Degree one loading by pressure variations at the CMB

Hemispherical asymmetry in core dynamics induces degree-1 pressure variations at the core mantle boundary (CMB), which in turn deforms the overlaying elastic mantle, at the same time keeps center of mass of the whole Earth stationary in space. We develop a systematic procedure to deal with the degree-1 CMB pressure loading. We find by direct calculation a surprisingly negative load Love number h[subscript 1]=−1.425 for vertical displacement. Further analysis indicates that the negative h[subscript 1] corresponds to thickening above the positive load that defies intuition that pressure inflation pushes overlaying material up and thins the enveloping shell. We also redefine the pressure load Love numbers in general to enable comparison between the surface mass load and the CMB pressure load for the whole spectrum of harmonic degrees. We find that the gravitational perturbations from the two kinds of loads at degrees n>1 are very similar in amplitude but opposite in sign. In particular, if the CMB pressure variation at degree 2 is at the level of ∼1 hpa/yr (1 cm water height per year), it would perturb the variation of Earth’s oblateness, known as the J[subscript 2], at the observed level.United States. National Aeronautics and Space Administration (No. NNX09AK 70G

Analysis of Absorption Characteristics of Walnut Peptides by Everted Rat Sacs and Identification of Antioxidant Peptides

This study investigated the absorption characteristics of <3 kDa walnut protein peptides simulating gastrointestinal digestion products using the everted rat sacs method. The optimal conditions for walnut peptide absorption in the intestine were selected based on antioxidant capacity (DPPH free radical clearance rate, ABTS+ free radical clearance rate, Fe2+ chelation rate) and active peptide absorption rate. The absorbed peptide components were screened and identified using simulated molecular docking technology and Nano-HPLC-MS/MS technology to obtain new walnut derived peptides that could be fully absorbed and had antioxidant activity. The results showed that when the absorption concentration of walnut peptide digestion product was 6 mg/mL, and the absorption time was 2 h, its antioxidant activity was the highest and the absorption rate in the small intestine was the highest. Further identification by Nano-HPLC-MS/MS showed that, the 0.5~1 kDa active peptide was the most numerous, with the C-terminal/N-terminal amino acids mainly concentrated in Pro, Thr, and Leu. Thirty-three active peptides were fully absorbed and crossed the intestinal barrier. By combining molecular docking technology with DPP-IV, the three active peptides NLRFPL, NPDDEFRPQ, and KGHLFPN with the lowest binding energies of −8.8, −8.6, and −8.6 kal/mol, respectively were obtained. Among these, KGHLFPN displayed the strongest antioxidant capacity. In summary, simulating gastrointestinal digestion with <3 kDa walnut peptides could release the active peptide KGHLFPN, which had the highest antioxidant activity and could be absorbed by the small intestine. These findings would provide new ideas for studies exploring the intestinal absorption characteristics of exogenous peptides, and the screening and identification of antioxidant peptides

Systems consequences of amplicon formation in human breast cancer

Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. This series of events appeared to be unusually common when examined in larger genomic data sets of breast cancers albeit using approaches with lesser resolution. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently coamplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in ERBB2-transfected human normal mammary epithelial cells. Coamplification of other functionally tested oncogenic elements in other breast tumors examined, such as RIPK2 and MYC on chromosome 8, also parallel these findings. Our analyses suggest that structural variations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously and that such oncogenic cassettes are favored during the evolution of a cancer.Singapore. Agency for Science, Technology and ResearchNational Science Foundation (U.S.) (East Asia and Pacific Summer Institutes (OISE-1108282)

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multi-regional phase 2 study, RATIONALE-208, examined single-agent tislelizumab (200 mg intravenously every three weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018 and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. Number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. Disease control rate was 53% and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data