138 research outputs found

    Nickel Phosphides Fabricated through a Codeposition–Annealing Technique as Low-Cost Electrocatalytic Layers for Efficient Hydrogen Evolution Reaction

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    Water splitting will be one of the most strategic techniques in the upcoming hydrogen-based economy. In this context, the development of efficient and low-cost Pt-free electrocatalysts is crucial t..

    Enhancement of the Biological and Mechanical Performances of Sintered Hydroxyapatite by Multiple Ions Doping

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    In the present work, hydroxyapatite (HA) nanoparticles doped with Mg2+, Sr2+, and Zn2+ ions are developed by wet neutralization method and then sintered at 1,250°C to obtain bulk consolidated materials. Physicochemical and microstructural analyses show that the presence of doping ions in the HA structure induced the formation of βTCP as secondary phase, during the sintering process, and we found that this effect is depending on the stability of the various doping ions in the hydroxyapatite lattice itself. We also found that the formation of βTCP as secondary phase, in turn, confines the grain growth of HA induced by the high-temperature sintering process, thus leading to a strong increase of the flexural strength of the bulk materials, according to Hall-Petch-like law. Furthermore, we found that the doping ions enter also in the structure of the βTCP phase; besides the grain growth confinement, also the solubility and ion release ability of the final materials were enhanced. In addition to ameliorate the mechanical performance, the described phenomena also activate multiple biofunctionalities: (i) ability to upregulate various genes involved in the osteogenesis, as obtained by human adipose stem cells culture and evaluated by array technology; (ii) enhanced resistance to the adhesion and proliferation of Gram+ and Gram– bacterial strains. Hence, our results open a perspective for the use of sintered multiple ion-doped HA to develop ceramic biodevices, such as plates, screws, or other osteosynthesis media, with enhanced strength, osteointegrability, and the ability to prevent post-surgical infections

    Use of observed ice crystal sizes and shapes to calculate mean-scattering properties and multispectral radiances: CEPEX April 4, 1993, case study

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    During the Central Equatorial Pacific Experiment, ice crystal sizes and shapes were measured in an outflow anvil. A habit (i.e., column, bullet rosette, Koch fractal polycrystal, sphere) was assigned to each particle using a self-organized neural network based on simulations of how the maximum particle dimension and area ratio varied for random orientations of these crystals. Average ice crystal size and shape distributions were calculated for 25 km long segments at six altitudes using measurements from a two-dimensional cloud probe for crystals larger than 90 μm and a parameterization for smaller crystals based on measurements from the Video Ice Particle Sampler (VIPS). Mean-scattering properties were determined by weighting the size and shape dependent single-scattering properties computed with ray-tracing algorithms according to scattering cross-section. Reflectances at 0.664, 0.875, 1.621, and 2.142 μm were then calculated using a Monte Carlo radiative transfer routine. Although these reflectances agree reasonably with those measured by the MODIS airborne simulator (MAS) above the anvil, uncertainties in cloud base and system evolution prevent a determination of whether ray-tracing or anomalous diffraction theory better predict reflectance. The calculated reflectances are as sensitive to the numbers and shapes of crystals smaller than 90 μm as to those of larger crystals. The calculated reflectances were insensitive to the classification scheme (i.e., neural network, discriminator analysis, and previously used classification scheme) for assigning particle shape to observed crystals. However, the reflectances significantly depended on assumed particle shape

    Enhancement of the Biological and Mechanical Performances of Sintered Hydroxyapatite by Multiple Ions Doping

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    In the present work, hydroxyapatite (HA) nanoparticles doped with Mg2+, Sr2+, and Zn2+ ions are developed by wet neutralization method and then sintered at 1,250°C to obtain bulk consolidated materials. Physicochemical and microstructural analyses show that the presence of doping ions in the HA structure induced the formation of βTCP as secondary phase, during the sintering process, and we found that this effect is depending on the stability of the various doping ions in the hydroxyapatite lattice itself. We also found that the formation of βTCP as secondary phase, in turn, confines the grain growth of HA induced by the high-temperature sintering process, thus leading to a strong increase of the flexural strength of the bulk materials, according to Hall-Petch-like law. Furthermore, we found that the doping ions enter also in the structure of the βTCP phase; besides the grain growth confinement, also the solubility and ion release ability of the final materials were enhanced. In addition to ameliorate the mechanical performance, the described phenomena also activate multiple biofunctionalities: (i) ability to upregulate various genes involved in the osteogenesis, as obtained by human adipose stem cells culture and evaluated by array technology; (ii) enhanced resistance to the adhesion and proliferation of Gram+ and Gram– bacterial strains. Hence, our results open a perspective for the use of sintered multiple ion-doped HA to develop ceramic biodevices, such as plates, screws, or other osteosynthesis media, with enhanced strength, osteointegrability, and the ability to prevent post-surgical infections

    E2F1-Mediated Upregulation of p19INK4d Determines Its Periodic Expression during Cell Cycle and Regulates Cellular Proliferation

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    BACKGROUND: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. CONCLUSIONS/SIGNIFICANCE: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity

    E2F1 drives chemotherapeutic drug resistance via ABCG2

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    Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1—a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1–ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy

    Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

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    Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12R beta 1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12R. 1 chain when cocultured with activated T cells or CD40L(+) cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies
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