1,006 research outputs found

    Citrus trade liberalization with Japan

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    trade liberalization, Japan, citrus, Agribusiness, International Relations/Trade,

    IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals

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    Dendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation. Using serial analysis of gene expression, we show that IL-10 pretreatment of murine bone marrow-derived DCs alone causes significant changes in gene expression. Furthermore, these cells retain the ability to respond to Toll-like receptor agonists, but in a manner skewed toward the selective induction of mediators known to enhance local inflammation and innate immunity, among which we highlight a novel CXCR2 ligand, DC inflammatory protein-1. These data suggest that, while the presence of a protolerogenic and purportedly anti-inflammatory agent such as IL-10 precludes DCs from acquiring their potential as initiators of adaptive immunity, their ability to act as initiators of innate immunity in response to Toll-like receptor signaling is enhanced

    A macroinvertebrate assessment of Ozark streams located in lead–zinc mining areas of the Viburnum Trend in southeastern Missouri, USA

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    The Viburnum Trend lead–zinc mining subdistrict is located in the southeast Missouri portion of the Ozark Plateau. In 2003 and 2004, we assessed the ecological effects of mining in several watersheds in the region. We included macroinvertebrate surveys, habitat assessments, and analysis of metals in sediment, pore water, and aquatic biota. Macroinvertebrates were sampled at 21 sites to determine aquatic life impairment status (full, partial, or nonsupport) and relative biotic condition scores. Macroinvertebrate biotic condition scores were significantly correlated with cadmium, nickel, lead, zinc, and specific conductance in 2003 (r = −0.61 to −0.68) and with cadmium, lead, and pore water toxic units in 2004 (r = −0.55 to −0.57). Reference sites were fully supporting of aquatic life and had the lowest metals concentrations and among the highest biotic condition scores in both years. Sites directly downstream from mining and related activities were partially supporting, with biotic condition scores 10% to 58% lower than reference sites. Sites located greater distances downstream from mining activities had intermediate scores and concentrations of metals. Results indicate that elevated concentrations of metals originating from mining activities were the underlying cause of aquatic life impairment in several of the streams studied. There was a general concurrence among the adversely affected sites in how the various indicators responded to the mining activities during the overall study

    Fabrication and electrical characterization of three-dimensional graphitic microchannels in single crystal diamond

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    We report on the systematic characterization of conductive micro-channels fabricated in single-crystal diamond with direct ion microbeam writing. Focused high-energy (~MeV) helium ions are employed to selectively convert diamond with micrometric spatial accuracy to a stable graphitic phase upon thermal annealing, due to the induced structural damage occurring at the end-of-range. A variable-thickness mask allows the accurate modulation of the depth at which the microchannels are formed, from several {\mu}m deep up to the very surface of the sample. By means of cross-sectional transmission electron microscopy (TEM) we demonstrate that the technique allows the direct writing of amorphous (and graphitic, upon suitable thermal annealing) microstructures extending within the insulating diamond matrix in the three spatial directions, and in particular that buried channels embedded in a highly insulating matrix emerge and electrically connect to the sample surface at specific locations. Moreover, by means of electrical characterization both at room temperature and variable temperature, we investigate the conductivity and the charge-transport mechanisms of microchannels obtained by implantation at different ion fluences and after subsequent thermal processes, demonstrating that upon high-temperature annealing, the channels implanted above a critical damage density convert to a stable graphitic phase. These structures have significant impact for different applications, such as compact ionizing radiation detectors, dosimeters, bio-sensors and more generally diamond-based devices with buried three-dimensional all-carbon electrodes

    Third-Line Nivolumab Monotherapy in Recurrent Small Cell Lung Cancer : CheckMate 032

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    Introduction: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third- or later-line nivolumab monotherapy treatment in SCLC. Methods: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third- or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5\u201319.5) with a median duration of response of 17.9 months (range 3.0\u201342.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events. Conclusions: Nivolumab monotherapy provided durable responses and was well tolerated as a third- or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third- or later-line treatment for this patient population

    Artifacts resembling Ediacaran or Cambrian fossils: how to identify them and avoid their generation

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    The generation of artifacts during sample preparation must be considered in paleobiological studies, particularly during the Ediacaran and Cambrian, since such artifacts can assume forms similar to those of cloudinids and other problematic taxa commonly described in samples from these systems. Chemical reactions between hydrogen peroxide and sulfides from the samples can lead to the formation of tubular and vase-shaped structures. The visual description alone does not allow a conclusion about whether their origin is organic or inorganic. In these cases, chemical composition and ultrastructure analysis are tools that help to distinguish artifacts from bona fide fossils. Scanning electron microscopy can be successfully employed to characterize and differentiate fossils from artifacts. The presence or absence of these structures in thin sections is also an essential piece of information to discuss their biogenicity. Furthermore, not using hydrogen peroxide avoids the risk of formation of the artifacts described here.</p

    Rare-earth monosulfides as durable and efficient cold cathodes

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    In their rocksalt structure, rare-earth monosulfides offer a more stable alternative to alkali metals to attain low or negative electron affinity when deposited on various III-V and II-VI semiconductor surfaces. In this article, we first describe the successful deposition of Lanthanum Monosulfide via pulsed laser deposition on Si and MgO substrates and alumina templates. These thin films have been characterized by X-ray diffraction, atomic force microscopy, high resolution transmission electron microscopy, ellipsometry, Raman spectroscopy, ultraviolet photoelectron spectroscopy and Kelvin probe measurements. For both LaS/Si and LaS/MgO thin films, the effective work function of the submicron thick thin films was determined to be about 1 eV from field emission measurements using the Scanning Anode Field Emission Microscopy technique. The physical reasons for these highly desirable low work function properties were explained using a patchwork field emission model of the emitting surface. In this model, nanocrystals of low work function materials having a orientation perpendicular to the surface and outcropping it are surrounded by a matrix of amorphous materials with higher work function. To date, LaS thin films have been used successfully as cold cathode emitters with measured emitted current densities as high as 50 A/cm2. Finally, we describe the successful growth of LaS thin films on InP substrates and, more recently, the production of LaS nanoballs and nanoclusters using Pulsed Laser Ablation.Comment: 61 pages, 24 figure

    Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

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    This study was designed to experimentally evaluate the optimal X-ray energy for increasing the radiation energy absorbed in tumours loaded with iodinated compounds, using the photoelectric effect. SQ20B human cells were irradiated with synchrotron monochromatic beam tuned at 32.8, 33.5, 50 and 70 keV. Two cell treatments were compared to the control: cells suspended in 10 mg ml1 of iodine radiological contrast agent or cells pre-exposed with 10 mM of iodo-desoxyuridine (IUdR) for 48 h. Our radiobiological end point was clonogenic cell survival. Cells irradiated with both iodine compounds exhibited a radiation sensitisation enhancement. Moreover, it was energy dependent, with a maximum at 50 keV. At this energy, the sensitisation calculated at 10% survival was equal to 2.03 for cells suspended in iodinated contrast agent and 2.60 for IUdR. Cells pretreated with IUdR had higher sensitisation factors over the energy range than for those suspended in iodine contrast agent. Also, their survival curves presented no shoulder, suggesting complex lethal damages from Auger electrons. Our results confirm the existence of the 50 keV energy optimum for a binary therapeutic irradiation based on the presence of stable iodine in tumours and an external irradiation. Monochromatic synchrotron radiotherapy concept is hence proposed for increasing the differential effect between healthy and cancerous tissue irradiation

    Isotope hydrology of dripwaters in a Scottish cave and implications for stalagmite palaeoclimate research

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    Dripwater hydrology and hydrogeochemistry is particularly useful in constraining the meaning of speleothem palaeoclimate archives, for example using &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O signatures. Here, we calibrate the relationship between &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O in precipitation, percolation waters and contemporary calcite deposits, at Tartair cave, Sutherland, NW Scotland, an Atlantic site sensitive to regional changes both of temperature and precipitation. Monthly precipitation displayed a 7.1&amp;permil; range in &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O, a negative linear relationship with rainfall amount, and no correlation with temperature. Autogenically-derived cave percolation waters show little variation in &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O during the same period and their annual weighted mean is the same as that of the local precipitation. This evidence together with hydrological data and electroconductivity values indicates that percolation waters are well mixed and dominated by stored water. Calculated values of &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O of calcite deposited in this cave environment indicate that the cave deposits are forming close to isotopic equilibrium and kinetic effects are negligible. Comparison of a high-resolution &amp;delta;&lt;sup&gt;18&lt;/sup&gt;O stalagmite record with the instrumental record of climate indicates that isotopically heavy values are reflective of relatively cold, dry conditions (and vice-versa for warm, wet condition) and hence that stalagmite oxygen isotopes provide an appropriate means of investigating the palaeoclimate in this location
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