Resilience-based seismic design of reinforced concrete (RC) tall buildings has become an important trend in earthquake engineering. Seismic isolation technology is an effective and important method ...to improve the resiliency of RC frame-core tube tall buildings located in high seismic regions. However, the traditional design method for this type of building does not focus on the key design parameter, namely, the yield ratio of the isolation system and has therefore been proved to be highly inefficient. To address these issues, the rational yield ratio of isolation system for such buildings is investigated based on 28 carefully designed cases, considering the influences of total heights, yield ratios and seismically isolated schemes. The rational range of the yield ratio is recommended to be 2-3%. Based on this, a high-efficiency design method is proposed for seismically isolated RC frame-core tube tall buildings. Subsequently, a seismically isolated RC frame-core tube tall building with a height of 84.1 m is designed using the proposed design method. The rationality, reliability and efficiency of the proposed method are validated. The research outcome can serve as a reference for further development of the seismic design method for seismically isolated RC frame-core tube tall buildings.
In addition to acting as a physical barrier against microorganisms, the skin produces antimicrobial peptides and proteins. After wounding, growth factors are produced to stimulate the regeneration of ...tissue. The growth factor response ceases after regeneration of the tissue, when the physical barrier protecting against microbial infections is re-established. We found that the growth factors important in wound healing, insulin-like growth factor I and TGF-alpha, induce the expression of the antimicrobial peptides/polypeptides human cationic antimicrobial protein hCAP-18/LL-37, human beta-defensin 3, neutrophil gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor in human keratinocytes. Both an individual and a synergistic effect of these growth factors were observed. These findings offer an explanation for the expression of these peptides/polypeptides in the skin disease psoriasis and in wound healing and define a host defense role for growth factors in wound healing.
Intact human epidermis resists invasion by pathogenic microbes but the biochemical basis of its resistance is not well understood. Recently, an antimicrobial peptide, human β-defensin-2, was ...discovered in inflamed epidermis. We used a recombinant baculovirus/insect cell system to produce human β-defensin-2 and confirmed that at micromolar concentrations it has a broad spectrum of antimicrobial activity, with the striking exception of Staphylococcus aureus. Immunostaining with a polyclonal antibody to human β-defensin-2 showed that the expression of human β-defensin-2 peptide by human keratinocytes required differentiation of the cells (either by increased calcium concentration or by growth and maturation in epidermal organotypic culture) as well as a cytokine or bacterial stimulus. Interleukin-1α, interleukin-1β, or live Pseudomonas aeruginosa proved to be the most effective stimuli whereas other bacteria and cytokines had little or no ability to induce human β-defensin-2 synthesis. In interleukin-1α-stimulated epidermal cultures, human β-defensin-2 first appeared in the cytoplasm in differentiated suprabasal layers of skin, next in a more peripheral web-like distribution in the upper layers of the epidermis, and then over a few days migrated to the stratum corneum. By semiquantitative Western blot analysis of epidermal lysates, the average concentration of human β-defensin-2 in stimulated organotypic epidermal culture reached 15–70 µg per gram of tissue, i.e., 3.5–16 µM, well within the range required for antimicrobial activity. Because of the restricted pattern of human β-defensin-2 distribution in the epidermis, its local concentration must be much higher. Defensins and other antimicrobial peptides of inflamed epidermis are likely to play an important antimicrobial role in host defense against cutaneous pathogens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The iron-regulatory hormone hepcidin has been proposed as the mediator of anemia of inflammation (AI). We examined the acute and chronic effects of hepcidin in the mouse. Injections of human hepcidin ...(50 μg/mouse), but not of its diluent, induced hypoferremia within 4 hours. To examine the chronic effects of hepcidin, we implanted either tumor xenografts engineered to overexpress human hepcidin or control tumor xenografts into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Despite abundant dietary iron, mice with hepcidin-producing tumors developed more severe anemia, lower serum iron, and increased hepatic iron compared with mice with control tumors. Hepcidin contributes to AI by shunting iron away from erythropoiesis and sequestering it in the liver, predominantly in hepatocytes. (Blood. 2005;105:1797-1802)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epithelia react to microbial pathogens by mounting a defensive response that includes the production of antimicrobial peptides. In this study, we show that, in human epidermal cultures, Escherichia ...coli LPS was a very weak direct inducer of human beta-defensin (HBD)-2 mRNA and peptide, but the induction was greatly amplified when monocyte-derived cells (MoDeC) acted as intermediaries between LPS and the epidermis. IL-1R antagonist largely reversed the effect of MoDeC on epidermal HBD-2, indicating that, from among the many products of MoDeC, IL-1 was the dominant inducer of HBD-2 synthesis. In normal fresh human skin, which contains Langerhans cells and other myeloid cell types, in addition to keratinocytes, LPS also induced HBD-2 in an IL-1-dependent manner. In DNA microarray expression studies, HBD-2 was one of the most abundant mRNAs induced in epidermis by LPS-treated MoDeC, and its induction was reversed by IL-1Ra. Thus, epidermal response to LPS is potently amplified by MoDeC through IL-1-mediated signaling, leading to a selective increase in the synthesis of the antimicrobial peptide HBD-2. This pattern of responses establishes a key role for both IL-1 and HBD-2 in the host defense reaction of the epidermis.
Recent reports highlighted the chemotactic activities of antimicrobial peptide defensins whose structure, charge, and size resemble chemokines. By assaying representative members of the four known ...families of chemokines we explored the obverse: whether some chemokines exert antimicrobial activity. In a radial diffusion assay, only recombinant monokine induced by IFN-gamma (MIG/CXCL9), IFN-gamma-inducible protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11), members of the IFN-gamma-inducible tripeptide motif Glu-Leu-Arg (ELR)(-) CXC chemokines, were antimicrobial against Escherichia coli and Listeria monocytogenes. Similar to human defensins, antimicrobial activities of the chemokines were inhibited by 50 and 100 mM NaCl. The concentration of MIG/CXCL9 and IP-10/CXCL10 released from IFN-gamma-stimulated PBMC in 24 h were, respectively, 35- and 28-fold higher than from unstimulated cells. Additionally, the amounts of chemokines released per monocyte suggest that, in tissues with mononuclear cell infiltration, IFN-gamma-inducible chemokines may reach concentrations necessary for microbicidal activity. IFN-gamma-inducible chemokines may directly inactivate microbes before attracting other host defense cells to the area of infection.
Human β -defensins (HBDs) are antimicrobial peptides that may play a role in mucosal defense. Diminished activity of these peptides has been implicated in the pathogenesis of cystic fibrosis (CF) ...lung disease. We show that HBD-1 and HBD-2 mRNAs are expressed in excised surface and submucosal gland epithelia from non-CF and CF patients. The pro-inflammatory cytokine interleukin-1β stimulated the expression of HBD-2 but not HBD-1 mRNA and peptide in primary cultures of airway epithelia. HBD-1 was found in bronchoalveolar lavage (BAL) fluid from normal volunteers, CF patients, and patients with inflammatory lung diseases, whereas HBD-2 was detected in BAL fluid from patients with CF or inflammatory lung diseases, but not in normal volunteers. Both HBD-1 and HBD-2 were found in BAL fluid in concentrations of several ng/ml, and both recombinant peptides showed salt-sensitive bactericidal activity. These data suggest that in the lung HBD-2 expression is induced by inflammation, whereas HBD-1 may serve as a defense in the absence of inflammation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The fluidity of fresh concrete undergoes changes during transportation, exerting a direct influence on the pumping process and the ultimate quality of the hardened concrete. This study utilized the ...discrete element method to explore the impact of the time-dependence of fresh concrete on the transportation process. Specifically, a JKR contact model incorporating surface energy was employed to characterize the constitutive behavior of fresh concrete. The research established a relationship between surface energy and transportation time. The investigation delved into the mixing process after varying transportation durations through numerical simulations. The relative velocity between coarse aggregate and mortar increase with transportation time. The findings reveal a diminishing trend in both mixing and discharging homogeneity as transportation time increases. Enhancing the mixing speed of the drum to a critical value before discharge can ameliorate discharging homogeneity. However, excessive mixing speed may lead to detrimental effects on homogeneity.
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•A numerical method was developed to investigate time dependence of fresh concrete.•Discharge homogeneity decreases with transportation time.•Homogeneity can be improved by increasing the stirring speed appropriately.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
While laccase of Cryptococcus neoformans is implicated in the virulence of the organism, our recent studies showing absence of melanin in the infected mouse brain has led us to a search for ...alternative roles for laccase in cryptococcosis. We investigated the role of laccase in protection of C. neoformans against murine alveolar macrophage (AM)-mediated antifungal activity by using a pair of congenic laccase-positive (2E-TUC) and laccase-deficient (2E-TU) strains. The laccase-positive cells with laccase derepression were more resistant to the antifungal activity of AM than a laccase-deficient strain (28.9 +/- 1.2% versus 40.2 +/- 2.6% killing). Addition of L-dopa to Cryptococcus to produce melanin in a laccase-positive strain resulted in a slight increase in protection of C. neoformans from the antifungal activity of macrophages (25.4 +/- 3.4% versus 28.9 +/- 1.2% killing). Recombinant cryptococcal laccase exhibited iron oxidase activity in converting Fe(II) to Fe(III). Moreover, recombinant laccase inhibited killing of C. neoformans by hydroxyl radicals catalyzed by iron in a cell-free system. Addition of the hydroxyl radical scavenger mannitol or dimethyl sulfoxide to AMs prior to the introduction of cryptococcal cells decreased killing of both strains and reduced the difference in susceptibility between the laccase-positive and laccase-deficient strains. Furthermore, laccase-mediated protection from AM killing was inhibited by the addition of Fe(II), presumably by overcoming the effects of the iron oxidase activity of cryptococcal laccase. These results suggest that the iron oxidase activity of laccase may protect C. neoformans from macrophages by oxidation of phagosomal iron to Fe(III) with a resultant decrease in hydroxyl radical formation.
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