The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live ...virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant.
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•Antibodies from infected and vaccinated individuals bind to the B.1.351 RBD•Convalescent sera through eight months can neutralize the B.1.351 variant•Serum from vaccinated individuals retains neutralization against the B.1.351 variant
In this study, Edara et al. (2021) report that, despite reduced antibody binding to the B.1.351 RBD, sera from infected (acute and convalescent) and Moderna (mRNA-1273)-vaccinated individuals were still able to neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective humoral immunity may be retained against this variant.
Mass spectrometry (MS) has been instrumental for the analysis of elemental species in numerous situations, such as heavy metal contaminants in the environment and isotope-ratio assays in nuclear ...safeguards. Measurement of elements and their isotopes by MS are some of the most established analytical methods in the field. There have been countless advances in MS, and ionization sources for MS, which have improved detection limits and measurement uncertainties. However, developments in elemental MS typically improve upon preexisting instrumentation and continue to have a number of disadvantages. Some of the disadvantages of these instruments include physical size, high operational costs, excessive power requirements, extensive sample preparation, and complex sample-introduction approaches. Prime examples are the widely used inductively coupled plasma MS (ICP MS) instruments that requires extensive external cooling as well as more than 15 L min-1 of argon and 10 kW of power. Another example includes thermal ionization MS (TIMS) which has lower sample throughput than ICP MS and necessitates extensive sample preparation procedures to attain matrix free samples. However, organizations like the International Atomic Energy Agency (IAEA) that monitors the enrichment of uranium worldwide would also greatly benefit from an inexpensive, rapid and transportable methods for on-site elemental and isotope-ratio analyses.Here, a flowing atmospheric pressure afterglow (FAPA) ionization source was utilized for elemental mass spectrometry. The FAPA is a low power (<12 W) plasma based ionization source that utilizes >2 L min-1 of helium. The FAPA enables direct and rapid analyses of gaseous, liquid and solid samples with minimal sample preparation. Typically, the FAPA has been utilized for desorption/ionization of small organic species while only a few examples have explored the sources capabilities for elemental analyses. A volatile chelating ligand, acetylacetone, was explored to aid desorption/ionization efficiencies of low vapor pressure elements. With this reactive FAPA MS approach it was possible to detect over 20 elemental species from liquid and solid samples.Current research explores the use of the solution-cathode glow discharge (SCGD) as a compact ionization source for elemental and isotope-ratio measurements. Originally, the SCGD was developed as an inexpensive alternative to ICP for optical emission spectroscopy with comparable analytical capabilities. The SCGD consists of a low-power (70 W), direct-current plasma between a metal anode and the surface of a flowing, conductive sample solution with ambient air serving as the discharge gas. The SCGD does not require cooling, nebulization, or external gases for plasma operation, which reduces operational costs and makes the source more amenable to transportable/fieldable analyses.Optimization of the SCGD for elemental analysis has enabled limits-of-detection obtainable in the low parts-per-trillion (pg/mL) for numerous elements. Further method developments have resulted in 235U/238U precisions as low as 0.06% relative standard deviation (RSD) for a 1 part-per-million U-solution of ca. 0.322% 235U abundance within a few minutes of measurement time. For comparison, the precision International Target Value (ITV), published by the IAEA, for natural-abundance uranium (0.3%< 235U< 1%) isotope-ratio assay with MC ICP MS and TIMS is 0.20% RSD. The analytical performance attained has demonstrated that SCGD MS is capable of exceeding the IAEA’s ITVs for established techniques, and shows great promise as a transportable ionization source for on-site isotope-ratio measurements.As part of the concerted strides in the development of a transportable system, the SCGD has been coupled with additional instruments that utilize mass analyzers more amenable to miniaturized systems, such as linear ion traps and quadrupoles. Additionally, the development of a closed sample introduction system has resulted in a significant decrease in the amount of sample required for analysis and, more importantly the volume of generated waste, with negligible impact on analytical performance. Overall, this research has advanced the understanding of the SCGD as an ionization source for elemental and isotope-ratio mass spectrometry while demonstrating that it is capable of being a competitive, inexpensive, and transportable alterative to current laboratory based instrumentation.
This thesis describes a new method of magnetic resonance detection based on mechanical displacements caused by magnetic forces, which is general with respect to sample and pulse sequence. A ...spin-bearing sample placed inside a flexible magnet assembly distorts that assembly in proportion to the sample's magnetization. Radio-frequency fields that modulate the sample's spin magnetization at this detector's mechanical resonance frequency encode magnetic resonance spectra into the detector's trajectory. A key insight is that such mechanical detection can be performed within optimized detectors with no need for field gradients inside the sample volume, circumventing the deleterious consequences of such gradients for sensitivity and resolution. The new method is called Better Observation of Magnetization, Enhanced Resolution, and No Gradient (BOOMERANG), and its sensitivity is predicted to exceed that of inductive detection at microscopic size scales.
A prototype BOOMERANG spectrometer optimized for 3 mm diameter liquid and solid samples is described. The device uses direct digital synthesis of radio-frequency waveforms in its operation and fiber-optic interferometry to detect picometer-scale motions of a detector magnet. This magnet is bound to a tuned mechanical oscillator inside a magnet assembly designed for homogeneity of the magnetic field in the sample. Several types of time-domain FT-NMR spectra on test samples are presented. The data confirm theory and design principles.
The favorable scaling of BOOMERANG's sensitivity and the numerous potential uses for NMR at reduced size scales motivate construction of spectrometers optimized for microscopic samples. Geometric concerns in scaling down BOOMERANG are addressed quantitatively. At size scales where the number of spins is such that mean magnetization is smaller than fluctuations, such fluctuations, if not accounted for, can dominate the noise regardless of the physical detection method used. A measurement paradigm using correlations of these fluctuations to encode spectra is proposed to suppress this quantum noise, and the sensitivity of this method, which we call Correlated Observations Narrow Quantum Uncertainty, Enhancing Spectroscopic Transients (CONQUEST), is analyzed. BOOMERANG and CONQUEST promise to extend the applicability of nuclear magnetic resonance (NMR) for chemical analysis to samples and problems that are currently inaccessible by NMR due to poor sensitivity.
This thesis describes a new method of magnetic resonance detection based on mechanical displacements caused by magnetic forces, which is general with respect to sample and pulse sequence. A ...spin-bearing sample placed inside a flexible magnet assembly distorts that assembly in proportion to the sample's magnetization. Radio-frequency fields that modulate the sample's spin magnetization at this detector's mechanical resonance frequency encode magnetic resonance spectra into the detector's trajectory. A key insight is that such mechanical detection can be performed within optimized detectors with no need for field gradients inside the sample volume, circumventing the deleterious consequences of such gradients for sensitivity and resolution. The new method is called Better Observation of Magnetization, Enhanced Resolution, and No Gradient (BOOMERANG), and its sensitivity is predicted to exceed that of inductive detection at microscopic size scales. A prototype BOOMERANG spectrometer optimized for 3 mm diameter liquid and solid samples is described. The device uses direct digital synthesis of radio-frequency waveforms in its operation and fiber-optic interferometry to detect picometer-scale motions of a detector magnet. This magnet is bound to a tuned mechanical oscillator inside a magnet assembly designed for homogeneity of the magnetic field in the sample. Several types of time-domain FT-NMR spectra on test samples are presented. The data confirm theory and design principles. The favorable scaling of BOOMERANG's sensitivity and the numerous potential uses for NMR at reduced size scales motivate construction of spectrometers optimized for microscopic samples. Geometric concerns in scaling down BOOMERANG are addressed quantitatively. At size scales where the number of spins is such that mean magnetization is smaller than fluctuations, such fluctuations, if not accounted for, can dominate the noise regardless of the physical detection method used. A measurement paradigm using correlations of these fluctuations to encode spectra is proposed to suppress this quantum noise, and the sensitivity of this method, which we call Correlated Observations Narrow Quantum Uncertainty, Enhancing Spectroscopic Transients (CONQUEST), is analyzed. BOOMERANG and CONQUEST promise to extend the applicability of nuclear magnetic resonance (NMR) for chemical analysis to samples and problems that are currently inaccessible by NMR due to poor sensitivity.
A current trend in public education is toward high-stakes, standards-based assessment and accountability systems. In Virginia, the systems are known as the Standards of Learning (SOL) and the ...Standards of Accreditation (SOA). The recent No Child Left Behind (NCLB) initiative put forth by President Bush requires that schools develop programs that ensure success for all students. Extracurricular activities may be one such program. Unfortunately, at the middle school level, opportunities for students to become involved in extracurricular sports programs have decreased over the last ten years. The lack of extracurricular activities in middle schools is not congruent with the developmental needs of many adolescents. In one urban, public middle school in Southeastern Virginia, teachers and staff members were concerned that many students were not “engaged” in school. They believed that this lack of engagement resulted in a lack of student motivation, which in turn contributed to poor academic performance. In this middle school many students were at risk of academic failure, as characterized by high rates of grade retention and suspension. Teachers proposed the creation of an intramural, extracurricular sports program in an attempt to better meet the needs of these adolescents. This study sought to assess the impact of that program. The purpose of the study was to determine the impact of student participation in an extracurricular, intramural sports program on 8th grade students in the areas of student/teacher relationships, peer relationships, self-esteem, and behavior. An interview protocol and survey were developed by the researcher to ascertain the perceptions of program participants concerning the impact of the program on participating students' relationships with teachers, relationships with peers, self-esteem development and behavior. Findings suggest that both students and teachers perceived that involvement in the intramural program had a positive impact upon student/teacher relationships, peer relationships, student self-esteem, and one aspect of student behavior, staying out of trouble. It might be inferred from these findings that student involvement in extracurricular sports programs may result in outcomes that facilitate student academic achievement.
Na+/H+ exchangers are directly involved in a variety of an animal's essential physiological processes such as ionoregulation, acid-base regulation, nitrogenous waste excretion, and nutrient ...absorption. While nine NHX isoforms have been identified in Caenorhabditis elegans, the physiological importance of each isoform is not understood. The current study aimed to further our knowledge of NHX-3 which has previously been suggested to be involved in the movement of ammonia and acid-base equivalents across the nematode's hypodermis. Although NHX-3 knockout mutant nematodes exported H+ and imported Na+ at slower rates than wild-type nematodes, attempts to inhibit the NHX activity of mutant nematodes using amiloride and EIPA caused an unexpected increase in hypodermal H+ export and did not impact Na+ fluxes suggesting that the different H+ and Na+ transport profiles of the nematodes are likely due to compensatory changes in the mutants in response to the NHX-3 knockout, rather than the loss of NHX-3's physiological function. Significant changes in the mRNA expression of 7 other NHX isoforms, 2 Na+/H+ antiporter isoforms, and the V-type H+-ATPase were detected between wild-type and mutant nematodes. Furthermore, mutant nematodes possessed significantly reduced rates of cytochrome C oxidase activity and ammonia excretion rates, indicating the knockout of NHX-3 induced fundamental changes in metabolism that could impact the nematode's need to eliminate metabolic end-products like H+ and ammonia that relate to NHX transport. While C. elegans is a popular genetic model with cheap and accessible commercial mutants, our findings suggest caution in interpretation of results in studies using mutants to study physiological traits and the biological significance of specific transporters.
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•ΔNHX-3 mutants show a lower rate of H+ secretion compared to N2 wild-type nematodes.•ΔNHX-3 mutants display substantial compensatory responses of other cation/H+ exchangers.•ΔNHX-3 mutant have a lower metabolic capacity compared to N2 wild-type nematodes.•ΔNHX-3 and N2 wild-type nematodes show similar Na+ uptake rates.
Hip dislocation is one of the leading causes of failure and revision surgery for total hip arthroplasty. To reduce dislocation rates, lipped liners have been designed with an elevated portion of the ...rim, to increase jump distance and maintain greater contact area. While it has been documented that lipped liners help reduce dislocation, the objective of this study is to investigate whether lipped liners also help reduce smaller instances of hip micromotion, separation, and edge loading. This study uses an advanced three-dimensional preoperative planning tool to analyze 10 patients, each implanted with both a neutral and lipped liner. Patients within the simulation performed stance phase of gait, and each cup was implanted with the rotation center aligned with the preoperative acetabulum center as well as shifted medially by 2, 4, 6, 8, and 10 mm, yielding 120 total simulations. Specific postoperative outcomes-of-interest included specified component offset, resultant in vivo hip forces, hip separation, and contact area to evaluate edge loading. The planner predicted a reduction in hip separation and an increase in articulating contact area for when using a lipped liner compared to a neutral liner. Additionally, regardless of liner type, increases in hip separation corresponded to decreases in contact area, therefore resulting in edge loading of the liner. Together, this indicates that improper component alignment and offsets may lead to an increase in hip separation and edge loading, but the use of a lipped liner may provide improved stability and resistance to this micromotion.
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