Local Relaxation Time Research Articles

Different or the same? exploring the physicochemical properties and molecular mobility of celecoxib amorphous forms

The influence of different preparation methods on the physicochemical properties of amorphous solid forms have gained considerable attention, especially with recent publications on pharmaceutical polyamorphism. In the present study, we have investigated the possible occurrence of polyamorphism in the drug celecoxib (CEL) by investigating the thermal behavior, morphology, structure, molecular mobility and physical stability of amorphous CEL obtained by quench-cooling (QC), ball milling (BM) and spray drying (SD). Similar glass transition temperatures but different recrystallization behaviors were observed for CEL-QC, CEL-BM and CEL-SD using modulated differential scanning calorimetry analysis. A correlation between the different recrystallization behaviors of the three CEL amorphous forms and the respective distinct powder morphologies, was also found. Molecular dynamics simulations however, reveal that CEL presents similar molecular conformational distributions when subjected to QC and SD. Moreover, the obtained molecular conformational distributions of CEL are different from the ones found in its crystal structure and also from the ones found in the lowest-energy structure obtained by quantum mechanical calculations. The type and strength of CEL hydrogen bond interactions found in CEL-QC and CEL-SD systems are almost identical, though different from the ones presented in the crystal structure. Pair distribution function analyses and isothermal microcalorimetry show similar local structures and structural relaxation times, respectively, for CEL-QC, CEL-BM and CEL-SD. The present work shows that not only similar physicochemical properties (glass transition temperature, and structural relaxation time), but also similar molecular conformational distributions were observed for all prepared CEL amorphous systems. Hence, despite their different recrystallization behaviors, the three amorphous forms of CEL did not show any signs of polyamorphism.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Volume viscosity of inhomogeneous fluids: a Maxwell relaxation model

Volume viscosity is one of the most important and fundamental parameters in hydrodynamics. It measures the momentum loss caused by a volume deformation rather than shape deformation. So it is closely related to numerous phenomena in fluid dynamics. However, most of the existing related researches focus on the bulk fluids, but there is still a lack of in-depth understanding of the bulk viscosity of inhomogeneous fluids. In this work, a novel theoretical method is proposed for the inhomogeneous volume viscosity in the framework of Maxwell viscoelastic theory. In this proposal, the local relaxation time is calculated by using the viscous and elastic properties of the bulk fluids. Accordingly, the inhomogeneous volume viscosity can be obtained by combining the calculations of the local relaxation time and the local relaxation modulus. It is advantageous in the theoretical sense over the conventional LADM, because it takes into account the underlying correlation much better. On the one hand, the local infinite-frequency modulus is more accurate. On the other hand, by using an appropriate weight function to calculate the weight, the correlation effect can be better considered . As an application, the volume viscosity of the confined Lennard-Jones fluid in slit pore is investigated, and the influences of bulk density, temperature, pore width and adsorption strength are calculated and analyzed. The results indicate that these factors can significantly modulate the volume viscosity of the confined fluid. Specifically, the positive correlation between the volume viscosity and the local density leads to the oscillation of viscosity profile in the pore. Besides, the occurrence of capillary condensation in the cases of lower density and lower temperature makes the inhomogeneous viscosity rather different from that of bulk gaseous phase. Further, this study shows that the inhomogeneous volume viscosity usually increases with temperature decreasing, or with adsorption strength increasing. This is again the result of its dependence on the fluid structure in the pore. Furthermore, the influence of pore width on the inhomogeneous volume viscosity indicates that the excluded volume plays a decisive role. This can be attributed to the fact that it exerts a direct influence on the deformation of the fluid. Moreover, comparison between the volume and shear viscosity is also conducted and analyzed. In general, this study can be beneficial to deepening the understanding of volume viscosity in the confined fluids, and can provide reliable theoretical support for studying related issues in hydrodynamics.

2D capsid formation within an oscillatory energy landscape: orderly self-assembly depends on the interplay between a dynamic potential and intrinsic relaxation times.

Multiple dissipative self-assembly protocols designed to create novel structures or to reduce kinetic traps have recently emerged. Specifically, temporal oscillations of particle interactions have been shown effective at both aims, but investigations thus far have focused on systems of simple colloids or their binary mixtures. In this work, we expand our understanding of the effect of temporally oscillating interactions to a two-dimensional coarse-grained viral capsid-like model that undergoes a self-limited assembly. This model includes multiple intrinsic relaxation times due to the internal structure of the capsid subunits and, under certain interaction regimes, proceeds via a two-step nucleation mechanism. We find that oscillations much faster than the local intrinsic relaxation times can be described via a time averaged inter-particle potential across a wide range of interaction strengths, while oscillations much slower than these relaxation times result in structures that adapt to the attraction strength of the current half-cycle. Interestingly, oscillation periods similar to these relaxation times shift the interaction window over which orderly assembly occurs by enabling error correction during the half-cycles with weaker attractions. Our results provide fundamental insights to non-equilibrium self-assembly on temporally variant energy landscapes.

Fine characterization of the capillary instability of free viscoelastic jets

The experimental approach presented in this article investigates low-velocity small-diameter cylindrical viscoelastic jets. It consists in producing and analyzing sets of jet portion images taken at different positions along the jet axis, i.e., from the nozzle producing the jet down to the spray region. A very significant part of the work was dedicated to develop analyzing tools: a proper orthogonal decomposition to identify the onset of the capillary instability, a procedure to determine the mean jet breakup length and a multi-scale tool to describe the jet local shape and its evolution along the jet axis. Used in a similar previous study, the multi-scale analysis has been extended in the present work. These tools are shown to be well suited to the experimental study conducted here, and in particular to meet the need for statistical analysis that free jets impose. They are applied to study the capillary instability of free jets of dilute polyethylene oxide solutions produced from a micrometer nozzle. The parameters of the study are the molar mass of the polymer and the velocity of the jet. Results on the detection of the capillary instability onset, the jet evolution dynamics towards the Bead On A String (BOAS) pattern, the local extensional relaxation time and the terminal elongational viscosity of the solutions, the bead coalescence mechanism and its influence on the size of the spray drops are obtained. Analysis of these results reveals that the polymers undergo two episodes of mechanical degradation during the process: the first one at injection, the second one during the elasto-capillary regime of the jet breakup. Moreover, the scenario in the literature suggesting a sufficiently relaxed axial tension of the flow for the capillary instability to occur is found to be not always valid. It is also shown that the average size of the drops correlates with the intensity of the bead coalescence mechanism that takes place on the BOAS. These results demonstrate the richness of the adopted approach and in particular of the multi-scale analysis to study the development of a fluid interfacial instability.

Novel methodology for the shear viscosity of confined fluids within the Maxwell viscoelastic regime

Within the framework of Maxwell viscoelastic theory, a novel methodology for the shear viscosity of confined fluids is proposed. In this proposal, the correlation effect is well considered via the accurate calculations of local shear modulus and local relaxation time, which is treated by an unequally-weighted density approximation (uE-WDA). In its application to the confined Lennard-Jones fluid, it is found that both the fluid and the pore parameters can markedly modulate the local viscosity. The results suggest that the competition between the translational and configurational contributions of viscosity plays a decisive role in determining its dependence on temperature and density. Moreover, in the low density and low temperature cases, the occurrence of capillary condensation can dramatically enhance the local viscosity. Furthermore, the variations in pore width and wall potential strength can also result in remarkable modulation of the local viscosity, especially in its value and oscillation amplitude.

Dynamic Electric Field Alignment Determines the Water Rotational Motion around Protein.

Water rotational dynamics in biomolecular solution is crucial to evaluating and controlling biomolecule stability. In this molecular dynamics simulation (MD) study on lysozyme solutions, we present how the exerted internal electric field determines water rotational dynamics. We find that the relaxation time of water rotation is equivalent to that of the reorientation of the exerted overall electric field for every single water molecule, regardless of its translation mode. Namely, water molecular rotation synchronizes with the exerted field reorientation. We also map the reorientation process of the electric field at fixed points relative to protein in the solution, which displays the local hydration dynamics commensurate with the reported time-dependent fluorescence Stokes shift (TDFSS) measurements. Comparing the spatial distribution of local field reorientation relaxation time with that of rotational relaxation time, we further suggest that water rotation dynamics are subject to the reorientation of the local overall field within the hydration layer. While outside the hydration layer, the relaxation time of the local electric field reorientation is short enough (subpicosecond) to assume the δ function, showing the electric force with randomly changing orientation is applied to each water molecule.

Analyzing work zone effects on vehicular flow on an annular freeway with a tunnel

This paper develops a three lane continuum model to analyze the effects of a work zone on vehicular flow on an annular freeway with a tunnel. The model expresses the mandatory lane changing rate just upstream of the work zone in an explicit algebraic form with the relevant random parameter generated from golden section analysis, and describes the discretionary lane changing rate between adjacent lanes with a lane changing time depending on local traffic flow density and relaxation time. It is assumed that the annular freeway has three lanes, a work zone with a length of 0.2 km and lane II completely blocked, an upstream tunnel of 1.5km long, and an initial jam between the tunnel and work zone. The three lane continuum model is applied in vehicular flow simulation with a 3rd order accuracy numerical scheme. Numerical results also indicate that golden section application in the analysis of work zone effects is helpful in obtaining density thresholds of traffic jam formation, the time averaged traffic speed through the tunnel, dependencies of mean travel time, and vehicle fuel consumption on the initial density normalized by jam density. Numerical results reveal that there are two density thresholds of traffic jam formation, if both density thresholds are normalized by traffic jam density, the first threshold relating to the work zone is 0.14, while the second depending on the tunnel is 0.21. In the absence of a work zone, the mean travel time through lane I is slightly longer than that estimated for cases with a work zone. As soon as initial density is above the second threshold, the time averaged speed through the tunnel is 31.91 km/h, which agrees well with published data.

Early Strides in NMR Dynamics Measurements.

The study of protein dynamics using the measurement of relaxation times by NMR was based on a set of studies in the mid-20th century that outlined theories and methods. However, the complexity of protein NMR was such that these simple experiments were not practical for application to proteins. The advent of techniques in the 1980s for isotopic labeling of proteins meant that pulse sequences could now be applied in multidimensional NMR experiments to enable per-residue information about the local relaxation times. One of the earliest advances was published in Biochemistry in 1989. The paper "Backbone dynamics of proteins as studied by 15N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease" by Lewis Kay, Dennis Torchia, and Ad Bax delineated a set of pulse sequences that are used with minor modifications even today. This paper, with others from a limited number of other laboratories, forms the basis for the experimental determination of the backbone dynamics of proteins. The biological insights obtained from such measurements have only increased in the past 30 years. Sometimes, the best and perhaps only way to advance a field is an advancement in the technical capabilities that allows new perspectives to be reached.

Mapping Viscoelastic Properties Using Helical Magnetic Nanopropellers

Artificial micro/nanomachines have been envisioned and demonstrated as potential candidates for targeted drug or gene delivery, cell manipulation, environmental and biological sensing and in lab on chip applications. Here, we have used helical nanomachines to measure the local rheological properties of a viscoelastic media. The position of the helical nanomachine/nanopropeller was controlled precisely using magnetic fields with simultaneous measurements of the mechanical properties of a complex and heterogeneous fluidic environment. We demonstrated that the motion of the helical nanopropeller is extremely sensitive to fluid elasticity and the speed of propulsion of the nanopropeller can be used as a measure of the local elastic relaxation time. Taken together, we report a promising new technique of mapping the rheological properties by helical nanopropellers with very high spatial and temporal resolutions, with performance superior to existing techniques of passive or active microrheology.

Dynamics of water confined in mesopores with variable surface interaction.

We have investigated the dynamics of liquid water confined in mesostructured porous silica (MCM-41) and periodic mesoporous organosilicas (PMOs) by incoherent quasielastic neutron scattering experiments. The effect of tuning the water/surface interaction from hydrophilic to more hydrophobic on the water mobility, while keeping the pore size in the range 3.5 nm-4.1 nm, was assessed from the comparative study of three PMOs comprising different organic bridging units and the purely siliceous MCM-41 case. An extended dynamical range was achieved by combining time-of-flight (IN5B) and backscattering (IN16B) quasielastic neutron spectrometers providing complementary energy resolutions. Liquid water was studied at regularly spaced temperatures ranging from 300 K to 243 K. In all systems, the molecular dynamics could be described consistently by the combination of two independent motions resulting from fast local motion around the average molecule position and the confined translational jump diffusion of its center of mass. All the molecules performed local relaxations, whereas the translational motion of a fraction of molecules was frozen on the experimental timescale. This study provides a comprehensive microscopic view on the dynamics of liquid water confined in mesopores, with distinct surface chemistries, in terms of non-mobile/mobile fraction, self-diffusion coefficient, residence time, confining radius, local relaxation time, and their temperature dependence. Importantly, it demonstrates that the strength of the water/surface interaction determines the long-time tail of the dynamics, which we attributed to the translational diffusion of interfacial molecules, while the water dynamics in the pore center is barely affected by the interface hydrophilicity.

The former companion of hyper-velocity star S5-HVS1

ABSTRACT The hyper-velocity star S5-HVS1, ejected 5 Myr ago from the Galactic Centre at 1800 km s−1, was most likely produced by tidal break-up of a tight binary by the supermassive black hole SgrA*. Taking a Monte Carlo approach, we show that the former companion of S5-HVS1 was likely a main-sequence star between 1.2 and 6 M⊙ and was captured into a highly eccentric orbit with pericentre distance in the range of 1–10 au and semimajor axis about 103 au. We then explore the fate of the captured star. We find that the heat deposited by tidally excited stellar oscillation modes leads to runaway disruption if the pericentre distance is smaller than about $3\rm \, au$. Over the past 5 Myr, its angular momentum has been significantly modified by orbital relaxation, which may stochastically drive the pericentre inwards below $3\rm \, au$ and cause tidal disruption. We find an overall survival probability in the range 5 per cent to 50 per cent, depending on the local relaxation time in the close environment of the captured star, and the initial pericentre at capture. The pericentre distance of the surviving star has migrated to 10–100 au, making it potentially the most extreme member of the S-star cluster. From the ejection rate of S5-HVS1-like stars, we estimate that there may currently be a few stars in such highly eccentric orbits. They should be detectable (typically $K_{\rm s}\lesssim 18.5\,$ mag) by the GRAVITY instrument and by future Extremely Large Telescopes and hence provide an extraordinary probe of the spin of SgrA*.

The microscopic origins of stretched exponential relaxation in two model glass-forming liquids as probed by simulations in the isoconfigurational ensemble.

The origin of stretched exponential relaxation in supercooled glass-forming liquids is one of the central questions regarding the anomalous dynamics of these fluids. The dominant explanation for this phenomenon has long been the proposition that spatial averaging over a heterogeneous distribution of locally exponential relaxation processes leads to stretching. Here, we perform simulations of model polymeric and small-molecule glass-formers in the isoconfigurational ensemble to show that stretching instead emerges from a combination of spatial averaging and locally nonexponential relaxation. The results indicate that localities in the fluid exhibiting faster-than-average relaxation tend to exhibit locally stretched relaxation, whereas slower-than-average relaxing domains exhibit more compressed relaxation. We show that local stretching is predicted by loose local caging, as measured by the Debye-Waller factor, and vice versa. This phenomenology in the local relaxation of in-equilibrium glasses parallels the dynamics of out of equilibrium under-dense and over-dense glasses, which likewise exhibit an asymmetry in their degree of stretching vs compression. On the basis of these results, we hypothesize that local stretching and compression in equilibrium glass-forming liquids results from evolution of particle mobilities over a single local relaxation time, with slower particles tending toward acceleration and vice versa. In addition to providing new insight into the origins of stretched relaxation, these results have implications for the interpretation of stretching exponents as measured via metrologies such as dielectric spectroscopy: measured stretching exponents cannot universally be interpreted as a direct measure of the breadth of an underlying distribution of relaxation times.

Particle dynamics predicts shear rheology of soft particle glasses

Soft particle glasses are amorphous materials made of soft and deformable particles that are jammed above close-packing. They behave like weak solids at rest, but they yield and flow under external mechanical constraints. Although soft particle glasses are widely used in applications, little is known about how the particle softness and microscopic dynamics determine the macroscopic rheology. Here, we use three-dimensional particle dynamic simulations to analyze the dynamical properties of soft particle glasses at different scales. We demonstrate how the dynamics is determined by the persistence time and the magnitude of the fluctuating elastic forces that develop at contact in the flow. The shear-induced diffusion coefficient, the local structural relaxation times, the shear stress, and the normal stress differences are interconnected through simple relationships that allow the prediction of the macroscopic rheology from the microscopic dynamics.

Asymptotic Exponential Law for the Transition Time to Equilibrium of the Metastable Kinetic Ising Model with Vanishing Magnetic Field

We consider a Glauber dynamics associated with the Ising model on a large two-dimensional box with minus boundary conditions and in the limit of a vanishing positive external magnetic field. The volume of this box increases quadratically in the inverse of the magnetic field. We show that at subcritical temperature and for a large class of starting measures, including measures that are supported by configurations with macroscopic plus-spin droplets, the system rapidly relaxes to some metastable equilibrium—with typical configurations made of microscopic plus-phase droplets in a sea of minus spins—before making a transition at an asymptotically exponential random time towards equilibrium—with typical configurations made of microscopic minus-phase droplets in a sea of plus spins inside a large contour that separates this plus phase from the boundary. We get this result by bounding from above the local relaxation times towards metastable and stable equilibria. This makes possible to give a pathwise description of such a transition, to control the asymptotic behaviour of the mixing time in terms of soft capacities and to give estimates of these capacities.

Strong Correlation Between Atomic-Level Pressures and Viscous Shear Relaxations in Liquids

Liquids are ubiquitous, but the atomic origin of viscosity remains unknown because of structural disorder and dynamic complexities. By using molecular dynamics simulation for liquid iron, we find a strong local correlation between the atomic-level pressure and the relaxation of atomic-level shear stress that is directly connected to viscosity. The results show that atomic sites under compression are more unstable against shear than those under tension, which causes fast relaxation in atomic-level shear stress. This result indicates spatial heterogeneities in the local viscosity in a liquid. We also find a temperature-independent relation between the local shear relaxation time and atomic-level volume strain, which suggests a universal structure-dynamics relationship in liquids. To explain our new findings, we discuss the relationships between the atomic-level pressure and various other parameters, such as the atomic-level shear stress, von Mises stress, local coordination number, and mean-squared displacements of atoms.

Local magnetism and spin fluctuation behavior of extremely dilute Fe impurity in Pd-U binary alloys: An experimental and theoretical investigation

We report the magnetic behavior of isolated Fe impurity atoms in Pd1−xUx (0 ≤ x ≤ 0.12) alloys studied through measurements of the local susceptibility (χloc) and spin relaxation time for 54Fe nuclear probe using the time differential perturbed angular distribution (TDPAD) technique. With an increase of the U concentration in Pd-U alloys, the magnetic response of Fe, exhibiting Curie-Weiss type χloc(T), reflects a steady decrease of the giant magnetic moment arising from ferromagnetic polarization of host Pd-4d band electrons. Concomitantly, we find an exponential rise in the spin fluctuation temperature TSF. The experimental observation of U induced suppression of giant magnetic moment of Fe in Pd is supported by ab intio electronic structure calculations based on density functional theory. The results presented here support the idea that sign and strength of spin polarization of host conduction band electrons play a crucial role on the spin fluctuation rate and hence moment stability.

Local versus Global Stretched Mechanical Response in a Supercooled Liquid near the Glass Transition.

Amorphous materials have a rich relaxation spectrum, which is usually described in terms of a hierarchy of relaxation mechanisms. In this work, we investigate the local dynamic modulus spectra in a model glass just above the glass transition temperature by performing a mechanical spectroscopy analysis with molecular dynamics simulations. We find that the spectra, at the local as well as on the global scale, can be well described by the Cole-Davidson formula in the frequency range explored with simulations. Surprisingly, the Cole-Davidson stretching exponent does not change with the size of the local region that is probed. The local relaxation time displays a broad distribution, as expected based on dynamic heterogeneity concepts, but the stretching is obtained independently of this distribution. We find that the size dependence of the local relaxation time and moduli can be well explained by the elastic shoving model.

Exact Results on the First Hitting via Conditional Strong Quasi-Stationary Times and Applications to Metastability

In the setting of non-reversible Markov chains on finite or countable state space, exact results on the distribution of the first hitting time to a given set G are obtained. A new notion of “conditional strong quasi stationary time” is introduced to describe the local relaxation time. This time is defined via a generalization of the strong stationary time. Rarity of the target set G is not required and the initial distribution can be completely general. The results clarify the the role played by the initial distribution on the exponential law; they are used to give a general notion of metastability and to discuss the relation between the exponential distribution of the first hitting time and metastability.

Fluctuating phases and fluctuating relaxation times in glass forming liquids

The presence of fluctuating local relaxation times, τr→(t) has been used for some time as a conceptual tool to describe dynamical heterogeneities in glass-forming systems. However, until now no general method is known to extract the full space and time dependent τr→(t) from experimental or numerical data. Here we report on a new method for determining a local phase field, ϕr→(t)≡∫tdt′τr→(t′) from snapshots {r→(ti)}i=1…M of the positions of the particles in a system, and we apply it to extract ϕr→(t) and τr→(t) from numerical simulations. By studying how this phase field depends on the number of snapshots, we find that it is a well defined quantity. By studying fluctuations of the phase field, we find that they describe heterogeneities well at long distance scales.