We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
Ignition is needed to make fusion energy a viable alternative energy source, but has yet to be achieved. A key step on the way to ignition is to have the energy generated through fusion reactions in ...an inertially confined fusion plasma exceed the amount of energy deposited into the deuterium-tritium fusion fuel and hotspot during the implosion process, resulting in a fuel gain greater than unity. Here we report the achievement of fusion fuel gains exceeding unity on the US National Ignition Facility using a 'high-foot' implosion method, which is a manipulation of the laser pulse shape in a way that reduces instability in the implosion. These experiments show an order-of-magnitude improvement in yield performance over past deuterium-tritium implosion experiments. We also see a significant contribution to the yield from α-particle self-heating and evidence for the 'bootstrapping' required to accelerate the deuterium-tritium fusion burn to eventually 'run away' and ignite.
Abstract
The role of the cosmic web in shaping galaxy properties is investigated in the Galaxy And Mass Assembly (GAMA) spectroscopic survey in the redshift range 0.03 ≤ z ≤ 0.25. The stellar mass, ...u − r dust corrected colour and specific star formation rate (sSFR) of galaxies are analysed as a function of their distances to the 3D cosmic web features, such as nodes, filaments and walls, as reconstructed by DisPerSE. Significant mass and type/colour gradients are found for the whole population, with more massive and/or passive galaxies being located closer to the filament and wall than their less massive and/or star-forming counterparts. Mass segregation persists among the star-forming population alone. The red fraction of galaxies increases when closing in on nodes, and on filaments regardless of the distance to nodes. Similarly, the star-forming population reddens (or lowers its sSFR) at fixed mass when closing in on filament, implying that some quenching takes place. These trends are also found in the state-of-the-art hydrodynamical simulation Horizon-AGN. These results suggest that on top of stellar mass and large-scale density, the traceless component of the tides from the anisotropic large-scale environment also shapes galactic properties. An extension of excursion theory accounting for filamentary tides provides a qualitative explanation in terms of anisotropic assembly bias: at a given mass, the accretion rate varies with the orientation and distance to filaments. It also explains the absence of type/colour gradients in the data on smaller, non-linear scales.
Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small ...subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.
Abstract
Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely ...unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.
Starting from April 1st, 2020, the nationwide partial lockdown in Vietnam has shown the effectiveness in stopping the community transmission of COVID-19, however, it also produced adverse impacts on ...the economy and inhabitants’ life. A cross-sectional study using a web-based approach was conducted in the second week of April 2020 to examine the influence of the national social distancing on the quality of life and economic well-being of Vietnamese citizens under COVID-19 pandemic. The data included socio-economic characteristics, impact of COVID-19 on household income, health status, and health-related quality of life (HRQOL). Ordered logistic regression and multivariable Tobit regression model were employed to examine factors correlated to income change and HRQOL. Results showed that among 341 participants, 66.9% reported household income loss due to the impact of COVID-19. People holding undergraduate degrees, working in other sectors rather than healthcare, and having definite-term contract had a higher likelihood of income reduction. The mean score of EQ-5D-5L and EQ-VAS was 0.95 (± 0.07) and 88.2 (± 11.0), respectively. The domain of Anxiety/Depression had the highest proportion of reporting any problems among 5 dimensions of EQ-5D-5L (38.7%). Being female, having chronic conditions and living in the family with 3–5 members were associated with lower HRQOL scores. A comprehensive assessment of the influence of COVID-19 along with public health interventions, especially mental health programs, should be implemented to mitigate the negative effects of this pandemic on the economic status and quality of life of citizens.
Healthy aging is a complex biological process with progressive accumulation of senescent cells characterized by stable cell cycle arrest, resulting in impaired homeostasis, regenerative potential, ...and gradual functional decline in multiple tissues and organs, whereby the aberrant activation of mammalian target of rapamycin (mTOR) signaling networks plays a central role. Herein, we explored the effects of extracellular vesicles (EVs) released by gingiva-derived mesenchymal stem cells (GMSC-EVs) on oxidative stress–induced cellular senescence in human endothelial cells and skin fibroblasts and their antiaging potentials. Our results showed that GMSC-EVs robustly abrogated oxidative stress–induced upregulation in the expression of cellular senescence-related genes, such as β-galactosidase, p21, p53, and γH2AX, and mTOR/pS6 signaling pathway, in human umbilical vein endothelial cells (HUVECs) and skin fibroblasts. Meanwhile, GMSC-EVs restored oxidative stress–induced impairment in proliferation and tube formation by HUVECs. Systemic administration of GMSC-EVs attenuated aging-associated elevation in the expression levels of p21, mTOR/pS6, interleukin 6, and tumor necrosis factor α in skin and heart tissues of aged mice. These findings suggest that GMSC-EVs could be a potential alternative source of cell-free product for attenuation of aging-related skin and vascular dysfunctions due to their potent inhibitory effects on oxidative stress–induced cellular senescence in endothelial cells and skin fibroblasts.
LKB1/STK11 is a tumor suppressor and a negative regulator of mammalian target of rapamycin signaling. It is inactivated in 30% of lung cancer cell lines but only 5-15% of primary lung ...adenocarcinomas. There is evidence that homozygous deletion (HD) of chromosome 19p at the LKB locus contributes to the inactivation of the gene in primary human lung cancers. Here, we used several complementary genetic approaches to assess the LKB1 locus in primary non-small cell lung cancers (NSCLCs). We first analyzed 124 NSCLC cases for allelic imbalance using eight microsatellite markers on chromosome 19p, which revealed an overall rate of 65% (80 of 124) loss of heterozygosity (LOH). We next used chromogenic in situ hybridization (CISH) to directly examine the chromosomal status of the LKB1 locus. In all, 65 of 124 LOH tested samples were available for CISH and 58 of those (89%) showed either loss of one copy of chromosome 19p (LOH, 40 of 65 cases, 62%) or both copies (HD 18 of 65 cases, 28%). The occurrence of HD was significantly more frequent in Caucasian (35%) than in African-American patients (6%) (P=0.04). A total of 62 of 124 samples with LOH at one or both markers immediately flanking the LKB1 gene were further analyzed by directly sequencing the complete coding region, which identified 7 of 62 (11%) tumors with somatic mutations in the gene. Jointly, our data identified total inactivation of the LKB1 gene by either HD or LOH with somatic mutation in 39% of tested samples, whereas loss of chromosome 19p region by HD or LOH at the LKB1 region occured in 90% of NSCLC.
Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was ...“caged” by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell line monolayers, 3D lung cancer tumor spheroids (A549), and a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also remarkably in hypoxic conditions (1% O2). In vivo, low toxicity was observed at a dose of 1 mg·kg–1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of ruthenium-based photoactivated chemotherapy compounds in a tumor xenograft.
This Letter reports on a series of high-adiabat implosions of cryogenic layered deuterium-tritium (DT) capsules indirectly driven by a "high-foot" laser drive pulse at the National Ignition Facility. ...High-foot implosions have high ablation velocities and large density gradient scale lengths and are more resistant to ablation-front Rayleigh-Taylor instability induced mixing of ablator material into the DT hot spot. Indeed, the observed hot spot mix in these implosions was low and the measured neutron yields were typically 50% (or higher) of the yields predicted by simulation. On one high performing shot (N130812), 1.7 MJ of laser energy at a peak power of 350 TW was used to obtain a peak hohlraum radiation temperature of ∼300 eV. The resulting experimental neutron yield was (2.4±0.05)×10(15) DT, the fuel ρR was (0.86±0.063) g/cm2, and the measured Tion was (4.2±0.16) keV, corresponding to 8 kJ of fusion yield, with ∼1/3 of the yield caused by self-heating of the fuel by α particles emitted in the initial reactions. The generalized Lawson criteria, an ignition metric, was 0.43 and the neutron yield was ∼70% of the value predicted by simulations that include α-particle self-heating.
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