Time-dependent Interaction Research Articles

Defining the cross-reactivity between peanut allergens Ara h 2 and Ara h 6 using monoclonal antibodies.

In peanut allergy, Arachis hypogaea 2 (Ara h 2) and Arachis hypogaea 6 (Ara h 6) are two clinically relevant peanut allergens with known structural and sequence homology and demonstrated cross-reactivity. We have previously utilized X-ray crystallography and epitope binning to define the epitopes on Ara h 2. We aimed to quantitatively characterize the cross-reactivity between Ara h 2 and Ara h 6 on a molecular level using human monoclonal antibodies (mAbs) and structural characterization of allergenic epitopes. We utilized mAbs cloned from Ara h 2 positive single B cells isolated from peanut-allergic, oral immunotherapy-treated patients to quantitatively analyze cross-reactivity between recombinant Ara h 2 (rAra h 2) and Ara h 6 (rAra h 6) proteins using biolayer interferometry and indirect inhibitory ELISA. Molecular dynamics simulations assessed time-dependent motions and interactions in the antibody-antigen complexes. Three epitopes-conformational epitopes 1.1 and 3, and the sequential epitope KRELRNL/KRELMNL-are conserved between Ara h 2 and Ara h 6, while two more conformational and three sequential epitopes are not. Overall, mAb affinity was significantly lower to rAra h 6 than it was to rAra h 2. This difference in affinity was primarily due to increased dissociation of the antibodies from rAra h 6, a phenomenon explained by the higher conformational flexibility of the Ara h 6-antibody complexes in comparison to Ara h 2-antibody complexes. Our results further elucidate the cross-reactivity of peanut 2S albumins on a molecular level and support the clinical immunodominance of Ara h 2.

Interactions of drosophila cryptochrome.

In this study, we investigate the intricate regulatory mechanisms underlying the circadian clock in Drosophila, focusing on the light-induced conformational changes in the cryptochrome (DmCry). Upon light exposure, DmCry undergoes conformational changes that prompt its binding to Timeless and Jetlag proteins, initiating a cascade crucial for the starting of a new circadian cycle. DmCry is subsequently degraded, contributing to the desensitization of the resetting mechanism. The transient and short-lived nature of DmCry protein-protein interactions (PPIs), leading to DmCry degradation within an hour of light exposure, presents a challenge for comprehensive exploration. To address this, we employed proximity-dependent biotinylation techniques, combining engineered BioID (TurboID) and APEX (APEX2) enzymes with mass spectrometry. This approach enabled the identification of the invitro DmCry interactome in Drosophila S2 cells, uncovering several novel PPIs associated with DmCry. Validation of these interactions through a novel co-immunoprecipitation technique enhances the reliability of our findings. Importantly, our study suggests the potential of this method to reveal additional circadian clock- or magnetic field-dependent PPIs involving DmCry. This exploration of the DmCry interactome not only advances our understanding of circadian clock regulation but also establishes a versatile framework for future investigations into light- and time-dependent protein interactions in Drosophila.

Effect of methanol and photoinduced surface oxygen vacancies on the charge carrier dynamics in TiO2

The migration of holes in metal-oxide semiconductors such as TiO2 plays a vital role in (photo)catalytic applications. The dynamics of charge carriers under operation conditions can be influenced by both methanol addition and photoinduced surface oxygen vacancies (PI-SOVs). Nevertheless, the existing knowledge of the effect of methanol as a function of PI-SOVs solely concentrates on the chemical reduction process. For this reason, the fundamental understanding of the time-dependent charge carrier-vacancy interactions in the presence of methanol is impaired. Here, we conducted time-resolved atomic force microscopy measurements to quantitatively disclose the effect of methanol adsorption on the dynamics of hole migration in TiO2. Our results show that time constants associated with the migration of charge carriers significantly change due to methanol adsorption. Moreover, the energy landscape of the hole migration barrier was dominated and lowered by PI-SOVs. Our findings contribute to the physics of charge carrier dynamics by enabling the engineering of charge carrier-vacancy interactions.

Compact bright pulse in inhomogeneous and nonlinear medium: Case of the Bose–Einstein Condensate

The extended one-dimensional Gross–Pitaevskii equation which describes the dynamics of localized wave in nonlocal nonlinear media, in particular the Bose–Einstein condensates (BECs) with time-dependent interatomic interactions in a parabolic potential in the presence of feeding or loss of atoms, is investigated. Through analytical methods invoking a modified lens-type transformation, an equivalent nonlocal GP equation with constant coefficients is derived as well as the integrability conditions. In the limit of zero transverse kinetic energy, we show that the nonlocal GP equation exhibits a stationary bright pulse with strictly localized support and with the width independent of the amplitude. However due to the property of conservation of the norm, the BEC amplitude will be a function of both the pulse width and the number of trap atoms. Similarly, the obtained integrability conditions also appear as the conditions under which the compact bright waves describing the BECs can be managed by controlling the parameters of the external potential. Thus, the number of trap atoms can be managed through the functional gain or loss which is not sensitive to the strength of the magnetic trap. It also appears that, in the presence of the nonlocal interaction, the shape of the BEC interpolates between the shape of the compact bright pulse and that of the NLS bright pulse, and the number of condensed atoms participating to the formation of the BEC increases with the strength of the nonlocal interactions.

Analytical soliton solutions for the beta fractional derivative Gross–Pitaevskii system with linear magnetic and time dependent laser interactions

The local conformable beta Atangana derivative will be considered for the introduction of the fractional Gross–Pitaevskii model with conformable derivatives of beta type. Analytical expressions for soliton solutions are constructed by sub-equation method with elliptical functions. The main goal of the current research is to determine the general behavior of the soliton solutions, their dependence on the elliptical parameter and the influence of the fractional order parameter on the time and space scales of the solutions. New entire family of solitons were determined by considering the arising constrains over the parameters of the nonlinear fractional Gross–Pitaevskii system. The analytical expressions for the soliton solutions constructed for the fractional order case reduce to the well known solitons previously reported for hyperbolic and periodic tan-type singular solutions for the integer order limit value, when special cases of the Jacobi elliptic functions are considered. Solitons properties are depicted in 3-D level and 2-D illustrations. The fractional solitons here introduced possess some interesting time evolution behavior observed in the 3-D representations, these time properties are not present in the integer order case and has an important dependency on the fractional parameter of the beta derivative. The solitons here introduced for the nonlinear fractional Gross–Pitaevskii equation will be very useful in future works where additional interactions will be introduced for the study of different Bose–Einstein condensation phenomena, the coupled quasi-one dimensional Gross- Pitaevskii equation or other nonlinear phenomena where non regular oscillations will be involved.

Analytic results for loop-level momentum space Witten diagrams

This paper presents an evaluation of the wave function coefficients for conformally coupled scalars at both one and two-loop levels at leading order in the coupling constant, in momentum space. We take cues from time-dependent interactions in flat spacetime and under suitable approximations, these can also be used to study the wave function coefficients for general cosmologies. We make use of recursion relations developed in [20] to regularize certain bulk-point integrals and express the wave function coefficients in a form that simplifies the loop integrals. We utilize hard-cutoff regularization to regularize the loop integrals and further provide a discussion on their renormalization. Our results can also be analytically continued to obtain answers for transition amplitudes in AdS.

Tailoring light-induced charge transfer and intersystem crossing in FeCO using time-dependent spin-orbit configuration interaction.

Real-time (RT) electronic structure methods provide a natural framework for describing light-matter interactions in arbitrary time-dependent electromagnetic fields (EMF). Optically induced excited state transitions are of particular interest, which require tuned EMF to drive population transfer to and from the specific state(s) of interest. Intersystem crossing, or spin-flip, may be driven through shaped EMF or laser pulses. These transitions can result in long-lived "spin-trapped" excited states, which are especially useful for materials requiring charge separation or protracted excited state lifetimes. Time-dependent configuration interaction (TDCI) is unique among RT methods in that it may be implemented in a basis of eigenstates, allowing for rapid propagation of the time-dependent Schrödinger equation. The recent spin-orbit TDCI (TD-SOCI) enables a real-time description of spin-flip dynamics in an arbitrary EMF and, therefore, provides an ideal framework for rational pulse design. The present study explores the mechanism of multiple spin-flip pathways for a model transition metal complex, FeCO, using shaped pulses designed to drive controlled intersystem crossing and charge transfer. These results show that extremely tunable excited state dynamics can be achieved by considering the dipole transition matrix elements between the states of interest.

Analysis of nonlinear poroviscoelastic flows with discontinuous porosities *

Abstract Existence and uniqueness of solutions is shown for a class of viscoelastic flows in porous media with particular attention to problems with nonsmooth porosities. The considered models are formulated in terms of the time-dependent nonlinear interaction between porosity and effective pressure, which in certain cases leads to porosity waves. In particular, conditions for well-posedness in the presence of initial porosities with jump discontinuities are identified.

Effect of the Oersted field on the dynamics of magnetic drop solitons formed at a nanocontact

The magnon drop soliton is a non-topological structure formed at a nanocontact, and it is referred to as a dynamic soliton since it is stabilized by uniform precession of the magnetization. Because of magnetization precession there is a time dependent interaction between the magnetization and the magnetic field produced by the nanocontact current (referred to as the Oersted field). At a particular instant of precession the Oersted field forces the soliton off-center, but owing to precession this force will average to zero over one precession period. However, when the soliton orbits the nanocontact center at a period equal to the precession period, this force will become constant forcing the soliton off-center. This lowers the Oersted energy with an increase in the soliton orbital kinetic energy. A balance is attained with the soliton undergoing circular orbital motion about the nanocontact, and the orbit radius is determined by minimization of these energies. Previous low frequency approximations are used semi-analytically obtain these energies as well as the orbit radius.

Quantum nonlinear ac transport theory at low frequency

Based on the nonequilibrium Green’s function (NEGF), we develop a quantum nonlinear theory to study time-dependent ac transport properties in the low frequency and nonlinear bias voltage regimes. By expanding NEGF in terms of time to the linear order in Wigner representation, we can explicitly include the time-dependent self-consistent Coulomb interaction induced by external ac bias. Hence this theory automatically satisfies two basic requirements, i.e. current conservation and gauge invariance. Within this theory, the nonlinear ac current can be evaluated at arbitrarily large bias voltages under the low frequency limit. In addition, we obtain the expression of time-dependent current under the wide band limit and derive the relation between the nonlinear electrochemical capacitance and the bias voltage, which are very useful in predicting the dynamical properties of nanoelectronic devices. This quantum theory can be directly combined with density functional theory to investigate time-dependent ac transport from first-principles calculation.

Understanding NFV-Enabled Vehicle Platooning Application: A Dependability View

This paper aims to use analytical modeling technique to quantitatively study the dependability of Vehicle Platooning Application, which consists of Multiple Sub-Services (VPP-MSS) to achieve its functionality. Each sub-service (SS), based on network function virtualization technology, is executed in a container. Both SSes and OSes which SSes run on can suffer from software aging after a long and continuous running, reducing VPP-MSS dependability. Rejuvenation techniques are usually used to combat software aging, but they require the support of backup components. Quantitative study of VPP-MSS dependability enables in-depth understanding of the effectiveness of rejuvenation techniques based on analytical models. In contrast to the existing studies, we develop a semi-Markov process (SMP) model to jointly analyze the impact of rejuvenation technique trigger intervals (RTTIs), backup components' behaviors, time-dependent interactions between various behaviors and the number of active SSes deployed on an OS on the effectiveness of rejuvenation technique. Sensitivity analysis helps identify key parameters for improving the dependability of VPP-MSS. Extensive numerical experiments demonstrate the necessity of considering backup components' behaviors and investigating non-exponentially distributed failure times. We also determine both the optimal RTTI combination and the optimal combination of SSes and OSes, which can maximize VPP-MSS dependability.

Effectiveness of Regular Aerobic Exercise in Improving Vascular Stiffness in Elderly Korean Women.

The purpose of this study was to determine the effects of aerobic exercise on carotid to femoral pulse wave velocity (cf-PWV), cell adhesion molecules (intracellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), endothelial selectin (E-selectin), and oxidized LDL in elderly women aged 70-85 years, and to identify the effect of and correlation with vascular stiffness. Forty participants were recruited and divided into three groups; vascular stiffness (VSG, n = 14), obesity (OG, n = 14), and normal (NG, n = 12). All groups were given a 16-week intervention of aerobic exercise, and the data collected before and after exercise were analyzed using SPSS Ver. 23.0. Two-way repeated-measures ANOVA was used to evaluate between-group and time-dependent interaction effects. One-way ANOVA was used to evaluate between-group variations. In addition, the significance was tested using a post hoc test (Scheffe). The within-group variations by time before and after exercise were examined using a paired t-test, and correlation analysis was performed using Pearson correlation coefficients. Simple regression analysis was performed for variables showing significant differences. The results indicate interaction effects for cf-PWV (p < 0.001), VCAM-1 (p < 0.01), E-selectin (p < 0.05), and oxidized LDL (p < 0.001). The rate of change of cf-PWV was positively correlated with that of VCAM-1 (r = 0.352, p < 0.05) and that of oxidized LDL (r = 0.325, p < 0.05) with statistical significance. To determine the effect of the rate of change of cf-PWV on the rate of change of VCAM-1, the variables were tested, and the coefficient of determination in the regression analysis was 0.124, indicating that 12.4% of the tested variables fit the standard regression line. The variables for the effect of the rate of change of cf-PWV on the rate of change of oxidized LDL were also tested, and the coefficient of determination in the regression analysis was 0.106, indicating that 10.6% of the tested variables fit the standard regression line. Thus, the 16-week regular and consistent aerobic exercise program had significant effects on the cf-PWV, ICAM-1, VCAM-1, E-selectin, and oxidized LDL in elderly Korean women with vascular stiffness, suggesting improvements in vascular stiffness, based on which the intervention is predicted to contribute to the prevention of vascular dysfunction by lowering the risk of cardiovascular disease due to atherosclerosis, as well as having a positive effect in the prevention of impairment of vascular endothelial cells.

Beneficial or harmful: Time-dependent hormesis induced by typical disinfectants and their mixtures with toxicological interaction

Disinfectants and their mixtures can induce hormesis. However, how the mixture hormesis is related to those of components and the interactions in disinfectant mixtures remain unclear. In this paper, the luminescence inhibition toxicities of chlorinated sodium phosphate (CSP), dodecyl dimethyl benzyl ammonium bromide (DOB), dodecyl dimethyl benzyl ammonium chloride (DOC), ethanol (EtOH), glutaraldehyde (GLA), hydrogen peroxide (H2O2), isopropyl alcohol (IPA), n-propanol (NPA), and 20 mixture rays in four mixture systems (EtOH-H2O2, DOB-H2O2, DOC-EtOH, and EtOH-IPA-NPA) containing at least one component showing hormesis to Vibrio qinghaiensis sp.-Q67 (Q67) were determined at 0.25, 3, 6, 9, and 12 h. The synergism-antagonism heatmap based on independent action model (noted as SAHmapIA) was developed to systematically evaluate the interactions in various mixtures. It was shown that five disinfectants (CSP, EtOH, H2O2, NPA, and IPA) and 17 mixture rays exhibited time-dependent hormesis. The hormetic component was responsible for the hormesis of the mixture rays. Most mixture rays showed low- concentration/dose additive action and high-concentration/dose synergism at different time. This study further exemplified the interrelationship between the hormesis in the mixtures and their components and implied the need to pay attention to the time-dependent hormesis and interactions induced by the disinfectants.

Ultrafast internal conversion and photochromism in gas-phase salicylideneaniline.

Salicylideneaniline (SA) is an archetypal system for excited-state intramolecular proton transfer (ESIPT) in non-planar systems. Multiple channels for relaxation involving both the keto and enol forms have been proposed after excitation to S1 with near-UV light. Here, we present transient absorption measurements of hot gas-phase SA, jet-cooled SA, and SA in Ar clusters using cavity-enhanced transient absorption spectroscopy (CE-TAS). Assignment of the spectra is aided by simulated TAS spectra, computed by applying time-dependent complete active space configuration interaction (TD-CASCI) to structures drawn from nonadiabatic molecular dynamics simulations. We find prompt ESIPT in all conditions followed by the rapid generation of the trans keto metastable photochrome state and fluorescent keto state in parallel. Increasing the internal energy increases the photochrome yield and decreases the fluorescent yield and fluorescent state lifetime observed in TAS. In Ar clusters, internal conversion of SA is severely hindered, but the photochrome yield is unchanged. Taken together, these results are consistent with the photochrome being produced via the vibrationally excited keto population after ESIPT.

Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists.

Background: The P2Y12 receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI) symptoms. The unique pharmacological profile of selatogrel (fast, potent, and short-acting) can bridge the time gap between the onset of AMI and first medical care. A clinical Phase 1 study showed a time-dependent pharmacodynamic interaction between selatogrel and loading doses of clopidogrel and prasugrel. As treatment switching is a common clinical practice, the assessment of subsequent switching from a clopidogrel loading dose to the first maintenance dose of oral P2Y12 receptor antagonists is highly relevant. Objectives: Model-based predictions of inhibition of platelet aggregation (IPA) for the drugs triggering pharmacodynamic interactions were to be derived to support clinical guidance on the transition from selatogrel to oral P2Y12 receptor antagonists. Methods: Scenarios with selatogrel 16 mg administration or placebo followed by a clopidogrel loading dose and, in turn, prasugrel or ticagrelor maintenance doses at different times of administration were studied. Population pharmacokinetic/pharmacodynamic modeling and simulations of different treatment scenarios were used to derive quantitative estimates for IPA over time. Results: Following selatogrel/placebo and a clopidogrel loading dose, maintenance treatment with ticagrelor or a prasugrel loading dose followed by maintenance treatment quickly achieved sustained IPA levels above 80%. Prior to maintenance treatment, a short time span from 18 to 24 h was identified where IPA levels were predicted to be lower with selatogrel than with placebo if clopidogrel was administered 12 h after selatogrel or placebo. Predicted IPA levels reached with placebo alone and a clopidogrel loading dose at 4 h were consistently lower than with selatogrel administration, followed by a clopidogrel loading dose at 12 h. If a clopidogrel loading dose is administered at 12 h, selatogrel maintains higher IPA levels up to 16 h. IPA levels are subsequently lower than on the placebo until the administration of the first maintenance dose. Conclusions: Model-based predictions informed the transition from selatogrel subcutaneous administration to oral P2Y12 therapy. The application of modeling techniques illustrates the value of employing pharmacokinetic and pharmacodynamic modeling for the simulation of various clinical scenarios of switching therapies.

Role of Inner Molecular Orbitals in High-Harmonic Generation Spectra of Aligned Uracil.

In this work, we decompose the high-harmonic generation (HHG) signal of aligned gas-phase uracil into single molecular-orbital (MO) contributions. We compute HHG spectra for a pulse linearly polarized perpendicular to the molecular plane, with an intensity of 0.6 and 0.85 × 1014 W/cm2 and a wavelength of 800 nm. We use the real-time time-dependent Configuration Interaction with singles method, coupled to a Gaussian-based representation of the time-dependent wavefunction. The strong-field dynamics is affected by the energy of the ionization/recombination channels and by the coupling between the orbital symmetry and laser polarization. In the configuration studied here, we expect that π-type MOs favorably couple with the incoming pulse and play a substantial role in generating the HHG spectrum. Indeed, we show that HOMO, HOMO - 1, and HOMO - 4, which all are π-like, determine the intensity of harmonic peaks at different energies, while HOMO - 2 and HOMO - 3 provide a smaller contribution. It is worth mentioning that HOMO - 4 produces a stronger signal than that from HOMO - 1, even though the corresponding ionization energy, in an one-electron picture, is around 2.5 eV larger and more than 4 eV larger than the HOMO one.

Construction of chiral capillary electrochromatography microsystems based on Aspergillus sp. CM96.

Novel chiral capillary electrochromatography (CEC) microsystems were constructed based on Aspergillus sp. CM96. As a newly discovered intrinsic characteristic of the cell, cell chirality occupies an essential position in life evolution. Aspergillus sp. CM96 spore (CM96s) was chosen as a proof of concept to develop chiral capillary columns. Interestingly, various types of amino acid (AA) enantiomers were baseline separated under the optimized conditions. Furthermore, the time-dependent chiral interactions between AAs and CM96s were explored in a wider space. Pectinases generated from Aspergillus sp. CM96 fermentation were immobilized onto graphene oxide-functionalized capillary silica monoliths for separating AA enantiomers. Molecular docking simulations were performed to explore chiral separation mechanisms of pectinase for AA enantiomers. These results indicated that Aspergillus sp. CM96-based CEC microsystems have a significant advantage for chiral separation.

DRGEP-based mechanism reduction considering time dependency of reaction rate

Importance of the method to determine interaction coefficient in the DRGEP method is explored by considering the pyrolysis reaction with time variation of temperature. To take into account time dependency, the interaction coefficients were determined using four different methods: the original method and three alternative methods. Two of the three alternative methods use the overall interaction coefficient computed from direct interaction coefficient determined by maximum value of ratio of production rate in each time, and the overall interaction coefficient computed from direct interaction coefficient determined by the averaged value of ratio of production rate in each time, respectively. The other method considers overall interaction coefficient computed from time-dependent direct interaction coefficient. The analytical condition for the mechanism reduction and the assessment of reduction accuracy are the pyrolysis of the gas composed of C2H2, C2H4, and N2 at 1000–1600 K and 0.1 MPa. The concentration of benzene during the simulation by the reduced mechanism was compared with original mechanism. In case of the DRGEP with method, the smallest reduced mechanism with accuracy has 60 species. In contrast, the reduced mechanisms constructed by the DRGEP with the latter two methods of the four accurately predict the concentration with only 45 species. In particular, the method that takes into account the time dependence of the reaction rate was able to describe the behavior in which the formation rate of the target chemical species, benzene, gradually approaches zero near equilibrium, even when the number of chemical species is 40.

The importance of initial states in polariton simulation

Nonadiabatic simulation methods are indispensable tools to investigate the dynamical processes, including the polariton formed by the hybridisation of molecule and photon. The direct product state, say ( ), is a convenient choice to start the simulation, with and denoting the molecular and photon ground state, respectively. Here, by using exact quantum dynamics simulation, we show that the LiF molecule in a cavity can become self-excited if the simulation starts with the direct product state , leading to a finite probability to dissociate. The physical picture behind the product state simulation is that we turn on the light-matter interaction suddenly, which causes the system to occupy the high energy states that are directly coupled with the initial state even though the total energy of the whole system is conserved. Through a time-dependent light-matter interaction model, we show that the self-excited state will disappear if the molecule moves into the cavity more slowly, i.e. adiabatically. Our results and model highlight the importance of the initial state of polariton simulation and the direct product state is unfeasible to be the initial state to investigate the dynamics of polariton, which provides new insights into the theoretical investigation of polariton dynamics.

Charge Migration in HCCI Cations Probed by Strong Field Ionization: Time-Dependent Configuration Interaction and Vibrational Wavepacket Simulations.

Strong field ionization of neutral iodoacetylene (HCCI) can produce a coherent superposition of the X and A cations and results in charge migration between the CC π orbital and the iodine π-type lone pair. This charge migration causes oscillations in the rate of strong field ionization of the cation to the dication that can be monitored using intense few-cycle probe pulses. The dynamics and strong field ionization of the coherent superposition the X and A states of HCCI+ have been modeled by time-dependent configuration interaction (TDCI) simulations. When the nuclei are allowed to move, the electronic wavefunctions need to be multiplied by vibrational wavefunctions. Nuclear motion has been modeled by vibrational packets moving on quadratic approximations to the potential energy surfaces for the X and A states of the cation. The overlap of the vibrational wavepackets decays in about 10-15 fs. Consequently, the oscillations in the strong field ionization decay on the same time scale. A revival of the vibrational overlap and in the oscillations of the strong field ionization is seen at 60-110 fs. TDCI simulations show that the decay and revival of the charge migration can be monitored by strong field ionization with intense 2- and 4-cycle linearly polarized 800 nm pulses. The revival is also seen with 7-cycle pulses.