1,724,317 research outputs found
Microstructure of As-Cast 7085 Aluminum Alloy by Homogenization
No full text7085 aluminum alloy has been widely used in aviation and aerospace because of high fracture toughness, high strength, slow quench sensitivity and low density. In the as-cast microstructure, it is not avoidable for massive un-dissolved secondary phases and dendritic segregation. The microstructure of as-cast high strength 7085 aluminum alloy after two-stage homogenization was studied by optical microscopy (OM), X-ray diffractometer (XRD), scanning election microscopy (SEM), energy dispersive spectrometer (EDS) and differential scanning calorimeter (DSC). It was found that the severe dendritic segregation exists in as-cast 7085 aluminum alloy and a small amount of Al7Cu2Fe exists in the as-cast 7085 alloy. The evolution of primary eutectic structure of 7085 alloy consists of three processes: the dissolution of non-equilibrium eutectic phase α (Al) + Mg (Zn)2, the transformation from Mg (Zn)2 to Al2CuMg and the dissolution of new phase Mg (Zn)2. A suitable two-stage homogenization scheme for as-cast 7085 aluminum alloy is 300°C/8 h + 465°C/24 h.</jats:p
Bay11-7085 treatment of PEL cells activates mitochondrial apoptotic pathway in PEL cell lines.
No full text<p>(<b>A</b>) <b>Bay11-7085-induced Bax activation in PEL cells.</b> After treating with 10 µM Bay11-7085 for indicated time periods, BC1 cells were lysed in 1% Chaps lysis buffer and subjected to immuno-precipitation with anti-Bax 6A7 antibody for detection of conformationally changed Bax protein. In addition, the total cell lysates were applied directly to SDS–PAGE, transferred to immobilon membrane and immuno-blotted with specific anti-Bax polyclonal antibody. (<b>B</b>) <b>Bay11-7085 treatment causes change in mitochondrial membrane potential in PEL cells.</b> PEL cells were treated with and without 5 and 10 µM Bay11-7085 for 24 hours. Live cells with intact mitochondrial membrane potential and dead cells with lost mitochondrial membrane potential was measured by JC-1 staining and analyzed by flow cytometry as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039945#s2" target="_blank">Materials and Methods</a>. (<b>C</b>) <b>Bay11-7085 treatment causes release of cytochrome c from mitochondria into cytosole in PEL cells.</b> BC1 cells were treated with 5 and 10 µM Bay11-7085 for 24 hours. Mitochondrial free cytosolic fractions and cytosolic extracts were isolated and immunoblotted with antibody against cytochrome c and Beta-actin. (<b>D</b>) <b>Bay11-7085 treatment causes down-regulation of IAPs in PEL cells.</b> BC1 and BC3 cells were treated with 5 and 10 µM Bay11-7085 for 24 hours. Cells were lysed and equal amounts of proteins were separated by SDS-PAGE, transferred to PVDF membrane, and immunoblotted with antibodies against cIAP1 and cIAP2. Beat actin was used for equal loading.</p
Bay11-7085 induced apoptosis is caspase dependent in PEL cell lines.
No full text<p>(<b>A</b>) <b>Activation of caspases-9, -3, and cleavage of PARP induced by Bay11-7085 treatment in PEL cells.</b> BC1 and BC3 cells were treated with 5 and 10 µM Bay11-7085 for 24 hours. Cells were lysed and equal amounts of proteins were separated by SDS-PAGE, transferred to PVDF membrane, and immunoblotted with antibodies against caspase-9, caspase-3, cleaved caspase-3 and PARP. Beta-actin was used for equal loading. (<b>B</b>) <b>Bay11-7085 treatment causes cleavage of caspase-8 and truncation of Bid in PEL cells.</b> After treatment with 5 and 10 µM Bay11-7085 for 24 hours, cells were lysed, and equal amount of proteins were separated by SDS-PAGE, transferred to PVDF membrane, and immunoblotted with antibodies against caspase-8 and Bid. (<b>C, D and E</b>) <b>Bay11-7085-induced apoptosis is caspase dependent in PEL cells.</b> PEL cells were pre-treated with 80 µM zVAD-fmk for 2 hours and then treated with 10 µM Bay11-7085 for 24 hours. Following treatment, cells were either lysed and equal amounts of proteins were separated by SDS-PAGE, transferred to PVDF membrane, and immunoblotted with antibodies against caspase-3, cleaved caspase-3 and PARP (<b>C</b>) or stained with FITC conjugated annexin V/PI and analyzed by flow cytometry (<b>D</b>). Bar graph denotes percentage apoptosis from three independent experiments (<b>E</b>).</p
Repurposing Kinase Inhibitor Bay 11-7085 to Combat Staphylococcus aureus and Candida albicans Biofilms
No full textStaphylococcus aureus and Candida spp. are commonly linked with topical biofilm-associated infections such as those found on chronic wounds. These biofilms are notoriously difficult to treat, highlighting the grave need to discover and study new broad-spectrum agents to combat associated infections. Here we report that the kinase inhibitor Bay 11-7085 exhibited bactericidal activity against multidrug-resistant S. aureus with a minimum inhibitory concentration (MIC) of 4 mu g/ml. In addition, S. aureus strain MW2 did not acquire resistance to antibiotic pressure. Furthermore, Bay 11-7085 exhibited potency against Candida albicans and the emerging pathogen Candida auris with a MIC of 0.5-1 mu g/ml. Bay 11-7085 partially inhibited and eradicated biofilm formation of various pathogens, such as VRSA (vancomycin-resistant S. aureus), as well as antifungal-resistant Candida spp. isolates. Notably, Bay 11-7085 partially inhibited initial cell attachment and formation of a VRSA-C. albicans polymicrobial biofilm in vitro. In contrast to C. albicans, inhibition of VRSA biofilm was linked to initial cell attachment independent of its bactericidal activity. Finally, Bay 11-7085 was effective in vivo at increasing the lifespan of C. elegans during an S. aureus and a C. albicans infection. Our work proposes kinase inhibitor Bay 11-7085 as a potential compound capable of combating biofilms associated with primary multidrug-resistant bacteria and yeast pathogens associated with wound infections
Small fatigue crack nucleation and growth in aluminium alloy 7085-T7452
No full textAluminium alloy (AA) 7085 is a recent addition to the 7XXX series of aluminium (Al), zinc (Zn), magnesium (Mg) and copper (Cu) high strength aerospace alloys with applications in primary airframe structure of the Airbus A380 and all variants of the Lockheed Martin (LM) F-35. T7452 is the temper and designation of the die-forged product, which was developed for large unitized, lightweight airframe structures since its low quench sensitivity and good through-thickness fracture-toughness enables forgings of up to 12 inches (305mm) thickness. AA 7085 has a lower Mg and higher Zn content than comparable alloys such as 7050. As a relatively new material at the time of publication, there is little fatigue data available in the published literature and none with a focus on the small or near-threshold fatigue crack growth regime where sub-millimetre fatigue cracks spend most of their lives in service structures. Further, there is little research into fatigue crack nucleation mechanisms in this material in its final, surface-finished airframe part production form with applied service loading. This research project examines small fatigue crack nucleation and growth in AA 7085-T7452, comparing it with other 7XXX series alloys. The role of material composition, microstructure and production surface finish treatments in fatigue crack nucleation and growth are given prominence and more accurate fatigue crack growth tools are sought.
This research addresses gaps in the open literature centred on AA 7085-T7452 small fatigue crack nucleation mechanisms and growth rates with an applied, aircraft industry focus. The objectives of this research were to:
i. establish the importance of accurate fatigue crack growth rate data and models in the small crack and near-threshold regime in the context of engineered, AA 7XXX aircraft production parts;
ii. quantify the small and near-threshold fatigue crack growth behaviour of AA 7085-T7452 relative to other 7XXX alloys including AA 7050-T7451 and AA 7075-T7351;
iii. determine the extent to which microstructure can be significant in influencing small fatigue crack nucleation and growth rates in AA 7085-T7452;
iv. establish the causal factors and significant influences on small fatigue crack nucleation and equivalent initial damage sizes (EIDS) in AA 7085 versus AA 7050 for Type 1C anodised airframe production parts; and to
v. establish the fundamental material mechanisms that give rise to improved resistance to fatigue crack nucleation of AA 7085-T7452 over AA 7050-T7451 in Type 1C anodised material representative of aircraft production parts.
Significant new knowledge arising from this research project includes:
i. characterisation and validation of small and near-threshold fatigue crack growth rates in AA 7085-T7452 and ranking relative to other AA 7XXX alloys;
ii. an evaluation of the role of microstructure and common aircraft production surface finish treatments on small fatigue nucleation and growth rates in AA 7085-T7452;
iii. development of EIDS distributions for crack nucleating etch pits associated with Type 1C anodising of AA 7085-T7452 and AA 7050-T7451 alloys and establishing the significant role of material microstructure and stress;
iv. material characterisation of crack nucleation sites in Type 1C anodised AA 7085-T7452 and AA 7050-T7451 specimens demonstrating the significance of the population, size, shape and distribution of Al7Cu2Fe intermetallics on fatigue crack nucleation.
While this dissertation identifies various avenues for further inquiry and investigation, it records substantial progress in the understanding of the nucleation and growth of small fatigue cracks in AA 7085-T7452 and how these behaviours may be incorporated into fatigue design and fatigue tools for the certification and sustainment of aircraft structures
Study of Hydrogen-Induced Plastic Damage Response of 7085-T7651 High-Strength Aluminum Alloy
No full textThe hydrogen-induced plastic loss behavior of titanium alloys is often reported, but there are relatively few studies on high-strength aluminum alloys. In this article, the hydrogen-induced plastic damage behavior of 7085-T7651 high-strength aluminum alloy was investigated using a tensile specimen with pre-charging hydrogen, and the microstructure was characterized by transmission electron microscopy, scanning electron microscopy and time-of-flight secondary ion mass spectrometry. The results showed that 7085-T7651 high-strength aluminum alloy material has certain hydrogen embrittlement sensitivities, and with the increase of hydrogen-charging time, the hydrogen content and sensitivity of the material increases significantly. For the first time, the theoretical analysis and intuitive quantitative characterization of the hydrogen-induced plastic loss behavior mechanism on 7085-T7651 high-strength aluminum alloy is stated as the formation of Mg and H segregation formed at the crystal boundary, which will result in the weakening of the crystal boundary
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellular signal-regulated kinase phosphorylation and apoptosis in human articular chondrocytes and synovial fibroblasts
Get PDFpeer reviewedWe have previously shown that nuclear factor-kappaB inhibition by adenovirus
expressing mutated IkappaB-alpha or by proteasome inhibitor increases human
articular chondrocytes sensibility to apoptosis. Moreover, the nuclear
factor-kappaB inhibitor BAY11-7085, a potent anti-inflammatory drug in rat
adjuvant arthritis, is itself a proapoptotic agent for chondrocytes. In this
work, we show that BAY 11-7085 but not the proteasome inhibitor MG-132 induced a
rapid and sustained phosphorylation of extracellular signal-regulated kinases
(ERK1/2) in human articular chondrocytes. The level of ERK1/2 phosphorylation
correlated with BAY 11-7085 concentration and chondrocyte apoptosis.
15-Deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and its precursor prostaglandin
(PG) D2 but not PGE2 and PGF2alpha rescued chondrocytes from BAY 11-7085-induced
apoptosis. 15d-PGJ2 markedly inhibited BAY 11-7085-induced phosphorylation of
ERK1/2. BAY 11-7085 also induced ERK1/2 phosphorylation and apoptosis in human
synovial fibroblasts, and these reactions were down-regulated by 15d-PGJ2.
Further analysis in synovial fibroblasts showed that only molecules that
suppressed BAY 11-7085-induced phosphorylation of ERK1/2 (i.e. 15d-PGJ2, PGD2,
and to a lesser extent, MEK1/2 inhibitor UO126, but not prostaglandins E2 and
F2alpha or peroxisome proliferator-activated receptor-gamma agonist ciglitazone)
were able protect cells from apoptosis. These results suggested that the
antiapoptotic effect of 15d-PGJ2 on chondrocytes and synovial fibroblasts might
involve inhibition of ERK1/2 phosphorylation
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