摘要 :
Rationale. We previously demonstrated pre-B-cell colony enhancing factor (PBEF) as a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility. Objectives: To explore mechan...
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Rationale. We previously demonstrated pre-B-cell colony enhancing factor (PBEF) as a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility. Objectives: To explore mechanistic participation of PBEF in ALI and ventilator-induced lung injury (VILI).
Methods: Two models of VILI were utilized to explore the role of PBEF using either recombinant PBEF or PBEF~(+/-) mice. Measurements and Main Results: Initial in vitro studies demonstrated recombinant human PBEF (rhPBEF) as a direct rat neutrophil chemo-tactic factor with in vivo studies demonstrating marked increases in bronchoalveolar lavage (BAL) leukocytes (PMNs) after intratracheal injection in C57BL/6) mice. These changes were accompanied by increased BAL levels of PMN chemoattractants (KC and MIP-2) and modest increases in lung vascular and alveolar permeability. We next explored the potential synergism between rhPBEF challenge (intratracheal) and a model of limited VILI (4 h, 30 ml/kg tidal volume) and observed dramatic increases in BAL PMNs, BAL protein, and cytokine levels (IL-6, TNF-α, KC) compared with either challenge alone. Gene expression profiling identified induction of ALI- and VILI-associated gene modules (nuclear factor-KB, leukocyte extravasation, apoptosis, Toll receptor pathways). Heterozygous PBEF~(+/-) mice were significantly protected (reduced BAL protein, BAL IL-6 levels, peak inspira-tory pressures) when exposed to a model of severe VILI (4 h, 40 ml/kg tidal volume) and exhibited significantly reduced expression of VILI-associated gene expression modules. Finally, strategies to reduce PBEF availability (neutralizing antibody) resulted in significant protection from VILI.
Conclusions: These studies implicate PBEF as a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI.
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A new sensitive microwave life-detection which can be used to locate human subjects buried earthquake rubble or hidden behind various barriers has been constructed. This system operating at 1150 MHz or 450 MHz can detect the breat...
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A new sensitive microwave life-detection which can be used to locate human subjects buried earthquake rubble or hidden behind various barriers has been constructed. This system operating at 1150 MHz or 450 MHz can detect the breathing and heartbeat signals of human subjects through an earthquake rubble or a construction barrier of about 10-ft thickness. The basic physical principle for the operation of a microwave life-detection system is rather simple. When a microwave beam of appropriate frequency (L or S band) is aimed at a pile of earthquake rubble covering a human subject or illuminated through a barrier obstructing a human subject, the microwave beam can penetrate the rubble or the barrier to reach the human subject. When the human subject is illuminated by a microwave beam, the reflected wave from the human subject will be modulated by tile subject's body movements, which include the breathing and the heartbeat. If the clutter consisting of the reflected wave from stationary background can be completely eliminated and the reflected wave from the human subject's body is properly modulated, the breathing and heartbeat signals of the subject can be extracted. Thus, a human subject buried under earthquake rubble or hidden behind barriers can be located. This system has been tested extensively in a simulated earthquake rubble in the laboratory and also in a field test using realistic earthquake rubble conducted by a Federal Emergency Management Agency (FEMA) Task Force.
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Micro/nanoscale mechanical characterization of laminated Si_3N_4/BN composites was carried out by nanoindentation techniques. A custom-designed micro mechanical tester was integrated with an optical microscope and an atomic force ...
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Micro/nanoscale mechanical characterization of laminated Si_3N_4/BN composites was carried out by nanoindentation techniques. A custom-designed micro mechanical tester was integrated with an optical microscope and an atomic force microscope to perform in situ three-point bending tests on notched Si_3N_4/BN composite bend specimens where the crack initiation and propagation were imaged simultaneously with the optical microscope and atomic force microscope during bending loading. The whole fracture process was in situ captured. It was found that crack deflection was initiated/induced by the pre-existing microvoids and microcracks in BN interfacial layers. New fracture mechanisms were proposed to provide guidelines for the design of biomimetic nacre-like composites.
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Assembly of organic-inorganic nanocomposite with nacre-like structure has long been considered a valuable bio-inspired route to design materials with excellent mechanical properties. However, effective control of nanostructure and...
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Assembly of organic-inorganic nanocomposite with nacre-like structure has long been considered a valuable bio-inspired route to design materials with excellent mechanical properties. However, effective control of nanostructure and organic content concurrently is a key problem. In this research, a special assembly method-hydrothermal-electrophoretic assembly was introduced into preparing nanocomposite that mimics nacre, both in structure and composition. The two-step assembly process included intercalation of polymer into interlayer space of montmorillonite by hydrothermal process and the subsequent electrophoretic deposition. X-ray diffraction, Fourier transform infrared spectroscopy, thermal gravimetric analysis and scanning electronic microscopy were employed to characterize the structure and composition of the films. Reduced Young's modulus was determined by nanoindentation. Results showed that by constructing brick-and-mortar nanostructure, reduced Young's modulus of the composite film was effectively enhanced even when organic content was low.
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In this paper, a natural innoxious polymer is used to consolidate alumina ceramic suspensions. The gelling behavior of sodium alginate is studied for the process. Chelator is employed here, which combines the free calcium ions in ...
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In this paper, a natural innoxious polymer is used to consolidate alumina ceramic suspensions. The gelling behavior of sodium alginate is studied for the process. Chelator is employed here, which combines the free calcium ions in the chelate complex; therefore, the reaction between calcium ions and sodium alginate is avoided in the stage before casting. By adding hexanedioic acid, the calcium ions are released slowly from the chelate complex, which reacts with sodium alginate and results in the gelation. The time-delayed release of calcium ions allows the slurry to be molded into complex geometry before gelation occurs. This novel technique for the fabrication of near-net-shape complex parts is studied here. Special attention is given to the choice of the chelator, the solidified agent and the gelation behavior in the process.
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An investigation was carried out concerning mullite formation in reaction sintering of ZrSiO_4/α-Al_2O_3 mixtures using XRD, TEM and SEM techniques. It was demonstrated that mullite might nucleate within the Al_2O_3-rich amorphou...
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An investigation was carried out concerning mullite formation in reaction sintering of ZrSiO_4/α-Al_2O_3 mixtures using XRD, TEM and SEM techniques. It was demonstrated that mullite might nucleate within the Al_2O_3-rich amorphous matrix, which was formed from the solid state reaction between α-Al_2O_3 and ZrSiO_4. The formation of Al_2O_3-rich mullite and amorphous phase may imply that dissolution of Al_2O_3 is easier than dissociation of ZrSiO_4 in the present system, and that dissociation of ZrSiO_4 is a rate-limiting step in mullite grain growth at low temperatures, although the exact mechanism is still unclear. Available evidences indicate that, at final stage of mullization, Al~(3+) or Si~(4+) diffusion process through mullite layer might control mullite grain growth.
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In situ consolidation colloidal-forming processes, such as gel casting , are promising techniques for complex shaping of materials with high density, high uniformity and, thus, high reliability of performance. Non-oxide powders, e...
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In situ consolidation colloidal-forming processes, such as gel casting , are promising techniques for complex shaping of materials with high density, high uniformity and, thus, high reliability of performance. Non-oxide powders, e.g. Si, SiC and Si_3N_4, are suitable for being well dispersed in alkaline solutions. However, silicon powder and free silicon contained in silicon carbide and silicon nitride powders have a tendency to hydrolize, especially in a basic aqueous solution for gelcasting, causing a large amount of macropores in green bodies as a consequence of hydrogen gas evolution. Moreover, silicon nitride itself is chemically unstable in aqueous solutions and reacts with other reagents when processed by aqueous gelcasting, which also affects the microstructure of green bodies. After indentifying the causes of macropore formation in the gelcast green bodies, some solutions are proposed to overcome there problems.
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MicroRNAs and siRNAs interact with target sequences in mRNAs, inducing cleavage- and non-cleavage-based gene repression through the RNA-induced silencing complex (RISC) that consists of one of four mammalian Argonaute proteins, Ag...
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MicroRNAs and siRNAs interact with target sequences in mRNAs, inducing cleavage- and non-cleavage-based gene repression through the RNA-induced silencing complex (RISC) that consists of one of four mammalian Argonaute proteins, Ago1-Ago4. The process of how Dicer substrate small hairpin RNAs (shRNAs) are loaded into different mammalian Agos in vivo is not well established. Here we report that shRNAs are loaded into mammalian Agos in two stepwise processes, physical association and activation, with the latter being the rate-limiting step with noncleaving RISC. We establish that, although RNA duplexes processed from shRNAs bind to Agos in cells with similar affinity, the degree by which the complexes are activated (coupled with the removal of the passenger strand) correlates with the thermodynamic instability of RNA duplexes being loaded rather than the structure of the RNA, as was previously demonstrated in Drosophila. Interestingly, Ago loading of siRNAs is less sensitive to thermostability than that of their shRNA equivalents. These results may have important implications for the future design of RNAi-based therapeutics.
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Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of autosomal recessive familial Parkinson's disease (PD). Efforts in deducing the PINK1 signaling pathway have been hindered by controversy around its subcellular and...
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Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of autosomal recessive familial Parkinson's disease (PD). Efforts in deducing the PINK1 signaling pathway have been hindered by controversy around its subcellular and submitochondrial localization and the authenticity of its reported substrates. We show here that this mitochondrial protein exhibits a topology in which the kinase domain faces the cytoplasm and the N-terminal tail is inside the mitochondria. Although deletion of the transmembrane domain disrupts this topology, common PD-linked PINK1 mutations do not. These results are critical in rectifying the location and orientation of PINK1 in mitochondria, and they should help decipher its normal physiological function and potential pathogenic role in PD.
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The influence of solid loading and rheological properties of ZrO_2-Al_2O_3 suspension containing 15vol. /100 ZrO_2 on the mechanical properties of ZTA ceramics prepared by gelcasting was investigated. The flow behavior of the susp...
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The influence of solid loading and rheological properties of ZrO_2-Al_2O_3 suspension containing 15vol. /100 ZrO_2 on the mechanical properties of ZTA ceramics prepared by gelcasting was investigated. The flow behavior of the suspension changed obviously as the solid loading increased. It varied from a nearly Newtonian-type fluid (solid loading ≤ 50 vol. /100) to a non-Newtonian-type (solid loading > 50 vol. /100). The mechanical properties of sintered samples made from different suspensions were very different.
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