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1.
Infect Immun ; 88(10)2020 09 18.
Article in English | MEDLINE | ID: mdl-32747603

ABSTRACT

Antibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients. Antibodies to BPI and bacterial antigens were measured in sera by ELISA from five patient cohorts (n = 214). Antibody avidity was investigated. Bacteremic patient sera (n = 32) exhibited IgG antibody autoreactivity against BPI in 64.7% and 46.7% of patients with positive blood cultures for P. aeruginosa and Escherichia coli, respectively. Autoantibody titers correlated with IgG responses to bacterial extracts and lipopolysaccharide (LPS). A prospective cohort of bacteremic patient sera exhibited anti-BPI IgG responses in 23/154 (14.9%) patients with autoreactivity present at the time of positive blood cultures in patients with Gram-negative and Gram-positive bacteria, including 8/60 (13.3%) patients with Staphylococcus aureus Chronic tissue infection with S. aureus was associated with BPI antibody autoreactivity in 2/15 patients (13.3%). Previously, we demonstrated that BPI autoreactivity in CF patient sera exhibits high avidity. Here, a similar pattern was seen in BE patient sera. In contrast, sera from patients with bacteremia exhibited low avidity. These data indicate that low-avidity IgG responses to BPI can arise acutely in response to bacteremia and that this association is not limited to P. aeruginosa This is to be contrasted with chronic respiratory infection with P. aeruginosa, suggesting that either the chronicity or the site of infection selects for the generation of high-avidity responses, with biologic consequences for airway immunity.


Subject(s)
Antimicrobial Cationic Peptides/immunology , Autoantibodies/immunology , Bacteremia/immunology , Blood Proteins/immunology , Gram-Negative Bacterial Infections/immunology , Gram-Positive Bacterial Infections/immunology , Immunoglobulin G/immunology , Acute Disease , Antibody Affinity , Antigens, Bacterial/immunology , Autoantibodies/blood , Bacteremia/microbiology , Chronic Disease , Escherichia coli/immunology , Escherichia coli/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/microbiology , Humans , Immunoglobulin G/blood , Kinetics , Prospective Studies , Pseudomonas aeruginosa/immunology , Pseudomonas aeruginosa/isolation & purification , Staphylococcus aureus/immunology , Staphylococcus aureus/isolation & purification
2.
Phys Rev Lett ; 123(4): 045501, 2019 Jul 26.
Article in English | MEDLINE | ID: mdl-31491265

ABSTRACT

Understanding the local atomic order in amorphous thin film coatings and how it relates to macroscopic performance factors, such as mechanical loss, provides an important path towards enabling the accelerated discovery and development of improved coatings. High precision x-ray scattering measurements of thin films of amorphous zirconia-doped tantala (ZrO_{2}-Ta_{2}O_{5}) show systematic changes in intermediate range order (IRO) as a function of postdeposition heat treatment (annealing). Atomic modeling captures and explains these changes, and shows that the material has building blocks of metal-centered polyhedra and the effect of annealing is to alter the connections between the polyhedra. The observed changes in IRO are associated with a shift in the ratio of corner-sharing to edge-sharing polyhedra. These changes correlate with changes in mechanical loss upon annealing, and suggest that the mechanical loss can be reduced by developing a material with a designed ratio of corner-sharing to edge-sharing polyhedra.

3.
Phys Rev Lett ; 120(26): 263602, 2018 Jun 29.
Article in English | MEDLINE | ID: mdl-30004721

ABSTRACT

Thermal noise of highly reflective mirror coatings is a major limit to the sensitivity of many precision laser experiments with strict requirements such as low optical absorption. Here, we investigate amorphous silicon and silicon nitride as an alternative to the currently used combination of coating materials, silica, and tantala. We demonstrate an improvement by a factor of ≈55 with respect to the lowest so far reported optical absorption of amorphous silicon at near-infrared wavelengths. This reduction was achieved via a combination of heat treatment, final operation at low temperature, and a wavelength of 2 µm instead of the more commonly used 1550 nm. Our silicon-based coating offers a factor of 12 thermal noise reduction compared to the performance possible with silica and tantala at 20 K. In gravitational-wave detectors, a noise reduction by a factor of 12 corresponds to an increase in the average detection rate by three orders of magnitude (≈12^{3}).

4.
Phys Rev Lett ; 121(19): 191101, 2018 Nov 09.
Article in English | MEDLINE | ID: mdl-30468587

ABSTRACT

Amorphous silicon has ideal properties for many applications in fundamental research and industry. However, the optical absorption is often unacceptably high, particularly for gravitational-wave detection. We report a novel ion-beam deposition method for fabricating amorphous silicon with unprecedentedly low unpaired electron-spin density and optical absorption, the spin limit on absorption being surpassed for the first time. At low unpaired electron density, the absorption is no longer correlated with electron spins, but with the electronic mobility gap. Compared to standard ion-beam deposition, the absorption at 1550 nm is lower by a factor of ≈100. This breakthrough shows that amorphous silicon could be exploited as an extreme performance optical coating in near-infrared applications, and it represents an important proof of concept for future gravitational-wave detectors.

5.
Rev Sci Instrum ; 82(1): 011301, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21280809

ABSTRACT

In 2000 the first mirror suspensions to use a quasi-monolithic final stage were installed at the GEO600 detector site outside Hannover, pioneering the use of fused silica suspension fibers in long baseline interferometric detectors to reduce suspension thermal noise. Since that time, development of the production methods of fused silica fibers has continued. We present here a review of a novel CO(2) laser-based fiber pulling machine developed for the production of fused silica suspensions for the next generation of interferometric gravitational wave detectors and for use in experiments requiring low thermal noise suspensions. We discuss tolerances, strengths, and thermal noise performance requirements for the next generation of gravitational wave detectors. Measurements made on fibers produced using this machine show a 0.8% variation in vertical stiffness and 0.05% tolerance on length, with average strengths exceeding 4 GPa, and mechanical dissipation which meets the requirements for Advanced LIGO thermal noise performance.

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