Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

Based on the characterization by Atomic Force Microscopy (AFM), we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young’s moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton (CSK) and the intracellular fluid when the fixed chondrocytes is mainly governed by their intracellular fluid which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic (PHE) constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen- activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

Minimization of bauxite residue neutralization products using nanofiltered seawater

Currently, open circuit Bayer refineries pump seawater directly into their operations to neutralize the caustic fraction of the Bayer residue. The resulting supernatant has a reduced pH and is pumped back to the marine environment. This investigation has assessed modified seawater sources generated from nanofiltration processes to compare their relative capacities to neutralize bauxite residues. An assessment of the chemical stability of the neutralization products, neutralization efficiency, discharge water quality, bauxite residue composition, and associated economic benefits have been considered to determine the most preferable seawater filtration process based on implementation costs, savings to operations and environmental benefits. The mechanism of neutralization for each technology was determined to be predominately due to the formation of Bayer hydrotalcite and calcium carbonate, however variations in neutralization capacity and efficiencies have been observed. The neutralization efficiency of each feed source has been found to be dependent on the concentration of magnesium, aluminium, calcium and carbonate. Nanofiltered seawater with approximately double the amount of magnesium and calcium required half the volume of seawater to achieve the same degree of neutralization. These studies have revealed that multiple neutralization steps occur throughout the process using characterization techniques such as X-ray diffraction (XRD), infrared (IR) spectroscopy and inductively coupled plasma optical emission spectroscopy (ICP-OES).

Improvements to bauxite residue neutralisation efficiency through the use of alternative feed sources

Currently, open circuit Bayer refineries pump seawater directly into their operations to neutralise the caustic fraction of the Bayer residue. The resulting supernatant has a reduced pH and is pumped back to the marine environment. This investigation has assessed modified seawater sources generated from different ion filtration processes to compare their relative capacities to neutralise bauxite residues. An assessment of the chemical stability of the neutralisation products, neutralisation efficiency, discharge water quality, bauxite residue composition, and associated economic benefits have been considered to determine the most preferable seawater filtration process based on implementation costs, savings to operations and environmental benefits. The mechanism of neutralisation for each technology was determined to be predominately due to the formation of Bayer hydrotalcite and calcium carbonate, however variations in neutralisation capacity and efficiencies have been observed. The neutralisation efficiency of each feed source has been found to be dependent on the concentration of magnesium, aluminium, calcium and carbonate. These studies have revealed that multiple neutralisation steps occur throughout the process. Environmental, economic and social advantages and disadvantages of the different filtration technologies have been explored to determine the most sustainable method for the neutralisation of bauxite residues. The relative degree of “green” associated with nanofiltered seawater and reverse osmosis filtered seawater are discussed.

MT1-MMP-dependent and -independent regulation of gelatinase A activation in long-term, ascorbate-treated fibroblast cultures: Regulation by fibrillar collagen

Human skin fibroblasts were cultured long-term in the presence of ascorbic acid to allow formation of a three-dimensional collagen matrix, and the effects of this on activation of secreted matrix metalloproteinase-2 (MMP-2) were examined. Accumulation of collagen over time correlated with increased levels of both mature MMP-2 and cell-associated membrane type 1-MMP (MT1-MMP), and subsequently increased mRNA levels for MT1-MMP, providing temporal resolution of the "nontranscriptional" and "transcriptional" effects of collagen on MT-1MMP functionality. MMP-2 activation by these cultures was blocked by inhibitors of prolyl-4-hydroxylase, or when fibroblasts derived from the collagen α1(I) gene-deficient Mov-13 mouse were used. MMP-2 activation by the Mov-13 fibroblasts was rescued by transfection of a full-length α1(I) collagen cDNA, and to our surprise, also by transfection with an α1(I) collagen cDNA carrying a mutation at the C-proteinase cleavage, which almost abrogated fibrillogenesis. Although studies with ascorbate-cultured MT1-MMP-/- fibroblasts showed that MT1-MMP played a significant role in the collagen-induced MMP-2 activation, a residual MT1-MMP-independent activation of MMP-2 was seen which resembled the level of MMP-2 activation persisting when wild-type fibroblasts were cultured in the presence of both ascorbic acid and MMP inhibitors. We were also unable to block this residual activation with inhibitors specific for serinyl, aspartyl, or cysteinyl enzymes.

Characterization and novel activation of 72-kDa metalloproteinase in retinal interphotoreceptor matrix and Y-79 cell culture medium

Analysis of bovine interphotoreceptor matrix and conditioned medium from human Y-79 retinoblastoma cells by gelatin SDS-PAGE zymography reveals abundant activity of a 72-kDa M(r) gelatinase. The 72-kDa gelatinase from either source is inhibited by EDTA but not aprotinin or NEM, indicating that it is a metalloproteinase (MMP). The 72-kDa MMP is converted to a 62-kDa species with APMA treatment after gelatin sepharose affinity purification typical of previously described gelatinase MMP-2. The latent 72-kDa gelatinase from either bovine IPM or Y-79 media autoactivates without APMA in the presence of calcium and zinc after 72 hr at 37°C, producing a fully active mixture of proteinase species, 50 (48 in Y-79 medium), 38 and 35 kDa in size. The presence of inhibitory activity was examined in both whole bovine IPM and IPM fractions separated by SDS-PAGE. Whole IPM inhibited gelatinolytic activity of autoactivated Y-79-derived MMP in a dose-dependent manner. Inhibitory activities are observed in two protein fractions of 27-42 and 20-25 kDa. Western blots using antibodies to human tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) reveal the presence of two TIMP-1-like proteins at 21 and 29 kDa in inhibitory fractions of the bovine IPM. TIMP-2 was not detected in the inhibitory IPM fractions, consistent with the observed autoactivation of bovine IPM 72-kDa gelatinase. Potential roles for this IPM MMP-TIMP system include physiologic remodelling of the neural retina-RPE cell interface and digestion of shed rod outer segment as well as pathological processes such as retinal detachment, PE cell migration, neovascularization and tumor progression. Cultured Y-79 cells appear to be a good model for studying the production and regulation of this proteinase system.

Critical review of time-dependent shortest path algorithms: A multimodal trip planner perspective

A multimodal trip planner that produces optimal journeys involving both public transport and private vehicle legs has to solve a number of shortest path problems, both on the road network and the public transport network. The algorithms that are used to solve these shortest path problems have been researched since the late 1950s. However, in order to provide accurate journey plans that can be trusted by the user, the variability of travel times caused by traffic congestion must be taken into consideration. This requires the use of more sophisticated time-dependent shortest path algorithms, which have only been researched in depth over the last two decades, from the mid-1990s. This paper will review and compare nine algorithms that have been proposed in the literature, discussing the advantages and disadvantages of each algorithm on the basis of five important criteria that must be considered when choosing one or more of them to implement in a multimodal trip planner.

BM18 : a novel androgen-dependent human prostate cancer xenograft model derived from a bone metastasis

BACKGROUND Androgen-dependent prostate cancer (PrCa) xenograft models are required to study PrCa biology in the clinically relevant in vivo environment. METHODS Human PrCa tissue from a femoral bone metastasis biopsy (BM18) was grown and passaged subcutaneously through male severe combined immune-deficient (SCID) mice. Human mitochondria (hMt), prostate specific antigen (PSA), androgen receptor (AR), cytokeratin-18 (CK-18), pan-cytokeratin, and high molecular weight-cytokeratin (HMW-CK) were assessed using immunohistochemistry (IHC). Surgical castration was performed to examine androgen dependence. Serum was collected pre- and post-castration for monitoring of PSA levels. RESULTS: BM18 stained positively for hMt, PSA, AR, CK-18, pan keratin, and negatively for HMW-CK, consistent with the staining observed in the original patient material. Androgen-deprivation induced tumor regression in 10/10 castrated male SCID mice. Serum PSA levels positively correlated with BM18 tumor size. CONCLUSIONS BM18 expresses PSA and AR, and rapidly regresses in response to androgen withdrawal. This provides a new clinically significant PrCa model for the study of androgen-dependent growth.

Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.

Removal of methyl orange from aqueous solutions through adsorption by calcium aluminate hydrates

Methyl orange (MO) is a kind of anionic dye and widely used in industry. In this study, tricalcium aluminate hydrates (Ca-Al-LDHs) are used as an adsorbent to remove methyl orange (MO) from aqueous solutions. The resulting products were studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), thermal analysis (TG-DTA) and scanning electron microscope (SEM). The XRD results indicated that the MO molecules were successfully intercalated into the tricalcium aluminate hydrates, with the basal spacing of Ca-Al-LDH expanding to 2.48 nm. The MIR spectrum for CaAl-MO-LDH shows obvious bands assigned to the N@N, N@H stretching vibrations and S@O, SO_ 3 group respectively, which are considered as marks to assess MO_ ion intercalation into the interlayers of LDH. The overall morphology of CaAl-MOLDH displayed a ‘‘honey-comb’’ like structure, with the adjacent layers expanded.

Structure- and composition-dependent electron field emission from nitrogenated carbon nanotips

The electron field emission (EFE) properties of nitrogenated carbon nanotips (NCNTPs) were studied under high-vacuum conditions. The NCNTPs were prepared in a plasma-assisted hot filament chemical vapor deposition system using CH4 and N2 as the carbon and nitrogen sources, respectively. The work functions of NCNTPs were measured using x-ray photoelectron spectroscopy. The morphological and structural properties of NCNTPs were studied by field emission scanning electron microscopy, micro-Raman spectroscopy, and x-ray photoelectron spectroscopy. The field enhancement factors of NCNTPs were calculated using relevant EFE models based on the Fowler-Nordheim approximation. Analytical characterization and modeling results were used to establish the relations between the EFE properties of NCNTPs and their morphology, structure, and composition. It is shown that the EFE properties of NCNTPs can be enhanced by the reduction of oxygen termination on the surface as well as by increasing the ratio of the NCNTP height to the radius of curvature at its top. These results also suggest that a significant amount of electrons is emitted from other surface areas besides the NCNTP tops, contrary to the common belief. The outcomes of this study advance our knowledge on the electron emission properties of carbonnanomaterials and contribute to the development of the next-generation of advanced applications in the fields of micro- and opto-electronics.

Composition-dependent structural and electronic properties of α-(Si1−xCx)3N4

The highly unusual structural and electronic properties of the α-phase of (Si1-xCx)3N4 are determined by density functional theory (DFT) calculations using the Generalized Gradient Approximation (GGA). The electronic properties of α-(Si 1-xCx)3N4 are found to be very close to those of α-C3N4. The bandgap of α-(Si 1-xCx)3N4 significantly decreases as C atoms are substituted by Si atoms (in most cases, smaller than that of either α-Si3N4 or α-C3N4) and attains a minimum when the ratio of C to Si is close to 2. On the other hand, the bulk modulus of α-(Si1-xCx)3N 4 is found to be closer to that of α-Si3N 4 than of α-C3N4. Plasma-assisted synthesis experiments of CNx and SiCN films are performed to verify the accuracy of the DFT calculations. TEM measurements confirm the calculated lattice constants, and FT-IR/XPS analysis confirms the formation and lengths of C-N and Si-N bonds. The results of DFT calculations are also in a remarkable agreement with the experiments of other authors.

Temperature-dependent growth mechanisms of low-dimensional ZnO nanostructures

One-dimensional ZnO nanostructures were successfully synthesized on single-crystal silicon substrates via a simple thermal evaporation and vapour-phase transport method under different process temperatures from 500 to 1000 °C. The detailed and in-depth analysis of the experimental results shows that the growth of ZnO nanostructures at process temperatures of 500, 800, and 1000 °C is governed by different growth mechanisms. At a low process temperature of 500 °C, the ZnO nanostructures feature flat and smooth tips, and their growth is primarily governed by the vapour-solid mechanism. At an intermediate process temperature of 800 °C, the ZnO nanostructures feature cone-shape tips, and their growth is primarily governed by the self-catalyzed and saturated vapour–liquid–solid mechanism. At a high process temperature of 1000 °C, the alloy tip appears on the front side of the ZnO nanostructures, and their growth is primarily governed by the common catalyst-assisted vapour–liquid–solid mechanism. It is also shown that the morphological, structural, optical, and compositional properties of the synthesized ZnO nanostructures are closely related to the process temperature. These results are highly relevant to the development of light-emitting diodes, chemical sensors, energy conversion devices, and other advanced applications.

Temperature-dependent properties of nc-Si thin films synthesized in low-pressure, thermally nonequilibrium, high-density inductively coupled plasmas

Silicon thin films were synthesized simultaneously on single-crystal silicon and glass substrates by lowpressure, thermally nonequilibrium, high-density inductively coupled plasma-assisted chemical vapor deposition from the silane precursor gas without any additional hydrogen dilution in a broad range of substrate temperatures from 100 to 500 °C. The effect of the substrate temperature on the morphological, structural and optical properties of the synthesized silicon thin films is systematically studied by X-ray diffractometry, Raman spectroscopy, UV-vis spectroscopy, and scanning electron microscopy. It is shown that the formation of nanocrystalline silicon (nc-Si) occurs when the substrate temperature is higher than 200 °C and that all the deposited nc-Si films have a preferential growth along the (111) direction. However, the mean grain size of the (111) orientation slightly and gradually decreases while the mean grain size of the (220) orientation shows a monotonous increase with the increased substrate temperature from 200 to 500 °C. It is also found that the crystal volume fraction of the synthesized nc-Si thin films has a maximum value of ∼69.1% at a substrate temperature of 300 rather than 500 °C. This rather unexpected result is interpreted through the interplay of thermokinetic surface diffusion and hydrogen termination effects. Furthermore, we have also shown that with the increased substrate temperature from 100 to 500 °C, the optical bandgap is reduced while the growth rates tend to increase. The maximum rates of change of the optical bandgap and the growth rates occur when the substrate temperature is increased from 400 to 500 °C. These results are highly relevant to the development of photovoltaic thin-film solar cells, thin-film transistors, and flat-panel displays.

Asymptotic minimax robust and misspecified Lorden quickest change detection for dependent stochastic processes

The quick detection of an abrupt unknown change in the conditional distribution of a dependent stochastic process has numerous applications. In this paper, we pose a minimax robust quickest change detection problem for cases where there is uncertainty about the post-change conditional distribution. Our minimax robust formulation is based on the popular Lorden criteria of optimal quickest change detection. Under a condition on the set of possible post-change distributions, we show that the widely known cumulative sum (CUSUM) rule is asymptotically minimax robust under our Lorden minimax robust formulation as a false alarm constraint becomes more strict. We also establish general asymptotic bounds on the detection delay of misspecified CUSUM rules (i.e. CUSUM rules that are designed with post- change distributions that differ from those of the observed sequence). We exploit these bounds to compare the delay performance of asymptotically minimax robust, asymptotically optimal, and other misspecified CUSUM rules. In simulation examples, we illustrate that asymptotically minimax robust CUSUM rules can provide better detection delay performance at greatly reduced computation effort compared to competing generalised likelihood ratio procedures.