Linking complement C3 and B cells in nasal polyposis

Nasal polyposis often is characterized by a persistent inflammation of the sinonasal mucosa, disease recurrence after medical or surgical intervention, and asthma comorbidity. Dysregulated complement activation may contribute to immunologic alterations and disease. To date, there is only scattered knowledge on the source and regulation of the central complement factors in the pathogenesis of nasal polyps. Here, we aim to study complement signatures, especially the C3-C3aR axis, and focus on cellular sources and targets in nasal polyps. Expression of complement factors, including C3, C5, and the anaphylatoxin receptors, was analyzed in nasal polyp tissue samples, the corresponding inferior turbinates, and healthy controls using transcriptomic methods and protein measurements. Distinct patterns of complement expression were found in nasal polyps compared to controls, characterized by an increased C3 activation and an increase in C3aR-bearing cells. In contrast, no difference was shown for epithelial-dependent C3 production. Besides low intracellular C3-expression levels for lymphocytes in general, we could identify an enlarged B lymphocyte population in nasal polyps displaying high amounts of intracellular C3. Our data suggest a prominent role for the C3-C3aR-axis in nasal polyps and, for the first time, describe a B cell population containing high levels of intracellular C3, suggesting a new role of B cells in the maintenance of the inflammation by complement

A Spread-Spectrum SQUID Multiplexer

The Transition-Edge Sensors (TES) is a mature, high-resolution x-ray spectrometer technology that provides a much higher efficiency than dispersive spectrometers such as gratings and crystal spectrometers. As larger arrays are developed, time-division multiplexing schemes operating at MHz frequencies are being replaced by microwave SQUID multiplexers using frequency-division multiplexing at GHz frequencies. However, the multiplexing factor achievable with microwave SQUIDs is limited by the high slew rate on the leading edge of x-ray pulses. In this paper, we propose a new multiplexing scheme for high-slew-rate TES x-ray calorimeters: the spread-spectrum SQUID multiplexer, which has the potential to enable higher multiplexing factors, especially in applications with lower photon arrival rates.Comment: 12 pages, 2 figures, Submitted to the Journal of Low Temperature Physics (Proceedings of the 17th International Workshop on Low Temperature Detectors

Cytokine expression in subjects with Mycobacterium avium ssp. paratuberculosis positive blood cultures and a meta-analysis of cytokine expression in Crohn's disease.

OBJECTIVES: 1) Culture Mycobacterium avium ssp. paratuberculosis (MAP)from blood, 2) assess infection persistence, 3) determine Crohn's disease (CD) cytokine expression, 4) compare CD cytokine expression to tuberculosis, and 5) perform a meta-analysis of cytokine expression in CD. METHODS: The Temple University/Abilene Christian University (TU/ACU) study had a prospective case control design with 201 subjects including 61 CD patients and 140 non-CD controls. The culture methods included MGIT, TiKa and Pozzato broths, and were deemed MAP positive, if IS900 PCR positive. A phage amplification assay was also performed to detect MAP. Cytokine analysis of the TU/ACU samples was performed using Simple Plex cytokine reagents on the Ella ELISA system. Statistical analyses were done after log transformation using the R software package. The meta-analysis combined three studies. RESULTS: Most subjects had MAP positive blood cultures by one or more methods in 3 laboratories. In our cytokine study comparing CD to non-CD controls, IL-17, IFNγ and TNFα were significantly increased in CD, but IL-2, IL-5, IL-10 and GM-CSF were not increased. In the meta-analysis, IL-6, IL-8 and IL-12 were significantly increased in the CD patients. CONCLUSION: Most subjects in our sample had MAP infection and 8 of 9 subjects remained MAP positive one year later indicating persistent infection. While not identical, cytokine expression patterns in MAP culture positive CD patients in the TU/ACU study showed similarities (increased IL-17, IFNγ and TNFα) to patterns of patients with Tuberculosis in other studies, indicating the possibilities of similar mechanisms of pathogen infection and potential strategies for treatment

The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees

DMRadio-m3^3: A Search for the QCD Axion Below 1 μ1\,\mueV

The QCD axion is one of the most compelling candidates to explain the dark matter abundance of the universe. With its extremely small mass ($\ll 1\,\mathrm{eV}/c^2$), axion dark matter interacts as a classical field rather than a particle. Its coupling to photons leads to a modification of Maxwell's equations that can be measured with extremely sensitive readout circuits. DMRadio-m$^3$ is a next-generation search for axion dark matter below $1\,\mu$eV using a $>4$ T static magnetic field, a coaxial inductive pickup, a tunable LC resonator, and a DC-SQUID readout. It is designed to search for QCD axion dark matter over the range $20\,\mathrm{neV}\lesssim m_ac^2\lesssim 800\,\mathrm{neV}$ ($5\,\mathrm{MHz}<\nu<200\,\mathrm{MHz}$). The primary science goal aims to achieve DFSZ sensitivity above $m_ac^2\approx 120$ neV (30 MHz), with a secondary science goal of probing KSVZ axions down to $m_ac^2\approx40\,\mathrm{neV}$ (10 MHz).Comment: 8 pages, 4 figures. Updated to fix small errors and correct acknowledgement

Microwave multiplexing on the Keck Array

We describe an on-sky demonstration of a microwave-multiplexing readout system in one of the receivers of the Keck Array, a polarimetry experiment observing the cosmic microwave background at the South Pole. During the austral summer of 2018-2019, we replaced the time-division multiplexing readout system with microwave-multiplexing components including superconducting microwave resonators coupled to radio-frequency superconducting quantum interference devices at the sub-Kelvin focal plane, coaxial-cable plumbing and amplification between room temperature and the cold stages, and a SLAC Microresonator Radio Frequency system for the warm electronics. In the range 5-6 GHz, a single coaxial cable reads out 528 channels. The readout system is coupled to transition-edge sensors, which are in turn coupled to 150-GHz slot-dipole phased-array antennas. Observations began in April 2019, and we report here on an initial characterization of the system performance.Comment: 9 pages, 11 figures, Accepted by the Journal of Low Temperature Physics (Proceedings of the 18th International Workshop on Low Temperature Detectors