421 research outputs found
Effects Of Large-Scale Environment On The Assembly History Of Central Galaxies
No full textWe examine whether large-scale environment affects the mass assembly history of central galaxies. To facilitate this, we constructed dark matter halo merger trees from a cosmological N-body simulation and calculated the formation and evolution of galaxies using a semi-analytic method. We confirm earlier results that smaller halos show a notable difference in formation time with a mild dependence on large-scale environment. However, using a semi-analytic model, we found that on average the growth rate of the stellar mass of central galaxies is largely insensitive to large-scale environment. Although our results show that the star formation rate (SFR) and the stellar mass of central galaxies in smaller halos are slightly affected by the assembly bias of halos, those galaxies are faint and the difference in the SFR is minute, therefore it is challenging to detect it in real galaxies given the current observational accuracy. Future galaxy surveys, such as the BigBOSS experiment and the Large Synoptic Survey Telescope, which are expected to provide observational data for fainter objects, will provide a chance to test our model predictions.National Research Foundation of Korea Doyak FY2014Astronom
Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation
No full textIn cancer patients, metastasis of tumors to sentinel lymph nodes (LNs) predicts disease progression and often guides treatment decisions. The mechanisms underlying tumor LN metastasis are poorly understood. By using comparative transcriptomics and metabolomics analyses of primary and LN-metastatic tumors in mice, we found that LN metastasis requires that tumor cells undergo a metabolic shift toward fatty acid oxidation (FAO). Transcriptional coactivator yes-associated protein (YAP) is selectively activated in LN-metastatic tumors, leading to the up-regulation of genes in the FAO signaling pathway. Pharmacological inhibition of FAO or genetic ablation of YAP suppressed LN metastasis in mice. Several bioactive bile acids accumulated to high levels in the metastatic LNs, and these bile acids activated YAP in tumor cells, likely through the nuclear vitamin D receptor. Inhibition of FAO or YAP may merit exploration as a potential therapeutic strategy for mitigating tumor metastasis to LNs. 2017 © The Author
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Constraining the end of reionization with Lyα spectroscopy
No full textThe reionization of the intergalactic medium (IGM) marks the time in the early universe when the first stars and galaxies began to affect the universe around them, as during this last major phase transition high-energy ultraviolet photons from these objects ionized the gas in the IGM, and it remains ionized to the present day. Studying reionization is a key frontier in observational cosmology, as it can therefore provide key insights into the formation and evolution of galaxies in the early universe. As Lyα photons are resonantly scattered by neutral hydrogen in the IGM, an analysis of this line can be used to trace the existence of neutral hydrogen in the IGM at different points in the history of the universe (i.e., when the IGM becomes neutral, we should stop seeing these photons, as they are likely scattered out of our line-of-sight). The work in this dissertation focuses on completing a spectroscopic survey of galaxies in the early universe, to measure the Lyα equivalent width (EW) distribution into the epoch of reionization and investigate the evolution of the IGM during reionization, pinning down the late time-evolution of reionization. To measure the Lyα EW distribution in the reionization era, we utilize deep spectroscopic observations of candidate galaxies from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) using both the DEIMOS (optical) and MOSFIRE (near-infrared; NIR) spectrographs on the Keck telescopes. Our large spectroscopic dataset compiled with both Keck telescope observations represent the deepest and most complete spectroscopic survey for galaxies in the epoch of reionization. We study the Lyα emission strength through constraining the Lyα equivalent width (EW) distribution with our spectroscopic dataset by constructing detailed simulations of mock emission lines, accounting for the observational conditions (e.g., exposure time, wavelength coverage, and sky emission) and galaxy photometric redshift probability distribution functions. The measurements of the EW distribution with the detected Lyα emission lines from our DEIMOS and MOSFIRE observations provide additional evidence that the Lyα EW distribution declines at z > 6, suggesting an increasing fraction of neutral hydrogen in the IGM. Thanks to plenty of high-quality observational data from space telescopes such as the Hubble Space Telescope and the Spitzer Space Telescope, observational studies of the evolution of galaxies in the early universe have been performed over the past decade. Those studies have revealed statistical trends of the star formation history and the evolution of those galaxies over the cosmic time. However, since the star formation happens in a complex way, an analysis of the integrated properties of galaxies is not enough to grasp the physical processes governing the star formation and the growth of galaxies. The advent of a spatially resolved study of each individual galaxy has provided us an excellent approach to explore star formation processes inside a galaxy and to examine the inside-out / outside-in growth scenarios of galaxies. We perform a spatially resolved study of galaxies in the early universe at z ≳ 4 using the CANDELS Survey and HAWK-I UDS GOODS (HUGS) survey data. We estimate stellar mass, star formation rate, and dust extinction for galaxy inner and outer regions via spatially resolved spectral energy distribution fitting based on a Markov Chain Monte Carlo algorithm. By comparing specific star formation rates (sSFRs) between inner and outer parts of the galaxies we find that the majority of galaxies with high central mass densities show evidence for a preferentially lower sSFR in their centers than in their outer regions, indicative of reduced sSFRs in their central regionsAstronom
Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration
No full textChoriocapillary loss is a major cause of neovascular age-related macular degeneration (NV-AMD). Although vascular endothelial growth factor (VEGF) blockade for NV-AMD has shown beneficial outcomes, unmet medical needs for patients refractory or tachyphylactic to anti-VEGF therapy exist. In addition, the treatment could exacerbate choriocapillary rarefaction, necessitating advanced treatment for fundamental recovery from NV-AMD. In this study, Tie2 activation by angiopoietin-2–binding and Tie2-activating antibody (ABTAA) presents a therapeutic strategy for NV-AMD. Conditional Tie2 deletion impeded choriocapillary maintenance, rendering eyes susceptible to NV-AMD development. Moreover, in a NV-AMD mouse model, ABTAA not only suppressed choroidal neovascularization (CNV) and vascular leakage but also regenerated the choriocapillaris and relieved hypoxia. Conversely, VEGF blockade degenerated the choriocapillaris and exacerbated hypoxia, although it suppressed CNV and vascular leakage. Together, we establish that angiopoietin-Tie2 signaling is critical for choriocapillary maintenance and that ABTAA represents an alternative, combinative therapeutic strategy for NV-AMD by alleviating anti-VEGF adverse effects. Copyright © 2019 The Author
Inducing thermodynamically blocked atomic ordering via strongly driven nonequilibrium kinetics
No full textUltrafast light-matter interactions enable inducing exotic material phases by promoting access to kinetic processes blocked in equilibrium. Despite potential opportunities, actively using nonequilibrium kinetics for material discovery is limited by the poor understanding on intermediate states of driven systems. Here, using single-pulse time-resolved imaging with x-ray free-electron lasers, we found intermediate states of photoexcited bismuth nanoparticles that showed kinetically reversed surface ordering during ultrafast melting. This entropy-lowering reaction was further investigated by molecular dynamics simulations to reveal that observed kinetics were thermodynamically buried in equilibrium, which emphasized the critical role of electron-mediated ultrafast free-energy modification in inducing exotic material phases. This study demonstrated that ultrafast photoexcitations of electrons provide an efficient strategy to induce hidden material phases by overcoming thermodynamic barriers via nonequilibrium reaction pathways.11Nsciescopu
Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid
No full text© 2019, The Author(s), under exclusive licence to Springer Nature Limited.Recent work has shown that meningeal lymphatic vessels (mLVs), mainly in the dorsal part of the skull, are involved in the clearance of cerebrospinal fluid (CSF), but the precise route of CSF drainage is still unknown. Here we reveal the importance of mLVs in the basal part of the skull for this process by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF. Unlike dorsal mLVs, basal mLVs have lymphatic valves and capillaries located adjacent to the subarachnoid space in mice. We also show that basal mLVs are hotspots for the clearance of CSF macromolecules and that both mLV integrity and CSF drainage are impaired with ageing. Our findings should increase the understanding of how mLVs contribute to the neuropathophysiological processes that are associated with agein
Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs
No full textJinhyang Choi,1,2 Eunjung Ko,1 Hye-Kyung Chung,3 Jae Hee Lee,1 Eun Jin Ju,1 Hyun Kyung Lim,4 Intae Park,1 Kab-Sig Kim,5 Joo-Hwan Lee,5 Woo-Chan Son,6 Jung Shin Lee,1,7 Joohee Jung,1,4 Seong-Yun Jeong,1,2 Si Yeol Song,1,8 Eun Kyung Choi1,3,8 1Institute for Innovative Cancer Research, 2Asan Institute for Life Sciences, 3Center for Development and Commercialization of Anti-cancer Therapeutics, 4College of Pharmacy, Duksung Women’s University, 5Bio-Synectics, 6Department of Pathology, 7Department of Internal Medicine, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Abstract: Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO2), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs. Keywords: Nufs-DTX, docetaxel, anticancer efficacy, toxicit
A Metaphysics for Mathematical and Structural Realism
No full textThe goal of this paper is to preserve realism in both ontology and truth for the philosophy of mathematics and science. It begins by arguing that scientific realism can only be attained given mathematical realism due to the indispensable nature of the latter to the prior. Ultimately, the paper argues for a position combining both Ontic Structural Realism and Ante Rem Structuralism, or what the author refers to as Strong Ontic Structural Realism, which has the potential to reconcile realism for both science and mathematics. The paper goes on to claims that this theory does not succumb to the same traditional epistemological problems, which have damaged the credibility of its predecessors
The significant inputs of trace elements and rare earth elements from melting glaciers in Antarctic coastal waters
No full textTo evaluate the impact of modern glacier melting on the chemical enrichment of Antarctic coastal waters, we measured trace elements, including dissolved iron (Fe) and rare earth elements (REEs), together with dissolved inorganic nitrogen, phosphorous, silicate and dissolved organic carbon (DOC) in ice, snow and coastal seawater of Marian Cove in the northernmost part of Antarctica (62°S). There was an increase in the concentrations of Fe and other trace elements (Al, Mn, Cr, Ni, Co, Pb and REEs) between the bay mouth and the glacier valleys. Good correlations between salinity and these chemical elements indicate that the trend was mainly due to the influence of glacier meltwater (GMW). When the effect of GMW was quantified based on plots of its presence (average 5.7%) in the surface water of the cove, the concentrations of trace elements in seawater increased 18-fold for Fe, eight- to 10-fold for Al and Mn and up to four-fold for Cr, Ni, Co, Pb and REEs by GMW. However, the contribution of GMW to inorganic nutrients and DOC was negligible. The significance of GMW-borne REE contribution in this cove was further evidenced by middle REE enrichment in cove water. Our results suggest that the currently increasing glacier melting in Antarctica has a significant influence on the level of trace elements, particularly Fe, in cove water, which in turn may have a significant impact on the biogeochemistry of coastal seawater in Antarctica
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