and (3) Hb level with the successful completion of successive cycles of palliative chemotherapy where it becomes invariably the only modality to palliate the cancer disease. SETTING AND DESIGN: This single-institutional retrospective observational study included seventy gastric carcinoma patients with a chief complaint of frequent hematemesis. They were divided according to the cause behind inoperability or irresectability: (1) Metastatic disease, (2) locally advanced irresectable disease, (3) uncontrolled comorbidities, (4) poor GC (PGC), and (5) refused to give surgical consent. SUBJECTS AND METHODS: Following baseline evaluation and prechemotherapy workups, patients were subjected to three-weekly chronomodulated modified EOX regimen. Relevant parameters, i.e., (1) average episodes per-week (AEP) score, (2) Hb, and (3) average CTCAE grade value for UGIB were recorded after every cycle. RESULTS: At 12-week follow-up, there was a significant decrease in mean AEP score from baseline (from 2.6691 ± 0.7047 to 1.5033 ± 0.6272) for the entire cohort (P < 0.001). Maximum benefit in terms of mean Hb (increase by 1.0737% above baseline) took place for PGC group (P < 0.001). Mean CTCAE grade value for the entire cohort decreased from baseline by 0.6428, which was statistically significant with a P < 0.001. CONCLUSIONS: PGC group was maximally benefited considering all three parameters. Though surgery defines the mainstay of treatment for gastric carcinoma, yet in inoperable cases, only chronomodulated chemotherapy significantly affects the severity of UGIB and thus may improve QoL.

Universal scaling in active single-file dynamics.

We study the single-file dynamics of three classes of active particles: run-and-tumble particles, active Brownian particles and active Ornstein-Uhlenbeck particles. At high activity values, the particles, interacting via purely repulsive and short-ranged forces, aggregate into several motile and dynamical clusters of comparable size, and do not display bulk phase-segregation. In this dynamical steady-state, we find that the cluster size distribution of these aggregates is a scaled function of the density and activity parameters across the three models of active particles with the same scaling function. The velocity distribution of these motile clusters is non-Gaussian. We show that the effective dynamics of these clusters can explain the observed emergent scaling of the mean-squared displacement of tagged particles for all the three models with identical scaling exponents and functions. Concomitant with the clustering seen at high activities, we observe that the static density correlation function displays rich structures, including multiple peaks that are reminiscent of particle clustering induced by effective attractive interactions, while the dynamical variant shows non-diffusive scaling. Our study reveals a universal scaling behavior in the single-file dynamics of interacting active particles.

Colloidal crystallites under external oscillation.

We study the two-dimensional assemblies of interacting colloidal particles in a loosely focussed optical trap. As the optical confinement is increased, the system becomes ordered and we investigate how these crystallites maintain their order under externally imposed oscillation. For small amplitudes, the crystalline order remains intact and the system behaves like a rigid body as predicted by numerical simulations. However, the rigidity breaks at large amplitudes, which we infer to be caused by the anharmonic component of the confinement potential. These studies are general enough to be applied to other physical systems comprising ordered finite-sized assemblies under external dynamic perturbation.

Extreme active matter at high densities.

We study the remarkable behaviour of dense active matter comprising self-propelled particles at large Péclet numbers, over a range of persistence times, from τp â†’ 0, when the active fluid undergoes a slowing down of density relaxations leading to a glass transition as the active propulsion force f reduces, to τp â†’ ∞, when as f reduces, the fluid jams at a critical point, with stresses along force-chains. For intermediate τp, a decrease in f drives the fluid through an intermittent phase before dynamical arrest at low f. This intermittency is a consequence of periods of jamming followed by bursts of plastic yielding associated with Eshelby deformations. On the other hand, an increase in f leads to an increase in the burst frequency; the correlated plastic events result in large scale vorticity and turbulence. Dense extreme active matter brings together the physics of glass, jamming, plasticity and turbulence, in a new state of driven classical matter.

Aging effects on thermal conductivity of glass-forming liquids.

Thermal conductivity of a model glass-forming system in the liquid and glass states is studied using extensive numerical simulations. We show that near the glass transition temperature, where the structural relaxation time becomes very long, the measured thermal conductivity decreases with increasing age. Second, the thermal conductivity of the disordered solid obtained at low temperatures is found to depend on the cooling rate with which it was prepared. For the cooling rates accessible in simulations, lower cooling rates lead to lower thermal conductivity. Our analysis links this decrease of the thermal conductivity with increased exploration of lower-energy inherent structures of the underlying potential energy landscape. Further, we show that the lowering of conductivity for lower-energy inherent structures is related to the high-frequency harmonic modes associated with the inherent structure being less extended. Possible effects of considering relatively small systems and fast cooling rates in the simulations are discussed.

Complex dynamics of a sheared nematic fluid.

Nonlinearities in constitutive equations of extended objects in shear flow lead to novel phenomena, e.g. 'rheochaos' in solutions of wormlike micelles and 'elastic turbulence' in polymer solutions. Since both phenomena involve anisotropic objects, their contributions to the deviatoric stress are likely to be similar. However, these two fields have evolved rather independently and an attempt at connecting these fields is still lacking. We show that a minimal model in which the anisotropic nature of the constituting objects is taken into account by a nematic alignment tensor field reproduces several statistical features found in rheochaos and elastic turbulence. We numerically analyse the full non-linear hydrodynamic equations of a sheared nematic fluid under shear stress and strain rate controlled situations, incorporating spatial heterogeneity only in the gradient direction. For a certain range of imposed stress and strain rates, this extended dynamical system shows signatures of spatiotemporal chaos and transient shear banding. In the chaotic regime the power spectra of the order parameter stress, velocity fluctuations and the total injected power show power law behavior and the total injected power shows a non-gaussian, skewed probability distribution. These dynamical features bear resemblance to elastic turbulence phenomena observed in polymer solutions. The scaling behavior is independent of the choice of shear rate/stress controlled method.

Scalar activity induced phase separation and liquid-solid transition in a Lennard-Jones system.

We report scalar activity induced phase separation and crystallization in a system of 3-d Lennard-Jones particles taken at state points spanning from the gas to the liquid regime using molecular dynamics simulation (MD). Scalar activity was introduced by increasing the temperature of half of the particles (labeled 'hot') while keeping the temperature of the other half constant at a lower value (labeled 'cold'). The relative temperature difference between the two subsystems is considered as a measure of the activity. From our simulations we observe that the two species tend to phase separate at sufficiently high activity ratio. The extent of separation is quantified by the defined order parameter and the entropy production during this process is determined by employing the two-phase thermodynamic (2PT) model and the standard modified Benedict-Webb-Rubin (MBWR) equation of state for a LJ fluid. We observe that the extent of the phase separation and entropy production increases with the density of the system. From a cluster analysis, we obtain the mean number of clusters ncl, and the mean size of the largest cluster n0 in the system, complementing each other. Bond orientation order parameters reveal that the so formed largest cluster also develops solid-like order consisting of both FCC and HCP packing. The presence of such crystalline order is also supported by a common neighbor analysis.

Phase Transition in Monolayer Water Confined in Janus Nanopore.

The ubiquitous nature of water invariably leads to a variety of physical scenarios that can result in many intriguing properties. We investigate the thermodynamics and associated phase transitions for a water monolayer confined within a quasi-two-dimensional nanopore. An asymmetric nanopore constructed by combining a hydrophilic (hexagonal boron nitride) sheet and a hydrophobic (graphene) sheet leads to an ordered water structure at much higher temperatures compared to a symmetric hydrophobic nanopore consisting of two graphene sheets. The discontinuous change in the thermodynamic quantities, potential energy ( U), and entropy ( S) of confined water molecules computed from the all-atom molecular dynamics simulation trajectories, uncovers a first-order phase transition in the temperature range of T = 320-330 K. Structural analysis reveals that water molecules undergo a disorder-to-order phase transformation in this temperature range with a 4-fold symmetric phase persisting at lower temperatures. Our findings predict a novel confinement system which has the melting transition for monolayer water above the room temperature, and provide a microscopic understanding which will have important implications for other nanofludic systems as well.

Glass Transition in Supercooled Liquids with Medium-Range Crystalline Order.

The origin of the rapid dynamical slowdown in glass forming liquids in the growth of static length scales, possibly associated with identifiable structural ordering, is a much debated issue. Growth of medium range crystalline order (MRCO) has been observed in various model systems to be associated with glassy behavior. Such observations raise the question of whether molecular mechanisms for the glass transition in liquids with and without MRCO are the same. In this study we perform extensive molecular dynamics simulations of a number of glass forming liquids and show that the static and dynamic properties of glasses with MRCO are different from those of other glass forming liquids with no predominant local order. We also resolve an important issue regarding the so-called point-to-set method for determining static length scales, and demonstrate it to be a robust method for determining static correlation lengths in glass formers.

Influence of surface commensurability on the structure and relaxation dynamics of a confined monatomic fluid.

Molecular dynamics simulations are carried out for a single component, monatomic Lennard-Jones fluid confined between two mica surfaces to investigate the structure and relaxation dynamics of the confined fluid as a function of surface separation. Due to the underlying symmetry of the potassium ions on the mica surface, the contact layers prefer to adopt an incommensurate square or rhombic symmetry. The inner layers adopt a symmetry varying between rhombic, triangular, and square, depending on the density and surface separation. When the surface separation is an integral multiple of the particle diameter, distinct layering is observed, whereas jammed layers are formed at intermediate surface separations. This leads to the formation of both commensurate and incommensurate layering with varying intralayer symmetry. The self-intermediate scattering function exhibits a gamut of rich dynamics ranging from a distinct two-step relaxation indicative of glassy dynamics to slow relaxation processes where the correlations do not relax to zero over a microsecond for specific surface separations. An extended ß relaxation is observed for both commensurate and incommensurate layering. Stretched exponential fits are used to obtain the relaxation times for the late α-relaxation regime of the self-intermediate scattering function. In some cases, we also observed dynamic and structural heterogeneities within individual layers. Although a single-component Lennard-Jones fluid does not exhibit a glass transition in the bulk, this study reveals that such a fluid can display, without supercooling, complex relaxation dynamics with signatures of a fluid approaching a glass transition upon confinement at constant temperature.

A random first-order transition theory for an active glass.

How does nonequilibrium activity modify the approach to a glass? This is an important question, since many experiments reveal the near-glassy nature of the cell interior, remodeled by activity. However, different simulations of dense assemblies of active particles, parametrized by a self-propulsion force, [Formula: see text], and persistence time, [Formula: see text], appear to make contradictory predictions about the influence of activity on characteristic features of glass, such as fragility. This calls for a broad conceptual framework to understand active glasses; here, we extend the random first-order transition (RFOT) theory to a dense assembly of self-propelled particles. We compute the active contribution to the configurational entropy through an effective model of a single particle in a caging potential. This simple active extension of RFOT provides excellent quantitative fits to existing simulation results. We find that whereas [Formula: see text] always inhibits glassiness, the effect of [Formula: see text] is more subtle and depends on the microscopic details of activity. In doing so, the theory automatically resolves the apparent contradiction between the simulation models. The theory also makes several testable predictions, which we verify by both existing and new simulation data, and should be viewed as a step toward a more rigorous analytical treatment of active glass.