Large Number Of Independent Measurements Research Articles

Ensemble Simulations and Experimental Free Energy Distributions: Evaluation and Characterization of Isoxazole Amides as SMYD3 Inhibitors.

Optimization of binding affinities for ligands to their target protein is a primary objective in rational drug discovery. Herein, we report on a collaborative study that evaluates various compounds designed to bind to the SET and MYND domain-containing protein 3 (SMYD3). SMYD3 is a histone methyltransferase and plays an important role in transcriptional regulation in cell proliferation, cell cycle, and human carcinogenesis. Experimental measurements using the scintillation proximity assay show that the distributions of binding free energies from a large number of independent measurements exhibit non-normal properties. We use ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling) protocols to predict the binding free energies and to provide a detailed chemical insight into the nature of ligand–protein binding. Our results show that the 1-trajectory ESMACS protocol works well for the set of ligands studied here. Although one unexplained outlier exists, we obtain excellent statistical ranking across the set of compounds from the ESMACS protocol and good agreement between calculations and experiments for the relative binding free energies from the TIES protocol. ESMACS and TIES are again found to be powerful protocols for the accurate comparison of the binding free energies.

Quantum estimation via parametric amplification in circuit-QED arrays

We propose a scheme for quantum estimation by means of parametric amplification in circuit Quantum Electrodynamics. The modulation of a SQUID interrupting a superconducting waveguide transforms an initial thermal two-mode squeezed state in such a way that the new state is sensitive to the features of the parametric amplifier. We find the optimal initial parameters which maximize the Quantum Fisher Information. In order to achieve a large number of independent measurements we propose to use an array of non-interacting resonators. We show that the combination of both large QFI and large number of measurements enables -in principle- the use of this setup for Quantum Metrology applications.

Nucleation of shear bands in amorphous alloys

The initiation and propagation of shear bands is an important mode of localized inhomogeneous deformation that occurs in a wide range of materials. In metallic glasses, shear band development is considered to center on a structural heterogeneity, a shear transformation zone that evolves into a rapidly propagating shear band under a shear stress above a threshold. Deformation by shear bands is a nucleation-controlled process, but the initiation process is unclear. Here we use nanoindentation to probe shear band nucleation during loading by measuring the first pop-in event in the load-depth curve which is demonstrated to be associated with shear band formation. We analyze a large number of independent measurements on four different bulk metallic glasses (BMGs) alloys and reveal the operation of a bimodal distribution of the first pop-in loads that are associated with different shear band nucleation sites that operate at different stress levels below the glass transition temperature, Tg. The nucleation kinetics, the nucleation barriers, and the density for each site type have been determined. The discovery of multiple shear band nucleation sites challenges the current view of nucleation at a single type of site and offers opportunities for controlling the ductility of BMG alloys.

NEW POLARIZATION TECHNIQUES FOR PRECISE CHARACTERIZATION OF SECOND-ORDER THIN FILMS

We present two new techniques with increased precision to determine the second-harmonic susceptibility tensor of thin films. The tensor is associated with the macroscopic structure of such samples but cannot be measured directly. Instead, it must be extracted from experimental results using a theoretical model. The first technique is based on regression analysis of a large number of independent measurements. The second technique relies on the use of two, instead of one, input beams at the fundamental frequency. Both techniques allow for addressing the quality of the theoretical models used to describe the experiment.

Bulk flows of hot plasma in the Jovian magnetosphere: A model of anisotropic fluxes of energetic ions

Since the Ulysses flyby of Jupiter in February 1992, a consistent picture of the bulk flows of hot plasma has yet to be formed. The present study reports a comprehensive analysis of energetic particle anisotropies from the Ulysses mission. We present an empirical model which separates flow from gradient anisotropies. The model employs a multidimensional minimization routine to fit simultaneously 13 free parameters using 98 measurements. The large number of independent measurements is possible because the Ulysses Heliosphere Instrument for Spectra, Composition, and Anisotropy at Low Energy (HI‐SCALE) has nearly full angular coverage at high time resolution and moderately high angular resolution. The model uses the full energy range (∼50–3000 keV) of the low‐energy magnetic spectrometers and also the pure proton channels of the composition aperture on the instrument. We present flow results during the inbound pass of Ulysses in which the radial velocity component shows a persistent radial outflow. The azimuthal component is in the sense of planetary rotation but generally below rigid corotation, and the azimuthal velocity is greater near the plasma current sheet than at higher magnetic latitudes. Outbound, the flows in the high‐latitude duskside magnetosphere inferred from the particle anisotropies indicate, surprisingly, sunward flows opposite to planetary rotation. We find evidence of gradient anisotropies especially near the magnetospheric current sheet on the dayside. We present a picture of the global magnetic field configuration and flows of hot plasma, consistent with our model results, dominated by subcorotation at low latitudes but by sunward flow at high latitudes.

Pulsed neutron sources from measurement of nuclear constants

The neutron laboratories at Soviet institutes have many kinds of intense sources which make it possible to do a large number of independent measurements of cross sections and constants needed to solve scientific and applied problems. It is important that neutron spectrometers be planned and built in time for specializing in different research areas important to practical applications. This will shorten the time from the appearance of a need for a nuclear constant to completion of the corresponding research.

High resolution image estimation in a turbulent environment

The very small temporal and spatial correlation scales of wavefronts at optical frequencies severely limits the angular resolution in the usual telescope focal plane image when viewing through the turbulent atmosphere. Reliable determination of spatial frequencies beyond the nominal atmospheric cut off may still be possible if one takes a large number of independent measurements of the short-term mutual coherence and then averages the results in the proper manner.