936 research outputs found

    Interhemispheric coupling, the West Antarctic Ice Sheet and warm Antarctic interglacials

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    Ice core evidence indicates that even though atmospheric CO2 concentrations did not exceed 300 ppm at any point during the last 800 000 years, East Antarctica was at least 3–4 C warmer than preindustrial (CO2 280 ppm) in each of the last four interglacials. During the previous three interglacials, this anomalous warming was short lived (3000 years) and apparently occurred before the completion of Northern Hemisphere deglaciation. Hereafter, we refer to these periods as “Warmer than Present Transients” (WPTs). We present a series of experiments to investigate the impact of deglacial meltwater on the Atlantic Meridional Overturning Circulation (AMOC) and Antarctic temperature. It is well known that a slowed AMOC would increase southern sea surface temperature (SST) through the bipolar seesaw and observational data suggests that the AMOC remained weak throughout the terminations precedingWPTs, strengthening rapidly at a time which coincides closely with peak Antarctic temperature. We present two 800 kyr transient simulations using the Intermediate Complexity model GENIE-1 which demonstrate that meltwater forcing generates transient southern warming that is consistent with the timing of WPTs, but is not sufficient (in this single parameterisation) to reproduce the magnitude of observed warmth. In order to investigate model and boundary condition uncertainty, we present three ensembles of transient GENIE-1 simulations across Termination II (135 000 to 124 000 BP) and three snapshot HadCM3 simulations at 130 000 BP. Only with consideration of the possible feedback of West Antarctic Ice Sheet (WAIS) retreat does it become possible to simulate the magnitude of observed warming

    Generalized Born Implicit Solvent Models Do Not Reproduce Secondary Structures of De Novo Designed Glu/Lys Peptides

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    [Image: see text] We test a range of standard generalized Born (GB) models and protein force fields for a set of five experimentally characterized, designed peptides comprising alternating blocks of glutamate and lysine, which have been shown to differ significantly in α-helical content. Sixty-five combinations of force fields and GB models are evaluated in >800 μs of molecular dynamics simulations. GB models generally do not reproduce the experimentally observed α-helical content, and none perform well for all five peptides. These results illustrate that these models are not usefully predictive in this context. These peptides provide a useful test set for simulation methods

    Transsynaptic entrainment of cerebellar nuclear cells by alternating currents in a frequency dependent manner

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    Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique that is being tested clinically for treatment of a variety of neural disorders. Animal studies investigating the underlying mechanisms of tACS are scarce, and nearly absent in the cerebellum. In the present study, we applied 10–400 Hz alternating currents (AC) to the cerebellar cortex in ketamine/xylazine anesthetized rats. The spiking activity of cerebellar nuclear (CN) cells was transsynaptically entrained to the frequency of AC stimulation in an intensity and frequency-dependent manner. Interestingly, there was a tuning curve for modulation where the frequencies in the midrange (100 and 150 Hz) were more effective, although the stimulation frequency for maximum modulation differed for each CN cell with slight dependence on the stimulation amplitude. CN spikes were entrained with latencies of a few milliseconds with respect to the AC stimulation cycle. These short latencies and that the transsynaptic modulation of the CN cells can occur at such high frequencies strongly suggests that PC simple spike synchrony at millisecond time scales is the underlying mechanism for CN cell entrainment. These results show that subthreshold AC stimulation can induce such PC spike synchrony without resorting to supra-threshold pulse stimulation for precise timing. Transsynaptic entrainment of deep CN cells via cortical stimulation could help keep stimulation currents within safety limits in tACS applications, allowing development of tACS as an alternative treatment to deep cerebellar stimulation. Our results also provide a possible explanation for human trials of cerebellar stimulation where the functional impacts of tACS were frequency dependent

    Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer.

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    The poor prognosis for patients with inflammatory breast cancer (IBC) compared to patients with other types of breast cancers emphasizes the need to better understand the molecular underpinnings of this disease with the goal of developing effective targeted therapeutics. Dysregulation of matriptase expression, an epithelial-specific member of the type II transmembrane serine protease family, has been demonstrated in many different cancer types. To date, no studies have assessed the expression and potential pro-oncogenic role of matriptase in IBC. We examined the functional relationship between matriptase and the HGF/c-MET signaling pathway in the IBC cell lines SUM149 and SUM190, and in IBC patient samples. Matriptase and c-Met proteins are localized on the surface membrane of IBC cells and their expression is strongly correlated in infiltrating cancer cells and in the cancer cells of lymphatic emboli in patient samples. Abrogation of matriptase expression by silencing with RNAi or inhibition of matriptase proteolytic activity with a synthetic inhibitor impairs the conversion of inactive pro-HGF to active HGF and subsequent c-Met-mediated signaling, leading to efficient impairment of proliferation and invasion of IBC cells. These data show the potential of matriptase inhibitors as a novel targeted therapy for IBC, and lay the groundwork for the development and testing of such drugs

    Characteristics of Lightning Within Electrified Snowfall Events Using Lightning Mapping Arrays

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    This study examined 34 lightning flashes within four separate thundersnow events derived from lightning mapping arrays (LMAs) in northern Alabama, central Oklahoma, and Washington, DC. The goals were to characterize the in-cloud component of each lightning flash, as well as the correspondence between the LMA observations and lightning data taken from national lightning networks like the National Lightning Detection Network (NLDN). Individual flashes were examined in detail to highlight several observations within the dataset. The study results demonstrated that the structures of these flashes were primarily normal polarity. The mean area encompassed by this set of flashes is 375 square kilometers, with a maximum flash extent of 2300 square kilometers, a minimum of 3 square kilometers, and a median of 128 square kilometers. An average of 2.29 NLDN flashes were recorded per LMA-derived lightning flash. A maximum of 11 NLDN flashes were recorded in association with a single LMA-derived flash on 10 January 2011. Additionally, seven of the 34 flashes in the study contain zero NLDN identified flashes. Eleven of the 34 flashes initiated from tall human-made objects (e.g., communication towers). In at least six lightning flashes, the NLDN detected a return stroke from the cloud back to the tower and not the initial upward leader. This study also discusses lightning's interaction with the human built environment and provides an example of lightning within heavy snowfall observed by GOES-16's Geostationary Lightning Mapper

    IR Sounder Small Satellite for Polar Orbit Weather Measurements

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    The National Environmental Satellite, Data, and Information Service (NESDIS) acquires and manages the Nation\u27s operational environmental satellites. NESDIS environmental satellite observations support a variety of civil and military environmental monitoring missions, including weather and climate prediction. A key input to weather forecast and climate models are atmospheric sounder observations from polar-orbiting satellites. These satellites are traditionally large, complex, and expensive, and take several years to design and build. The community must look for ways to reduce the cost and complexity of environmental satellites while meeting weather and climate sensing needs. This paper describes a new IR sounder concept that significantly reduces the size, mass, complexity, and consequent costs. This is accomplished through higher spectral resolution and the use of new large-area focal plane arrays, combined with novel dispersive optical design. In this design, one spectrometer with one FPA is required to perform both temperature and humidity sounding by imaging both bands onto the same FPA with an order sorting filter to separate the two bands. This paper details the design of the sensor and validation of sensor noise performance. Additionally, a thermal and spacecraft design are discussed to show the feasibility of a small-satellite scale instrument
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