354 research outputs found
âCommingled souvenirs and propheciesâ: the hybrid reality of Stevensâs Aesthetic Ecology of Mind
Combining close readings that highlight structural techniques Wallace Stevens uses to lead readers to see the world through his imagination with historical/biographical information and scholarship that provides context for their production, publication and content, I study how Wallace Stevens's, "The Poems of Our Climate," "Dutch Graves in Bucks County," and "Examination of the Hero in a Time of War" rely on rhetorical/aesthetic strategies characteristic of hybridity to complete his subsumption of reality into the ecosystem of the imagination. The results of my investigation reveal Stevens's rhetorical/aesthetic use of the characteristics of hybridity allow him to use the failures and successes of tradition and both skepticism and faith in the positivist present as tools whereby he can fulfill his aim of having readers experience the ways these poems take form in his mind. In other words, with the aid of these hybrid rhetorical/aesthetic strategies, Stevens strives to pull off a feat of telepathy through the medium of poetry and recreate the images and questions about knowing he experiences in his own mind in the mind of readers
Dynamic Visualization of mTORC1 Activity in Living Cells
SummaryThe mechanistic target of rapamycin complex 1 (mTORC1) senses diverse signals to regulate cell growth and metabolism. It has become increasingly clear that mTORC1 activity is regulated in time and space inside the cell, but direct interrogation of such spatiotemporal regulation is challenging. Here, we describe a genetically encoded mTORC1 activity reporter (TORCAR) that exhibits a change in FRET in response to phosphorylation by mTORC1. Co-imaging mTORC1 activity and calcium dynamics revealed that a growth-factor-induced calcium transient contributes to mTORC1 activity. Dynamic activity maps generated with the use of subcellularly targeted TORCAR uncovered mTORC1 activity not only in cytosol and at the lysosome but also in the nucleus and at the plasma membrane. Furthermore, a wide distribution of activities was observed upon growth factor stimulation, whereas leucine ester, an amino acid surrogate, induces more compartmentalized activities at the lysosome and in the nucleus. Thus, mTORC1 activities are spatiotemporally regulated in a signal-specific manner
Scientific Value of Real-Time Global Positioning System Data
The Global Positioning System (GPS) is an example of a Global Navigation Satellite System (GNSS) that provides an essential complement to other geophysical networks because of its high precision, sensitivity to the longestâperiod bands, ease of deployment, and ability to measure displacement and atmospheric properties over local to global scales. Recent and ongoing technical advances, combined with decreasing equipment and data acquisition costs, portend rapid increases in accessibility of data from expanding global geodetic networks. Scientists and the public are beginning to have access to these highârate, continuous data streams and eventâspecific information within seconds to minutes rather than days to months. These data provide the opportunity to observe Earth system processes with greater accuracy and detail, as they occur
Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I
Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I
Scientific Value of Real-Time Global Positioning System Data
The Global Positioning System (GPS) is an example of a Global Navigation Satellite System (GNSS) that provides an essential complement to other geophysical networks because of its high precision, sensitivity to the longestâperiod bands, ease of deployment, and ability to measure displacement and atmospheric properties over local to global scales. Recent and ongoing technical advances, combined with decreasing equipment and data acquisition costs, portend rapid increases in accessibility of data from expanding global geodetic networks. Scientists and the public are beginning to have access to these highârate, continuous data streams and eventâspecific information within seconds to minutes rather than days to months. These data provide the opportunity to observe Earth system processes with greater accuracy and detail, as they occur
Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells
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initMIP-Antarctica: an ice sheet model initialization experiment of ISMIP6
Ice sheet numerical modeling is an important tool to estimate the dynamic contribution of the Antarctic ice sheet to sea level rise over the coming centuries. The influence of initial conditions on ice sheet model simulations, however, is still unclear. To better understand this influence, an initial state intercomparison exercise (initMIP) has been developed to compare, evaluate, and improve initialization procedures and estimate their impact on century-scale simulations. initMIP is the first set of experiments of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6), which is the primary Coupled Model Intercomparison Project Phase 6 (CMIP6) activity focusing on the Greenland and Antarctic ice sheets. Following initMIP-Greenland, initMIP-Antarctica has been designed to explore uncertainties associated with model initialization and spin-up and to evaluate the impact of changes in external forcings. Starting from the state of the Antarctic ice sheet at the end of the initialization procedure, three forward experiments are each run for 100 years: a control run, a run with a surface mass balance anomaly, and a run with a basal melting anomaly beneath floating ice. This study presents the results of initMIP-Antarctica from 25 simulations performed by 16 international modeling groups. The submitted results use different initial conditions and initialization methods, as well as ice flow model parameters and reference external forcings. We find a good agreement among model responses to the surface mass balance anomaly but large variations in responses to the basal melting anomaly. These variations can be attributed to differences in the extent of ice shelves and their upstream tributaries, the numerical treatment of grounding line, and the initial ocean conditions applied, suggesting that ongoing efforts to better represent ice shelves in continental-scale models should continue
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The future sea-level contribution of the Greenland ice sheet: A multi-model ensemble study of ISMIP6
The Greenland ice sheet is one of the largest contributors to global mean sea-level rise today and is expected to continue to lose mass as the Arctic continues to warm. The two predominant mass loss mechanisms are increased surface meltwater run-off and mass loss associated with the retreat of marine-terminating outlet glaciers. In this paper we use a large ensemble of Greenland ice sheet models forced by output from a representative subset of the Coupled Model Intercomparison Project (CMIP5) global climate models to project ice sheet changes and sea-level rise contributions over the 21st century. The simulations are part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6).We estimate the sea-level contribution together with uncertainties due to future climate forcing, ice sheet model formulations and ocean forcing for the two greenhouse gas concentration scenarios RCP8.5 and RCP2.6. The results indicate that the Greenland ice sheet will continue to lose mass in both scenarios until 2100, with contributions of 90-50 and 32-17mm to sea-level rise for RCP8.5 and RCP2.6, respectively. The largest mass loss is expected from the south-west of Greenland, which is governed by surface mass balance changes, continuing what is already observed today. Because the contributions are calculated against an unforced control experiment, these numbers do not include any committed mass loss, i.e. mass loss that would occur over the coming century if the climate forcing remained constant. Under RCP8.5 forcing, ice sheet model uncertainty explains an ensemble spread of 40 mm, while climate model uncertainty and ocean forcing uncertainty account for a spread of 36 and 19 mm, respectively. Apart from those formally derived uncertainty ranges, the largest gap in our knowledge is about the physical understanding and implementation of the calving process, i.e. the interaction of the ice sheet with the ocean. © Author(s) 2020
Defective Interfering Viral Particles in Acute Dengue Infections
While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3âČ and 5âČ ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6â36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses
The future sea-level contribution of the Greenland ice sheet: a multi-model ensemble study of ISMIP6
The Greenland ice sheet is one of the largest contributors to global mean sea-level rise today and is expected to continue to lose mass as the Arctic continues to warm. The two predominant mass loss mechanisms are increased surface meltwater run-off and mass loss associated with the retreat of marine-terminating outlet glaciers. In this paper we use a large ensemble of Greenland ice sheet models forced by output from a representative subset of the Coupled Model Intercomparison Project (CMIP5) global climate models to project ice sheet changes and sea-level rise contributions over the 21st century. The simulations are part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). We estimate the sea-level contribution together with uncertainties due to future climate forcing, ice sheet model formulations and ocean forcing for the two greenhouse gas concentration scenarios RCP8.5 and RCP2.6. The results indicate that the Greenland ice sheet will continue to lose mass in both scenarios until 2100, with contributions of 90±50 and 32±17âmm to sea-level rise for RCP8.5 and RCP2.6, respectively. The largest mass loss is expected from the south-west of Greenland, which is governed by surface mass balance changes, continuing what is already observed today. Because the contributions are calculated against an unforced control experiment, these numbers do not include any committed mass loss, i.e. mass loss that would occur over the coming century if the climate forcing remained constant. Under RCP8.5 forcing, ice sheet model uncertainty explains an ensemble spread of 40âmm, while climate model uncertainty and ocean forcing uncertainty account for a spread of 36 and 19âmm, respectively. Apart from those formally derived uncertainty ranges, the largest gap in our knowledge is about the physical understanding and implementation of the calving process, i.e. the interaction of the ice sheet with the ocean
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