All members of the Eph receptor family of tyrosine kinases contain a SAM domain near the C terminus, which has been proposed to play a role in receptor homotypic interactions and/or interactions with ...binding partners. The SAM domain of EphA2 is known to be important for receptor function, but its contribution to EphA2 lateral interactions in the plasma membrane has not been determined. Here we use a FRET-based approach to directly measure the effect of the SAM domain on the stability of EphA2 dimers on the cell surface in the absence of ligand binding. We also investigate the functional consequences of EphA2 SAM domain deletion. Surprisingly, we find that the EphA2 SAM domain inhibits receptor dimerization and decreases EphA2 tyrosine phosphorylation. This role is dramatically different from the role of the SAM domain of the related EphA3 receptor, which we previously found to stabilize EphA3 dimers and increase EphA3 tyrosine phosphorylation in cells in the absence of ligand. Thus, the EphA2 SAM domain likely contributes to a unique mode of EphA2 interaction that leads to distinct signaling outputs.
Abstract
The optical properties of silver and gold based bimetallic alloys make possible to adjust their plasma frequency. The direct alloying and plasmonic activity of thin layers from the Au-Sb ...system are presented in the present work. The thin films were deposited by thermal co-evaporation of gold and antinomy. The chemical and phase composition of thin films, were analysed by X-ray microanalysis and X-ray diffraction (XRD), respectively. The results of the X-ray microanalysis show that the composition of the thin layers corresponds well to the predetermined. The XRD patterns, depending on the envisaged compositions, show formation of intermetallic compound AuSb
2
and binary alloys between the initial elements and the intermediate compound, which is in accordance with the Au-Sb phase diagram.
The dispersion of the complex permittivity was determined by spectroscopic ellipsometry. The results show that the increase of the antimony content leads to an increase of the values of the imaginary part of the complex permittivity in the visible spectral region at photon energies greater than 3 eV, and a decrease in the ultraviolet spectral region. Based on the obtained dispersions of the complex permittivity, extinction cross-sections and local field enhancement of spherical Au-Sb nanoparticles were determined and their plasmon activity was evaluated.
In this paper a model of Hopfield’s graded response neural network is investigated. A network whose neurons are subject to a certain impulsive state displacement at random times is considered. The ...model is set up and studied. The presence of random moments of impulses in the model leads to a change of the solutions to stochastic processes. Also, we use the Riemann–Liouville fractional derivative to model adequately the long-term memory and the nonlocality in the neural networks. We set up in an appropriate way both the initial conditions and the impulsive conditions at random moments. The application of the Riemann–Liouville fractional derivative leads to a new definition of the equilibrium point. We define mean-square Mittag-Leffler stability in time of the equilibrium point of the model and study this type of stability. Some sufficient conditions for this type of stability are obtained. The general case with time varying self-regulating parameters of all units and time varying functions of the connection between two neurons is studied.
In bitumen recovery from oil sands, solvent addition is used to destabilize the water-in-diluted bitumen emulsions and separate the valuable oil product from water and solids. For each solvent, a ...critical solvent-to-bitumen ratio or critical dilution can be determined that coincides with the onset of bulk asphaltene precipitation, at which the system properties change abruptly. Above the critical dilution, solvent addition promotes bulk asphaltene precipitation and separation by the agglomeration of water droplets, solids and precipitated asphaltenes. Below the critical dilution, separation occurs by the coalescence of water droplets. The properties of the water-diluted bitumen interface could be key to improving the mechanistic understanding of water-in-diluted bitumen emulsions and bitumen recovery. In this work, we explore the behavior of water-in-diluted bitumen emulsions at macro- and microscopic scales, and provide novel insights at conditions below critical dilution. Bench scale bitumen froth treatment settling experiments highlight the possibility to attain effective water and solids separation based on agglomeration, without any noticeable bulk asphaltene precipitation. Light microscopy images reveal the inhibition of water droplet coalescence and the initiation of agglomeration due to the transformation of the oil continuous phase into a gel-like structure in the contact zone between water droplets. Thin liquid film observations show drastic changes in the continuous oil phase properties in the contact zone between water droplets at similar conditions that are attributed to the formation of both asphaltene aggregates at the interface and an oil gel-like structure that expands around them. These findings lead to the proposal that agglomeration can occur below critical dilution by surface asphaltene precipitation at the water-oil interface, without bulk asphaltene precipitation. The multiscale insights highlight opportunities to improve further not only bitumen froth treatment but also other oil-water-solids separation processes.
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•Effective water-solids-oil separation in the transition region without bulk asphaltene precipitation.•Transformation of the oil continuous phase to a gel-like structure at the water droplets contact zone.•Oil-gel structure expansion from interface into the contact zone prevents the liquid film drainage.•Coalescence inhibition and agglomeration initiation due to the contact zone transformations.•Agglomeration can occur below critical dilution initiated by surface asphaltene precipitation.
Aims
Availability of normative reference values for cardiac chamber quantitation is a prerequisite for accurate clinical application of echocardiography. In this study, we report normal reference ...ranges for cardiac chambers size obtained in a large group of healthy volunteers accounting for gender and age. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following chamber quantitation protocols approved by the European Association of Cardiovascular Imaging.
Methods
A total of 734 (mean age: 45.8 ± 13.3 years) healthy volunteers (320 men and 414 women) were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was performed on all subjects following pre-defined protocols. There were no gender differences in age or cholesterol levels. Compared with men, women had significantly smaller body surface areas, and lower blood pressure. Quality of echocardiographic data sets was good to excellent in the majority of patients. Upper and lower reference limits were higher in men than in women. The reference values varied with age. These age-related changes persisted for most parameters after normalization for the body surface area.
Conclusion
The NORRE study provides useful two-dimensional echocardiographic reference ranges for cardiac chamber quantification. These data highlight the need for body size normalization that should be performed together with age-and gender-specific assessment for the most echocardiographic parameters.
In the present work the synthesis of silver nanoparticles by the polyol method is investigated. The self-seeding polyol process was chosen from the number of variations of this method. In this ...approach AgNO3 was used as a precursor, poly (N-vinylpyrrolidone) (PVP) as capping agent and ethylene glycol as solvent and reducing agent. We investigated the influence of the molecular weight of PVP on the microstructure of the particles considering a polymer with molecular weight Mw = 58 and 360 K by changing the molar ratio of PVP/AgNO3 for both polymers. The molar ratios were varied from 0.5 to 2.5. The as prepared nanoparticles were characterized by microscopic and structural methods. The shape and the size distribution were characterized by Transmission Electron Microscopy. The crystal structure of the nanoparticles was studied by X-ray Diffraction and Selected Area Electron Diffraction. Due to their plasmonic properties, the silver nanoparticles find application for improvement of the efficiently of the solar cells, substrates for surface-enhanced Raman and florescence spectroscopies. All these applications require the frequencies of the localized surface plasmon resonance (LSPR) to appear at an exact position. Therefore we indicated the wavelength of the LSPR of the as prepared nanoparticles trough the absorbance spectra. A variation between 380 and 470 nm was observed.
Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a ...post‐translational modification caused by Ca+2‐regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue‐specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection lipopolysaccharide (LPS) stimulation murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan‐PAD inhibitor Cl‐amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS‐treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl‐amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug‐directed intervention in neurotrauma.
Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up‐regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage.
Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up‐regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage.
In this paper a search for associated charm production both in neutral and charged current ν-nucleus interactions is presented. The improvement of automatic scanning systems in the CHORUS experiment ...allows an efficient search to be performed in emulsion for short-lived particles. Hence a search for rare processes, like the associated charm production, becomes possible through the observation of the double charm-decay topology with a very low background. About 130000 ν interactions located in the emulsion target have been analysed. Three events with two charm decays have been observed in the neutral-current sample with an estimated background of 0.18±0.05. The relative rate of the associated charm cross-section in deep inelastic ν interactions, σ(cc̄ν)/σNCDIS=(3.62+2.95-2.42(stat)±0.54(syst))×10-3 has been measured. One event with two charm decays has been observed in charged-current νμ interactions with an estimated background of 0.18±0.06 and the upper limit on associated charm production in charged-current interactions at 90% C.L. has been found to be σ(cc̄μ-)/σCC<9.69×10-4.
Purulent wounds are associated with microbial persistence that alters healing and can lead to septic complications. Infected wound management includes use of antibacterial agents for providing fast ...and complete bacterial elimination with no adverse effects on tissue repair. The performance of chlorhexidine (Ch) irrigation as the main strategy for purulent wound treatment is still under debates and stimulates further development of antimicrobial strategies. In this study, the effects of silver nanoparticles (AgNP) on infected wound microbiology and healing were assessed in vitro and in vivo. AgNPs provided high antibacterial activity at the minimal inhibitory concentration (MIC) of 1.25 μg/mL for
E. coli
and
P. aeruginosa
, and 2.5 μg/mL for
S. aureus
. At the same time assessment of AgNPs, cytotoxicity in fibroblast culture demonstrated high cytocompatibility in concentrations 5 times higher than MIC. These data agreed with in vivo studies with purulent wound modeling followed by use of three treatment options: Ch-, AgNP, and Ch+AgNP wound dressings. It was shown that AgNP treatment effectively decreased the microbial contamination but had only slight effect on wound healing parameters. In contrast, Ch+AgNP combination was associated with significant acceleration of wound clearance and closure related with early M2 macrophage polarization and an enhanced healing process. In conclusion, adding of AgNPs to chlorhexidine treatment improves infected wound healing through acceleration of bacteria elimination and M2 macrophage polarization. Synergic effects of AgNPs and chlorhexidine could be a promising option for optimizing infected wound management.
Graphical abstract
Gemcitabine plus carboplatin (GC) is active as front-line treatment for advanced non-small-cell lung cancer (NSCLC). For patients without progression, timing of second-line chemotherapy for optimum ...clinical benefit remains uncertain. This phase III, randomized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression.
The chemotherapy-naïve patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC. Gemcitabine (1,000 mg/m(2)) was administered on days 1 and 8 followed by carboplatin (area under the curve = 5) on day 1. After four 21-day cycles, patients who did not have progression were randomly assigned either to an immediate docetaxel group (docetaxel 75 mg/m(2) on day 1 every 21 days, with maximum of six cycles) or to a delayed docetaxel group. The primary end point was overall survival (OS) measured from random assignment. Additional analyses included tumor response, toxicity, progression-free survival (PFS), and quality of life (QOL).
Enrollment totaled 566 patients; 398 patients completed GC; 309 patients were randomly assigned equally to the two docetaxel treatment groups. Toxicity profiles were generally comparable for the docetaxel groups. Median PFS for immediate docetaxel (5.7 months) was significantly greater (P = .0001) than for delayed docetaxel (2.7 months). Median OS for immediate docetaxel (12.3 months) was greater than for delayed docetaxel (9.7 months), but the difference was not statistically significant (P = .0853). QOL results were not statistically different (P = .76) between docetaxel groups.
We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC, without increasing toxicity or decreasing QOL.
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