Time Scale Of Transition Research Articles

CDR L3 Loop Rearrangement Switches Multispecific SPE-7 IgE Antibody From Hapten to Protein Binding.

The monoclonal IgE antibody SPE-7 was originally raised against a 2,4-dinitrophenyl (DNP) target. Through its ability to adopt multiple conformations, the antibody is capable of binding to a diverse range of small haptens and large proteins. The present study examines a dataset of experimentally determined crystal structures of the SPE-7 antibody to gain insight into the mechanisms that contribute to its multispecificity. With the emergence of more and more therapeutic antibodies against a huge repertoire of different targets, our research could be of great interest for future drug development. We are able to discriminate between the different paratope-binding states in the conformational ensembles obtained by enhanced sampling molecular dynamics simulations, and to calculate their transition timescales and state probabilities. Furthermore, we describe the key residues responsible for discriminating between the different binding capacities and identify a tryptophan in a central position of the CDR L3 loop as the residue of greatest interest. The overall dynamics of the paratope appear to be mainly influenced by the CDR L3 and CDR L1 loops.

Developing time-resolved x-ray diffraction diagnostics at the National Ignition Facility (invited).

As part of a program to measure phase transition timescales in materials under dynamic compression, we have designed new x-ray imaging diagnostics to record multiple x-ray diffraction measurements during a single laser-driven experiment. Our design places several ns-gated hybrid CMOS (hCMOS) sensors within a few cm of a laser-driven target. The sensors must be protected from an extremely harsh environment, including debris, electromagnetic pulses, and unconverted laser light. Another key challenge is reducing the x-ray background relative to the faint diffraction signal. Building on the success of our predecessor (Target Diffraction In Situ), we implemented a staged approach to platform development. First, we built a demonstration diagnostic (Gated Diffraction Development Diagnostic) with two hCMOS sensors to confirm we could adequately protect them from the harsh environment and also acquire acceptable diffraction data. This allowed the team to quickly assess the risks and address the most significant challenges. We also collected scientifically useful data during development. Leveraging what we learned, we recently developed a much more ambitious instrument (Flexible Imaging Diffraction Diagnostic for Laser Experiments) that can field up to eight hCMOS sensors in a flexible geometry and participate in back-to-back shots at the National Ignition Facility (NIF). The design also allows for future iterations, such as faster hCMOS sensors and an embedded x-ray streak camera. The enhanced capabilities of the new instrument required a much more complex design, and the unexpected issues encountered on the first few shots at NIF remind us that complexity has consequences. Our progress in addressing these challenges is described herein, as is our current focus on improving data quality by reducing x-ray background and quantifying the uncertainties of our diffraction measurements.

B1-B2 transition in shock-compressed MgO

Magnesium oxide (MgO) is a major component of the Earth’s mantle and is expected to play a similar role in the mantles of large rocky exoplanets. At extreme pressures, MgO transitions from the NaCl B 1 crystal structure to a CsCl B 2 structure, which may have implications for exoplanetary deep mantle dynamics. In this study, we constrain the phase diagram of MgO with laser-compression along the shock Hugoniot, with simultaneous measurements of crystal structure, density, pressure, and temperature. We identify the B 1 to B 2 phase transition between 397 and 425 gigapascal (around 9700 kelvin), in agreement with recent theory that accounts for phonon anharmonicity. From 425 to 493 gigapascal, we observe a mixed-phase region of B1 and B2 coexistence. The transformation follows the Watanabe-Tokonami-Morimoto mechanism. Our data are consistent with B 2-liquid coexistence above 500 gigapascal and complete melting at 634 gigapascal. This study bridges the gap between previous theoretical and experimental studies, providing insights into the timescale of this phase transition.

How nuclear receptors transition between active and inactive forms: An energetic perspective.

Nuclear receptors regulate transcriptional programs in response to the binding of natural and synthetic ligands. These ligands modulate the receptor by inducing dynamic changes in the ligand binding domain that shift the C-terminal helix (H12) between active and inactive conformations. Despite decades of study, many questions persist regarding the nature of the inactive state and how ligands shift receptors between different states. Here, we use molecular dynamics (MD) simulations to investigate the timescale and energetic landscape of the conformational transition between inactive and active forms of progesterone receptor (PR) bound to a partial agonist. We observe that the microsecond timescale is insufficient to observe any transitions; only at millisecond timescales achieved via accelerated MD simulations do we find the inactive PR switches to the active state. Energetic analysis reveals that both active and inactive PR states represent energy minima separated by a barrier that can be traversed. In contrast, little or no transition is observed between active and inactive states when an agonist or antagonist is bound, confirming that ligand identity plays a key role in defining the energy landscape of nuclear receptor conformations.

Transitional circulation patterns from full ice cover to ice-off in a seasonally ice-covered lake

There is consensus that under-ice circulation presents multiple phases through the winter, and that different mechanisms dominate each period. In this work, measurements of temperature, water velocity, conductivity, and dissolved oxygen from Lake Massawippi, Quebec, Canada, obtained during the ice-covered season in 2019, were used to characterize the time scales of different winter regimes and transitions among dominating circulation mechanisms. Lake circulation during this period began with a single-cell convection induced by sediment flux pulses in early winter. The single-cell convection decayed into a brief quiescent period. Radiatively driven convection then formed a convectively mixed layer in late winter. The defined mixed layer and temperature structure provided the necessary conditions for the formation of a potential rotational feature, which briefly formed immediately prior to ice break-up. Ice break-up led to complex hydrodynamics that persisted for nearly 28 days following full ice-off. Dissolved oxygen was directly correlated with the varying circulation features throughout the field campaign. This work provides a quantitative measure to delineate the transitions between under-ice regimes and provides novel insights into the subsequent circulation during and after ice break-up.

Sustaining Quasi De-Sitter Inflation with Bulk Viscosity

The de-Sitter spacetime is a maximally symmetric Lorentzian manifold with constant positive scalar curvature that plays a fundamental role in modern cosmology. Here, we investigate bulk-viscosity-assisted quasi de-Sitter inflation, that is the period of accelerated expansion in the early universe during which −H˙≪H2, with H(t) being the Hubble expansion rate. We do so in the framework of a causal theory of relativistic hydrodynamics, which takes into account non-equilibrium effects associated with bulk viscosity, which may have been present as the early universe underwent an accelerated expansion. In this framework, the existence of a quasi de-Sitter universe emerges as a natural consequence of the presence of bulk viscosity, without requiring introducing additional scalar fields. As a result, the equation of state, determined by numerically solving the generalized momentum-conservation equation involving bulk viscosity pressure turns out to be time dependent. The transition timescale characterising its departure from an exact de-Sitter phase is intricately related to the magnitude of the bulk viscosity. We examine the properties of the new equation of state, as well as the transition timescale in the presence of bulk viscosity pressure. In addition, we construct a fluid description of inflation and demonstrate that, in the context of the causal formalism, it is equivalent to the scalar field theory of inflation. Our analysis also shows that the slow-roll conditions are realised in the bulk-viscosity-supported model of inflation. Finally, we examine the viability of our model by computing the inflationary observables, namely the spectral index and the tensor-to-scalar ratio of the curvature perturbations, and compare them with a number of different observations, finding good agreement in most cases.

Changing-look Active Galactic Nuclei from the Dark Energy Spectroscopic Instrument. I. Sample from the Early Data

Changing-look active galactic nuclei (CL AGNs) can be generally confirmed by the emergence (turn-on) or disappearance (turn-off) of broad emission lines (BELs), associated with a transient timescale (about 100 ∼ 5000 days) that is much shorter than predicted by traditional accretion disk models. We carry out a systematic CL AGN search by crossmatching the spectra coming from the Dark Energy Spectroscopic Instrument and the Sloan Digital Sky Survey. Following previous studies, we identify CL AGNs based on Hα, Hβ, and Mg ii at z ≤ 0.75 and Mg ii, C iii], and C iv at z > 0.75. We present 56 CL AGNs based on visual inspection and three selection criteria, including 2 Hα, 34 Hβ, 9 Mg ii, 18 C iii], and 1 C iv CL AGN. Eight cases show simultaneous appearances/disappearances of two BELs. We also present 44 CL AGN candidates with significant flux variation of BELs, but remaining strong broad components. In the confirmed CL AGNs, 10 cases show additional CL candidate features for different lines. In this paper, we find: (1) a 24:32 ratio of turn-on to turn-off CL AGNs; (2) an upper-limit transition timescale ranging from 330 to 5762 days in the rest frame; and (3) the majority of CL AGNs follow the bluer-when-brighter trend. Our results greatly increase the current CL census (∼30%) and would be conducive to exploring the underlying physical mechanism.

Robust Detrending of Spatially Correlated Systematics in Kepler Light Curves Using Low-rank Methods

Light curves produced by wide-field exoplanet transit surveys such as CoRoT, Kepler, and the Transiting Exoplanet Survey Satellite are affected by sensor-wide systematic noise, which is correlated both spatiotemporally and with other instrumental parameters such as the photometric magnitude. Robust and effective systematics mitigation is necessary to achieve the level of photometric accuracy required to detect exoplanet transits and to faithfully recover other forms of intrinsic astrophysical variability. We demonstrate the feasibility of a new exploratory algorithm to remove spatially correlated systematic noise and detrend light curves obtained from wide-field transit surveys. This spatial systematics algorithm is data-driven and fits a low-rank linear model for the systematics conditioned on a total-variation spatial constraint. The total-variation constraint models spatial systematic structure across the sensor on a foundational level. The fit is performed using gradient descent applied to, a variable reduced least-squares penalty and a modified form of total-variation prior; both the systematics basis vectors and their weighting coefficients are iteratively varied. The algorithm was numerically evaluated against a reference principal component analysis, using both signal injection on a selected Kepler dataset, as well as full simulations within the same Kepler coordinate framework. We develop our algorithm to reduce the overfitting of astrophysical variability over longer signal timescales (days) while performing comparably relative to the reference method for exoplanet transit timescales. The algorithm performance and application are assessed, and future development is outlined.

Elucidating Interfacial Dynamics of Ti-Al Systems Using Molecular Dynamics Simulation and Markov State Modeling.

Due to their remarkable mechanical and chemical properties, Ti-Al-based materials are attracting considerable interest in numerous fields of engineering, such as automotive, aerospace, and defense. With their low density, high strength, and resistance to corrosion and oxidation, these intermetallic alloys and metal-compound composites have found diverse applications. However, additive manufacturing and heat treatment of Ti-Al alloys frequently lead to brittleness and severe formation of defects. The present study delves into the interfacial dynamics of these Ti-Al systems, particularly focusing on the behavior of Ti and Al atoms in the presence of TiAl3 grain boundaries under experimental heat treatment conditions. Using a combination of molecular dynamics and Markov state modeling, we scrutinize the kinetic processes involved in the formation of TiAl3. The molecular dynamics simulation indicates that at the early stage of heat treatment, the predominating process is the diffusion of Al atoms toward the Ti surface through the TiAl3 grain boundaries. Markov state modeling identifies three distinct dynamic states of Al atoms within the Ti/Al mixture that forms during the process, each exhibiting a unique spatial distribution. Using transition time scales as a qualitative measure of the rapidness of the dynamics, it is observed that the Al dynamics is significantly less rapid near the Ti surface compared to the Al surface. Put together, the results offer a comprehensive understanding of the interfacial dynamics and reveal a three-stage diffusion mechanism. The process initiates with the premelting of Al, proceeds with the prevalent diffusion of Al atoms toward the Ti surface, and eventually ceases as the Ti concentration within the mixture progressively increases. The insights gained from this study could contribute significantly to the control and optimization of manufacturing processes for these high-performing Ti-Al-based materials.

Improving Estimation of the Koopman Operator with Kolmogorov-Smirnov Indicator Functions.

It has become common to perform kinetic analysis using approximate Koopman operators that transform high-dimensional timeseries of observables into ranked dynamical modes. The key to the practical success of the approach is the identification of a set of observables that form a good basis on which to expand the slow relaxation modes. Good observables are, however, difficult to identify a priori and suboptimal choices can lead to significant underestimations of characteristic time scales. Leveraging the representation of slow dynamics in terms of Hidden Markov Models (HMM), we propose a simple and computationally efficient clustering procedure to infer surrogate observables that form a good basis for slow modes. We apply the approach to an analytically solvable model system as well as on three protein systems of different complexities. We consistently demonstrate that the inferred indicator functions can significantly improve the estimation of the leading eigenvalues of Koopman operators and correctly identify key states and transition time scales of stochastic systems, even when good observables are not known a priori.

Nonequilibrium Behavior in Isoprene Secondary Organic Aerosol.

Recent studies have shown that instantaneous gas-particle equilibrium partitioning assumptions fail to predict SOA formation, even at high relative humidity (∼85%), and photochemical aging seems to be one driving factor. In this study, we probe the minimum aging time scale required to observe nonequilibrium partitioning of semivolatile organic compounds (SVOCs) between the gas and aerosol phase at ∼50% RH. Seed isoprene SOA is generated by photo-oxidation in the presence of effloresced ammonium sulfate seeds at <1 ppbv NOx, aged photochemically or in the dark for 0.3-6 h, and subsequently exposed to fresh isoprene SVOCs. Our results show that the equilibrium partitioning assumption is accurate for fresh isoprene SOA but breaks down after isoprene SOA has been aged for as short as 20 min even in the dark. Modeling results show that a semisolid SOA phase state is necessary to reproduce the observed particle size distribution evolution. The observed nonequilibrium partitioning behavior and inferred semisolid phase state are corroborated by offline mass spectrometric analysis on the bulk aerosol particles showing the formation of organosulfates and oligomers. The unexpected short time scale for the phase transition within isoprene SOA has important implications for the growth of atmospheric ultrafine particles to climate-relevant sizes.

Energetic and Kinetic Origins of CALB Interfacial Activation Revealed by PaCS-MD/MSM.

The conformational dynamics of Candida antarctica lipase B (CALB) was investigated by molecular dynamics (MD) simulation, parallel cascade selection MD (PaCS-MD), and the Markov state model (MSM) and mainly focused on the lid-opening motion closely related to substrate binding. All-atom MD simulation of CALB was conducted in water and on the interface of water and tricaprylin. CALB initially situated in water and separated by layers of water from the interface is spontaneously adsorbed onto the tricaprylin surface during MD simulation. The opening and closing motions of the lid are simulated by PaCS-MD, and subsequent MSM analysis provided the free-energy landscape and time scale of the conformational transitions among the closed, semiopen, and open states. The closed state is the most stable in the water system, but the stable conformation in the interface system shifts to the semiopen state. These effects could explain the energetics and kinetics origin of the previously reported interfacial activation of CALB. These findings could help expand the application of CALB toward a wide variety of substrates.

Mass Accretion, Spectral, and Photometric Properties of T Tauri Stars in Taurus Based on TESS and LAMOST

We present the analysis of 16 classical T Tauri stars (CTTSs) using LAMOST and TESS data, investigating spectral properties, photometric variations, and mass accretion rates. All 16 stars exhibit emissions in Hα lines, from which the average mass accretion rate of 1.76 × 10−9 M ⊙ yr−1 is derived. Two of the stars, DL Tau and Haro 6-13, show mass accretion bursts simultaneously in TESS, ASAS-SN, and/or the ZTF survey. Based on these observations, we find that the mass accretion rates of DL Tau and Haro 6-13 reach their maxima of 2.5 × 10−8 M ⊙ yr−1 and 2 × 10−10 M ⊙ yr−1, respectively, during the TESS observation. We detect 13 flares among these stars. The flare frequency distribution shows that the CTTSs’ flare activity is not only dominated by strong flares with high energy but also much more active than those of solar-type and young low-mass stars. By comparing the variability classes reported in the literature, we find that the transition timescale between different classes of variability in CTTSs, such as from stochastic (S) to bursting (B) or from quasi-periodic symmetric to quasi-periodic dipping, may range from 1.6 to 4 yr. We observe no significant correlation between inclination and mass accretion rates derived from the emission indicators. This suggests that inner disk properties may be more important than those of outer disks. Finally, we find a relatively significant positive correlation between the asymmetric metric M and the cold disk inclination compared to the literature. A weak negative correlation between the periodicity metric Q value and inclination has also been found.

Two first-order phase transitions in hybrid compact stars: Higher-order multiplet stars, reaction modes, and intermediate conversion speeds

We study compact stars with hybrid equations of state consisting of a nuclear outer region and two nested quark phases, each separated from the lower density phase by a strong first-order phase transition. The stability of these models is determined by calculating their radial oscillation modes with different conversion rates between adjacent phases and hence junction conditions for the modes at the phase separation interface between them. In the case when the timescale of transition is faster than the period of oscillations, we recover the traditional stability criterion implying that $\ensuremath{\partial}M/\ensuremath{\partial}{\ensuremath{\rho}}_{c}&gt;0$ on the stable branch(es), where $M$ is the mass and ${\ensuremath{\rho}}_{c}$ is the central density. In the opposite limit of slow conversion, we find stable stellar multiplets beyond triplets consisting of stars that are stable by the usual criterion plus slow-conversion (denoted by $s$) hybrid stars with $\ensuremath{\partial}M/\ensuremath{\partial}{\ensuremath{\rho}}_{c}&lt;0$ that are stabilized due to an alternative junction condition on the fluid displacement field at the interface reflecting the slow rate of conversion. We also study the properties of the reaction mode, the radial mode that only exists for stars with rapid (abbreviated by $r$) phase transitions, in stars with either two rapid phase transitions or alternating rapid and slow phase transitions for the first time. The implications of alternative junction conditions are also examined, with these conditions generally being found to provide stability properties similar to those for a slow conversion rate.

Analysing ill-conditioned Markov chains.

Discrete state Markov chains in discrete or continuous time are widely used to model phenomena in the social, physical and life sciences. In many cases, the model can feature a large state space, with extreme differences between the fastest and slowest transition timescales. Analysis of such ill-conditioned models is often intractable with finite precision linear algebra techniques. In this contribution, we propose a solution to this problem, namely partial graph transformation, to iteratively eliminate and renormalize states, producing a low-rank Markov chain from an ill-conditioned initial model. We show that the error induced by this procedure can be minimized by retaining both the renormalized nodes that represent metastable superbasins, and those through which reactive pathways concentrate, i.e. the dividing surface in the discrete state space. This procedure typically returns a much lower rank model, where trajectories can be efficiently generated with kinetic path sampling. We apply this approach to an ill-conditioned Markov chain for a model multi-community system, measuring the accuracy by direct comparison with trajectories and transition statistics. This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'.

Ab initio simulation of peak evolutions and beating maps for electronic two-dimensional signals of a polyatomic chromophore.

By employing the doorway-window (DW) on-the-fly simulation protocol, we performed abinitio simulations of peak evolutions and beating maps of electronic two-dimensional (2D) spectra of a polyatomic molecule in the gas phase. As the system under study, we chose pyrazine, which is a paradigmatic example of photodynamics dominated by conical intersections (CIs). From the technical perspective, we demonstrate that the DW protocol is a numerically efficient methodology suitable for simulations of 2D spectra for a wide range of excitation/detection frequencies and population times. From the information content perspective, we show that peak evolutions and beating maps not only reveal timescales of transitions through CIs but also pinpoint the most relevant coupling and tuning modes active at these CIs.

Landau theory-based relaxational modeling of first-order magnetic transition dynamics in magnetocaloric materials

The magnetocaloric effect is often largest within the neighborhood of a first-order phase transition. This effect can be utilized in magnetocaloric refrigeration, which completely eliminates the need for the greenhouse gases utilized in conventional refrigeration. However, such transitions present unique dynamical effects and are accompanied by hysteresis, which can be detrimental for such refrigeration applications. In this work, a Landau theory-based relaxational model is used to study the magnetic hysteresis and dynamics of the first-order magnetic transition of LaFe13−x Si x . Fitting the experimental magnetization data as a function of applied magnetic field under different field sweep rates with this model provided the Landau parameters (A, B, and C) and the kinetic coefficient of the studied material. We demonstrate the tendency of the magnetic hysteresis to increase with the magnetic field sweep rate, underlining the importance of studying and minimizing the magnetic hysteresis in magnetic refrigerants at practical field sweep rates. While evaluating the temperature dependence of the time required for a complete transition to occur, a nonmonotonic behavior and a sharp peak were found for temperatures near the transition temperature. Such peaks occur at the same temperature as the peak of the magnetic entropy change for low fields, whereas for higher fields the two peaks decouple. This information is critical for technological applications (such as refrigerators/heat pumps) as it provides guidelines for the optimization of the magnetic field amplitude in order to reduce the transition timescale and consequently maximize the machine operational frequency and amount of heat that is pumped in/out per second.

Role of Thermodynamics and Dynamics in the Diurnal Cycle, Propagation, and Progression of Convective Storms in the Eastern Flank of the Indian Monsoon Trough

Abstract This study investigates the diurnal cycle, propagation, and progression of convective storms (CSs) on the eastern edge of India’s monsoon trough (MT) using 9 years of S-band radar measurements with satellite and reanalysis datasets. CSs initiate over ocean during midnight–early morning hours and propagate onshore in succeeding hours. CSs exhibit two semidiurnal peaks, one during afternoon hours over inland areas and another during midnight–early morning hours in oceanic/coastal locations. The deep and intense afternoon peak over inland regions is attributed to land surface heating and associated destabilization. The weak and shallower but organized midnight–morning peak and propagation of CSs toward the coast are attributed to the nocturnal land breeze and its interaction with prevailing onshore flow. The observed lead–lag of a few hours in the diurnal cycle of different cumulus modes correspond to the transition of congestus into deep and then, often, into overshooting modes. Moisture budget analysis showed atmospheric regulation of this transition through thermodynamic (congestus moistening) and dynamic processes (vertical advection). Theoretical time scales were invoked to estimate the relative role of vertical advective versus congestus moistening for promoting the afternoon transition from congestus to deeper modes. Comparing the time scales for congestus moistening (18–46 h) and dynamics (3 h) with the actual transition time scales (2–4 h) reveal that congestus moistening is too slow to explain the observed lead–lag in CS modes. Though both thermodynamic and dynamic processes moisten the midlevel prior to deep/overshooting convection, vertical advection is the dominant dynamic process for the observed congestus–deep–overshooting transition. Significance Statement Tropical rainfall is usually linked with convection in the morning and afternoon hours. We look at the basic physical processes that lead to those convective activities peaks. The afternoon peak is linked to maximum heating, resulting in an unstable environment, whereas the morning peak is linked to the interaction of large-scale monsoon flow with a land breeze. Furthermore, daily solar heating visually shows a shallow-to-deep progression of convection. The moist midlevel environment was shown to precede such convective development in a day. The large-scale monsoon flow is a dominant cause of this moistening. The monsoon dynamic flow takes roughly 2–3 h to sufficiently moist shallow storms into deep storms, whereas the local thermodynamic moistening process takes about 18–46 h.

How Good Is the Vibronic Hamiltonian Repetition Approach for Long-Time Nonadiabatic Molecular Dynamics?

Multiple applied studies of slow nonadiabatic processes in nanoscale and condensed matter systems have adopted the "repetition" approximation in which long trajectories for such simulations are obtained by concatenating shorter trajectories, directly available from ab initio calculations, many times. Here, we comprehensively assess this approximation using model Hamiltonians with parameters covering a wide range of regimes. We find that state transition time scales may strongly depend on the length of the repeated data, although the convergence is not monotonic and may be slow. The repetition approach may under- or overestimate the time scales by a factor of ≤7-8, does not directly depend on the dispersion of energy gap and nonadiabatic coupling (NAC) frequencies, but may depend on the magnitude of the NACs. We suggest that the repetition-based nonadiabatic dynamics may be inaccurate in simulations with very small NACs, where intrinsic transition times are on the order of ≥100 ps.

Ocean dynamics and tracer transport over the south pole geysers of Enceladus

ABSTRACT Over the south pole of Enceladus, an icy moon of Saturn, geysers eject water into space in a striped pattern, making Enceladus one of the most attractive destinations in the search for extraterrestrial life. We explore the ocean dynamics and tracer/heat transport associated with geysers as a function of the assumed salinity of the ocean and various core-shell heat partitions and bottom heating patterns. We find that, even if heating is concentrated into a narrow band on the seafloor directly beneath the south pole, the warm fluid becomes quickly mixed with its surroundings due to baroclinic instability. The warming signal beneath the ice is diffuse and insufficient to prevent the geyser from freezing over. Instead, if heating is assumed to be local to the geyser (either generated in the ice due to tidal dissipation or friction or generated in the ocean as water flushes in/out of the geyser slot under tidal forcing), geyser can be sustained. In this case, the upper ocean beneath the ice becomes stably stratified creating a barrier to vertical communication, leading to transit time-scales from the core to the ice shell of hundreds of years in contrast to purported transit time-scales of weeks to months.