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At least 1,693 records · Page 94

SU-F-I-34: How Does Longitudinal Dose Profile Change with Tube Current Distribution in CT?

Purpose: To investigate how longitudinal dose profile D{sub L}(z) in 30 cm-diameter water cylinder change with tube current (mA) distribution and scan length. Methods: A constant and four variable mA distributions from two previous papers [Dixon et al., Med. Phys. 40, 111920 (14pp.) (2013); Zhang et al., Med. Phys. 41, 091911 (9pp.) (2014)] were adopted in three scan lengths of 10, 28.6, and 50 cm, and all mA distributions had the same average mA over scan ranges. Using the symmetry based dose calculation algorithms and the previously published CT dose equilibration data [Li et al., Med. Phys. 40, 031903 (10pp.) (2013); 41, 111910 (5pp.) (2014)], the authors calculated DL(z) on the phantom central and peripheral axes. Kolmogorov-Smirnov (K-S) test was used to compare the lineshapes of two arbitrary distributions. Results: In constant mA scans, D{sub L}(z) was “bell-shaped”. In variable mA scans, D{sub L}(z) approximately followed the mA lineshape, and the K-S distance generally changed with mA distribution. The distance decreased with scan length, and was larger on the central axis than on the peripheral axis. However, the opposite trends were found in the K-S distance between the D{sub L}(z) distributions of constant and variable mA distributions. Conclusion: Radiation dose from TCM scan is best evaluated using the specific tube current distribution. A constant mA based evaluation may lead to inconsistent longitudinal dose profile with that of TCM scan. Their difference in lineshape is larger on the phantom peripheral axis than on the central axis and increases with scan length. This work confirms that radiation dose in CT depends on not only local mA but also the overall mA distribution and scan length. On the other hand, the concept of regional tube current may be useful when scan length is large, tube current peaks near scan range edge, or the target site is superficial.

60 APPLIED LIFE SCIENCES↗

Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti–COVID-19 drug design

Viral papain-like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial substrate library and performed comprehensive activity profiling of SARS-CoV-2 PLpro. On the scaffold of the best hits from positional scanning, we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro. We determined crystal structures of two of these inhibitors in complex with SARS-CoV-2 PLpro that reveals their inhibitory mechanisms and provides a molecular basis for the observed substrate specificity profiles. Last, we demonstrate that SARS-CoV-2 PLpro harbors deISGylating activity similar to SARSCoV-1 PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Together, this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repurposing.

59 BASIC BIOLOGICAL SCIENCES↗

Pharmacological Profiling of a Brugia malayi Muscarinic Acetylcholine Receptor as a Putative Antiparasitic Target

The diversification of anthelmintic targets and mechanisms of action will help ensure the sustainable control of nematode infections in response to the growing threat of drug resistance. G protein-coupled receptors (GPCRs) are established drug targets in human medicine but remain unexploited as anthelmintic substrates despite their important roles in nematode neuromuscular and physiological processes. Bottlenecks in exploring the druggability of parasitic nematode GPCRs include a limited helminth genetic toolkit and difficulties establishing functional heterologous expression. In an effort to address some of these challenges, we profile the function and pharmacology of muscarinic acetylcholine receptors in the human parasite Brugia malayi, an etiological agent of human lymphatic filariasis. While acetylcholine-gated ion channels are intensely studied as targets of existing anthelmintics, comparatively little is known about metabotropic receptor contributions to parasite cholinergic signaling. Using multivariate phenotypic assays in microfilariae and adults, we show that nicotinic and muscarinic compounds disparately affect parasite fitness traits. We identify a putative G protein-linked acetylcholine receptor of B. malayi (Bma-GAR-3) that is highly expressed across intramammalian life stages and adapt spatial RNA in situ hybridization to map receptor transcripts to critical parasite tissues. Tissue-specific expression of Bma-gar-3 in Caenorhabditis elegans (body wall muscle, sensory neurons, and pharynx) enabled receptor deorphanization and pharmacological profiling in a nematode physiological context. Finally, we developed an image-based feeding assay as a reporter of pharyngeal activity to facilitate GPCR screening in parasitized strains. We expect that these receptor characterization approaches and improved knowledge of GARs as putative drug targets will further advance the study of GPCR biology across medically important nematodes.

60 APPLIED LIFE SCIENCES↗

Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles

During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.

59 BASIC BIOLOGICAL SCIENCES↗

X-shaped and Y-shaped Andreev resonance profiles in a superconducting quantum dot

The quasi-bound states of a superconducting quantum dot that is weakly coupled to a normal metal appear as resonances in the Andreev reflection probability, measured via the differential conductance. We study the evolution of these Andreev resonances when an external parameter (such as the magnetic field or gate voltage) is varied, using a random-matrix model for the N × N scattering matrix. We contrast the two ensembles with broken time-reversal symmetry, in the presence or absence of spin-rotation symmetry (class C or D). The poles of the scattering matrix in the complex plane, encoding the center and width of the resonance, are repelled from the imaginary axis in class C. In class D, in contrast, a number ∝ √N of the poles has zero real part. The corresponding Andreev resonances are pinned to the middle of the gap and produce a zero-bias conductance peak that does not split over a range of parameter values (Y-shaped profile), unlike the usual conductance peaks that merge and then immediately split (X-shaped profile)

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Dynamics of straight vortex filaments in a Bose–Einstein condensate with the Gaussian density profile

The dynamics of interacting quantized vortex filaments in a rotating Bose–Einstein condensate existing in the Thomas–Fermi regime at zero temperature and obeying the Gross–Pitaevskii equation has been considered in the hydrodynamic “nonelastic” approximation. A noncanonical Hamilton equation of motion for the macroscopically averaged vorticity has been derived for a smoothly inhomogeneous array of filaments (vortex lattice) taking into account spatial nonuniformity of the equilibrium density of the condensate, which is determined by the trap potential. The minimum of the corresponding Hamiltonian describes the static configuration of the deformed vortex lattice against the preset density background. The condition of minimum can be reduced to a nonlinear second-order partial differential vector equation for which some exact and approximate solutions are obtained. It has been shown that if the condensate density has an anisotropic Gaussian profile, the equation of motion for the averaged vorticity has solutions in the form of a vector exhibiting a nontrivial time dependence, but homogeneous in space. An integral representation has also been obtained for the matrix Green function that determines the nonlocal Hamiltonian of a system of several quantized vortices of an arbitrary shape in a Bose–Einstein condensate with the Gaussian density. In particular, if all filaments are straight and oriented along one of the principal axes of the ellipsoid, we have a finitedimensional reduction that can describe the dynamics of the system of pointlike vortices against an inhomogeneous background. A simple approximate expression is proposed for the 2D Green function with an arbitrary density profile and is compared numerically with the exact result in the Gaussian case. The corresponding approximate equations of motion, describing the long-wavelength dynamics of interacting vortex filaments in condensates with a density depending only on transverse coordinates, have been derived.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Lateral pressure profile in lipid membranes with curvature: Analytical calculation

An analytical expression is obtained for the lateral pressure profile in the hydrophobic part of a lipid bilayer of finite curvature. Calculations are carried out within a microscopic model of a lipid bilayer, according to which the energy of a lipid chain represents the energy of a flexible string of finite thickness and the interaction between lipid chains is considered as a steric (entropic) repulsion. This microscopic model allows one to obtain an expression for the distribution of lateral pressure in membranes with given curvature if one considers the bending of a membrane as a small deviation from a flat conformation and applies perturbation theory in the small parameter L{sub 0}J, where L{sub 0} is the hydrophobic thickness of a monolayer and J is the mean curvature of the lipid bilayer. The resulting pressure profile depends on the microscopic parameters of the lipid chain: the bending modulus of the lipid chain, incompressible area per lipid chain, and the thickness of a flat monolayer. The coefficient of entropic repulsion between lipids is calculated self-consistently. The analytical results obtained for the lateral pressure distribution are in qualitative agreement with molecular dynamic simulations.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

An Optical Differentiator Based on a Three-Layer Structure with a W-Shaped Refractive Index Profile

An optical differentiator based on a three-layer resonant structure with a W-shaped refractive index profile is proposed. The differentiation operation is performed in reflection and is associated with the resonant excitation of an eigenmode of the structure localized in the central layer. The presented results of numerical simulations demonstrate the possibility of spatial differentiation of the transverse profile of an incident optical beam, temporal differentiation of the envelope of an incident optical beam, and simultaneous spatial and temporal differentiation with a high quality. The proposed structure can find applications in designing analog optical computing and optical information processing systems.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Tungsten quasispherical wire loads with a profiled mass

Wire arrays made from micrometer tungsten wires with linear mass profiled along their height are developed for experiments on the generation of X-ray radiation upon pinch compression with a current of ∼3 MA at a pulse duration of ∼100 ns. Wires are imaged with a scanning electron microscope, and their diameter is determined. It is shown that the arrays have such a profile of height distribution of linear mass that allows for compact spherical compression upon current implosion.

36 MATERIALS SCIENCE↗

Simulation of the effective concentration profiles in InGaAs/GaAs heterostructures containing δ-doped layers

InGaAs/GaAs heterostructures containing quantum wells and δ-doped layers are studied theoretically and experimentally. On the basis of the procedure of self-consistently solving the Schrödinger equation and Poisson equation, the differential capacitance and the apparent electron concentration profiles are numerically calculated for structures with different mutual arrangements of the quantum well and the δ layer. The results of the calculations are compared with the result of analyzing the experimental capacitance-voltage characteristics of the structures. The systematic features of the behavior of the apparent concentration profiles and capacitance-voltage characteristics in relation to the geometric properties of the structure, the temperature, and the doping level are established.

36 MATERIALS SCIENCE↗

Study of the distribution profile of iron ions implanted into silicon

Iron ions with energies of 90 and 250 keV and a dose of 10{sup 16} cm{sup –2} are implanted into a silicon single crystal with the (110) orientation. The method of Rutherford backscattering in combination with channeling is used to study the distribution profiles of the introduced impurity and also the profiles of the distribution of radiation-induced defects in the crystal lattice. Experimental data are compared with the results of simulation performed using the TRIM software package. It is shown that, at an energy of 4.6 keV/nucleon, the average projected ranges coincide; however, at an energy of 1.6 keV/nucleon, the difference amounts to 35%. In addition, it is shown that the calculation incorrectly takes into account the dose dependence at energies of 1.6–4.6 keV/nucleon.

36 MATERIALS SCIENCE↗

Сomposition Depth Profiling of the GaAs Native Oxide Irradiated by an Ar{sup +} Ion Beam

The elemental and chemical compositions throughout the thickness of the GaAs native oxide layer slightly irradiated by Ar{sup +} ions have been studied by synchrotron-based photoelectron spectroscopy at different photon energies enabling variation of probing depth. The presence of only two phases was observed: of the gallium oxide Ga{sub 2}O{sub 3} and elementary arsenic As{sup o} generated due to complete decay of arsenic oxides under the ion irradiation. Depth composition profiles were determined nondestructively. Despite inhomogeneous depth distribution, these profiles demonstrated domination (90 at %) of the dielectric Ga{sub 2}O{sub 3} phase virtually throughout all the oxide thickness (~2 nm).

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

IR Spectroscopy for Precision Monitoring of Iron and Chromium Impurity Diffusion Profiles in Zinc Chalcogenides

A technique for precision rapid nondestructive monitoring of the dopant behavior in zinc chalcogenide–based laser media is reported. Results suggest that it is possible to determine the concentration profiles of Fe{sup 2+} and Cr{sup 2+} dopant ions in zinc chalcogenide by IR spectroscopy combined with an IR microscope in the concentration rage 5 × 10{sup 17}–2.5 × 10{sup 20} atoms/cm{sup 3} with a spatial resolution of several micrometers. The diffusion profiles of dopants have been taken for zinc chalcogenide codoped by several impurities.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

A New Limitation of the Depth Resolution in TOF-SIMS Elemental Profiling: the Influence of a Probing Ion Beam

New data concerning the influence of a probing beam of bismuth ions on the depth resolution in elemental depth profiling by secondary ion mass spectrometry (SIMS) have been obtained on a TOF.SIMS-5 system using the principle of two separate ion beams. It is established that the existing criterion of nondestructive character of the probing beam, on which this principle is based, is insufficient. Additional processes must be taken into account so as to formulate a more adequate criterion. A regime of depth profiling is proposed that allows the depth resolution to be improved at low energies of sputtering ions.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

TCP Throughput Profiles Using Measurements over Dedicated Connections

Wide-area data transfers in high-performance computing infrastructures are increasingly being carried over dynamically provisioned dedicated network connections that provide high capacities with no competing traffic. We present extensive TCP throughput measurements and time traces over a suite of physical and emulated 10 Gbps connections with 0-366 ms round-trip times (RTTs). Contrary to the general expectation, they show significant statistical and temporal variations, in addition to the overall dependencies on the congestion control mechanism, buffer size, and the number of parallel streams. We analyze several throughput profiles that have highly desirable concave regions wherein the throughput decreases slowly with RTTs, in stark contrast to the convex profiles predicted by various TCP analytical models. We present a generic throughput model that abstracts the ramp-up and sustainment phases of TCP flows, which provides insights into qualitative trends observed in measurements across TCP variants: (i) slow-start followed by well-sustained throughput leads to concave regions; (ii) large buffers and multiple parallel streams expand the concave regions in addition to improving the throughput; and (iii) stable throughput dynamics, indicated by a smoother Poincare map and smaller Lyapunov exponents, lead to wider concave regions. These measurements and analytical results together enable us to select a TCP variant and its parameters for a given connection to achieve high throughput with statistical guarantees.

Rao, Nageswara S.↗

Comparing Theoretical Salt Concentration Profiles in a Polymer Electrolyte with Experimental Measurements using Operando Raman Spectroscopy

Concentrated solution theory has furthered our understanding of ion transport in electrolytes. This theory can be used to predict salt concentration profiles under an applied current if the transport properties of the electrolyte (conductivity ( κ ), restricted diffusion coefficient ( D ), and the cation transference number with respect to the solvent velocity ( t + 0 )), and the thermodynamic factor ( T f ) are known. In this work, we provide the first study comparing the predicted salt concentration profiles with measurements based on operando Raman spectroscopy. Concentration polarization is asymmetrical; the increase in salt concentration near the positive electrode is a factor of two greater than the decrease in salt concentration near the negative electrode. We find qualitative agreement between theory and experiment. Further work is needed to resolve the quantitative differences.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Optimal Charging Profiles with Minimal Intercalation-Induced Stresses for Lithium-Ion Batteries Using Reformulated Pseudo 2-Dimensional Models

This paper illustrates the application of dynamic optimization in obtaining the optimal current profile for charging a lithium-ion battery by restricting the intercalation-induced stresses to a pre-determined limit estimated using a pseudo 2-dimensional (P2D). model. This paper focuses on the problem of maximizing the charge stored in a given time while restricting capacity fade due to intercalation-induced stresses. Conventional charging profiles for lithium-ion batteries (e.g., constant current followed by constant voltage or CC-CV) are not derived by considering capacity fade mechanisms, which are not only inefficient in terms of life-time usage of the batteries but are also slower by not taking into account the changing dynamics of the system. (C) The Author(s) 2014. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives 4.0 License (CC BY-NC-ND, http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is not changed in any way and is properly cited. For permission for commercial reuse, please email: oa@electrochem.org. All rights reserved.

Suthar, B↗

Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males

Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders ( n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([ 13 C]glucose and [6,6- 2 H 2 ]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower ( P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA ( P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate ( r = -0.738) and Δγ-glutamylalanine ( r = -0.810), were inversely associated ( P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate ( r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate ( r = -0.738) were inversely associated ( P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.

59 BASIC BIOLOGICAL SCIENCES↗