Hardening of the nanoparticle-protein corona in metal (Au, Ag) and oxide (Fe3O4, CoO, and CeO2) nanoparticles

The surface modifications of metal and metal oxide nanoparticles with sizes ranging from 7 to 20 nm dispersed in commonly used cell culture medium supplemented with serum are investigated. All the tested nanoparticles adsorb proteins onto their surface, thereby forming a protein corona through a dynamic process evolving towards an irreversible coating (hard protein corona). Despite the fact that the studied nanomaterials have similar characteristics of hydrophobicity and surface charge, different temporal patterns of the protein corona formation are observed that can be considered a fingerprint for nanoparticle identification. Some of the biological and toxicological implications of the formation of the nanoparticle-protein corona are studied using the human monocytic cell line THP-1 exposed to cobalt oxide nanoparticles. Results show that production of reactive oxygen species is decreased if the nanoparticles are preincubated for 48 h with serum.     

Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples

The metabolic ratios lactate/pyruvate and β-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of the four metabolites in plasma and liver tissue. The procedure included an o-phenylenediamine microwave-assisted derivatization, followed by liquid-liquid extraction with ethyl acetate and silylation with bis(trimethylsilyl)trifluoroacetamide:trimethylchlorosilane 99:1. The calibration curves presented acceptable linearity, with a limit of quantification of 0.001 mM for pyruvate, β-hydroxybutyrate and acetoacetate and of 0.01 mM for lactate. The intra-day and inter-day accuracy and precision were within the European Medicines Agency’s Guideline specifications. No significant differences were observed in the slope coefficient of three-point standard metabolite-spiked curves in plasma or liver and water, and acceptable recoveries were obtained in the metabolite-spiked samples. Applicability of the method was tested in precision-cut liver rat slices and also in HepG2 cells incubated under different experimental conditions challenging the redox state. In conclusion, the validated method presented good sensitivity, specificity and reproducibility in the quantification of lactate/pyruvate and β-hydroxybutyrate/acetate metabolites and may be useful in the evaluation of in vivo redox states.     

Performance Evaluation of Layer 3 Low Latency Handoff Mechanisms

This paper investigates the performance of two Layer 3 low latency handoff mechanisms proposed by the IETF, namely Pre- and Post-Registration. These protocols use Layer 2 triggers to reduce the built-in delay components of Mobile IP. We propose a simple analytical model that allows assessing the packet loss and the delay characteristics of these mechanisms. We describe several handoff implementations over a wireless access based on the IEEE 802.11 standard and analyze several implementation issues. Finally we study the scalability of the protocols using an OPNET simulation.     

Auto-adaptive robot-aided therapy using machine learning techniques

This paper presents an application of a classification method to adaptively and dynamically modify the therapy and real-time displays of a virtual reality system in accordance with the specific state of each patient using his/her physiological reactions. First, a theoretical background about several machine learning techniques for classification is presented. Then, nine machine learning techniques are compared in order to select the best candidate in terms of accuracy. Finally, first experimental results are presented to show that the therapy can be modulated in function of the patient state using machine learning classification techniques.     

Fabrication and electrical characterization of circuits based on individual tin oxide nanowires

Two-?and four-probe electrical measurements on individual tin oxide (SnO(2)) nanowires were performed to evaluate their conductivity and contact resistance. Electrical contacts between the nanowires and the microelectrodes were achieved with the help of an electron-?and ion-beam-assisted direct-write nanolithography process. High contact resistance values and the nonlinear current-bias (I-V) characteristics of some of these devices observed in two-probe measurements can be explained by the existence of back-to-back Schottky barriers arising from the platinum-nanowire contacts. The nanoscale devices described herein were characterized using impedance spectroscopy, enabling the development of an equivalent circuit. The proposed methodology of nanocontacting and measurements can be easily applied to other nanowires and nanometre-sized materials.     

Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver.