Engineering topics

others, and

Publications and source records attributed to others, and.

At least 199 records · Page 11

DOE OSTI2021

MiR-205–5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1

Highlights: • MiR-205-5p was commonly downregulated in GC tissues from TCGA database and our hospital, and these events were associated with a worse TNM stagedistant metastasis and poor survival. • MiR-205-5p and CD31 expressions were negatively inter-related within GC tissues from TCGA database and our hospital. • GC cell lines expressed lower level of miR-205-5p significantly as compared with the normal gastric cell line. • MiR-205-5p upregulation significantly impaired proliferation and colony formation of GC cells and neovascularization induced by GC cells in vitro and in vivo. • The angiogenesis and ERK-signaling were depressed by VEGFA and FGF1 downregulation induced by miR-205-5p overexpression. The miR-205-5p inhibitor promoted malignant phenotypes by enhancing VEGFA and FGF1 expressions, as well as the activation of ERK-signaling. Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205–5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205–5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205–5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205–5p expression and clinical characteristics were analyzed using either Pearson's χ{sup 2} test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205–5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205–5p, and miR-205–5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205–5p. MiR-205–5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205–5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205–5p. Xenograft mouse models revealed that miR-205–5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205–5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205–5p may represent as an antiangiogenic therapy for GC.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

KMT-2019-BLG-0371 and the Limits of Bayesian Analysis

We show that the perturbation at the peak of the light curve of microlensing event KMT-2019-BLG-0371 is explained by a model with a mass ratio between the host star and planet of q ∼ 0.08. Due to the short event duration (t {sub E} ∼ 6.5 days), the secondary object in this system could potentially be a massive giant planet. A Bayesian analysis shows that the system most likely consists of a host star with a mass M{sub h}=0.09{sub −0.05}{sup +0.14}M{sub ⊙} and a massive giant planet with a mass M{sub p}=7.70{sub −3.90}{sup +11.34}M{sub Jup}. However, the interpretation of the secondary as a planet (i.e., as having M {sub p} < 13M {sub Jup}) rests entirely on the Bayesian analysis. Motivated by this event, we conduct an investigation to determine which constraints meaningfully affect Bayesian analyses for microlensing events. We find that the masses inferred from such a Bayesian analysis are determined almost entirely by the measured value of θ {sub E} and are relatively insensitive to other factors such as the direction of the event (ℓ, b), the lens–source relative proper motion μ {sub rel}, or the specific Galactic model prior.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2021

ACCESS and LRG-BEASTS: A Precise New Optical Transmission Spectrum of the Ultrahot Jupiter WASP-103b

We present a new ground-based optical transmission spectrum of the ultrahot Jupiter WASP-103b (T{sub eq}=2484 K). Our transmission spectrum is the result of combining five new transits from the ACCESS survey and two new transits from the LRG-BEASTS survey with a reanalysis of three archival Gemini/GMOS transits and one VLT/FORS2 transit. Our combined 11-transit transmission spectrum covers a wavelength range of 3900–9450 Å with a median uncertainty in the transit depth of 148 parts per million, which is less than one atmospheric scale height of the planet. In our retrieval analysis of WASP-103b’s combined optical and infrared transmission spectrum, we find strong evidence for unocculted bright regions (4.3σ) and weak evidence for H{sub 2}O (1.9σ), HCN (1.7σ), and TiO (2.1σ), which could be responsible for WASP-103b’s observed temperature inversion. Our optical transmission spectrum shows significant structure that is in excellent agreement with the extensively studied ultrahot Jupiter WASP-121b, for which the presence of VO has been inferred. For WASP-103b, we find that VO can only provide a reasonable fit to the data if its abundance is implausibly high and we do not account for stellar activity. Our results highlight the precision that can be achieved by ground-based observations and the impacts that stellar activity from F-type stars can have on the interpretation of exoplanet transmission spectra.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2021

The Breakthrough Listen Search For Intelligent Life Near the Galactic Center. I

A line of sight toward the Galactic Center (GC) offers the largest number of potentially habitable systems of any direction in the sky. The Breakthrough Listen program is undertaking the most sensitive and deepest targeted SETI surveys toward the GC. Here, we outline our observing strategies with Robert C. Byrd Green Bank Telescope (GBT) and Parkes telescope to conduct 600 hr of deep observations across 0.7–93 GHz. We report preliminary results from our survey for extraterrestrial intelligence (ETI) beacons across 1–8 GHz with 7.0 and 11.2 hr of observations with Parkes and GBT, respectively. With our narrowband drifting signal search, we were able to place meaningful constraints on ETI transmitters across 1–4 GHz and 3.9–8 GHz with EIRP limits of ≥4 × 10{sup 18} W among 60 million stars and ≥5 × 10{sup 17} W among half a million stars, respectively. For the first time, we were able to constrain the existence of artificially dispersed transient signals across 3.9–8 GHz with EIRP ≥1 × 10{sup 14} W/Hz with a repetition period ≤4.3 hr. We also searched our 11.2 hr of deep observations of the GC and its surrounding region for Fast Radio Burst–like magnetars with the DM up to 5000 pc cm{sup -3} with maximum pulse widths up to 90 ms at 6 GHz. We detected several hundred transient bursts from SGR J1745–2900, but did not detect any new transient bursts with the peak luminosity limit across our observed band of ≥10{sup 31} erg s{sup -1} and burst rate of ≥0.23 burst hr{sup -1}. These limits are comparable to bright transient emission seen from other Galactic radio-loud magnetars, constraining their presence at the GC.

47 OTHER INSTRUMENTATION↗

DOE OSTI2021

Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1

Mounting evidence demonstrates that combining radiation therapy (RT) with immunotherapy can reduce tumor burden in a subset of patients. However, conventional systemic delivery of immunotherapeutics is often associated with significant adverse effects, which force treatment cessation. The aim of this study was to investigate a minimally invasive therapeutics delivery approach to improve clinical response while attenuating toxicity.