Experimental Estimates Research Articles

Understanding the Differences of Danusertib's Residence Time in Aurora Kinases A/B: Dissociation Paths and Key Residues Identified using Conventional and Enhanced Molecular Dynamics Simulations.

The accurate experimental estimation of protein-ligand systems' residence time (τ) has become very relevant in drug design projects due to its importance in the last stages of refinement of the drug's pharmacodynamics and pharmacokinetics. It is now well-known that it is not sufficient to estimate the affinity of a protein-drug complex in the thermodynamic equilibrium process in in vitro experiments (closed systems), where the concentrations of the drug and protein remain constant. On the contrary, it is mandatory to consider the conformational dynamics of the system in terms of the binding and unbinding processes between protein and drugs in in vivo experiments (open systems), where their concentrations are in constant flux. This last model has been proven to dictate much of several drugs' pharmacological activities in vivo. At the atomistic level, molecular dynamics simulations can explain why some drugs are more effective than others or unveil the molecular aspects that make some drugs work better in one molecular target. Here, the protein kinases Aurora A/B, complexed with its inhibitor Danusertib, were studied using conventional and enhanced molecular dynamics (MD) simulations to estimate the dissociation paths and, therefore, the computational τ values and their comparison with experimental ones. Using classical molecular dynamics (cMD), three differential residues within the Aurora A/B active site, which seems to play an essential role in the observed experimental Danusertib's residence time against these kinases, were characterized. Then, using WT-MetaD, the relative Danusertib's residence times against Aurora A/B kinases were measured in a nanosecond time scale and were compared to those τ values observed experimentally. In addition, the potential dissociation paths of Danusertib in Aurora A and B were characterized, and differences that might be explained by the differential residues in the enzyme's active sites were found. In perspective, it is expected that this computational protocol can be applied to other protein-ligand complexes to understand, at the molecular level, the differences in residence times and amino acids that may contribute to it.

Quantum Speed Limit for States and Observables of Perturbed Open Systems.

Quantum speed limits provide upper bounds on the rate with which a quantum system can move away from its initial state. Here, we provide a different kind of speed limit, describing the divergence of a perturbed open system from its unperturbed trajectory. In the case of weak coupling, we show that the divergence speed is bounded by the quantum Fisher information under a perturbing Hamiltonian, up to an error which can be estimated from system and bath timescales. We give three applications of our speed limit. First, it enables experimental estimation of quantum Fisher information in the presence of decoherence that is not fully characterized. Second, it implies that large quantum work fluctuations are necessary for a thermal system to be driven quickly out of equilibrium under a quench. Moreover, it can be used to bound the response to perturbations of expectation values of observables in open systems.

Nitrification in a Subterranean Estuary: An Ex Situ and In Situ Method Comparison Determines Nitrate Is Available for Discharge

AbstractSubterranean estuaries (STEs) form in the subsurface where fresh groundwater and seawater meet and mix. Subterranean estuaries support a variety of biogeochemical processes including those transforming nitrogen (N). Groundwater is often enriched with dissolved inorganic nitrogen (DIN), and transformations in the STE determine the fate of that DIN, which may be discharged to coastal waters. Nitrification oxidizes ammonium (NH4+) to nitrate, making DIN available for N removal via denitrification. We measured nitrification at an STE, in Virginia, USA using in situ and ex situ methods including conservative mixing models informed by in situ geochemical profiles, an in situ experiment with 15NH4+ tracer injection, and ex situ sediment slurry incubations with 15NH4+ tracer addition. All methods indicated nitrification in the STE, but the ex situ sediment slurries revealed higher rates than both the in situ tracr experiment and mixing model estimations. Nitrification rates ranged 55.0–183.16 μmol N m−2 d−1 based on mixing models, 94.2–225 μmol N m−2 d−1 in the in situ tracer experiment, and 36.6–109 μmol N m−2 d−1 slurry incubations. The in situ tracer experiment revealed higher rates and spatial variation not captured by the other methods. The geochemical complexity of the STE makes it difficult to replicate in situ conditions with incubations and calculations based on chemical profiles integrate over longer timescales, therefore, in situ approaches may best quantify transformation rates. Our data suggest that STE nitrification produces NO3−, altering the DIN pool discharged to overlying water via submarine groundwater discharge.

Generation of Bessel vortex beams in the subterahertz range using reflecting diffractive optical elements

In this work, we propose a simple method for generating Bessel vortex beams in the subterahertz (subTHz) range with the orbital angular momentum with l = 1 based on reflecting metal diffractive optical elements with a continuous helical microrelief. The elements are fabricated by micromilling in a polished duralumin substrate and by tin casting, and tested using a backward wave oscillator (wavelength λ = 855 µm). When using the micromilled element, Bessel vortex beams are shown to be generated and retain a Bessel intensity profile at a distance of 20–50 mm from the reflecting element, which is in good agreement with the results of numerical simulation. An experimental estimate of the energy efficiency of this element is 63%. When using elements made by tin casting, the vortex beams are generated with a distorted profile due to the presence of residual deformations of tin, which has plasticity. Due to their high conductivity, metallic reflecting elements can be used with high power density sub-THz radiation sources such as free electron lasers and gyrotrons.

Machine learning-aided first-principles calculations of redox potentials

We present a method combining first-principles calculations and machine learning to predict the redox potentials of half-cell reactions on the absolute scale. By applying machine learning force fields for thermodynamic integration from the oxidized to the reduced state, we achieve efficient statistical sampling over a broad phase space. Furthermore, through thermodynamic integration from machine learning force fields to potentials of semi-local functionals, and from semi-local functionals to hybrid functionals using Δ-machine learning, we refine the free energy with high precision step-by-step. Utilizing a hybrid functional that includes 25% exact exchange (PBE0), this method predicts the redox potentials of the three redox couples, Fe3+/Fe2+, Cu2+/Cu+, and Ag2+/Ag+, to be 0.92, 0.26, and 1.99 V, respectively. These predictions are in good agreement with the best experimental estimates (0.77, 0.15, 1.98 V). This work demonstrates that machine-learned surrogate models provide a flexible framework for refining the accuracy of free energy from coarse approximation methods to precise electronic structure calculations, while also facilitating sufficient statistical sampling.

Experimental Estimates of College Coaching on Postsecondary Reenrollment

Abstract College attendance has increased significantly over the last few decades, but dropout rates remain high, with fewer than half of all adults ultimately obtaining a postsecondary credential. This project investigates whether one-on-one college coaching improves college attendance and completion outcomes for former income state aid recipients identified as low- and middle-income who attended college but left prior to earning a degree. We conducted a randomized control trial with approximately 8,000 former students in their early to mid 20s. Half of the participants assigned to the treatment group were offered the opportunity to receive coaching services from InsideTrack, with all communication done remotely via phone or video. Intent-to-treat analyses based on assignment to coaching show no impacts on college enrollment and we can rule out effects larger than a 2 percentage point (5 percent) increase in subsequent Fall enrollment.

An experimental estimation method of diffusion coefficients in ternary and multicomponent systems from a single diffusion profile

Until recently, it was textbook knowledge that the diffusion coefficients could not be estimated in a multi-component system following the widely practised diffusion couple method. The recently proposed constrained diffusion couple method largely solved the problems. The need to produce two intersecting diffusion paths in a multi-component space with very well-controlled compositions of the diffusion couple end members may be tricky in certain situations, depending on the complications of diffusion paths. In this study, we have shown the estimation of all types of diffusion coefficients from a single diffusion profile without neglecting Onsager's cross terms in concentrated ternary Ni-Co-Fe, Fe-rich quaternary Fe-Ni-Co-Cr and concentrated Ni-Co-Fe-Cr-Al quinary alloys. This is applicable in ternary and multicomponent component systems (n≥3) at a stable Kirkendall marker plane position. One can even estimate the impurity diffusion coefficients utilizing the composition profiles at the ends of the diffusion couples following the Hall method, which has been rarely practised in multicomponent systems until now. We have further demonstrated the importance of estimating the tracer and intrinsic diffusion coefficients in a concentrated or multi-principal element alloy in which interdiffusion coefficients can be vague and misleading for understanding the elements' diffusional interactions and relative mobilities. We have also shown the importance of considering the vacancy wind effect in concentrated alloys. The method proposed in this study will help to generate a mobility database with relative ease in various multicomponent systems important for various applications, which was considered impossible until recently.

Membrane Tilt Drives Phase Separation of Adhesion Receptors.

Cell adhesion receptors are transmembrane proteins that bind cells to their environment. These proteins typically cluster into disk-shaped or linear structures. Here, we show that such clustering patterns spontaneously emerge when the receptor senses the membrane deformation gradient, for example, by reaching a lower-energy conformation when the membrane is tilted relative to the underlying binding substrate. Increasing the strength of the membrane gradient-sensing mechanism first yields isolated disk-shaped clusters and then long linear structures. Our theory is coherent with experimental estimates of the parameters, suggesting that a tilt-induced clustering mechanism is relevant in the context of cell adhesion.

Iron dissolution from Patagonian dust in the Southern Ocean: under present and future conditions

Although the input of desert dust as a key source of trace metals in the Southern Ocean (SO) has been previously studied, the dissolution process of metals in surface waters, particularly iron (Fe), remain poorly understood. Given the crucial role of Fe in primary production and the biological carbon pump in the SO, we focused on experimental estimations of Fe dissolution from Patagonian dust, the primary natural dust source in the SO. Our study considered both current and projected future conditions, encompassing sea-surface warming, acidification, increased photosynthetically active radiation, and doubled dust inputs. Through controlled laboratory experiments using filtered SO seawater, conducted over 7 days, we assessed changes in particulate Fe (pFe) concentrations, Fe redox speciation (Fe(II)/Fe(III)), and in the mineralogy of Fe-bearing dust in abiotic condition. The predominant minerals in the dust included quartz and aluminosilicates, with silicon (Si), aluminum (Al), and Fe as the major elements. No significant alterations in the mineralogy and the elemental composition of the dust were recorded during the dissolution experiments, neither under present nor under projected future conditions. The particulate Fe(II)/Fe(III) ratio remained consistently at 0.25 during the experiments, unaffected by changed conditions. Consequently, changes in environmental conditions in the SO would therefore not significantly alter the mineralogy and redox speciation of pFe in the Patagonian dust. On the contrary, pFe exhibited a dissolution rate of 3.8% and 1.6% per day under present and future conditions, respectively. The environmental changes anticipated for 2100 in the SO will likely to result in a decrease in the dissolution rate of pFe. Thus, even though a doubling of dust input by 2100 is anticipated, it will unlikely provide significantly more dissolved Fe (dFe) in seawater in the SO. Consequently, the future intensification of Patagonian dust inputs may not alleviate the Fe limitation in the SO.

Bearings fault diagnosis under variable speed conditions by hypothesis-based FRFT technique

The vibration signals of faulty bearings under non-stationary conditions are inherently multi-component and time-varying, which presents a challenge for effective fault diagnosis. Considering the vibration characteristics of rolling bearings under non-stationary conditions and taking advantage of the Fractional Fourier Transform (FRFT), a novel diagnosis method based on the hypothesis-based FRFT has been proposed to separate the fault components. First, the fault characteristic frequencies (FCFs) are extracted from the time-frequency representation of the vibration signals, and the Vold-Kalman filtering is employed to eliminate the influence of noises and other interference components. Subsequently, the fractional feature model is constructed to obtain speed information by the hypothesis approach, whose central idea is that the rotational frequency (RF)-related frequencies under different fault types are estimated, based on the extracted FCFs and the fault characteristic orders. Finally, fault diagnosis is completed by the RF-related peaks in the final spectrum. The method eliminates the need for rotational speed measurement devices and angular resampling. Simulation and experiment estimation results show that the hypothesis-based FRFT method can accurately locate fault characteristic components of bearings under non-stationary conditions.

Experimental estimation of sample entropy in a semiconductor laser with optical feedback for random number generation

Estimating the entropy rate of physical random number generators with uncertainty is crucial for information security applications. We evaluate the sample entropy of chaotic temporal waveforms generated experimentally by a semiconductor laser with time-delayed optical feedback. We demonstrate random number generation with uncertainty using a quantitative measurement of the entropy rate.

Initiation mechanism of arcing generated in RF capacitively coupled plasma

In our previous study, we established an arcing generation and measurement system and we observed prior light emission before arcing current development. However, we briefly analyzed those light emissions with strong assumptions without detailed experiment evaluations and thus, the investigation of the formation mechanism in the initiation phase with detailed experiment evaluations has yet to be conducted. In this work, we investigated the initiation mechanism of arcing generated on an arcing inducing probe (AIP) in a radio frequency capacitively coupled plasma (CCP) environment. Here, the AIP is an aluminum rod covered by anodized film and its tip edge is partially stripped to localize arcing on this edge. We measured emission light, voltage, and current waveforms induced by arcing. The spatiotemporal image of the emission light revealed that the tip glow is the brightest intensity and has longest lifetime during arcing, meaning that it is the primary process in whole arcing process. The current waveform induced by arcing corresponds to the time evolution of the tip glow and estimations revealed that the electron emission is the predominant component of the current formation. Furthermore, snapshot images with AIPs having enlarged stripping area exhibited that arcing occurs at the boundary between the alnuminum and anodized film (dielectric), where charging of ions from the CCP on the film surface can induce high-electric field. In addition, we found that the energy relaxation length of emitted electrons for collisions with Ar atoms, which are the background gas, is much larger than the tip glow diameter, meaning that the electon-Ar collision cannot maintain tip glow. This result supports additional source of atoms to sustain the tip glow such as the surface evaporation from arcing spot, of which evidence was speculated our previous study. We estimated minimum aluminum vapor density and surface temperature, which is sufficiently high enough to induce surface vaporization. Combining those experiment results and estimations, that are electron emission, high surface temperature, and surface evaporation, we can speculate that the initiation mechanism of arcing near dielectric surface in radio-frequency CCP environment is the thermionic emission and surface evaporation from arcing spot.

Experimental and numerical estimation of wall effect and drag coefficient on hollow frustum settling in annular and non-annular channels

The wall effect and drag coefficient of hollow frustum particles (Tapered hollow cylinders) settling in cylindrical non-annular and annular channels were experimentally investigated. The terminal velocity, V, of the hollow frustum particles is measured by considering flow channels of different diameters filled with various working fluids. The present work deals with the study of drag coefficient for a range of 0.12 ≤ deq/D ≤ 0.44, 0.22 ≤ deq/L ≤ 0.43, and 0.22 ≤ di/do ≤ 0.77. The hollow frustum particle's terminal velocity, V, decreases with increased blockage ratios and di/do ratios. The experiment revealed that the frustum attains a steady-state orientation. The hollow frustum particle is affected by the wall's retardation, which is described by the wall factor. The hollow frustum particle's wall factor (f) depends on the Reynolds number (Re) and blockage ratio. The wall factor increases with increasing Reynolds number up to a certain point called critical Reynolds number, Rec; after that, the wall factor remains constant with increasing Reynolds number. The hollow frustum particles settling in the cylindrical non-annular channel were more subjected to wall effects than those in the annular channel. Simple correlations between the wall factor and the blockage ratio are developed. The current research also focuses on the relationship between Reynolds number (Re) and drag coefficient (CD). The wall effect is considered while estimating the hollow frustum particle's drag coefficient (CD). The numerical estimate of the experimental drag coefficient is made using Ansys- fluent 18.1, and the experimental and numerical results are consistent with each other.

Model-free robust motion control for biological optical microscopy using time-delay estimation with an adaptive RBFNN compensator

The field of large numerical aperture microscopy has witnessed significant advancements in spatial and temporal resolution, as well as improvements in optical microscope imaging quality. However, these advancements have concurrently raised the demand for enhanced precision, extended range, and increased load-bearing capacity in objective motion carrier (OMC). To address this challenge, this study introduces an innovative OMC that employs a ball screw mechanism as its primary driving component. Furthermore, a robust nonlinear motion control strategy has been developed, which integrates fast nonsingular terminal sliding mode, experimental estimation techniques, and adaptive radial basis neural network, to mitigate the impact of nonlinear friction within the ball screw mechanism on motion precision. The stability of the closed-loop control system has been rigorously demonstrated through Lyapunov theory. Compared with other enhanced sliding mode control strategies, the maximum error and root mean square error of this controller are improved by 33% and 34% respectively. The implementation of the novel OMC has enabled the establishment of a high-resolution bio-optical microscope, which has proven its effectiveness in the microscopic imaging of retinal organoids.

PLACKETT-BURMAN DESIGN

This article focuses on Placket t-Burman designs (P-B plans) for experiments, which represent an efficient tool for experimental designs, especially in investigating the influence of a large number of factors. Unlike traditional designs such as full factorial experiments (FFE) and fractional factorial experiments (FrFE), P-B plans allow for the effective processing of experiments with a higher number of factors without the need for an exponential increase in the number of trials. Although P-B plans do not directly enable the analysis of interactions between factors, they are ideal for exploring and analyzing the main effects of factors. The article examines in detail the advantages and disadvantages of P-B plans, including their ability to provide experimental error estimates and their efficiency in screening studies. The orthogonality and balance of P-B plans are emphasized, and their application in practice is illustrated with an example of a manufacturing process influenced by multiple factors. The approach based on P-B plans is shown to be a significant contribution to the field of experimental design, especially in situations where it is necessary to efficiently evaluate the impact of a large number of factors with a limited number of trials.

Advances in the Study of Techniques to Determine the Lithium-Ion Battery’s State of Charge

This study explores the challenges and advances in the estimation of the state of charge (SOC) of lithium-ion batteries (LIBs), which are crucial to optimizing their performance and lifespan. This review focuses on four main techniques of SOC estimation: experimental measurement, modeling approach, data-driven approach, and joint estimation approach, highlighting the limitations and potential inaccuracies of each method. This study suggests a combined approach, incorporating correction parameters and closed-loop feedback, to improve measurement accuracy. It introduces a multi-physics model that considers temperature, charging rate, and aging effects and proposes the integration of models and algorithms for optimal estimation of SOC. This research emphasizes the importance of considering temperature and aging factors in data-driven approaches. It suggests that the fusion of different methods could lead to more accurate SOC predictions, an important area for future research.

Experimental and ab initio derivation of interface stress in nanomultilayered coatings: Application to immiscible Cu/W system with variable in-plane stress

Interface stress is a fundamental descriptor for interphase boundaries and is defined in strict relation to the interface energy. In nanomultilayers with their intrinsically high interface density, the functional properties are dictated by the interface structure, which is governed by the delicate interaction of residual interface and volume stresses. In the present work, experimental estimations of the interface stress in Cu/W NMLs were compared with corresponding theoretical values as calculated using DFT (adopting an incoherent bcc W{110}/fcc Cu{111} interface with variable in-plane strain). The Cu/W interface stress was experimentally tuned monotonically from positive to negative values by changing the residual stress in the W nanolayers. Qualitative agreement between experiment and simulation was achieved, confirming a decrease of the interface stress from the compressive to the tensile regime. The DFT simulations showed that Cu atoms at the strained Cu/W interfaces are displaced along the in-plane and out-of-plane directions in response to the interface stress. Using a preliminary neural network potential for the Cu–W system, specific in-plane crystallographic orientation relationships for the Cu/W interfaces were also tested, which improved quantitative agreement between experiment and theory. Assumptions and limitations in experiments and theory for deriving the interface stress are critically discussed.

Results of the Studies of the Pump and Network Characteristics of the Plant for the Production of Grain Molasses

The article describes the results of an experimental and theoretical estimation of the pressure characteristics of the network of the plant for the production of grain molasses with a centrifugal pump 1SM 65-50-160/2-m. Measuring equipment and conditions for obtaining hydraulic characteristics are presented. For accelerated heating of water to 30C, a cavitator in the form of a cone with petals is proposed. The operating point of the pump has been defined.

A comprehensive study on the theoretical and experimental estimation of magnetocaloric effect and relative cooling power in ferromagnetic nanomaterials

In our study, we employed a phenomenological model to investigate the magnetic properties and magnetocaloric effects in ferromagnetic nanomaterials. Our findings revealed a noteworthy concordance between the model predictions and experimental data, providing a representative illustration. Notably, when examining nanoparticles, the model-based estimation of diverse refrigerant parameters exhibited qualitative agreement with the observed behavior reported in various manganite nanomaterials. These results underscore the potential efficacy of the phenomenological model in characterizing and comprehending magnetocaloric behavior within nanoscale systems.PACS numbers: 75.47.Lx, 73.63.Bd

An integrated 2D/3D numerical methodology to predict the thermal field of electric motors

The present work aims at providing a predictive numerical methodology for the thermal characterization of electric motors. The methodology relies on a 2D-FE simulation for the estimation of the electromagnetic (iron and joule) losses. The latter are then exploited in a 3D-CFD Conjugate Heat Transfer analysis for the evaluation of the thermal field.The CFD model includes both the solid components and the fluid domains. The main novelty of the paper is represented by the copper coil modelling. In fact, copper, air, epoxy resin and enamel are synthetized in a single homogeneous body able to reproduce the thermal behaviour without including the single components, to reduce the computational cost.The methodology is validated against experimental data on a three-phase squirrel-cage induction motor. As for the experimental data (available at three different operating conditions), temperature distributions are measured by thermocouples at the test bench for the validation of the 3D-CFD CHT model. In addition, experimental estimations of the losses are available for the validation of the 2D electromagnetic simulations.The numerical results in terms of motor performance, electromagnetic losses and thermal field are discussed and are proved to be close to the experimental counterparts, for all the investigated conditions.