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At least 217 records · Page 12

High glucose activates ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic foot ulcers

Increased matrix metalloproteinase 9 (MMP9) expression is involved in delayed wound healing in diabetic foot ulcers. We created skin wounds in normal SD rats and STZ-induced diabetic SD rats, then we found protein levels of activator protein-1 (AP1), a crucial transcription factor to increase MMP9 transcription, as well as MMP9 was up-regulated in epithelium of diabetic skin tissues. Then, we evaluated the mRNA and protein stability of AP1 subunits C-FOS/C-Jun in HaCaT cells after high glucose treatment. Results showed that high glucose could increase protein stability of C-FOS and C-Jun. Additionally, high glucose also activated extracellular signaling-related kinase 1/2 (ERK1/2). ERK1/2 inhibitor could rescue phosphorylation of C-FOS and C-Jun, increased protein stability of C-Jun, and increased MMP9 expressions. Thus, our study demonstrated that high glucose could activate ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic skin and HaCaT cells.

60 APPLIED LIFE SCIENCES↗

Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells with potential to inhibit SARS-CoV-2 infection and COVID-19 disease progression

COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 2.7 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface “spike” protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. In addition, we report that MASL also inhibits SARS-CoV-2 infection of kidney epithelial cells in culture. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.

60 APPLIED LIFE SCIENCES↗

The APOGEE Data Release 16 Spectral Line List

The updated H-band spectral-line list (from λ15000–17000) adopted by the Apache Point Observatory Galactic Evolution Experiment (APOGEE) for the SDSS-IV Data Release 16 (DR16) is presented in this work. The APOGEE line list is a combination of atomic and molecular lines, with data drawn from laboratory, theoretical, and astrophysical sources. Oscillator strengths and damping constants are adjusted using high signal-to-noise, high-resolution spectra of the Sun, and α Boo (Arcturus), as “standard stars.” Updates to the DR16 line list, as compared to the previous DR14 version, include the addition of molecular H{sub 2}O and FeH lines, as well as a much larger (by a factor of ∼4) atomic line list, including a significantly greater number of transitions with hyperfine splitting. More recent references and line lists for the crucial molecules, CO and OH, as well as for C{sub 2} and SiH, are also included. In contrast to DR14, DR16 contains measurable lines from the heavy neutron-capture elements cerium (as Ce ii), neodymium (as Nd ii), and ytterbium (as Yb ii), as well as one line from rubidium (as Rb i), which may be detectable in a small fraction of APOGEE red giants.

74 ATOMIC AND MOLECULAR PHYSICS↗

Detection Limits of Low-mass, Long-period Exoplanets Using Gaussian Processes Applied to HARPS-N Solar Radial Velocities

Radial velocity (RV) searches for Earth-mass exoplanets in the habitable zone around Sun-like stars are limited by the effects of stellar variability on the host star. In particular, suppression of convective blueshift and brightness inhomogeneities due to photospheric faculae/plage and starspots are the dominant contribution to the variability of such stellar RVs. Gaussian process (GP) regression is a powerful tool for statistically modeling these quasi-periodic variations. We investigate the limits of this technique using 800 days of RVs from the solar telescope on the High Accuracy Radial velocity Planet Searcher for the Northern hemisphere (HARPS-N) spectrograph. These data provide a well-sampled time series of stellar RV variations. Into this data set, we inject Keplerian signals with periods between 100 and 500 days and amplitudes between 0.6 and 2.4 m s{sup −1}. We use GP regression to fit the resulting RVs and determine the statistical significance of recovered periods and amplitudes. We then generate synthetic RVs with the same covariance properties as the solar data to determine a lower bound on the observational baseline necessary to detect low-mass planets in Venus-like orbits around a Sun-like star. Our simulations show that discovering planets with a larger mass (∼0.5 m s{sup −1}) using current-generation spectrographs and GP regression will require more than 12 yr of densely sampled RV observations. Furthermore, even with a perfect model of stellar variability, discovering a true exo-Venus (∼0.1 m s{sup −1}) with current instruments would take over 15 yr. Therefore, next-generation spectrographs and better models of stellar variability are required for detection of such planets.

47 OTHER INSTRUMENTATION↗

ARES. V. No Evidence For Molecular Absorption in the HST WFC3 Spectrum of GJ 1132 b

We present a study on the spatially scanned spectroscopic observations of the transit of GJ 1132 b, a warm (∼500 K) super-Earth (1.13 R {sub ⊕}) that was obtained with the G141 grism (1.125–1.650 μm) of the Wide Field Camera 3 (WFC3) on board the Hubble Space Telescope. We used the publicly available Iraclis pipeline to extract the planetary transmission spectra from the five visits and produced a precise transmission spectrum. We analyzed the spectrum using the TauREx3 atmospheric retrieval code, with which we show that the measurements do not contain molecular signatures in the investigated wavelength range and are best fit with a flat-line model. Our results suggest that the planet does not have a clear primordial, hydrogen-dominated atmosphere. Instead, GJ 1132 b could have a cloudy hydrogen-dominated atmosphere, have a very enriched secondary atmosphere, be airless, or have a tenuous atmosphere that has not been detected. Due to the narrow wavelength coverage of WFC3, these scenarios cannot be distinguished yet, but the James Webb Space Telescope may be capable of detecting atmospheric features, although several observations may be required to provide useful constraints.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

KMT-2019-BLG-1715: Planetary Microlensing Event with Three Lens Masses and Two Source Stars

We investigate the gravitational microlensing event KMT-2019-BLG-1715, the light curve of which shows two short-term anomalies from a caustic-crossing binary-lensing light curve: one with a large deviation and the other with a small deviation. We identify five pairs of solutions, in which the anomalies are explained by adding an extra lens or source component in addition to the base binary-lens model. We resolve the degeneracies by applying a method in which the measured flux ratio between the first and second source stars is compared with the flux ratio deduced from the ratio of the source radii. Applying this method leaves a single pair of viable solutions, in both of which the major anomaly is generated by a planetary-mass third body of the lens, and the minor anomaly is generated by a faint second source. A Bayesian analysis indicates that the lens comprises three masses: a planet-mass object with ∼2.6 M {sub J} and binary stars of K and M dwarfs lying in the galactic disk. We point out the possibility that the lens is the blend, and this can be verified by conducting high-resolution follow-up imaging for the resolution of the lens from the source.

79 ASTRONOMY AND ASTROPHYSICS↗

OGLE-2018-BLG-0567Lb and OGLE-2018-BLG-0962Lb: Two Microlensing Planets through the Planetary-caustic Channel

We present the analyses of two microlensing events, OGLE-2018-BLG-0567 and OGLE-2018-BLG-0962. In both events, the short-lasting anomalies were densely and continuously covered by two high-cadence surveys. The light-curve modeling indicates that the anomalies are generated by source crossings over the planetary caustics induced by planetary companions to the hosts. The estimated planet/host separation (scaled to the angular Einstein radius θ {sub E}) and mass ratio are (s, q × 10{sup 3}) = (1.81 ± 0.02, 1.24 ± 0.07) and (s, q × 10{sup 3}) = (1.25 ± 0.03, 2.38 ± 0.08), respectively. From Bayesian analyses, we estimate the host and planet masses as (M{sub h},M{sub p})=(0.25{sub −0.13}{sup +0.27} M{sub ⊙},0.32{sub −0.17}{sup +0.34} M{sub J}) and (M{sub h},M{sub p})=(0.54{sub −0.28}{sup +0.33} M{sub ⊙},1.34{sub −0.70}{sup +0.82} M{sub J}), respectively. These planetary systems are located at a distance of 7.06{sub −1.15}{sup +0.93} kpc for OGLE-2018-BLG-0567 and 6.50{sub −1.75}{sup +1.06} kpc for OGLE-2018-BLG-0962, suggesting that they are likely to be near the Galactic bulge. The two events prove the capability of current high-cadence surveys for finding planets through the planetary-caustic channel. We find that most published planetary-caustic planets are found in Hollywood events in which the source size strongly contributes to the anomaly cross-section relative to the size of the caustic.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Organs at Risk Considerations for Thoracic Stereotactic Body Radiation Therapy: What Is Safe for Lung Parenchyma?

Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Spinal Cord Dose Tolerance to Stereotactic Body Radiation Therapy

Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (D{sub max}) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD2{sub 2}) D{sub max} ≤70 Gy; SBRT thecal sac EQD2{sub 2} D{sub max} ≤25 Gy, thecal sac SBRT EQD2{sub 2} D{sub max} to cumulative EQD2{sub 2} D{sub max} ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Tumor Control Probability Modeling and Systematic Review of the Literature of Stereotactic Body Radiation Therapy for Prostate Cancer

Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response

Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Maximizing Tumor Control and Limiting Complications With Stereotactic Body Radiation Therapy for Pancreatic Cancer

Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa.

62 RADIOLOGY AND NUCLEAR MEDICINE↗